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Table of Content
18 April 2018, Volume 50 Issue 2
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  • Article
    Role of aquaporin-4 in the change of interstitial fluid drainage in Alzheimer’s disease
    LIU E, ZHANG Yi-xuan, SUN Lin-lin,TENG Ze, WANG Ai-bo, HAN Hong-bin, YAN Jun-hao
    2018, (2):  203-206.  doi: 10.3969/j.issn.1671-167X.2018.02.001     PMID: 29643515
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    Objective: To observe the characteristics of the interstitial fluid (ISF) drainage in the Alzheimer’s disease (AD) rats through magnetic resonance imaging (MRI) tracer gadolinium-diethylene triamine pentacetic acid (Gd-DTPA)spread in the brain extracellular space (ECS) and to discuss the role of aquaporin-4 (Aqp4) in the AD. Methods: Wild type SD rats (300-350 g) and Aqp4 gene knock out (Aqp4-/-) SD rats (300-350g) were divided into Sham group, AD group, Aqp4-/-Sham group and Aqp4-/--AD group. Sham group and Aqp4-/--Sham group were injected with saline by intraperitoneal each day for 6 weeks, and the AD group and Aqp4-/--AD group were injected with D-galactose by intraperitoneal each day for 6 weeks. MRI tracer Gd-DTPA (10 mmol/L, 2 μL) was injected into the hippocampus of the rats. MRI scan was performed at the end of 0.5 h, 1.5 h, 1 h, 2 h, and 3 h to observe the dynamic distribution of the Gd-DTPA in the hippocampus and the diffusion rate D*, clearance rate k′ and half-life t1/2 measured. Results: The diffusion rate D* in Sham group was (2.66±0.36)×10-6 mm2/s, the diffusion rate D* in AD group was (2.72±0.62)×10-6 mm2/s, the diffusion rate D* in Aqp4-/--Sham group was (2.75±0.47)×10-6  mm2/s, the diffusion rate D* in Aqp4-/--AD group was (2.802±0.55)×10-6  mm2/s, and there was no statistically significant difference in the four groups (One-Way ANOVA, P>0.05).The clearance rate k′ in Sham group was (4.57±0.14)×10-4/s, the clearance rate k′ in AD group was (3.68±0.22)×10-4/s, the clea-rance rate k′ in Aqp4-/-Sham group was (3.17±0.16)×10-4/s, the clearance rate k′ in Aqp4-/--AD group was (2.59±0.19)×10-4/s, and there was significant difference in the four groups (One-Way ANOVA, P<0.05). The halflife t1/2 in Sham group was (0.67±0.12) h, the halflife t1/2 in AD group was (0.88±0.08) h, the half-life t1/2 in Aqp4-/--Sham group was (1.12±0.15) h, the half-life t1/2 in Aqp4-/--AD group was (1.58±0.11) h, and there was significance difference in the four groups(oneway ANOVA,P<0.05). Conclusion: The ISF drainage is slow after AD and the loss of Aqp4 in the AD makes the ISF drainage obviously slow down, Aqp4 plays an important role in AD to remove the metabolism of waste out of the brain.
    Preliminary study of robot-assisted ankle rehabilitation for children with cerebral palsy
    WANG Rong-li, ZHOU Zhi-hao, XI Yu-cheng, WANG Qi-ning, WANG Ning-hua, HUANG Zhen
    2018, (2):  207-212.  doi: 10.3969/j.issn.1671-167X.2018.02.002     PMID: 29643516
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    Objective: To propose a kind of robotic ankle-foot rehabilitation system for children with cerebral palsy and to preliminarily verify its feasibility in clinical application. Methods: A robot assisted ankle-foot rehabilitation system was specially designed and developed for children with cerebral palsy and a preliminary clinical study was conducted in Department of Rehabilitation Medicine, Peking University First Hospital. Modified Tardieu Scale and joint biomechanical properties (ankle plantar flexion resis-tance torque under different ankle dorsiflexion angles) were measured to analyze the muscle tone and soft tissue compliance of the ankle plantar flexors pre- and post-robotic training intervention. Six children with cerebral palsy (4 girls and 2 boys, mean age: 7 years) were recruited in this study. Each subject received 5 session robotic training and each session included 10-cycle passive stretching and static hold. SPSS 19.0 software was used for data statistical analysis. Results: Both R1 and R2 angles of Modified Tardieu Scale for ankle plantar flexors after training were significantly higher than those before the treatments (Gastrocnemius: PR1=0.003, PR2=0.029; Soleus: PR1=0.002, PR2=0.034). The difference between R2 and R1 was of no statistical difference before and after the training (P=0.067 and P=0.067, respectively). After training, the ankle plantar flexion resistance torque under different dorsi-flexion angles (0°, 10°, 20°, 30°) were significantly reduced than those before training (P=0.001, P=0.001, P=0.014, P=0.002, respectively). Conclusion: The robot assisted ankle-foot rehabilitation system can improve the contracture and soft tissue compliance of cerebral palsy children’s ankle plantar flexors. All the children in the study were well tolerated and interested with the training, easy to accept and cooperate with it. This device may be suitable for application in the rehabilitation of children with cerebral palsy. However, further randomized clinical trials with larger sample size are still needed to verify the long term efficacy of this device.
    Application of scalp-recorded high-frequency oscillations in epileptic encephalopathy with continuous spike-and-wave during sleep
    GONG Pan, YANG Zhi-xian, XUE Jiao, QIAN Ping, YANG Hai-po, LIU Xiao-yan,BIAN Kai-gui
    2018, (2):  213-220.  doi: 10.3969/j.issn.1671-167X.2018.02.003     PMID: 29643517
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    Objective: To investigate the clinical significance of high-frequency oscillations (HFOs) on scalp electroencephalography (EEG) in patients with epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS). Methods: Twenty-one CSWS patients treated for epilepsy from January 2006 to December 2016 in Pediatric Department of Peking University First Hospital were enrolled into the study. Selected clinical variables including gender, age parameters, seizure frequencies and antiepileptic drugs were compared between (a). HFO-positive group and HFO-negative group before methylprednisolone treatment and (b). excellent seizure outcome group and not-excellent seizure outcome group after methylprednisolone treatment. Interictal HFOs and spikes in pre-and postmethylprednisolone scalp EEG were measured and analyzed. Results: Before methylprednisolone treatment, there were 12 of 21 (57%) CSWS patients had HFOs, with a mean value 43.17 per 60 s per patient. The 12 patients with HFOs tended to have more frequent epileptic negative myoclonus/atonic/myoclonus/atypical absences than those without HFOs in a month before methylprednisolone treatment. A total of 518 HFOs and 22 592 spikes were found in the pre-methylprednisolone EEG data of 21 patients, and 441 HFOs (86%) were associa-ted with spikes. The highest amplitudes of HFOs were significantly positively correlated with that of spikes (r=0.279, P<0.001). Rates reduced by methylprednisolone treatment were statistically significant for both HFOs (P=0.002) and spikes (P=0.006). The percentage of reduction was 91% (473/518) and 39% (8 905/22 592) for spikes and HFOs, respectively. The percentage of spike and HFOs changes was respectively 100% decrease and 47% decrease in the excellent seizure outcome group, and they were 79% decrease and 18% increase in the not-excellent seizure outcome group. Conclusion: Prevalence of HFOs might reflect some aspect of epileptic activity. HFOs were more sensitive to methylprednisolone treatment than spikes and had a good correlation with the prognosis of seizures, and HFOs could be applied to assess epilepsy severity and antiepileptic therapy.
    Application of anoptomagnetic probe Gd-DO3A-EA-FITC in imaging and analyzing the brain interstitial space
    LI Yun-qian1,2,3, SHENG Hui, LIANG Lei, ZHAO Yue, LI Huai-ye, BAI Ning, WAN Tong, YUAN Lan, HAN Hong-bin
    2018, (2):  221-225.  doi: 10.3969/j.issn.1671-167X.2018.02.004     PMID: 29643518
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    Objective: To investigate the application of the optical magnetic bimodal molecular probe Gd-DO3A-ethylthiouret-fluorescein isothiocyanate (Gd-DO3A-EAFITC) in brain tissue imaging and brain interstitial space (ISS). Methods: In the study, 24 male SD rats were randomly divided into 3 groups, including magnetic probe group (n=6), optical probe group (n=6) and optical magnetic bimodal probe group (n=12), then the optical magnetic bimodal probe group was divided equally into magnetic probe subgroup (n=6) and optical probe subgroup (n=6). Referencing the brain stereotaxic atlas, the coronal globus pallidus as center level, the probes including gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA), fluorescein isothiocyanate (FITC) and Gd-DO3A-EA-FITC of 2 μL (10 mmol/L) were injected into the caudate nucleus respectively, magnetic resonance imaging (MRI) was performed in the magnetic probe group and magnetic probe subgroup to image the dynamic diffusion and distribution of the probes in the brain ISS, a self-developed brain ISS image processing system was used to measure the diffusion coefficient, clearance, volume fraction and half-time in these two groups. Laser scanning confocal microscope (LSCM) was performed in vitro in the optical probe group and optical probe subgroup for fluorescence imaging at the time points 2 hours after the injection of the probe, and the distribution in the oblique sagittal slice was compared with the result of the first two groups. Results: For the magnetic probe group and magnetic probe subgroup, there were the same imaging results between the probes of Gd-DTPA and Gd-DO3A-EA-FITC. The diffusion parameters of Gd-DTPA and GdDO3A-EA-FITC were as follows: the average diffusion coefficients [(3.31±0.11)×10-4 mm2/s vs. (3.37±0.15)×10-4 mm2/s, t=0.942, P=0.360], the clearance [(3.04±0.37) mmol/L vs. (2.90±0.51) mmol/L, t=0.640, P=0.531], the volume fractions (17.18%±0.14% vs. 17.31%±0.15%, t=1.961, P=0.068), the half-time [(86.58±3.31) min vs. (84.61±2.38) min, t=1.412, P=0.177], the diffusion areas [(23.25±0.68) mm2 vs. (22.71±1.00) mm2, t=1.100, P=0.297]. The statistical analysis of each brain was made by t test, and the diffusion parameters were not statistically significant. Moreover, for the optical probe group and optical probe subgroup, the diffusion area of Gd-DO3A-EA-FITC [(22.61±1.16) mm2] was slightly larger than that of FITC [(22.10±1.29) mm2], the statistical analysis of each brain was made by t test, and the diffusion parameters were not statistically significant (t=0.713, P=0.492). Conclusion: Gd-DO3AEA-FITC shows the same imaging results as the traditional GD-DTPA, and it can be used in measuring brain ISS.
