Objective: To explore the association between de novo mutations (DNM) and non-syndromic cleft lip with or without palate (NSCL/P) using case-parent trio design. Methods: Whole-exome sequencing was conducted for twenty-two NSCL/P trios and Genome Analysis ToolKit (GATK) was used to identify DNM by comparing the alleles of the cases and their parents. Information of predictable functions was annotated to the locus with SnpEff. Enrichment analysis for DNM was conducted to test the difference between the actual number and the expected number of DNM, and to explore whether there were genes with more DNM than expected. NSCL/P-related genes indicated by previous studies with solid evidence were selected by literature reviewing. Protein-protein interactions analysis was conducted among the genes with protein-altering DNM and NSCL/P-related genes. R package "denovolyzeR" was used for the enrichment analysis (Bonferroni correction: P=0.05/n, n is the number of genes in the whole genome range). Protein-protein interactions among genes with DNM and genes with solid evidence on the risk factors of NSCL/P were predicted depending on the information provided by STRING database. Results: A total of 339 908 SNPs were qualified for the subsequent analysis after quality control. The number of high confident DNM identified by GATK was 345. Among those DNM, forty-four DNM were missense mutations, one DNM was nonsense mutation, two DNM were splicing site mutations, twenty DNM were synonymous mutations and others were located in intron or intergenic regions. The results of enrichment analysis showed that the number of protein-altering DNM on the exome regions was larger than expected (P < 0.05), and five genes (KRTCAP2, HMCN2, ANKRD36C, ADGRL2 and DIPK2A) had more DNM than expected (P < 0.05/(2×19 618)). Protein-protein interaction analysis was conducted among forty-six genes with protein-altering DNM and thirteen genes associated with NSCL/P selected by literature reviewing. Six pairs of interactions occurred between the genes with DNM and known NSCL/P-related genes. The score measuring the confidence level of the predicted interaction between RGPD4 and SUMO1 was 0.868, which was higher than the scores for other pairs of genes. Conclusion: Our study provided novel insights into the development of NSCL/P and demonstrated that functional analyses of genes carrying DNM were warranted to understand the genetic architecture of complex diseases.

Objective: To explore whether WNT signaling pathway genes were associated with non-syndromic oral clefts (NSOC) based on haplotypes analyses among 1 008 Chinese NSOC case-parent trios. Methods: The genome-wide association study (GWAS) data of 806 Chinese non-syndromic cleft lip with or without cleft palate (NSCL/P) trios and 202 Chinese non-syndromic cleft palate (NSCP) case-parent trios were drawn from the International Consortium to Identify Genes and Interactions Controlling Oral Clefts (ICOCs) study GWAS data set, whose Chinese study population were recruited from four provinces in China, namely Taiwan, Shandong, Hubei, and Sichuan provinces. The process of DNA genotyping was conducted by the Center for Inherited Disease Research in the Johns Hopkins University, using Illumina Human610-Quad v.1_B Bead Chip. The method of sliding windows was used to determine the haplotypes for analyses, including 2 SNPs haplotypes and 3 SNPs haplotypes. Haplotypes with a frequency lower than 1% were excluded for further analyses. To further assess the association between haplotypes and NSOC risks, and the transmission disequilibrium test (TDT) was performed. The Bonferroni method was adopted to correct multiple tests in the study, with which the threshold of statistical significance level was set as P < 0.05 divided by the number of tests, e.g P < 3.47×10^-4 in the current stu-dy. All the statistical analyses were performed by using plink (v1.07). Results: After quality control, a total of 144 single nucleotide polymorphisms (SNPs) mapped in seven genes in WNT signaling pathway were included for the analyses among the 806 Chinese NSCL/P trios and 202 Chinese NSCP trios. A total of 1 042 haplotypes with frequency higher than 1% were included for NSCL/P analyses and another 1 057 haplotypes with frequency higher than 1% were included for NSCP analyses. Results from the TDT analyses showed that a total of 69 haplotypes were nominally associated with the NSCL/P risk among Chinese (P < 0.05). Another 34 haplotypes showed nominal significant association with the NSCP risk among Chinese (P < 0.05). However, none of these haplotypes reached pre-defined statistical significance level after Bonferroni correction (P>3.47×10^-4). Conclusion: This study failed to observe any statistically significant associations between haplotypes of seven WNT signaling pathway genes and the risk of NSOC among Chinese. Further studies are warranted to replicate the findings here.

Objective: To investigate the protective effects of curcumin(CUR) and its mechanism on a rat model of neurotoxicity induced by manganese chloride (MnCl₂), which mimics mangnism. Methods: Sixty male SD rats were randomly divided into 5 groups, with 12 rats in each group. Control group received 0.9% saline solution intraperitoneally (ip) plus double distilled water (dd) H₂O intragastrically (ig), MnCl₂ group received 15 mg/kg MnCl₂(Mn²⁺ 6.48 mg/kg) intraperitoneally plus dd H₂O intragastrically, CUR group received 0.9% saline solution intraperitoneally plus 300 mg/kg CUR intragastrically, MnCl₂+ CUR1 group received 15 mg/kg MnCl₂ intraperitoneally plus 100 mg/kg curcumin intragastrically, MnCl₂+ CUR2 group received 15 mg/kg MnCl₂ intraperitoneally plus 300 mg/kg CUR intragastrically, 5 days/week, 4 weeks. Open-field and rotarod tests were used to detect animals' exploratory behavior, anxiety, depression, movement and balance ability. Morris water maze (MWM) experiment was used to detect animals' learning and memory ability. ICP-MS was used to investigate the Mn contents in striata. The rats per group were perfused in situ, their brains striata were removed by brains model and fixed for transmission electron microscope (TEM), histopathological and immunohistochemistry (ICH) analyses. The other 6 rats per group were sacrificed. Their brains striata were removed and protein expression levels of transcription factor EB (TFEB), mammalian target of rapamycin (mTOR), p-mTOR, Beclin, P62, microtubule-associated protein light chain-3 (LC3) were detected by Western blotting. Terminal deoxynucleotidyl transterase-mediated dUTP nick end labeling (TUNEL) staining was used to determine neurocyte apoptosis of rat striatum. Results: After exposure to MnCl₂ for four weeks, MnCl₂-treated rats showed depressive-like behavior in open-field test, the impairments of movement coordination and balance in rotarod test and the diminishment of spatial learning and memory in MWM (P < 0.05). The striatal TH⁺ neurocyte significantly decreased, eosinophilic cells, aggregative α-Syn level and TUNEL-positive neurocyte significantly increased in the striatum of MnCl₂ group compared with control group (P < 0.05). Chromatin condensation, mitochondria tumefaction and autophagosomes were observed in rat striatal neurocytes of MnCl₂ group by TEM. TFEB nuclear translocation and autophagy occurred in the striatum of MnCl₂ group. Further, the depressive behavior, movement and balance ability, spatial learning and memory ability of MnCl₂+ CUR2 group were significantly improved compared with MnCl₂ group (P < 0.05). TH+ neurocyte significantly increased, the eosinophilic cells, aggregative α-Syn level significantly decreased in the striatum of MnCl₂+ CUR2 group compared with MnCl₂ group. Further, compared with MnCl₂ group, chromatin condensation, mitochondria tumefaction was alleviated and autophagosomes increased, TFEB-nuclear translocation, autophagy was enhanced and TUNEL-positive neurocyte reduced significantly in the striatum of MnCl₂+ CUR2 group (P < 0.05). Conclusion: Curcumin alleviated the MnCl₂-induced neurotoxicity and α-Syn aggregation probably by promoting TFEB nuclear translocation and enhancing autophagy.