    Dynamic visual analysis of neutrophils chemotaxis in peritoneal cavity of schizophrenic model in mice
    BAI Ning,YANG Ling-fei,AN Li-hua,WANG wen,LI Yun-qian,SHENG Hui,WANG Tong,LI Hua-kan,YUAN Lan
    2018, (2):  226-230.  doi: 10.3969/j.issn.1671-167X.2018.02.005     PMID: 29643519
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    Objective: To compare the differences of neutrophils chemotaxis ability in  peritoneal cavity between normal rats and schizopherenic rats with cell dynamic visualization system. Methods: In the study,18 healthy Kunming rats were randomly divided into 3 groups which were control group(n=6), 0.3 mg/kg MK801 treatment group(n=6), 0.6 mg/kg dizocilpine maleate (MK-801) treatment group(n=6), extracted neutrophils separately, and observed the morphology and counted under a microscope. Each group of cells was divided into two parts for chemotactic experiment, called chemokine agent treatment group and no chemokine agent treatment group respectively, indicating control 1,0.3 mg/kg MK801 treatment 1,0.6 mg/kg MK-801 treatment 1 and control 2,0.3 mg/kg MK-801 treatment 2,0.6 mg/kg MK-801 treatment 2.The dynamic migration of cells was recorded using the NIS-Elements software, and TAXIScan Analyzer 2 software was used to select 30 cells (n=30) in each group of cells and analyze cells migration trajectory, speed and distance, and use pair test and One-Way analysis of variance for statistical analysis. Results: The number of neutrophils in control group, 0.3 mg/kg MK-801 treatment group and 0.6 mg/kg MK-801 treatment group were(1.00±0.03)×104/mL,(0.05±0.02)×104/mL,(0.32±0.01)×104/mL respectively, the differences of results were statistically significant(P<0.05).Under the effect of chemotactic agent,the directional migration capability of neutrophils in control group 1, 0.3 mg/kg MK-801 treatment group 1 and 0.6 mg/kg MK-801 treatment group 1 were(0.85±0.11) radian,(1.00±0.11) radian,(0.96±0.10) radian respectively (P<0.05); the migration velocities of neutrophils were (0.09±0.02) μm/s,(0.12±0.01) μm/s,(0.14±0.01) μm/s respectively (P<0.05);the migration distances of neutrophils were (94.26±0.02) μm,(134.61±0.01) μm,(156.19±0.01) μm respectively(P<0.05). Conclusion: Compared with neutrophils in peritoneal cavity of control group, the neutrophils in peritoneal cavity of schizophrenic rats have stronger chemotactic movement ability.
    Comparison of gut microbiotal compositional analysis of patients with irritable bowel syndrome through different bioinformatics pipelines
    ZHU Shi-wei, LIU Zuo-jing, LI Mo, ZHU Huai-qiu, DUAN Li-ping
    2018, (2):  231-238.  doi: 10.3969/j.issn.1671-167X.2018.02.006     PMID: 29643520
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    Objective: To assess whether the same biological conclusion, diagnostic or curative effects regarding microbial composition of irritable bowel syndrome (IBS) patients could be reached through different bioinformatics pipelines, we used two common bioinformatics pipelines (Uparse V2.0 and Mothur V1.39.5)to analyze the same fecal microbial 16S rRNA high-throughput sequencing data. Methods: The two pipelines were used to analyze the diversity and richness of fecal microbial 16S rRNA high-throughput sequencing data of 27 samples, including 9 healthy controls (HC group), 9 diarrhea IBS patients before (IBS group) and after Rifaximin treatment (IBStreatment, IBSt group). Analyses such as microbial diversity, principal coordinates analysis (PCoA), nonmetric multidimensional scaling (NMDS) and linear discriminant analysis effect size (LEfSe) were used to find out the microbial differences among HC group vs. IBS group and IBS group vs. IBSt group. Results: (1) Microbial composition comparison of the 27 samples in the two pipelines showed significant variations at both family and genera levels while no significant variations at phylum level; (2) There was no significant difference in the comparison of HC vs. IBS or IBS vs. IBSt (Uparse: HC vs. IBS, F=0.98,P=0.445;IBS vs. IBSt,F=0.47,P=0.926; Mothur:HC vs.IBS, F=0.82, P=0.646;IBS vs. IBSt, F=0.37, P=0.961). The Shannon index was significantly decreased in IBSt; (3) Both workshops distinguished the significantly enriched genera between HC and IBS groups. For example, Nitrosomonas and Paraprevotella increased while Pseudoalteromonadaceae and Anaerotruncus decreased in HC group through Uparse pipeline, nevertheless Roseburia 62 increased while Butyricicoccus and Moraxellaceae decreased in HC group through Mothur pipeline.Only Uparse pipeline could pick out significant genera between IBS and IBSt, such as Pseudobutyricibrio, Clostridiaceae 1 and Clostridiumsensustricto 1. Conclusion: There were taxonomic and phylogenetic diversity differences between the two pipelines, Mothur can get more taxonomic details because the count number of each taxonomic level is higher. Both pipelines could distinguish the significantly enriched genera between HC and IBS groups, but Uparse was more capable to identity the dif-ference between IBS and IBSt groups. To increase the reproducibility and reliability and to retain the consistency among similar studies, it is very important to consider the impact on different pipelines.
    Application of support vector machine in predicting in-hospital mortality risk of patients with acute kidney injury in ICU
    LIN Ke, XIE Jun-qing, HU Yong-hua, KONG Gui-lan
    2018, (2):  239-244.  doi: 10.3969/j.issn.1671-167X.2018.02.007     PMID: 29643521
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    Objective: To construct an in-hospital mortality prediction model for patients with acute kidney injury (AKI) in intensive care unit (ICU) by using support vector machine (SVM), and compare it with the simplified acute physiology score Ⅱ (SAPS-Ⅱ) which is commonly used in the ICU. Methods: We used Medical Information Mart for Intensive Care Ⅲ (MIMIC-Ⅲ) database as data source. The AKI patients in the MIMIC-Ⅲ database were selected according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) definition of AKI. We employed the same predictor variable set as used in SAPS-Ⅱ to construct an SVM model. Meanwhile, we also developed a customized SAPS-Ⅱ mo-del using MIMIC-Ⅲ database, and compared performances between the SVM model and the customized SAPS-Ⅱ model. The performance of each model was evaluated via area under the receiver operation characteristic curve (AUROC), root mean squared error (RMSE), sensitivity, specificity, Youden’s index and accuracy based on 5-fold cross-validation. The agreement of the results between the SVM mo-del and the customized SAPS-Ⅱ model was illustrated using Bland-Altman plots. Results: A total number of 19 044 patients with AKI were included. The observed in-hospital mortality of the AKI patients was 13.58% in MIMIC-Ⅲ. The results based on the 5-fold cross validation showed that the average AUROC of the SVM model and the customized SAPS-Ⅱ model was 0.86 and 0.81, respectively (The difference between the two models was statistically significant with t=13.0, P<0.001). The average RMSE of the SVM model and the customized SAPS-Ⅱ model was 0.29 and 0.31, respectively (The difference was statistically significant with t=-9.6, P<0.001). The SVM model also outperformed the customized SAPS-Ⅱ model in terms of sensitivity and Youden’s index with significant statistical differences (P = 0.002 and <0.001, respectively).The Bland-Altman plot showed that the SVM model and the custo-mized SAPS-Ⅱ model had similar mortality prediction results when the mortality of a patient was certain, but the consistency between the mortality prediction results of the two models was poor when the mortality of a patient was with high uncertainty. Conclusion: Compared with the SAPS-Ⅱ model, the SVM model has a better performance, especially when the mortality of a patient is with high uncertainty. The SVM model is more suitable for predicting the mortality of patients with AKI in ICU and early intervention in patients with AKI in ICU. The SVM model can effectively help ICU clinicians improve the quality of me-dical treatment, which has high clinical value.
    Three-dimensional architecture of intraosseous vascular anatomy of the hamate: a micro-computed tomography study
    WANG Ding-yu, LI Xu, SHEN Zhong-cheng, GU Pei-liang, PEI Yu-ru, ZENG Gang, LENG Hui-jie, ZHANG Wei-guang
    2018, (2):  245-248.  doi: 10.3969/j.issn.1671-167X.2018.02.008     PMID: 29643522
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    Objective: To obtain three-dimensional intraosseous artery of the hamate and to provide the vascular anatomy basis of hamate fracture fixation. Methods: PbO (lead monoxide, Sinopharm Chemical Reagent Beijing Co. Ltd) was ground into particles less than 40 μm and suspended in turpentine oil (Chemical Reagent Beijing Co. Ltd) at ratios of 1 g ∶1.5 mL, 1 g ∶1 mL and 1 g ∶0.5 mL. Three specimens were investigated. Brachial arteries were cannulated and perfused with lead-based contrast agent. Hamates were harvested and scanned using micro-computed tomography (microCT). The acquisition protocols were as follows: CT scan setup: total rotation [Degrees], 360; rotation steps, 360; X-ray detector setup: transaxial, 2048; axial, 2048; exposure time, 1 500 ms, Binning, 1; system magnification: high-med. X-ray tube setup: 80 kV, 500 mA current. The down-sampling factor used in the reconstruction was 2. The effective voxel size of the final image was 27.30 μm. The three-dimensional model of the hamate was generated and the distribution and pattern of vessels were evaluated. Results: There were abundant extraosseous vessels around the hamate. They were mainly running in the tendons and li-gaments around the hamate. Four vascular zones were identified on the hamate surface. They were on the palmar platform of the hamate body, on the dorsal side, on the ulnar side and on the tip of hamulus, namely. There were anastomoses among 4 vascular zones. We did not observe any vessels penetrating through the articular cartilage. The extraosseous vessels of the vascular zones gave a number of intraosseous branches into the hamate. The hamate body received intraosseous blood supply from the dorsal, palmar and ulnar while the hamulus from the palmar, ulnar and hamulus tip. There were some intraosseous branches anastomosing with each other. Conclusion: The extraosseous and intraosseous vessels of the hamate were more than what used to be considered. The hamate body and hamulus received blood supply from multiple directions and arteries anastomosed extensively both outside and inside the hamate, making it possible that the intraosseous perfusion survived after fracture. It is likely that the nonunion after the hamate fracture is not caused by the vascular damage but the malalignment of the fragments.
    Mesoporous nano-bioactive glass microspheres as a drug delivery system of mino-cycline
    ZHU Lin, WANG Yu-dong, DONG Yan-mei,CHEN Xiao-feng
    2018, (2):  249-255.  doi: 10.3969/j.issn.1671-167X.2018.02.009     PMID: 29643523
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    Objective: To construct mesoporous nano-bioactive glass (MNBG) microspheres load-release minocycline as an antibacterial drug delivery system. Methods: Sol-gel method was used to synthesze MNBG microspheres as drug carrier. The MNBG consisted of SiO2, CaO, and P2O5. According to the content of silicon, MNBG microspheres were divided into four groups (60S, 70S, 80S and 90S). Scanning electron microscopy (SEM) was used to observe the surface characteristic and particle size of MNBG; Nitrogen adsorption-desorption experiment was performed to calculate the MNBG’s specific surface area and the pore sizes; The Fourier transform infrared spectrum (FT-IR) and the thermogravimetric analysis were conducted to calculate the loading efficiencies of minocycline hydrochloride; UV spectrophotometric was used to determine the cumulative release of minocycline from drug-loaded particles in PBS solution within 21 d. Agar diffusion test (ADT) was performed to evaluate the antibacterial properties on Enterococcus faecalis. The inhibition zone was observed and the diameter was measured. Results: The MNBG microspheres had good dispersion, large surface area, and even particle size. The pore sizes ranged from 4.77 nm to 7.33 nm. The loading experiment results showed that the minocycline hydrochloride loading efficiency of MNBG was related to the pore size of the microspheres. Among 60S, 70S, 80S and 90S, 60S MNBG had the highest loading efficiency of 16.33% due to its high calcium content and large pore sizes. A slow minocycline release rate from MNBG particles in PBS solution until d 21 was observed. It was showed that a burst release of 28% of the total drug for the first 24 h. A cumulative release of 35% was found, and the final concentration of minocycline maintained at about 47 mg/L. ADT showed that mino-MNBG had inhibitory effect on the growth of Enterococcus faecalis. 1 g/L minocycline, 1 g/L mino-MNBG, and 0.1 g/L minocycline presented inhibition zone, however, PBS and 1 g/L MNBG didn’t. The diameter of the inhibition zone of minocycline groups was significant larger than that of mino-MNBG group (P<0.05), which was also significant larger than those of PBS and MNBG groups (P<0.05). It showed that mino-MNBG drug delivery system had antibacterial properties on Enterococcus faecalis.  Conclusion: The 60S MNBG that can effectively load and release minocycline may be an ideal drug carrier.
    A customized method for information extraction from unstructured text data in the electronic medical records
    BAO Xiao-yuan, HUANG Wan-jing, ZHANG Kai, JIN Meng, LI Yan, NIU Cheng-zhi
    2018, (2):  256-263.  doi: 10.3969/j.issn.1671-167X.2018.02.010     PMID: 29643524
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    Objective: There is a huge amount of diagnostic or treatment information in electronic me-dical record (EMR), which is a concrete manifestation of clinicians actual diagnosis and treatment details. Plenty of episodes in EMRs, such as complaints, present illness, past history, differential diagnosis, diagnostic imaging, surgical records, reflecting details of diagnosis and treatment in clinical process, adopt Chinese description of natural language. How to extract effective information from these Chinese narrative text data, and organize it into a form of tabular for analysis of medical research, for the practical utilization of clinical data in the real world, is a difficult problem in Chinese medical data processing. Methods: Based on the EMRs narrative text data in a tertiary hospital in China, a customized information extracting rules learning, and rule based information extraction methods is proposed. The overall method consists of three steps, which includes: (1) Step 1, a random sample of 600 copies (including the history of present illness, past history, personal history, family history, etc.) of the electronic medical record data, was extracted as raw corpora. With our developed Chinese clinical narrative text annotation platform, the trained clinician and nurses marked the tokens and phrases in the corpora which would be extracted (with a history of diabetes as an example). (2) Step 2, based on the annotated corpora clinical text data, some extraction templates were summarized and induced firstly. Then these templates were rewritten using regular expressions of Perl programming language, as extraction rules. Using these extraction rules as basic knowledge base, we developed extraction packages in Perl, for extracting data from the EMRs text data. In the end, the extracted data items were organized in tabular data format, for later usage in clinical research or hospital surveillance purposes. (3) As the final step of the method, the evaluation and validation of the proposed methods were implemented in the National Clinical Service Data Integration Platform, and we checked the extraction results using artificial verification and automated verification combined, proved the effectiveness of the method. Results: For all the patients with diabetes as diagnosed disease in the Department of Endocrine in the hospital, the medical history episode of these patients showed that, altogether 1 436 patients were dismissed in 2015, and a history of diabetes medical records extraction results showed that the recall rate was 87.6%, the accuracy rate was 99.5%, and F-Score was 0.93. For all the 10% patients (totally 1 223 patients) with diabetes by the dismissed dates of August 2017 in the same department, the extracted diabetes history extraction results showed that the recall rate was 89.2%, the accuracy rate was 99.2%, F-Score was 0.94. Conclusion: This study mainly adopts the combination of natural language processing and rule-based information extraction, and designs and implements an algorithm for extracting customized information from unstructured Chinese electronic medical record text data. It has better results than existing work.
    Association between chronic periodontitis and carotid intima-media thickness of middle-aged and older adults in Shijingshan community of Beijing
    LIU Yuan, LUAN Qing-xian
    2018, (2):  264-270.  doi: 10.3969/j.issn.1671-167X.2018.02.011     PMID: 29643525
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    Objective: To investigate the relationship between periodontal disease and subclinical atherosclerosis in middle-aged and older adults in Shijingshan community of Beijing. Methods: In 2005-2010, a total of 830 middle-aged and older adults were recruited from Shijingshan community of Beijing, who were divided into two groups by severity of periodontitis. A questionnaire, periodontal examination, blood biochemical examination, carotid intima-media thickness (CIMT), including common carotid arte-ry (CCA-IMT), internal carotid artery (ICA-IMT) and carotid bifurcation (CB-IMT), were measured of each subject. The associations of periodontitis with CIMT was evaluated by multivariable Logistic regression analysis and analysis of covariance, adjusted for age, gender, education level, hypertension, hyperlipidemia, obesity, smoking, drinking, and diabetes. And then anther definition of periodontitis (mild periodontitis: percentage of AL≥3 mm <10%; moderate periodontitis: percentage of AL≥3 mm 10%-30%; severe periodontitis: percentage of AL≥3 mm ≥30%) was used to investigate the hypotheses that different classification of periodontitis would affect results. Results: The subjects with moderate-severe periodontitis were characterized by significantly higher levels of CCAIMT, ICA-IMT, CB-IMT and mean CIMT than the mild group. In the univariate analysis, moderate-severe periodontitis was associated with an increased risk of ICA-IMT>0.9 mm (adjusted OR=1.230, 95% CI: 1.058-1.452, P=0.031). Furthermore, moderate periodontitis was associated with an increased risk of CB-IMT>0.9 mm (adjusted OR: 1.297, 95%CI: 1.117-1.753, P=0.011) and severe periodontitis was associated with an increased risk of CB-IMT>0.9 mm (adjusted OR=1.771, 95%CI: 1.176-3.503, P=0.042) accor-ding to another classification of periodontitis. Conclusion: Our data provided evidence that periodontitis was associated with CIMT among middle-aged and older adults in Shijingshan community of Beijing and different periodontitis classification would affect the results.