Objective: To explore the relationship between sleep habits (sleep duration, sleep efficiency, sleep onset timing) and ischemic stroke, and whether there is an interaction between sleep habits and ischemic stroke susceptibility gene loci. Methods: A questionnaire survey, physical examination, blood biochemical testing and genotyping were conducted among rural residents in Beijing, and the gene loci of ischemic stroke suggested by previous genome-wide association studies (GWAS) were screened. Multivariable generalized linear model was used to analyze the correlation between sleep habits, sleep-gene interaction and ischemic stroke. Results: A total of 4 648 subjects with an average age of (58.5±8.7) years were enrolled, including 1 316 patients with ischemic stroke. Compared with non-stroke patients, stroke patients with sleep duration ≥9 hours, sleep efficiency < 80%, and sleep onset timing earlier than 22:00 accounted for a higher proportion (P < 0.05). There was no significant association between sleep duration and risk of ischemic stroke (OR=1.04, 95%CI: 0.99-1.10, P=0.085). Sleep efficiency was inversely associated with the risk of ischemic stroke (OR=0.18, 95%CI: 0.06-0.53, P=0.002). The risk of ischemic stroke in the subjects with sleep efficiency < 80% was 1.47-fold (95%CI: 1.03-2.10, P=0.033) of that in the subjects with sleep efficiency ≥80%. Falling asleep earlier than 22:00 was associated with 1.26 times greater risk of stroke than falling asleep between 22:00 and 22:59 (95%CI: 1.04-1.52, P=0.017). Multifactorial adjustment model showed that rs579459 on ABO gene had an interaction with sleep time (P for interaction =0.040). When there were two T alleles for rs579459 on the ABO gene, those who fell asleep before 22:00 had 1.56 times (95%CI: 1.20-2.04, P=0.001) the risk of stroke compared with those who fell asleep between 22:00 and 22:59, and there was no significant difference when the number of pathogenic alleles was 0 or 1. In the model adjusted only for gender, age and family structure, sleep duration and the number of T allele rs2634074 on PITX2 gene had an interaction with ischemic stroke (P for interaction=0.033). Conclusion: Decreased sleep efficiency is associated with increased risk of ischemic stroke, and falling asleep earlier than 22:00 is associated with higher risk of ischemic stroke. Sleep onset timing interacted with rs579459 in ABO gene and the risk of ischemic stroke. Sleep duration and PITX2 rs2634074 may have a potential interaction with ischemic stroke risk.

Objective: To explore whether the using of mimetic peptide Gap27, a selective inhibitor of connexin 43 (Cx43), could block the death of dopamine neurons and influence the expression of Cx43 in 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease mouse models. Methods: Eighteen C57BL/6 mice were randomly divided into control group, 6-OHDA group and 6-OHDA+Gap27 group, with 6 mice in each group. Bilateral substantia nigra stereotactic injection was performed. The control group was injected with ascorbate solution, 6-OHDA group was injected with 6-OHDA solution, and 6-OHDA+Gap27 group was injected with 6-OHDA and Gap27 mixed solution. Immuno-histochemical staining was used to detect the number of dopamine neurons, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of Cx43 messenger ribonucleic acid (mRNA), immuno-fluorescence staining was used to detect the distribution of Cx43 protein, the contents of Cx43 protein and Cx43 phosphorylation at serine 368 (Cx43-ps368) in mouse midbrain were detected by Western blot. Results: After injection of 6-OHDA, numerous dopamine neurons in substantia nigra died as Cx43 content increased, Cx43-ps368 content decreased. Mixing Gap27 while injecting 6-OHDA could reduce the number of death dopamine neurons and weaken the changes of Cx43 and Cx43-ps368 content caused by 6-OHDA. The number of tyrosine hydroxylase (TH) immunoreactive positive neurons in 6-OHDA group decreased to 27.7% ± 0.02% of the control group (P < 0.01); The number of TH immunoreactive positive neurons in 6-OHDA+Gap27 group was (1.64±0.16) times higher than that in 6-OHDA group (P < 0.05); The content of total Cx43 protein in 6-OHDA group was (1.44±0.07) times higher than that in 6-OHDA+Gap27 group (P < 0.05) while (1.68±0.07) times higher than that in control group (P < 0.01). In 6-OHDA group, the content of Cx43-ps368 protein and its proportion in total Cx43 protein were significantly lower than that in 6-OHDA+Gap27 group (P < 0.05). Conclusion: In 6-OHDA mouse models, mimetic peptide Gap27 played a protective role in reducing the damage to substantia nigra dopamine neurons, which was induced by 6-OHDA. The overexpression of Cx43 protein might have neurotoxicity to dopamine neuron. Meanwhile, decreasing Cx43 protein level and keeping Cx43-ps368 protein level may be the protective mechanisms of Gap27.

Objective: To investigate the association between serum high sensitivity C-reaction protein (hsCRP) in early pregnancy and gestational diabetes mellitus (GDM) among twin pregnant women, and to explore the effects of the pre-pregnant body mass index (BMI) and gestational weight gain (GWG) status on such association. Methods: Twin pregnant women with pre-pregnant BMI greater than or equal to 18.5 kg/m² were recruited at Department of Obstetrics and Gynecology of Peking University Third Hospital from March 2017 to December 2020. Serum samples collected in early pregnancy were analyzed for hsCRP using particle-enhanced immunoturbidimetric method. In the following visits, the information about GWG and GDM were prospectively collected in every trimester. The association effect between hsCRP tertiles and GDM were estimated using Logistic regression, and further converted into risk ratio (RR). Cochran-Mantel-Haenszel test and mediation analysis were used to explore the effects of BMI and GWG status on the association. Results: Among the included 570 twin pregnant women, 31.6% deve-loped GDM, 26.1% were pre-pregnant overweight or obesity, and 49.5% with GWG out of referenced range. After adjustment for confounding factors, risk of developing GDM in twin gestations with the middle tertile and highest tertile of serum hsCRP in early pregnancy were 1.42 fold (95%CI: 1.02-1.89) and 1.54 fold (95%CI: 1.12-2.02), respectively, compared with the lowest tertile of serum hsCRP, and there existed significantly linear trend (P=0.022). Findings from mediation analysis illustrated that pre-pregnant BMI had partial mediating effect on the association, and BMI accounted for 23.84% (P < 0.001) of the increasing GDM risks with elevated hsCRP. Joint analysis with hsCRP and GWG found that those who were with GWG out of referenced range accompanied with the higher hsCRP tertiles (>1.21 mg/L) had significantly 2.31 fold increased risk according to those who were with GWG in the referenced range accompanied with the lowest hsCRP tertile (≤1.21 mg/L, P < 0.01). Conclusion: Elevated hsCRP in early pregnancy significantly increased GDM risk among twin pregnant women. The hsCRP-GDM association was dependent on GWG status, and pre-pregnant BMI had partial mediating effect on such association. It is suggested that twin pregnant women should consider systemic inflammation and gestational weight at the same time to reduce GDM risk.