    Exploring a new method for superimposition of pre-treatment and post-treatment mandibular digital dental casts in adults
    DAI Fan-fan, LIU Yi, XU Tian-min, CHEN Gui
    2018, (2):  271-278.  doi: 10.3969/j.issn.1671-167X.2018.02.012     PMID: 29643526
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    Objective: To explore a cone beam computed tomography (CBCT)-independent method for mandibular digital dental cast superimposition to evaluate threedimensional (3D) mandibular tooth movement after orthodontic treatment in adults, and to evaluate the accuracy of this method. Methods: Fifteen postextraction orthodontic treatment adults from the Department of Orthodontics, Peking University School and Hospital of Stomatology were included. All the patients had four first premolars extracted, and were treated with straight wire appliance. The pre- and post-treatment plaster dental casts and craniofacial CBCT scans were obtained. The plaster dental casts were transferred to digital dental casts by 3D laser scanning, and lateral cephalograms were created from the craniofacial CBCT scans by orthogonal projection. The lateral cephalogram-based mandibular digital dental cast superimposition was achieved by sequential maxillary dental cast superimposition registered on the palatal stable region, occlusal transfer, and adjustment of mandibular rotation and translation obtained from lateral cephalogram superimposition. The accuracy of the lateral cephalogram-based mandibular digital dental cast superimposition method was evaluated with the CBCT-based mandibular digital dental cast superimposition method as the standard reference. After mandibular digital dental cast superimposition using both methods, 3D coordinate system was established, and 3D displacements of the lower bilateral first molars, canines and central incisors were measured. Differences between the two superimposition methods in tooth displacement measurements were assessed using the paired t-test with the level of statistical significance set at P<0.05. Results: No significant differences were found between the lateral cephalogrambased and CBCT-based mandibular digital dental cast superimposition methods in 3D displacements of the lower first molars, and sagittal and vertical displacements of the canines and central incisors; transverse displacements of the canines and central incisors differed by (0.3±0.5) mm with statistical significance. Conclusion: The lateral cephalogram-based mandibular digital dental cast superimposition method has the similar accuracy as the CBCT-based mandibular digital dental cast superimposition method in 3D evaluation of mandibular orthodontic tooth displacement, except for minor differences for the transverse displacements of anterior teeth. This method is applicable to adult patients with conventional orthodontic treatment records, especially the previous precious orthodontic data in the absence of CBCT scans.
    Association between ADAMTS14 gene polymorphism and the temporomandibular joint osteoarthritis in Chinese Han females
    WANG Dan-dan, GAN Ye-hua, MA Xu-chen, MENG Juan-hong
    2018, (2):  279-283.  doi: 10.3969/j.issn.1671-167X.2018.02.013     PMID: 29643527
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    Objective: To investigate the association between single nucleotide polymorphisms (SNP) of ADAMTS14 gene rs4747096 and osteoarthritis of the temporomandibular joint in Chinese Han females. Methods: As a case-control study, a total of 213 Chinese Han females were involved in the present stu-dy, which contained 103 temporomandibular joint osteoarthritis patients and 110 healthy people who had no symptoms or signs of temporomandibular joint osteoarthritis as control. Peripheral blood samples were collected from each participant. Genomic DNAs of temporomandibular joint osteoarthritis patients and healthy control were extracted from peripheral venous blood, which were stored in -80 ℃ refrigerator by using DNA extraction kits. The designed primers were used for polymerase chain reaction (PCR) amplification of specific DNA fragments. Genotype was determined by sequencing the PCR products. The software Chromas 2.22 was used to analyze the genotype. The genotype distributions, allele frequencies and genetic models between the patients and controls were compared. The age distribution was checked by t-test. Genotype and allele frequency were detected by Chi-square test. Results: In the present study, there were no significant differences between the osteoarthritis patients and healthy controls in terms of age. The genotype distribution was in accordance with Hardy-Weinberg equilibrium in the two groups. The genotype frequency of the ADAMTS14 (rs4747096) in the experimental group was 38.8% (AA), 55.4% (AG), and 5.8% (GG), respectively. The genotype frequency in the control group was 40.9% (AA), 43.6% (AG), and 15.5% (GG), respectively. The difference of genotype frequency of the ADAMTS14 (rs4747096) was significant between the experimental group and the control group (P=0.047). There was no significant difference in allele frequency between the two groups (P=0.415). AA and AG genotypes significantly increased the risk of the disease compared with GG in dominant model (OR=1.114, 95% CI: 1.015-1.223, P=0.028). Conclusion: A significant correlationship was found between the ADAMTS14 (rs4747096) SNP and the temporomandibular joint osteo-arthritis in Chinese Han females. The distribution of rs4747096 may be different between temporomandibular joint osteoarthritis and healthy population.
    Comparison of the properties of CD146 positive and CD146 negative subpopulations of stem cells from human exfoliated deciduous teeth
    WANG Xiao-tong, RAO Nan-quan, FANG Teng-jiao-zi, ZHAO Yu-ming, GE Li-hong
    2018, (2):  284-292.  doi: 10.3969/j.issn.1671-167X.2018.02.014     PMID: 29643528
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    Objective: Stem cells from human exfoliated teeth (SHED) were sorted by magnetically activated cell sorting (MACS) technique to obtain the CD146 positive and negative cell subpopulation. Then the biological characteristics of these subpopulations were compared to explore their specific application potential in tissue engineering. Methods: In this study, freshly extracted deciduous teeth without any caries or dental pulp disease were obtained. SHED was isolated using enzyme digestion method and then sorted by MACS, CD146 positive cells and CD146 negative cells were obtained after cell sorting. The biological characteristics of the unsorted mixed cells, CD146 positive subpopulation and CD146 negative subpopulation were compared. The proliferation ability was detected through cell counting kit-8 (CCK-8) and colony-forming unit (CFU). After osteogenic induction, alizarin red staining was performed and the gene expression of osteogenic related markers was detected by quantitative real-time polymerase chain reaction(qPCR). After adipogenic induction, oil-red O staining was performed and the gene expression of adipogenic related markers was detected. After neurogenic differentiation induction, the expression of neural markers was detected by immunofluorescence and the gene expression of neural markers was detected by qPCR. Results: SHED of the fifth passage was sorted by MACS. And the CD146 positive cell subpopulation and CD146 negative cell subpopulation were obtained. CCK8 assay showed that the proliferative tendency of the three cell groups was consistent, but the proliferation potential of CD146 positive and negative cell subpopulations was significantly lower than that of the unsorted cells. The colony forming rates of the unsorted mixed cell group, CD146 positive and negative populations were 28.6%±3%,17.1%±2.3% and 27.5%±2.5%, respectively. After 21 days of osteogenic induction, alizarin red staining and qPCR showed that the CD146 positive cell population had more mine-ralized nodule formation and expressed higher level of osteogenic related genes compared with the other two groups. After 21 days of adipogenic induction, oil red O staining and qPCR results showed that the CD146 negative subpopulation produced more lipid droplets and the expression of lipid related genes increased more significantly. After 14 days of neural induction, cell immunofluorescence and qPCR results showed that the unsorted mixed cell group and CD146 positive subpopulation expressed glial cell marker, and the expressions of neural precursor cells and neuronal marker increased significantly in negative subpopulation. Conclusion: The unsorted mixed cells showed better proliferative potential than CD146 positive and negative subpopulations. The CD146 positive subpopulation was most potent in osteogenic dif-ferentiation; it was more suitable for bone tissue engineering. The CD146 negative cells had stronger adipogenic differentiation potential than the other two cell groups; different subpopulations differed in neural differentiation.
    Retrospective study of dental treatment under general anesthesia of 62 disabled children and adolescents
    WANG Nan, ZHAO Yu-ming
    2018, (2):  293-299.  doi: 10.3969/j.issn.1671-167X.2018.02.015     PMID: 29643529
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    Objective: To retrospectively figure out the oral health status, treatment and follow-ups after dental treatment under general anesthesia (DGA) of disabled children or adolescents. Methods: Clinical data of disabled children or adolescents and normal children as control received DGA in the Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology from August 2008 to September 2015 were recorded, including: gender, birth date, treatment date, disability type, oral health status before treatment, treatment content and follow-ups (in 1 year). Differences among ages and disabilities were analyzed statistically. Results: Sixty-two disabled patients and fifty-seven controls were recruited, mean aged (9.38±5.22) years and (3.00±1.41) years. Most patients had 10 to 15 problem teeth with which the mean number of the disabled children and adolescents was (11.79±4.98) while that of the normal controls was (12.40±4.11). Caries, pulpitis, periapical periodontitis, dental trauma and developmental tooth anomalies of the disabled patients accounted for 67.56%, 13.54%, 15.15%, 1.07%, and 2.68%, respectively and the DMFT/dmft index was 11.55±5.56 while in the control group those were at 65.35%,19.09%,14.14%,0,1.41% and 12.23±4.42. The DMFT/dmft index of the disabled patients in the group 6-12 years (8.35±4.69) was significantly less than that of the other three groups (P<0.01) while no differences were found in disabilities (P=0.239). Resin restoration, pit and fissure sealant, preventive resin restoration, pulpotomy, pulpectomy/RCT, extraction and crown of the disabled patients were performed as 52.71%, 7.24%, 8.56%, 0.72%, 17.13%, 10.01% and 3.62% respectively whereas those made up as 56.31%,1.27%,0.13%,2.29%,19.87%,7.90% and 12.23% in the control group. Thirtyfive (56.45%) disabled patients and forty-three (75.44%) controls recalled. Problem teeth within one year after operation in diabled patients and controls were both nearly twice as much as the number within half a year. Restoration loss/fractured mainly occurred in anterior primary teeth while secondary/ recurrent caries and pulpitis/perapical periodontitis mostly occurred in primary molars. Conclusion: Oral health status in our disabled children and adolescents is poor. Though dental treatment under GA is an effective way to improve the oral health of disabled children and adolescents, periodic follow-ups and family oral health care are equal important for oral health maintenance.