Objective: To explore the association of maternal periconceptional folic acid or multiple micronutrients supplementation during periconceptional period and the serum vitamin E (Vit.E) concentration in the 1st trimester of gestational period. Methods: A retrospective cohort study was conducted based on the prenatal health care system and clinical laboratory information system. Totally, 22 171 pregnant women who had their prenatal health care and gave birth in Tongzhou Maternal & Child Health Hospital of Beijing from Jan. 2016 to Dec. 2018 were recruited. The usage patterns of nutritional supplements [folic acid (FA) or multiple micronutrients (MM)] during periconceptional period were independent variables, and serum Vit.E concentration and serum Vit.E concentration≥11.2 mg/L in the 1st trimester of gestational period were outcome variables for generalized linear regression model and Logistic regression model, respectively, to analyze the relationships between the independent and outcome variables. Results: The range of the serum Vit.E concentration in the 1st trimester of gestational period was 5.2-24.0 mg/L, and the median concentration was 10.1 (8.8-11.6) mg/L; the excess rate of the serum Vit.E of those who took MM supplementation was 0.3%, and the rates for the groups of FA only or no nutritional supplements used were both 0.1%. Compared with women without nutritional supplement or the women taking FA, the women who took MM had higher serum Vit.E levels in the 1st trimester of gestational period (both P < 0.05). The women taking FA or MM initiated before the conception showed that the serum Vit.E concentration in the 1st trimester of gestational period was higher than that after the conception (P < 0.05), and the serum Vit.E concentration of women who took regularly was higher than that of irregular taking (P < 0.05); with taking compliance elevated, the serum Vit.E concentration of the two groups of women taking FA or MM increased (P < 0.05). The risk of serum Vit.E concentration≥11.2 mg/L among the women taking MM was higher than that of the women without nutritional supplements or taking FA only [odds ratio (OR)=1.36, 95% confidence interval (95%CI): 1.21-1.53; OR=1.39, 95%CI: 1.31-1.48)]; women who took FA or MM showed a lower risk for serum Vit.E concentration≥11.2 mg/L of taking it after the conception than before, the ORs (95%CI) were 0.86 (95%CI: 0.77-0.96) and 0.88 (95%CI: 0.81-0.95), respectively; the women taking the two supplements regularly had higher risk for serum Vit.E concentration≥11.2 mg/L than irregular taking, the ORs (95%CI) were 1.16 (95%CI: 1.05-1.29) and 1.13 (95%CI: 1.04-1.22) for FA and MM users, respectively; with the compliance increasing, the women taking MM had a higher risk of serum Vit.E levels≥11.2 mg/L in the 1st trimester [OR (95%CI) was 1.10 (1.07-1.14)], but for FA users, the OR (95%CI) was 1.04(1.00-1.08). Conclusion: Vit.E nutritional status in women in early gestational period in Beijing was generally good, and the excess rate of serum Vit.E was higher in women who took MM during periconceptional period than those without nutritional supplement or taking FA only, suggesting that women need to consider their own Vit.E nutritional status to choose the type of nutritional supplements during periconceptional period, so as to avoid related health hazards.

Objective: To evaluate the effectiveness of statin treatment strategies based on risk assessment for the primary prevention of cardiovascular diseases by the Western guidelines in a community-based Chinese population from economically developed areas using data from the Chinese electronic health records research in Yinzhou (CHERRY) study. Methods: A Markov model was used to evaluate the effectiveness of the following statin treatment strategies, including: (1) usual care without cardiovascular risk assessment(Strategy 0); (2) using the World Health Organization (WHO) non-laboratory-based risk charts with statin treatment for high-risk group (risk ≥ 20%) (Strategy 1); (3) using the WHO laboratory-based risk charts with statin treatment for high-risk group (risk ≥ 20%) (Strategy 2); and (4) using the Prediction for Atherosclerotic cardiovascular disease Risk in China (China-PAR) model with statin treatment for high-risk group (risk ≥ 10%, Strategy 3). According to the guidelines, adults in the medium-risk group received lifestyle intervention, and adults in the high-risk group received life-style intervention and statin treatment under these strategies. The Markov model simulated different strategies for ten years (cycles) using parameters from the CHERRY study, published data, meta-analyses and systematic reviews for Chinese. The number of cardiovascular events or deaths, as well as the number need to treat (NNT) with statin per cardiovascular event or death prevented, were calculated to compare the effectiveness of different strategies. One-way sensitivity analysis on the uncertainty of incidence rate of cardiovascular diseases, and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted. Results: Totally 225 811 Chinese adults aged 40-79 years without cardiovascular diseases at baseline were enrolled. In contrast to the usual care without risk assessment-based statin treatment strategy, Strategy 1 using the WHO non-laboratory-based risk charts could prevent 3 482 [95% uncertainty interval (UI): 2 110-4 661] cardiovascular events, Strategy 2 using the WHO laboratory-based risk charts could prevent 3 685 (95%UI: 2 255-4 912) events, and Strategy 3 using the China-PAR model could prevent 3 895 (95%UI: 2 396-5 181) events. NNTs with statin per cardiovascular event prevented were 22 (95%UI: 14-54), 21 (95%UI: 14-52), and 27 (95%UI: 17-67), respectively. Strategy 3 could prevent more cardiovascular events, while Strategies 1 and 2 required fewer numbers need to treat with statin per cardiovascular event prevented. The results were consistent in the sensitivity analyses. Conclusion: The statin treatment strategies based on risk assessment for the primary prevention of cardiovascular diseases recommended by the Western guidelines could achieve substantive health benefits in adults from developed areas of China. Using the China-PAR model for cardiovascular risk assessment could prevent more cardiovascular diseases while using the WHO risk charts seems more efficient.