    Clinical study of locking-taper implants in patients treated for periodontitis
    ZHANG Hai-dong, ZHANG Li, SHI Dong, HAN Jie, YAN Xia, XIE Ye-si, MENG Huan-xin
    2018, (2):  300-307.  doi: 10.3969/j.issn.1671-167X.2018.02.016     PMID: 29643530
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    Objective: To evaluate the survival rate and peri-implant clinical parameters of Locking-Taper implants in patients having lost their teeth due to non-periodontitis (NP) reasons, chronic perio-dontitis (CP) and aggressive periodontitis (AgP). Methods: In the study, 145 subjects were installed with 315 Bicon Locking-Taper implants and followed up for 1-5 years. The subjects and implants were classified into three groups, tooth loss by NP, CP and AgP. NP included 44 subjects with 100 implants, CP 70 subjects with 132 implants and AgP 31 subjects with 83 implants. Periodontal parameters before subgingival scaling and root planning (T0), at the end of active periodontal therapy (T1) and at the time of last recall (T2) were recorded. Right after the installation of final restoration and at the time of last recall (T2), periimplant probing parameters were recorded. Results: After active periodontal therapy, mean probing depth (PD) in CP and AgP were reduced from 4.05 mm, 5.20 mm at T0 to 3.07 mm, 2.96 mm at T1 (P<0.001, P<0.001), (PD≥6 mm)% were reduced from 33.2%, 58.5% at T0 to 14.4%, 10.5% at T1 (P<0.001, P<0.001). The periodontal parameters remained stable at T2 compared with T1 (P>0.05). Cumulative survival rates of implants in NP, CP and AgP were 100%, 97.6% and 100% for 1-5 years’ follow-ups with no statistical significance found. At T2, mean implant PD was 2.78 mm, 2.96 mm and 2.97 mm in NP, CP and AgP, with NP significantly lower than the other two groups (P=0.006, P=0.01). The percentage of implant sites with PD≥6 mm was 3.7% in CP and 4.8% in AgP, both significantly higher than NP (P=0.003, P<0.001). 8.4% implant sites showed at least 2 mm deeper than those at prosthesis installation were found in CP group, significantly higher than NP (4.3%, P=0.003). Conclusion: Periodontal conditions of patients having lost their teeth for chronic and aggressive periodontitis were significantly improved after active periodontal therapy and remained stable during 1-5 years. Short-term survival rates of Locking-Taper implants in patients treated for CP and AgP was no less than those who lost their teeth for non-periodontitis reasons. More sites with increasing peri-implant probing depth were found in CP and AgP patients, compared with NP.
    Extraction-orthodontic treatment on patients with chronicperiodontitis: a preliminary study
    ZHANG You-wen, XIN Tian-yi, JIAO Jian,ZHOU Yan-heng, SHI Jie
    2018, (2):  308-313.  doi: 10.3969/j.issn.1671-167X.2018.02.017     PMID: 29643531
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    Objective: To retrospectively evaluate clinical and radiographic records of chronic periodontitis patients who underwent extraction-orthodontic treatment, in order to determine the effect of the treatment on probing depth, alveolar bone height of teeth adjacent to the extraction sites. Methods: In the study, 33 chronic periodontitis patients who had finished extraction-orthodontic treatment were selec-ted, the periodontal examination system tables and panoramic tomography were recorded before treatment (T0) and after treatment (T1), and  the periodontal probing depth (PD), residual alveolar bone height(RBH) of the teeth adjacent to extraction sites (TAES) and the non-teeth adjacent to extraction sites (NTAES) were measured at T0 and T1. Results: There was insignificant difference in PD of TAES and NTAES at T0 [(2.40±0.51) mm vs. (2.42±0.55) mm,P>0.05], neither was that at T1 [(2.70±0.67) mm vs. (2.67±0.64) mm, P>0.05]; From T0 to T1, PD of TAES and NTAES had mean increases of 0.3 mm [(2.40±0.51) mm vs. (2.70±0.67) mm,P<0.01] and 0.25 mm [(2.42±0.55 mm vs. (2.67±0.64) mm, P<0.01], respectively. And PD of TAES and NTAES increased from T0 to T1 statistically in the same degree [(0.30±0.64) mm vs. (0.25±0.58) mm,P>0.05]; at T0, RBH of TAES was 0.024 smaller than that of NTAES (0.74±0.16 vs. 0.76±0.16,P<0.05), but there was no difference in RBH between the TAES and NTAES at T1 (0.78±0.14 vs. 0.79±0.12,P>0.05); From T0 to T1, RBH of TAES and NTAES had mean increases of 0.04 (0.74±0.16 vs.0.78±0.14,P<0.05) and 0.02 (0.76±0.16 vs. 0.79±0.12,P<0.05), respectively. And the change of RBH between TAES and NTAES from T0 to T1 had no statistical difference (0.04±0.11 vs. 0.02±0.08,P>0.05)RBH of TAES in the side close to extraction sites was as the same as that of TAES in the side away from the extraction sites at T0 (0.73±0.17 vs. 0.74±0.16,P>0.05). From T0 to T1, RBH of both sides of TAES had mean increases of 0.04 (0.73±0.11 vs. 0.77±0.11,P<0.05) and 0.04 (0.74±0.11 vs. 0.78±0.11,P<0.05), respectively. But for both sides of TAES, from T0 to T1, there was no significant difference in change of RBH (0.04±0.11 vs. 0.04±0.11,P>0.05). Conclusions: With strict control of periodontal inflammation and maintenance of oral hygiene, orthodontic treatment preserves the periodontal conditions in patients with chronic periodontitis, and the extraction-orthodontic treatment can preserve the bone height of the teeth adjacent to extraction sites.
    Three-year clinical effects of a modified semi-fixed bridge on restoring a missing posterior tooth
    TAN Jing, WEI Xiu-xia, ZHANG Qing-hui, ZHOU Yong-sheng
    2018, (2):  314-317.  doi: 10.3969/j.issn.1671-167X.2018.02.018     PMID: 29643532
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    Objective:To observe the effects of a modified semi-fixed bridge to restore a missing posterior tooth for three years. Methods: In the study, 38 cases with a posterior tooth missed were chosen as experiment group. The inclusion criteria for these cases required that one abutment tooth be defected, and another abutment  intact. The missed posterior tooth was restored with a modified semi-fixed bridge in which a metal wing retainer was applied to the intact abutment tooth and a full crown retainer was applied to the defected abutment tooth, and the non-rigid connector linked to the metal wing retainer and the pontic, while the rigid connector linked to the full crown retainer and the pontic. And 42 cases with same abutment conditions were chosen as control group. These control patients were treated with classical rigidly-fixed partial dentures. The clinical effects regarding the bridge survival, abutment conditions, and etc. were observed by examination. Results: The average observation time for experiment group was 40.3 months (from 9 to 60 months). One case failed with loose crown retainer after 7 months’ usage.  Another failed case was the same performance after 20 months’ wearing. The restorations were rebounded after the inner face of crowns was treated, and they were used normally. No loose abutment and retainer, no decayed abutment teeth were found, and the marginal adaptations between retainers and abutment teeth were good. The average observation time of control group was 44.7 months(from 22 to 50 months). No secondary decays and loose abutment teeth were detected and the marginal adaptation of the retainers was good.  Conclusion: This modified semifixed bridge has similar survival rate and clinical effects to restore a missing posterior tooth when compared with the traditional rigidlyfixed partial dentures. But the longterm observation is required.
    Topoisomerase inhibitor upregulates MICA/B expression in breast cancer cells through ATM/ATR and NF-κB pathway
    ZHU Yan,SHI Yong-jin,ZHAO Yu-liang, ZHU Ping
    2018, (2):  318-325.  doi: 10.3969/j.issn.1671-167X.2018.02.019     PMID: 29643533
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    Objective: To investigate the effects of chemotherapeutic agents widely used in clinical practice on major histocompatibility complex class Ⅰ-related chain A and B (MICA/B) expression in breast cancer cells, and to explore the molecular mechanisms involved. Methods: We examined MICA/B mRNA and surface protein expressions in breast cancer cells treated with chemotherapeutic agents by real-time RT-PCR and flow cytometry respectively. The blocking effects of ataxia telangiectasia mutated and Rad3-related kinase (ATM/ATR) inhibitor caffeine and nuclear factor κB (NF-κB) inhibitor pyno-lidine dithiocarbamate (PDTC) on etoposide-upregulated MICA/B mRNA and surface protein expressions were investigated. Electrophoretic mobility shift assay (EMSA) was taken to investigate whether etoposide enhanced the binding of NF-κB to MICA/B gene promoter. Results: Three topoisomerase inhibitors etoposide, camptothecin and doxorubicine upregulated MICA and MICB mRNA expressions in breast cancer cell MCF-7. Comparing to no-drug-treated cells, MICA mRNA levels increased to (1.68±0.17), (2.54±0.25) and (3.42±0.15) fold, and levels of MICB mRNA increased to (1.82±0.24), (1.56±0.05) and (5.84±0.57) fold respectively in cancer cells treated by etoposide at the concentrations of 5, 20 and 100 μmol/L (P<0.05). MICA and MICB mRNA levels also increased significantly when MCF-7 cells were incubated with camptothecin or doxorubicine at the specific concentrations (P<0.05). MICB mRNA expression also increased slightly in another breast cancer cell SK-BR-3 treated by topoisomerase Ⅱ inhibitors etoposide and camptothecin (P<0.05). Furthermore, etoposide and camptothecin upregulated MICA/B surface protein expression in MCF-7 cells (P<0.05), and the upregulation was found in both living and apoptotic cells. Our study showed that etoposide induced-MICA/B expression in MCF-7 was inhibited by caffeine at different concentrations. When cancer cells were treated by caffeine with 1, 5 and 10 mmol/L, MICA mRNA levels decreased from (3.75±0.25) to (0.89±0.05), (0.81±0.02) and (0.48±0.04) fold respectively (P<0.001), and MICB mRNA levels decreased from (6.85±0.35) to (1.36±0.13), (0.76±0.06) and (0.56±0.03) fold (P<0.05), while MICA/B protein levels decreased from (3.42±0.05) to (1.32±0.03), (1.21±0.06) and (1.14±0.03) fold (P<0.001), indicating that etoposide-induced MICA/B expression was inhibited by ATM/ATR inhibitor. Similarly, NF-κB inhibitor PDTC also inhibited MICA/B mRNA and protein expressions induced by etoposide significantly when MCF-7 cells were incubated with PDTC at the concentrations of 10, 50 and 100 μmol/L (P<0.05), indicating that NF-κB was also involved in this process. EMSA showed that the binding of NF-κB to MICA/B promoter enhanced in MCF-7 cells after etoposide treatment. Conclusion: Topoisomerase inhibitor increased MICA/B mRNA and protein expressions in breast cancer cells, indicating that chemotherapeutic agents might increase the recognizing and killing ability of immunocytes to breast cancer cells. ATM/ATR and NF-κB pathways might be involved in it.