Objective: To evaluate the effectiveness of different screening strategies for type 2 diabetes to prevent cardiovascular disease in a community-based Chinese population from economically developed areas based on the Chinese electronic health records research in Yinzhou (CHERRY) study. Methods: A Markov model was used to simulate different systematic diabetes screening strategies, including: (1) screening among Chinese adults aged 40-70 years recommended by the 2020 Chinese Guideline for the prevention and Treatment of Type 2 Diabetes (Strategy 1); (2) screening among Chinese adults aged 35 to 70 years recommended by the 2022 American Diabetes Association Standard of Medical Care in Diabetes (Strategy 2); and (3) screening among Chinese adults aged 35-70 years with overweight or obesity recommended by the 2021 United States Preventive Services Task Force Recommendation Statement on Screening for Prediabetes and Type 2 Diabetes (Strategy 3). According to the guidelines, individuals who were screened positively (fasting plasma glucose ≥ 7.0 mmol/L) would be introduced to intensive glycemic targets management (glycated hemoglobin < 7.0%).The Markov model simulated different screening scenarios for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Number of cardiovascular disease events or deaths could be prevented and number needed to screen (NNS) were calculated to compare the effectiveness of the different strategies. One-way sensitivity analysis on the sensitivity of screening methods and probabilistic sensitivity analysis on uncertainties of diabetes incidence, the sensitivity of screening methods, and intensive glycemic management effects were conducted. Results: Totally 289 245 Chinese adults aged 35-70 years without cardiovascular diseases or diagnosed diabetes at baseline were enrolled. In terms of the number of cardiovascular disease events could be prevented, Strategy 1 for systematic diabetes screening among the adults aged 35-70 years was 222 (95%UI: 180-264), Strategy 2 for systematic diabetes screening among the adults aged 40-70 years was 227 (95%UI: 185-271), and Strategy 3 for systematic diabetes screening among the adults aged 35-70 years with obesity or overweight (body mass index ≥ 24 kg/m²) was 131 (95%UI: 98-164), compared with opportunistic screening. NNS per cardiovascular disease event for the strategies 1, 2 and 3 were 1 184 (95%UI: 994-1 456), 1 274 (95%UI: 1 067-1 564) and 814 (95%UI: 649-1 091), respectively. Compared with Strategy 1, NNS per cardiovascular disease event for Strategy 2 increased by 90 (95%UI: -197-381) with similar effectiveness of cardiovascular prevention; however, NNS per cardiovascular disease event for Strategy 3 was reduced by 460 (95%UI: 185-724) in contrast to the Strategy 2, suggesting that the Strategy 3 was more efficient. The results were consistent in multiple sensitivity analyses. Conclusion: Systematic screening for diabetes based on the latest guidelines in economically developed areas of China can reduce cardiovascular events and deaths. However, merely lowering the starting age of screening from 40 to 35 years seems ineffective for preventing cardiovascular disease, while screening strategy for Chinese adults aged 35-70 years with overweight or obesity is recommended to improve efficiency.

Objective: To select variables related to mortality risk of stroke patients in intensive care unit (ICU) through long short-term memory (LSTM) with attention mechanisms and Logistic regression with L1 norm, and to construct mortality risk prediction model based on conventional Logistic regression with important variables selected from the two models and to evaluate the model performance. Methods: Medical Information Mart for Intensive Care (MIMIC)-Ⅳ database was retrospectively analyzed and the patients who were primarily diagnosed with stroke were selected as study population. The outcome was defined as whether the patient died in hospital after admission. Candidate predictors included demogra-phic information, complications, laboratory tests and vital signs in the initial 48 h after ICU admission. The data were randomly divided into a training set and a test set for ten times at a ratio of 8 ∶2. In training sets, LSTM with attention mechanisms and Logistic regression with L1 norm were constructed to select important variables. In the test sets, the mean importance of variables of ten times was used as a reference to pick out the top 10 variables in each of the two models, and then these variables were included in conventional Logistic regression to build the final prediction model. Model evaluation was based on the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. And the model performance was compared with the forward Logistic regression model which hadn't conducted variable selection previously. Results: A total of 2 755 patients with 2 979 ICU admission records were included in the analysis, of which 526 recorded deaths. The AUC of Logistic regression model with L1 norm was statistically better than that of LSTM with attention mechanisms (0.819±0.031 vs. 0.760±0.018, P < 0.001). Age, blood glucose, and blood urea nitrogen were at the top ten important variables in both of the two models. AUC, sensitivity, specificity, and accuracy of Logistic regression models were 0.85, 85.98%, 71.74% and 74.26%, respectively. And the final prediction model was superior to forward Logistic regression model. Conclusion: The variables selected by Logistic regression with L1 norm and LSTM with attention mechanisms had good prediction performance, which showed important implications on the mortality prediction of stroke patients in ICU.

Objective: To explore the effects of oral exposure to titanium dioxide nanoparticles (TiO₂ NPs) on the composition and structure of human gut microbiota. Methods: The particle size, shape, crystal shape and degree of agglomeration in ultrapure water of TiO₂ NPs were characterized. The in vitro human digestive tract microecological simulation system was established by simulating the fluid environment and physical conditions of stomach, small intestine and colon, and the stability of the simulation system was evaluated. The bacterial communities were extracted from human feces and cultured stably in the simulated system. They were exposed to 0, 20, 100 and 500 mg/L TiO₂ NPs, respectively, and the bacterial fluids were collected after 24 h of exposure. The effect of TiO₂ NPs on the composition and structure of human gut microbiota was analyzed by 16S rRNA sequencing technology. Linear discriminant analysis effect size (LEfSe) was used to screen differential bacteria, and the Kyoto encyclopedia of genes and genomes (KEGG) database for functional prediction. Results: The spherical and anatase TiO₂ NPs were (25.12±5.64) nm in particle size, while in ultra-pure water hydrated particle size was (609.43±60.35) nm and Zeta potential was (-8.33±0.22) mV. The in vitro digestive tract microecology simulation system reached a relatively stable state after 24 hours, and the counts of Enterococci, Enterobacte-rium, and Lactobacillus reached (1.6±0.85)×10⁷, (5.6±0.82)×10⁷ and (2.7±1.32)×10⁷, respectively. 16S rRNA sequencing results showed that compared with the control group, the number and evenness of gut microbiota were not significantly affected at phylum, class, order, family and genus levels in TiO₂ NPs groups (20, 100 and 500 mg/L). The relative abundance of some species was significantly changed, and a total of 42 different bacteria were screened between the TiO₂ NPs groups (20, 100 and 500 mg/L) and the control group [linear discriminant analysis(LDA) score>3], represented by Enterobacter, Bacteroidaceae, Lactobacillaceae, Bifidobacteriaceae and Clostridium. Further predictive analysis of gut microbiota function showed that TiO₂ NPs might affect oxidative phosphorylation, energy meta-bolism, phosphonate and phosphonate metabolism, and methane metabolism (P < 0.05). Conclusion: In human digestive tract microecological simulation system, TiO₂ NPs could significantly change the composition and structure of human gut microbiota, represented by Enterobacter and probiotics, and may further affect a variety of metabolism and function of the body.