    In vivo imaging of breast tumors by a 99mTc radiolabeled probe targeting microRNA-155 in mice models
    KANG Lei, HUO Yan, WANG Rong-fu, ZHANG Chun-li, YAN Ping, XU Xiao-jie
    2018, (2):  326-330.  doi: 10.3969/j.issn.1671-167X.2018.02.020     PMID: 29643534
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    Objective: MicroRNA-155 (miR-155) is significantly highly expressed in breast cancer, lung cancer, liver cancer and other malignant tumors. This study was to design and construct a radiolabeled probe targeting miR-155 for in vivo imaging in breast cancer. Methods: Anti-miR-155 oligonu-cleotide (AMO-155) was chemically synthesized with 2′-OMe modification. Its 5′ end was linked with acetyl amine group. After chelated with a bifunctional chelator NHSMAG3, AMO155 was radiolabeled with 99mTc using stannous chloride. The serum stability was evaluated at cellular level. In vivo imaging was performed in MCF-7 tumor bearing mice after the administration of 99mTc radiolabeled AMO-155 and scramble control probes, respectively. Furthermore, the blocked imaging of tumor bearing mice was obtained after the injection of unlabeled AMO-155 2 hours ahead. MCF-7 and MDA-MB-231 tumor bearing mice with different expression level of miR-155 were imaged, respectively. Quantitative real-time PCR (qRT-PCR) was used to identify the expression level of miR-155 in the bearing tumors. Results: 99mTc-AMO-155 was prepared with high radiolabeled efficiency (97%), radiochemical purity (greater than 98%), and radioactive specific activity (3.75 GBq/μg). 99mTc-AMO-155 was stable in fresh human serum for 12 hours. After the administration via tail vein, 99mTc-AMO-155 displayed significant accumulation in MCF-7 bearing tumors with high expression level of miR-155, whereas 99mTc-control showed little accumulation. After blocked with unlabeled AMO-155, the tumor could not be visualized clearly after the administration of 99mTc-AMO-155. Furthermore, 99mTc-AMO-155 could show the differential expression of miR-155 in vivo. MCF-7 tumor was shown with significantly higher radioactive accumulation than MDA-MB-231, based on its higher expression level of miR-155, which was verified by qRT-PCR. Conclusion: 99mTc-labeled AMO-155 with chemical modification showed good serum stability and in vivo tumor targeting ability. This study provides a potential probe for in vivo imaging of breast cancer.
    Effects of tetrandrine on proliferation and activation of cardiac fibroblasts
    LI Qian, CHANG Liang, SU Dong-mei, MA Xu
    2018, (2):  331-334.  doi: 10.3969/j.issn.1671-167X.2018.02.021     PMID: 29643535
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    Objective: To investigate the effects of tetrandrine (Tet) on proliferation and activation of rat cardiac fibroblasts. Methods: Firstly, the cell counting kit-8(cck-8) assay was applied to detect the effects of Tet with different concentrations on proliferation of cardiac fibroblasts. Secondly, transforming growth factor (TGF-β)with a concentration of 5 μg/L was used to induce the cardiac fibroblast activation, and Western blot was performed to measure the expression variation of βcatenin, vimentin (Vm), fibronectin (Fn) and smooth muscle α-actin (SMA). At last, the real-time PCR was conducted to mea-sure the expression change of collagen-1(Col-1) and collagen-3(Col-3). Results: The cck8 assay showed that the Tet with different concentrations respectively, which were 0.5 μmol/L, 1 μmol/L, 2 μmol/L, 4 μmol/L, and 8 μmol/L, significantly inhibited the proliferation of cardiac fibroblasts. The viability was decreased to 94.4%,84.9%,74.9%,63.8%and 50.3% respectively of the control group when the Tet concentration changed, and the difference was statistically significant, P=0.043,P<0.001,P<0.001,P<0.001,P<0.001 respectively. Western blot revealed that the expressions of β-catenin, Fn, SMA and Vm, were up-regulated by TGF-β(5 μg/L), the result showed that the difference was statistically significant, and the P values were 0.001,0.008,0.010,0.001 respectively. Then, the up-regulation of β-catenin, Fn and SMA was attenuated by pre-treatment of Tet, and the result also displayed that the difference was statistically significant, and the P values were 0.009,0.005,0.019,respectively. While there was no significant change in the expression of Vm, according to Western blotting, and P>0.05,at the same time, realtime PCR indicated that the up-regulations of Col-1 and Col-3 which were induced by TGF-β were blocked by pretreatment of Tet, the result showed that the difference was statistically significant, P<0.001. Conclusion: According to the experimental results, we can draw the conclusion that: the Tet can significantly inhibit the proliferation of cardiac fibroblasts, meanwhile, it can block the activation of cardiac fibroblasts, which is induced by TGF-β. It is supposed that the Tet may probably have anti myocardial fibrosis, which indicates that it may probably be a medicine which is used to block the cardiac remodeling.
    Genetic diagnosis of Caroli syndrome with autosomal recessive polycystic kidney disease: a case report and literature review
    YANG Xi-ying, ZHU Ling-ping, LIU Xue-qin, ZHANG Chun-yu, YAO Yong, WU Ye
    2018, (2):  335-339.  doi: 10.3969/j.issn.1671-167X.2018.02.022     PMID: 29643536
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    This case report is about one genetically specified diagnosed infant case of Caroli syndrome with autosomal recessive polycystic kidney disease (ARPKD) in China. The patient in this case report was an eightmonth infant boy with an atypical onset and the main clinical manifestation was non-symptomatic enlargement of the liver and kidneys. The imaging study demonstrated a diffused cystic dilatation of intrahepatic bile ducts as well as polycystic changes in bilateral kidneys. The basic blood biochemical tests indicated a normal hepatorenal function. Four serum biomarkers of hepatic fibrosis were all elevated and the urine test for an early detection of the renal injury was positive. The genetic sequencing proved two heterozygous missense mutations of polycystic kidney and hepatic disease 1 (PKHD1) gene, c.9292G>A and c.2507T>C, inherited from each of his parents respectively. The former was a novel mutation that had been verified as disease causing through the predicting software while the latter had been reported from one recent case study on Chinese twins, which was possibly unique among Chinese population. The relations between the gene type and the clinical phenotype were not clarified yet. Up till a follow-up eleven months later after the discharge, the patient had a normal hepatorenal function without occurrence of any severe complication yet. The clinical symptoms of Caroli syndrome with ARPKD at infant stage were atypical and the enlargement of liver and kidney was usually the sole symptom. From the above systematic retrospective clinical analysis, as well as the relevant literature review, it’s been concluded that the features of the hepatorenal images in patients with Caroli syndrome and ARPKD were distinctive. Genetic testing combined with the imaging study benefits a definite diagnosis as well as a diffe-rentiation from other hepatorenal fibrocystic diseases. Specific to the long-term management of this kind of patients, it’s necessary to schedule a regular follow-up to monitor the hepatorenal function and the occurrence of various complications for an appropriate intervention, meantime to devote efforts to the genetic counseling work for the patients’ family.
    Preparation and characterization of citric acid-modified superparamagnetic iron oxide nanoparticles
    WANG Huan, QIN Xiao-ya, LI Zi-yuan, ZHENG Zhuo-zhao, FAN Tian-yuan
    2018, (2):  340-346.  doi: 10.3969/j.issn.1671-167X.2018.02.023     PMID: 29643537
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    Objective: To prepare and characterize citric acid (CA)-modified super paramagnetic iron oxide nanoparticles (SPIONs) for magnetic targeting, hyperthermia and magnetic resonance imaging (MRI). Methods: CA-modified SPIONs (CA-SPIONs) were prepared by co-precipitation method and then the magnetic responsiveness, morphology, particle size, infrared feature, weight percentage of CA, magnetic property and X-ray diffraction pattern of CA-SPIONs were respectively characterized by magnet, transmission electron microscope, laser particle size analyzer, Fourier transform infrared (FT-IR) spectroscopy, thermogravimetry-differential thermal analyzer, vibrating sample magnetometer and X-ray diffractometer (XRD). The heating efficiency of the CA-SPIONs was investigated by a high frequency induction heater. The transverse relaxivity (r2) of the CA-SPIONs was evaluated by a 3.0 T MRI scanner. Results: The CA-SPIONs prepared were dispersed well in water with a dark black color and had good magnetic responsiveness. The CA-SPIONs were spherical in shape and uniform in size with an average size around 12 nm. The hydrodynamic average size of the CA-SPIONs was (72.35±4.47) nm with a polydispersity index of 0.231 ± 0.029. The result of infrared spectrum indicated that CA was successfully modified to the surface of SPIONs. The result of thermogravimetric analysis showed that the weight percentage of CA modified on the CA-SPIONs was 9.0%. The result of magnetic property evaluation demonstrated that the CA-SPIONs exhibited excellent superparamagetism with a saturation magnetism of 63.58 emu/g. The XRD result indicated that the CA-SPIONs were in inverse spinel structure. The crystallite size of the CA-SPIONs was calculated to be 12.4 nm by Debye-Scherrer equation. Under the high frequency alternating electromagnetic field with electric current of 9 A and frequency ranging from 45 to 50 kHz, the CA-SPIONs exhibited excellent heating efficiency and the specific absorption rate (SAR) value was calculated to be 26 W/g. The r2 of the CA-SPIONs was assessed to be 338 (mmol/L)-1·s-1 by a 3.0 T MRI scanner, which suggested the excellent negative contrast enhancement effect of the CA-SPIONs. Conclusion: The CA-SPIONs are expected to be used as a promising agent for magnetic targeting, hyperthermia and MRI detection.