Objective: To analyze the long-term trends of the changes in the equity of China's health workforce allocation to provide a reference for the more balanced and orderly development of China's health system. Methods: The Gini coefficient was used to evaluate the degree of equity in the allocation of health workforce between regions, and the Gini coefficients for the allocation of doctors and nurses based on population and regional gross domestic product (GDP) distribution were calculated respectively. Results: In 2019, the number of licensed (assistant) physicians per 1 000 population in China was 2.77, and the number of registered nurses per 1 000 population was 3.18. The Gini coefficient for the distribution of licensed (assistant) physicians by population was 0.141 in 2002, decreasing to 0.081 by 2014 and then remained stable. The Gini coefficient for the distribution of registered nurses by population was 0.164 in 2002 and decreased to 0.066 in 2018. The Gini coefficient for the distribution of licensed (assistant) physicians by GDP was 0.236 in 2002, decreased to 0.169 in 2013, then increased to 0.183 and remained stable. The Gini coefficient for the distribution of registered nurses by GDP was 0.206 in 2002, decreased to 0.150 in 2013, and then increased each year to 0.180 in 2019. The equity of the allocation of registered nurses by population was worse than the equity of the allocation of licensed (assistant) physicians in 2002, and in 2016, for the first time, exceeded that of licensed (assistant) physicians. Conclusion: Equity in the allocation of health workforce across China has improved, but the improvement in equity between regions has hit a bottleneck, with health workforce allocation in the western regions still relatively scarce. Although nursing workforce allocation equity caught up with licensed (assistant) physicians, the number of licensed (assistant) physicians is close to that of developed western countries, while there is a large gap in registered nurses. It is recommended that the relevant authorities make good long-term planning for health workforce, further increase the policy for the introduction of health workforce in the western region, and increase the supply of healthcare services in the western region with the help of digital transformation of healthcare and internet healthcare. At the same time, they should further increase investment in resources for higher nursing education and actively plan to cope with the ageing population.

Objective: To explore the relation of smoking status to family health and personality traits in residents aged over 18 years in China by binary Logistic regression analysis, to identify the psychosocial factors that influence tobacco use, and to provide evidence to predict smoking susceptibility based on personality traits and prevent smoking at individual and family levels. Methods: Residents aged over 18 years in China were selected from "the Survey of Chinese Family Health Index (2021)". General characteristic questionnaire, short-form of family health scale, 10-item big five inventory were used to collect sociodemographic information, family health function and personality traits. And the relation of smoking status to family health and personality traits were analyzed by binary Logistic regression analysis. Results: Totally 10 315 adults were collected, of whom there were 2 171 smokers. The smoking rate was 21.05%, 41.76% of the residents were male, 3.69% female, 20.03% urban, 23.77% rural, 12.60% aged between 18 and 35 years, 27.11% aged between 36 and 59 years, 34.35% aged over 60 years, and the smoking rate varied in gender, location, age, education, marital status, family types, and average household monthly income (P < 0.05). Furthermore, the scores of family health, family social and emotional health processes, family healthy lifestyle, family health resources, family external social support, agreeableness, openness, and neuroticism among smokers were lower than those of the non-smokers (P < 0.05). The results of binary Logistic regression analysis showed that the residents over 35 years old, with low educational level and divorced were the risk factors to smoking (P < 0.05), while female, unmarried, nuclear family, high scores of family social and emotional health processes and family health resources, openness, neuroticism, and agreeableness were the protective factors to smoking (P < 0.05). Conclusion: Besides gender, age, location, education, marital status, family types and average household monthly income, family health, and personality traits were also important factors influencing smoking status. Tobacco control based on personality traits and family health is essential, and more convincing research is necessary to determine the relation of tobacco use, tobacco dependence and smoking cessation to family health and personality traits.

Objective: To investigate the status and influencing factors of anxiety tendency among occupational population in China and to examine the joint association between sedentary behavior and physical activity with anxiety tendency. Methods: The data were from the 2021 Asia Best Workplace (Chinese mainland) program. The Generalized Anxiety Tendency scale was used to assess employees' anxiety status, and Logistic regression was used to analyze the factors influencing anxiety tendency and calculate the odds ratio (OR) within different groups. The OR of sitting for each sitting-physical activity (PA) combination group and within PA strata were calculated to explore the joint association. Results: A total of 11 903 workers with an average age of 32.9 years were included in this study. Among them, 3 562 workers had anxiety tendency (29.9%) and the prevalence of those under 40 years old (30.6%) was significantly higher than the other age group (26.7%). 41.0% of the respondents had the moderated to vigorous physical activity. Their average daily sitting time was 9.4 h, and the percentage of those who exceeded 8 h sitting reached 73.9% in the past week. The analysis of Logistic regression showed that smoking (OR=1.24, 95%CI: 1.23-1.39), longer sedentary time and lower physical activity level were risk factors for anxiety tendency, and longer average daily sleep time (OR=0.56, 95%CI: 0.51-0.61) was a protective factor. The joint association analysis and stratified analysis of physical activity and sedentary behavior with anxiety tendency showed that increased sedentary time combined with decreased physical activity intensity was significantly associated with increased risk of anxiety tendency (range of OR: 1.64-3.14). The threshold for sedentary time in total as a risk factor for anxiety tendency gradually decreased as physical activity intensity increased. Conclusion: The anxiety tendency and sedentary behavior among the occupational population should recieve more attention. Lack of physical activity and sedentary behavior are both risk factors for anxiety tendency, and strengthening the intensity of physical activity can attenuate the harmful effects of sedentary behavior on anxiety tendency.

Objective: To analyze the mortality of injuries among children and adolescents aged 5 to 24 in China from 1990 to 2019, and to provide the theoretical basis for the formulation of policies related to injury prevention. Methods: The mortality data of children and adolescents aged 5 to 24 years in China between 1990 and 2019 were obtained from Global Burden of Disease (GBD) 2019, and the change in mortality between 1990 and 2019 was described. Age-period-cohort analysis was utilized to determine the age effect, period effect and cohort effect for road injuries, drowning and self-harm. Results: Injury mortality of Chinese children and adolescents aged 5 to 24 years decreased from 46.22 [95% uncertainty interval (UI): 40.88-52.12] per 100 000 to 20.36 (95%UI: 17.58-23.38) per 100 000 between 1990 and 2019. Sub-group analysis revealed a pattern that was basically consistent with the overall trend. From 1990 to 2019, drowning declined from the first leading cause of injury death among children and adolescents aged 5 to 24 years in China to the second while road injuries became the one which caused the most death among them, and self-harm was the third leading cause of injury death. The top three causes of injury death in each subgroup were basically the same as the overall, but the order was different in each subgroup. Age-period-cohort analysis showed that the death risk of road injuries, drowning, and self-harm all decreased with period and cohort. Aside from that, the death risk of road injuries showed a U-shape trend, which decreased at first but increased soon afterwards, with the increase of age, while the death risk of drowning decreased with age and the death risk of self-harm increased with age. Conclusion: In China, the injuries mortality among children and adolescents aged 5 to 24 years has decreased over the last three decades. However, specific cause-related injury deaths, manifested differently in different sub-groups. Targeted policies and intervention should be proposed to reduce the mortality of children and adolescents in accordance with the characteristics of injuries death in different genders and age groups.