    Anterior cervical discectomy and fusion to treat cervical spondylosis with sympathetic symptoms#br#
    LIU Hong, YUE Lei, CHEN Shun-lun, HU Bo, LI Chun-de△, YI Xiao-dong, LI Hong, LU Hai-lin, WANG Yu, YU Zheng-rong, SUN Hao-lin, WANG Shi-jun, ZHAO Yao, QI Long-tao, WANG Rui
    2018, (2):  347-351.  doi: 10.3969/j.issn.1671-167X.2018.02.024     PMID: 29643538
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    Objective: To investigate the clinical effectiveness of polytheretherketone (PEEK) cages assisted anterior cervical discetomy and fusion (ACDF) to treat cervical spondylosis with sympathetic symptoms. Methods: Retrospective analysis was undertaken for 39 patients who were diagnosed as cervical spondylosis with sympathetic symptoms and underwent ACDF with PEEK cages. Radiographs obtained before surgery, after surgery, and at the final follow-up were assessed for quality of fusion. The following criteria were used for assessing radiographic success of fusion: (1) endplate obliterated with no lucent lines; (2) obliteration of disc space by bony trabeculae; (3) less than 2°of intervertebral motion or 2 mm of motion between the spinous processes at the operated segment on flexion-extension lateral radiographs. The sympathetic symptoms including vertigo, headache, tinnitus, nausea and vomiting, heart throb, hypomnesia and gastroenterological discomfort were scored by 20-point system preoperatively, 2 months postoperatively and at the final follow-up. The recovery rate and clinical satisfaction rate were also evaluated. Surgical complications were also assessed. Results: They were followed up for at least one year. The mean follow-up was 15.6 months. Radiographs of the cervical spine at the last follow-up revealed a solid fusion with no signs of a pseudoarthrosis in 36 cases. In two patients delayed union and bony fusion were achieved at the end of 9 and 11 months. Pseudoarthosis was found in 1 case but the patient had no symptoms. The score of sympathetic symptoms before surgery, 2 months after surgery and at the final follow-up were 8.4±1.0,2.2±0.3,and 2.4±0.3, respectively. There were 22 excellent cases, 15 good cases, 1 fair case and 1 bad case in terms of RR. Good to excellent results were attained in 95% of theses patients. The sympathetic symptoms improved in all the patients and the score was significantly improved after surgery. There was one patient who had cerebral spinal fluid leakage but he reco-vered one week after surgery. Two patients felt a mild swallowing discomfort, but it disappeared within one month after surgery. Subcutaneous hematoma occurred in one patient due to obstructed drainage. It was cleared two days after surgery. Conclusion: Cervical spondylosis patients with sympathetic symptoms may be managed successfully with ACDF using PEEK cages. Successful clinical results regarding symptom improvement and general satisfaction with the surgical procedure depend not only on obtaining successful decompression and radiographic fusion but also on patient selection.
    Construction of chemical information database based on optical structure recognition technique
    LV Chuan-yu, LI Ming-na, ZHANG Liang-ren, LIU Zhen-ming
    2018, (2):  352-357.  doi: 10.3969/j.issn.1671-167X.2018.02.025     PMID: 29643539
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    Objective: To create a protocol that could be used to construct chemical information database from scientific literature quickly and automatically. Methods: Scientific literature, patents and technical reports from different chemical disciplines were collected and stored in PDF format as fundamental datasets. Chemical structures were transformed from published documents and images to machine-readable data by using the name conversion technology and optical structure recognition tool CLiDE. In the process of molecular structure information extraction, Markush structures were enumerated into well-defined monomer molecules by means of QueryTools in molecule editor ChemDraw. Document management software EndNote X8 was applied to acquire bibliographical references involving title, author, journal and year of publication. Text mining toolkit ChemDataExtractor was adopted to retrieve information that could be used to populate structured chemical database from figures, tables, and textual paragraphs. After this step, detailed manual revision and annotation were conducted in order to ensure the accuracy and completeness of the data. In addition to the literature data, computing simulation platform Pipeline Pilot 7.5 was utilized to calculate the physical and chemical properties and predict molecular attributes. Furthermore, open database ChEMBL was linked to fetch known bioactivities, such as indications and targets. After information extraction and data expansion, five separate metadata files were generated, including molecular structure data file, molecular information, bibliographical references, predictable attributes and known bioactivities. Canonical simplified molecular input line entry specification as primary key, metadata files were associated through common key nodes including molecular number and PDF number to construct an integrated chemical information database. Results: A reasonable construction protocol of chemical information database was created successfully. A total of 174 research articles and 25 reviews published in Marine Drugs from January 2015 to June 2016 collected as essential data source, and an elementary marine natural product database named PKU-MNPD was built in accordance with this protocol, which contained 3 262 molecules and 19 821 records. Conclusion: This data aggregation protocol is of great help for the chemical information database construction in accuracy, comprehensiveness and efficiency based on original documents. The structured chemical information database can facilitate the access to medical intelligence and accelerate the transformation of scientific research achievements.
    Verification of skin paste electrodes used in wireless polysomnography
    MA Yun-dong1, HUANG Dong, CHEN Yu-feng, JIANG Hao-yun, LIU Jun-hua, SUN Hong-qiang, LI Zhi-hong
    2018, (2):  358-363.  doi: 10.3969/j.issn.1671-167X.2018.02.026     PMID: 29643540
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    Objective: To explore an electrode suitable for wireless portable sleep monitoring equipment and analyze the result of the signals of electrooculogram (EOG) and electroencephalography (EEG) collected by this kind of flexible electrodes. Methods: The flexible electrodes were prepared by microelectromechanical systems (MEMS) technology. This kind of electrodes consisted parylene, chromium, and gold. Parylene, the flexible substrate of this kind of flexible electrodes, was of biocompatibility. Between parylene and gold there was an adhesion layer of chromium, which connected parylene and gold tightly. Then the flexible electrodes were stuck to medical adhesive tape. The electrodes were designed and made into a grid to make sure that the medical adhesive tape could tape on the skin tightly, so that the contact impedance between the electrodes and the skin would be reduced. Then the alternating current impedance of the electrode were tested by the CHI660E electrochemical workstation after the electrode was achieved. To make sure that this kind of electrodes could be used in EOG monitoring, the electrodes were connected to a wireless signal acquisition suite containing special biological signal acquisition and digital processing chip to gather different sites around the eyes and the electrical signals of different directions of the eye movements, then analyzed the signal-to-noise ratio of the EOG. At the end, the Philips A6 polysomnography was used to compare the noise amplitude of the EEG signals collected by the flexible electrode and the gold cup electrode. Results: The electrodes stuck to the skin tightly, and these electrodes could collect signals that we wanted while the experiment was performed. The alternating current impedance of the flexible electrode was between 4 kΩ and 13 kΩ while with the frequency of alternating current under 100 Hz, most EEG signal frequencies were at this range. The EOG signals collected by the flexible electrodes were in line with the clinical requirements. The noise amplitude of EEG signals collected by the flexible electrodes was lower than that of the electrical signals collected by the gold cup electrodes. Conclusion: The flexible electrode could be taken into consideration as an alternative electrode for monitoring EOG and EEG signals, and the wireless portable sleep monitoring devices are to be further developed in the future.
    Preparation, quality control and thyroid molecule imaging of solid-target based radionuclide ioine-124
    ZHU Hua, WANG Feng,GUO Xiao-yi,LI Li-qiang, DUAN Dong-ban,LIU Zhi-bo, YANG Zhi
    2018, (2):  364-367.  doi: 10.3969/j.issn.1671-167X.2018.02.027     PMID: 29643541
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    Objective:To provide useful information for the further production and application of this novel radio-nuclide for potential clinical application. Methods:124Te(p,n)124I nuclide reaction was used for the 124I production. Firstly, the target material, 124TeO2 (200 mg) and Al2O3 (30 mg) mixture, were compressed into the round platinum based solid target by tablet device. HM-20 medical cyclotron was applied to irradiate the solid target slice for 6-10 h with helium and water cooling. Then, the radiated solid target was placed for 12 h (overnight) to decay the radioactive impurity; finally, 124I was be purified by dry distillation using 1 mL/min nitrogen for about 6 hours and radiochemical separation methods. Micro-PET imaging studies were performed to investigate the metabolism properties and thyroid imaging ability of 124I.After 740 kBq  124I was injected intravenously into the tail vein of the normal mice, the animals were imaged with micro-PET and infused with CT. The micro-PET/CT infusion imaging revealed actual state 124I’s metabolism in the mice. Results: It was been successfully applied for 200 mg 124TeO2 plating by the tablet device on the surface of platinum. It showed smooth, dense surface and without obviously pits and cracks. The enriched 124Te target was irradiated for 6 to 10 hours at about 12.0 MeV with 20 μA current on HM-20 cyclotron. Then 370-1 110 MBq 124I could be produced on the solid target after irradiation and 370-740 MBq high specific activity could be collected afterdry distillation separation and radio-chemical purification.124I product was finally dissolved in 0.01 mol/L NaOH for the future distribution. The gamma spectrum of the produced 124I-solution showed that radionuclide purity was over 80.0%. The micro-PET imaging of 124I in the normal mice exhibited the thyroid and stomach accumulations and kidney metabolism, the bladder could also be clearly visible, which was in accordance with what was previously reported. To the best of our knowledge, it was the first production of 124I report in China. Conclusion: In this study, the preparation of 124TeO2 solid target was successfully carried out by using the tablet device. After irradiation of the 124TeO2 solid target and radio-chemical purification, we successfully produced 370-740 MBq high specific activity 124I by a cyclotron for biomedical application, and microPET imaging of 124I in normal mice exhibited the thyroid accumulations. Also, slight uptake in stomach were also monitored with almost nonuptake in other organs in the micro-PET imaging. The production of 124I is expected to provide a new solid target radionuclide for the scientific research and potential clinical application of our country.