Objective: To analyze the influenza vaccination trend of hospitalized elderly people (≥ 60 years old) in Beijing from 2013 to 2019. Methods: The influenza vaccination status and hospitalization information of elderly people were extracted from the Beijing Elderly Influenza Vaccination database (2013-2019) and the Beijing Urban Employee Basic Medical Insurance database (2013-2019), se-parately. The influenza vaccine coverage rates and annual percentage change were calculated to compare the vaccination trends of elderly people hospitalized due to different diseases. The subjects in 2018-2019 influenza season were divided into different groups according to demographic status, health conditions and hospitalization outcomes to describe and compare the distribution of influenza vaccination rates. Results: The influenza vaccine coverage rates among the elderly people hospitalized due to cardiovascular diseases, cerebrovascular diseases, respiratory diseases or diabetes mellitus were 14.6%, 13.4%, 13.4% and 11.8%, respectively. The influenza vaccination rate among those hospitalized for cardiovascular diseases remained the highest across six influenza seasons and those hospitalized for diabetes mellitus remained the lowest. The largest annual decline of influenza vaccine coverage rate was observed among the hospitalized elderly due to diabetes mellitus (-7.85%). The distribution of vaccinated population was significantly associated with age, gender, hospitalization outcome and comorbidities among the hospitalized elderly people with specific diseases in 2018-2019. Among the elderly people hospitalized due to four different diseases, the vaccination rate of the patients aged 70-79 years was higher than that of the other age groups and that of the patients aged 60-69 years was the lowest. Among the elderly people hospitalized due to respiratory diseases, the vaccination rate of men was higher than that of women, while the situation reversed among the elderly people hospitalized due to cardiovascular diseases and diabetes mellitus. Vaccination rates decreased among the older adults with poor hospitalization outcomes. Among the elderly people hospitalized due to diabetes mellitus, those with 0 comorbidity had the lowest vaccination rate (7.9%). Conclusion: The trend of influenza vaccine coverage rates among the elderly people in Beijing from 2013 to 2019 was downward. We should pay more attention to influenza vaccination in elderly people with diabetes mellitus and aged 60-69 years, and carry out more research on the protective effects of influenza vaccine to promote influenza vaccine coverage among people with chronic diseases.

Objective: To describe the distribution characteristics of inflammatory bowel disease among permanent residents in Yinzhou District, Ningbo City, and to understand the disease burden and development trend of inflammatory bowel disease in this area. Methods: Using the retrospective cohort design, we collected the registration information of all permanent residents in the residents' health files of the Yinzhou Regional Health Information Platform from 2010 to 2020, and used electronic medical records to follow up their inflammatory bowel disease visits. A one-year wash-out period was set, and the patients who were diagnosed with the primary diagnosis for the first time after one year of registration were re-garded as new cases. The incidence density and 95% confidence interval (CI) of inflammatory bowel disease were estimated by Poisson distribution. Results: From 2011 to 2020, a total of 1 496 427 permanent residents in Yinzhou District were included, of which 729 996 were male (48.78%). The total follow-up person-years were 8 081 030.82, and the median follow-up person-years were 5.41 [interquartile range (IQR): 5.29]. During the study period, there were 1 217 new cases of inflammatory bowel disease, of which males (624 cases, 51.27%) were more than females (593 cases, 48.73%). The total incidence density was 15.06/100 000 person-years (95%CI: 14.23, 15.93). Among all new cases, there were 1 106 cases (90.88%) of ulcerative colitis, with an incidence density of 13.69 per 100 000 person-years (95%CI: 12.89, 14.52); 70 cases (5.75%) of Crohn's disease, with an incidence density of 0.87 per 100 000 person-years (95%CI: 0.68, 1.09); and 41 cases (3.37%) of indeterminate colitis, with an incidence density of 0.51 per 100 000 person-years (95%CI: 0.36, 0.69). The median age of onset of ulcerative colitis was 50.82 years old (IQR: 18.77), with the highest proportion (15.01%) in the 45-49 years group. The incidence density of ulcerative colitis gradually increased with age, reaching a relatively high level in the 45-49 years group (20.53/100 000 person-years; 95%CI: 17.63, 23.78), followed by a slight increase. And the incidence density in the 65-69 years group was the highest (25.44/100 000 person-years; 95%CI: 20.85, 30.75), with a rapid decrease in the 75-79 years group. The median age of onset of Crohn's disease was 44.34 years (IQR: 33.41), with the highest proportion (12.86%) in the 25-29 years group. Due to the small number of new cases of Crohn's disease, the age distribution fluctuated greatly, with peaks both in young and old people. From 2011 to 2020, the incidence density of inflammatory bowel disease in Yinzhou District was at a low level from 2011 to 2013, and showed a rapid upward trend from 2014 to 2016, reaching a peak of 24.62 per 100 000 person-years in 2016 (95%CI: 21.31, 28.30), and slightly decreased in 2017—2020. Conclusion: The incidence density of inflammatory bowel disease in Yinzhou District from 2011 to 2020 was at a relatively high level, and medical institutions and health departments need to pay attention to the burden of disease caused by it.

Objective: To explore potential categories of parental social support for young parents under the coronavirus disease 2019 (COVID-19) epidemic, and to examine correlations of different types of parents' social support with parental burnout. Methods: In April 2020, we conducted an online voluntary survey among young parents across China with scales and a self-designed questionnaire. The latent profile analysis method was used to analyze parents' received social support and perceived social support. The social support categories were taken as independent variables and parental burnout as dependent variables, and multiple regression analysis was carried out to explore the relationship between received social support, perceived social support and parental burnout. Finally, the moderating effect of resilience between social support groups and parental burnout was discussed. Results: The results of latent profile analysis revealed three potential types of received social support, namely isolate, normal, and multi-support and the proportions of the respondents with the three profiles were 14.1%, 78.0%, and 7.9%. Four potential types of perceived social support, namely, indigent, medium, affluent and divergent and the proportions of the respondents with the four profiles were 13.7%, 29.6%, 25.3%, and 31.3%. Among them, the parents with divergent perceived social support had more perception of social support from the couple, family and relatives, but less perception of social support from net-friend, social organizations and the government. Regression analysis showed that there was no statistically significant correlation between different profiles of received social support and parental burnout, and among the groups of perceived social support, there was a statistically significant correlation between indigent and divergent types of social support and parental burnout. The divergent parents had lower levels of parental burnout compared with indigent (β=-0.120, P=0.003). Also, resilience moderated the effect of divergent perceived social support and parental burnout. Compared with the parents with low resilience, the parents with high resilience perceived divergent social support with lower parenting burnout. Conclusion: There are prominent latent types of received social support and perceived social support under epidemic. People with divergent perceived social support (more perceived supports from partner, family and friends) are prone to have a relatively lower risk of parental burnout. Parents with higher resilience will be more sensitive to the support of close acquaintances, and can better resist parental burnout.

Objective: To investigate the introduction of vegetables and fruits in 4-8 months old infants, and to describe the maternal and infants' characteristics associated with the introduction of vegetables and fruits. Methods: Mother-infant dyads (n=228) were recruited from 12 to 16 weeks postpartum and formally entered the study at 4 months of age. Data collected via face to face interview at 4-8 months postpartum, including the timing and types of added vegetables and fruits, as well as a variety of maternal and infant characteristics (n=204). Rank sum test and multiple linear regression were used to analyze the maternal and infant characteristics related to the introduction of vegetables and fruits. Results: The time of introducing vegetables was concentrated at the age of 7 months, and the time of adding fruits was mainly at 6 months. Fruits were added earlier than vegetables (P < 0.001), and the variety of the added fruits was higher than that of vegetables (P=0.045). 48% (n=98) of infants had no more than three types of fruits and vegetables at 8 months. Only 9.8% (n=20) had added more than 10 kinds of fruits and vegetables at 8 months. Green leafy vegetables were the most commonly added vegetable, and apple was the most popular fruit. Compared with women who were 35 years of age or younger, women beyond 35 years old introduced vegetables to their babies 0.6 months later. 4-month-old exclusively breastfed infants had vegetables 0.4 months later than mixed-fed infants. Women with a bachelor's degree or above added 2-3 more types of fruits and vegetables to their babies than those with junior high school education and below. Conclusion: The adding time of fruits was earlier than that of vegetable. Apples and green leafy vegetables are commonly added. Women with lower educational backgrounds add fewer types of fruits and vegetables to their babies. Mothers who choose exclusive breastfeeding and those over 35 years of age at childbirth add vegetables to their babies later than others. They should be targeted for health promotion programs that aim to improve the intake of fruits and vegetables among infants.

Objective: To explore the amino acid metabolomics characteristics of myeloid-derived suppressor cells (MDSCs) in mice with sepsis induced by the cecal ligation and puncture (CLP). Methods: The sepsis mouse model was prepared by CLP, and the mice were randomly divided into a sham operation group (sham group, n = 10) and a CLP model group (n = 10). On the 7th day after the operation, 5 mice were randomly selected from the surviving mice in each group, and the bone marrow MDSCs of the mice were isolated. Bone marrow MDSCs were separated to measure the oxygen consumption rate (OCR) by using Agilent Seahorse XF technology and to detect the contents of intracellular amino acids and oligopeptides through ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) technology. Different metabolites and potential biomarkers were analyzed by univariate statistical analysis and multivariate statistical analysis. The major metabolic pathways were enriched using the small molecular pathway database (SMPDB). Results: The proportion of MDSCs in the bone marrow of CLP group mice (75.53% ± 6.02%) was significantly greater than that of the sham group (43.15%± 7.42%, t = 7.582, P < 0.001), and the basal respiratory rate [(50.03±1.20) pmol/min], maximum respiration rate [(78.07±2.57) pmol/min] and adenosine triphosphate (ATP) production [(25.30±1.21) pmol/min] of MDSCs in the bone marrow of CLP group mice were significantly greater than the basal respiration rate [(34.53±0.96) pmol/min, (t = 17.41, P < 0.001)], maximum respiration rate [(42.57±1.87) pmol/min, (t = 19.33, P < 0.001)], and ATP production [(12.63±0.96) pmol/min, (t = 14.18, P < 0.001)] of sham group. Leucine, threonine, glycine, etc. were potential biomarkers of septic MDSCs (all P < 0.05). The increased amino acids were mainly enriched in metabolic pathways, such as malate-aspartate shuttle, ammonia recovery, alanine metabolism, glutathione metabolism, phenylalanine and tyrosine metabolism, urea cycle, glycine and serine metabolism, β-alanine metabolism, glutamate metabolism, arginine and proline metabolism. Conclusion: The enhanced mitochondrial oxidative phosphorylation, malate-aspartate shuttle and alanine metabolism in MDSCs of CLP mice may provide raw materials for mitochondrial aerobic respiration, thereby promoting the immunosuppressive function of MDSCs. Blocking the above metabolic pathways may reduce the risk of secondary infection in sepsis and improve the prognosis.

Objective: To investigate the clinical characteristics and risk factor analysis of necrotizing pneumonia in children. Methods: A retrospective study was used to analyze the case data of 218 children with severe pneumonia hospitalized in the Department of Respiratory Medicine, Children's Hospital of Capital Institute of Pediatrics from January 2016 to January 2020, and they were divided into 96 cases in the necrotizing pneumonia group (NP group) and 122 cases in the non-necrotizing pneumonia group (NNP group) according to whether necrosis of the lung occurred. The differences in clinical characteristics (malnutrition, fever duration, hospitalization time, imaging performance, treatment and regression follow-up), laboratory tests [leukocytes, neutrophil ratio, platelet (PLT), C-reactive protein (CRP), procalcitonin (PCT), D-dimer, and lactate dehydrogenase (LDH)] and bronchoscopic performance between the two groups were compared, and Logistic regression analysis of clinical risk factors associated with necrotizing pneumonia was performed to further determine the maximum diagnostic value of each index by subject operating characteristic curve (ROC). The critical value of each index was further determined by the ROC. Results: The differences in age, gender, pathogenic classification, and bronchoscopic presentation between the two groups of children were not statistically significant (P>0.05); whereas the imaging uptake time of the children in the NP group was higher than that in the NNP group (P < 0.05). The differences in malnutrition, fever duration, length of stay, white blood cell count, neutrophil ratio, CRP, PCT, and D-dimer were statistically significant between the two groups (P < 0.05). The imaging uptake time was lower in children under 6 years of age than in those over 6 years of age, and the imaging uptake time for bronchoalveolar lavage within 10 d of disease duration was lower than that for those over 10 d; the imaging uptake time was significantly longer in the mixed infection group than that in the single pathogen infection group. Logistic regression analysis of the two groups revealed that the duration of fever, hospital stay, CRP, PCT, and D-dimer were risk factors for secondary pulmonary necrosis (P < 0.001, P < 0.001, P < 0.001, P=0.013, P=0.001, respectively). The ROC curves for fever duration, CRP, PCT, and D-dimer were plotted and found to have diagnostic value for predicting the occurrence of pulmonary necrosis when fever duration >11.5 d, CRP >48.35 mg/L, and D-dimer > 4.25 mg/L [area under ROC curve (AUC)=0.909, 0.836, and 0.747, all P < 0.001]. Conclusion: Children with necrotizing pneumonia have a longer heat course and hospital stay, and the imaging uptake time of mixed pathogenic infections is significantly longer than that of single pathogenic infections. Children with necrotizing pneumonia under 6 years of age have more advantageous efficacy of electronic bronchoscopic alveolar lavage within 10 d of disease duration compared with children in the group over 6 years of age and children in the group with disease duration >10 d. Inflammatory indexes CRP, PCT, and D-dimer are significantly higher. The heat course, CRP, PCT, and D-dimer are risk factors for secondary lung necrosis in severe pneumonia. Heat course >11.5 d, CRP >48.35 mg/L, and D-dimer >4.25 mg/L have high predictive value for the diagnosis of necrotizing pneumonia.