    A retrieval method of drug molecules based on graph collapsing
    QU Jing-wei, LV Xiao-qing, LIU Zhen-ming, LIAO Yuan, SUN Peng-hui, WANG Bei, TANG Zhi
    2018, (2):  368-374.  doi: 10.3969/j.issn.1671-167X.2018.02.028     PMID: 29643542
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    Objective: To establish a compact and efficient hypergraph representation and a graph-similarity-based retrieval method of molecules to achieve effective and efficient medicine information retrieval. Methods: Chemical structural formula (CSF) was a primary search target as a unique and precise identifier for each compound at the molecular level in the research field of medicine information retrieval. To retrieve medicine information effectively and efficiently, a complete workflow of the graph-based CSF retrieval system was introduced. This system accepted the photos taken from smartphones and the sketches drawn on tablet personal computers as CSF inputs, and formalized the CSFs with the corresponding graphs. Then this paper proposed a compact and efficient hypergraph representation for molecules on the basis of analyzing factors that directly affected the efficiency of graph matching. According to the characteristics of CSFs, a hierarchical collapsing method combining graph isomorphism and frequent subgraph mining was adopted. There was yet a fundamental challenge, subgraph overlapping during the collapsing procedure, which hindered the method from establishing the correct compact hypergraph of an original CSF graph. Therefore, a graph-isomorphism-based algorithm was proposed to select dominant acyclic subgraphs on the basis of overlapping analysis. Finally, the spatial similarity among graphical CSFs was evaluated by multi-dimensional measures of similarity. Results: To evaluate the performance of the proposed method, the proposed system was firstly compared with Wikipedia Chemical Structure Explorer (WCSE), the state-of-the-art system that allowed CSF similarity searching within Wikipedia molecules dataset, on retrieval accuracy. The system achieved higher values on mean average precision, discounted cumulative gain, rank-biased precision, and expected reciprocal rank than WCSE from the top-2 to the top-10 retrieved results. Specifically, the system achieved 10%, 1.41, 6.42%, and 1.32% higher than WCSE on these metrics for top-10 retrieval results, respectively. Moreover, several retrieval cases were presented to intuitively compare with WCSE. The results of the above comparative study de-monstrated that the proposed method outperformed the existing method with regard to accuracy and effectiveness. Conclusion: This paper proposes a graph-similarity-based retrieval approach for medicine information. To obtain satisfactory retrieval results, an isomorphism-based algorithm is proposed for dominant subgraph selection based on the subgraph overlapping analysis, as well as an effective and efficient hyper-graph representation of molecules. Experiment results demonstrate the effectiveness of the proposed approach.
    Airway foreign body caused by aspiration of artificial nasal sponge: a case report
    FU Tian-xu, WANG Xi, LIU Mei-lin
    2018, (2):  375-377.  doi: 10.3969/j.issn.1671-167X.2018.02.029     PMID: 29643543
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    57-year-old male was admitted to hospital for severe headache and seizure attacks on November 6th, 2016. After radiology and spinal fluid examination, he was diagnosed with viral encephalitis and treated with antiviral medicine, antibiotics and mannitol, but he was in sustained unconsciousness and weak in expectorating. The patient was given oxygen through artificial nasal after bedside tracheotomy.  At 1:00 am on January 12th, 2016, there was a sudden drop in blood pressure, heart rate and oxygen saturation with left lung breath sounds slightly lower than the other side. The patient was connected to a ventilator with tidal volume of 300-500 mL and airway pressure of 16-24 cmH2O (1 cmH2O=0.098 kPa). In the meanwhile, the left side sponge of artificial nasal was found missing. Bedside chest X-ray showed no significant atelectasis. At that time the evidence of airway foreign body aspiration was not sufficient, so no urgent bronchoscopy was performed. At 9:00 am on January 14th, 2016, there was another sudden decline in oxygen saturation with diminished left lung breath sounds and decreased left thoracic activity. Since left atelectasis could not be ruled out, bedside bronchoscopy was performed. In the operation, two spongelike objects were found at the left main bronchus and the opening of left upper lobe bronchial. Foreign body forceps were used to remove them. The foreign bodies were proved to be the left sponge of artificial nasal afterwards. Symptoms and signs caused by aspiration of foreign body in adults were widely various and depending on the nature of the foreign body, site, time and whether there was infection or not. Foreign body aspiration caused by artificial nasal sponge was rare in clinical practice. This case was a living reminder to perform bronchoscopy when foreign body aspiration was suspected. For the unconscious and elderly patient, whose history of foreign body aspiration usually could not be clearly provided, when atelectasis was suspected, bronchoscopy should be performed progressively, and more effective measures should be taken to prevent sponge of artificial nasal displacement.
    Bronchial adenoid cystic carcinoma masquerading as bronchial asthma:a case report
    LU Ming, WANG Min, ZHU Xiang, CHEN Ya-hong, YAO Wan-zhen
    2018, (2):  378-380.  doi: 10.3969/j.issn.1671-167X.2018.02.030     PMID: 29643544
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    Here we reported a case of bronchial adenoid cystic carcinoma from Peking University Third Hospital. A 40-year-old female presented with dry cough for 1 year and nocturnal paroxysmal attacks of wheezing for 4 months. She was a non-smoker, and did not have past histories of asthma or allergy. On physical examination, no stridor, wheezing and cyanosis were present and the general appearance was good. The results of the laboratory analysis, including blood eosinophils count, immunoglobulin E level and chest X-ray were normal. Spirometry revealed reversible airflow obstruction, and post-bronchodilator forced expiratory volume in one second (FEV1) showed an increase of 12% and 230 mL from baseline. Bronchial asthma was diagnosed, however, she responded poorly despite the adequate anti-asthma therapy including high dose inhaled corticosteroid plus long-acting beta2-agonist, theophylline and montelukast. Then chest computed tomography (CT) was performed which showed a polypoid mass occupying the lumen of left main bronchus. Then the bronchoscopy revealed a polypoid endobronchial mass arising from the left main bronchus, causing subtotal obstruction of the lumen. Biopsy was carried out through the bronchoscopy, the pathological findings showed characteristic cribriform and tubular pattern which was formed by two-layered cells with ductal and myoepithelial phenotypes, which were consistent with adenoid cystic carcinoma. Re-examining the patient, the lung was clear without any wheeze when she was seated. However, inspiratory wheeze was heard in her left upper lung when she was supine, and disappeared after sitting up again. Subsequently the patient underwent a resection surgery. At the operational site, the tumor was seen on the anterolateral wall of the left main bronchus, without submucosally expanding histologically. Therefore, a sleeve resection surgery of the left main bronchus was performed. Following surgery, chest CT scan revealed complete resolution of the tumor. Her symptoms improved significantly, as did her pulmonary function tests, although all the medicines for asthma were stopped. Now, two years after the operation, the patient remained asymptomatic, and spirometry was performed again which showed normal completely. The presenting case report emphasizes the fact that not all wheezes and reversible airflow obstruction are asthma. It is critical to bear in mind that if a “difficult asthma” patient does not respond to appropriate anti-asthma therapy; localized obstructions should be differentiated.
    Necessity and feasibility of data sharing of cohort studies#br# #br#
    YANG Yu, ZHAO Hou-yu, ZHAN Si-yan
    2018, (2):  381-385.  doi: 10.3969/j.issn.1671-167X.2018.02.031     PMID: 29643545
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    Cohort study is one of the important epidemiological methods which plays an irreplaceable status and role in etiological study. Using cohort study design, we can accurately and continuously collect genetic and environmental information, and identify and validate omics biomarkers to provide evidences for precision public health and medicine. However, results from a new cohort would not be available for at least ten years, as five years would be needed for funding, planning and enrolment, and another five for following up even the earliest analyses of the most common diseases; results for most cancers would take longer, with an unaffordable budget for many research investigators or institutions. That brings an alternative strategy of using existing cohort studies by sharing data between each other. Data sharing of cohort studies would be beneficial in many ways. Data sharing of cohort studies has the potential to make large samples unattainable in a single study, increase statistical power, enable more accurate and detailed subgroup analysis, increase the generalizability of results. It would also facilitate exchange of experiences and learning from each other, avoid for duplicated research and effectively promote the second use of existing data (i.e. using old data to discover new results). The data sharing would save staff recruitment, follow-up, laboratory analysis of the cost, with a high cost-benefit returns and economies of scale. Data sharing enables cross-validation and repeated verification across different data. Many international research funding agencies or leading research groups have also reached consensus on the principles and goals for promoting the sharing of medical research data. Due to rapid development of cohort studies in the past decades, China already has the basis for data sharing of cohort studies. Unfortunately, most of the existing cohort studies are self-contained, independent, lack of visibility, with insufficient co-operation and data sharing between each other. The academic value of the existing data collected in these cohort studies have not been fully exploited and utilized so far. Therefore, the China Cohort Consortium is trying to establish a multilevel three-dimensional cooperation and data sharing strategy. We hope that it will encourage researchers from public health, clinical and other related fields to work more closely through providing data management, data integration, data interaction, tools development, data repositories and other functions.

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Sponsor: Peking University
Editor-in-Chief: ZHAN Qi-min
Executive Editor-in-Chief: ZENG Gui-fang
Editing and Publishing: Editorial Department of Journal of Peking University (Health Sciences)
ISSN: 1671-167X
CN: 11-4691/R