Objective: To compare the effects of artificial liver treatment with double plasma molecular adsorption system(DPMAS) mode and traditional plasma exchange (PE) mode on platelets in patients, and to evaluate the clinical efficacy of recombinent human thrombopoietin (rhTPO) in the treatment of thrombocytopenia. Methods: A total of fifteen patients undergoing artificial liver with DPMAS model admitted to the Fifth Affiliated Hospital of Guangzhou Medical University from January 2018 to November 2020 were selected and included in the DPMAS group, and another 15 patients receiving PE were selected and included in the PE group. The improvement of clinical symptoms, such as fatigue, jaundice, oliguria, edema, etc. before and after artificial liver treatment was compared between the two groups, and the trend of blood routine (especially platelet), coagulation function and other indexes before and after treatment were compared between the two groups. The use of rhTPO and the number of platelets were recorded during treatment. Results: The improvement rate of clinical symptoms in DPMAS group was 86.67%, which was higher than that in PE group, but the difference was not statistically significant (P>0.05). There was no statistical significance in the outcome of the two groups within 90 days (P>0.05). There was no significant difference in white blood cell (WBC) and hemoglobin (HB) between the two groups after treatment (P>0.05). However, the level of platelet(PLT) in DPMAS group was significantly lower than that before treatment (P < 0.05), and was significantly lower than that in PE group (P < 0.05). After treatment, the international normalized ratio (INR) level in PE group was significantly improved (P < 0.05), but there was no significant difference in the INR level in DPMAS group (P>0.05). The patients in the DPMAS group received an average of (8.2±3.1) doses of rhTPO and (1.5±0.3) IU of platelet transfusions during hospitalization. In DMPAS group, platelets increased significantly after infusion of terbium. Conclusion: Compared with PE mode, the artificial liver with DPMAS mode can reduce platelet levels in patients, but the application of rhTPO can stimulate platelet regeneration and increase platelet levels in the patients, thereby reducing the risk of bleeding due to platelet hypoplasia.

Objective: To investigate the relationship between early lymphocyte responses and the prognosis in severely injured patients. Methods: Consecutive patients with severe trauma who were treated in Peking University People′s Hospital Trauma Medical Center between June 2017 and June 2020 were enrolled in this restropective chart-review study. According to the responses of lymphocyte after severe injury, the patients were divided into three groups, group 1: lymphopenia-returned to normal; group 2: persistent lymphopenia; group 3: never lymphopenic, and the outcome of 28 d were recorded. Clinical data such as gender, age, base excess, mechanism of injury, Glasgow coma scale (GCS), injury severity score (ISS) and massive blood transfusion were collected. Perform statistical analysis on the collected clinical data to understand the trend of lymphocyte changes in early trauma and the relationship with prognosis. In order to eliminate the interference of age, stratification was carried out according to whether the age was ≥ 65 years old, in different age groups, they were grouped according to whether the length of stay was ≥ 28 d, and the relationship between lymphocyte trend and length of stay was discussed. Results: A total of 83 patients were included, 66 males and 17 females. The main injury mechanisms were traffic accident injuries and high-altitude fall injuries. The average ISS was (30±11) points. 65 patients had lymphopenia on the day of injury, 32 of them returned to normal on the 5th day, and the rest did not recover; the other 18 patients had normal lymphocyte levels after injury. Patients which are failure to normalize lymphopenia within the first 5 days following admission was related with the long hospitalization time and higher 28 d mortality rate. After further stratification by age, failure to normalize lymphopenia within the first 5 days following admission in the elderly group (age ≥65 years) was a risk factor for prolonged hospital stay (≥28 d), P=0.04. While in younger group, a high level of neutrophils within the first 5 d following admission was a risk factor for bad outcome. Conclusion: A failure to normalize lymphopenia in severely injured patients is associated with significantly higher mortality and longer hospital stay. This study reveals lymphocytes can be used as a reliable indicator for the prognostic evaluation.

Objective: To compare the effects of three different crosslinkers on the biocompatibility, physical and chemical properties of decellularized small intestinal submucosa (SIS) porous scaffolds. Methods: The SIS porous scaffolds were prepared by freeze-drying method and randomly divided into three groups, then crosslinked by glutaraldehyde (GA), 1-ethyl-3-(3-dimethylaminopropyl) carbodi-imide (EDC) and procyanidine (PA) respectively. To evaluate the physicochemical property of each sample in different groups, the following experiments were conducted. Macroscopic morphologies were observed and recorded. Microscopic morphologies of the scaffolds were observed using field emission scanning electron microscope (FESEM) and representative images were selected. Computer software (ImageJ) was used to calculate the pore size and porosity. The degree of crosslinking was determined by ninhydrin experiment. Collagenase degradation experiment was performed to assess the resistance of SIS scaffolds to enzyme degradation. To evaluate the mechanical properties, universal mechanical testing machine was used to determine the stress-strain curve and compression strength was calculated. Human bone marrow mesenchymal cells (hBMSCs) were cultured on the scaffolds after which cytotoxicity and cell proliferation were assessed. Results: All the scaffolds remained intact after different crosslinking treatments. The FESEM images showed uniformed interconnected micro structures of scaffolds in different groups. The pore size of EDC group[(161.90±13.44) μm] was significantly higher than GA group [(149.50±14.65) μm] and PA group[(140.10±12.06) μm] (P < 0.05). The porosity of PA group (79.62%±1.14%) was significantly lower than EDC group (85.11%±1.71%) and GA group (84.83%±1.89%) (P < 0.05). PA group showed the highest degree of crosslinking whereas the lowest swelling ratio. There was a significant difference in the swelling ratio of the three groups (P < 0.05). Regarding to the collagenase degradation experiment, the scaffolds in PA group showed a significantly lower weight loss rate than the other groups after 7 days degradation. The weight loss rates of GA group were significantly higher than those of the other groups on day 15, whereas the PA group had the lowest rate after 10 days and 15 days degradation. PA group showed better mechanical properties than the other two groups. More living cells could be seen in PA and EDC groups after live/dead cell staining. Additionally, the proliferation rate of hBMCSs was faster in PA and EDC groups than in GA group. Conclusion: The scaffolds gained satisfying degree of crosslinking after three different crosslinking treatments. The samples after PA and EDC treatment had better physicochemical properties and biocompatibility compared with GA treatment. Crosslinking can be used as a promising and applicable method in the modification of SIS scaffolds.

Objective: To investigate the effect of polishing on surface roughness, gloss and optimum polishing time of various computer aided design/computer aided manufacturing (CAD/CAM) restorative materials and to provide a proper polishing procedure for dental clinicians. Methods: Five CAD/CAM restorative materials including vita mark Ⅱ (VM), vita enamic (VE), lava ultimate (LU), shofu block HC (SB) and brilliant crios (BC) were selected. Six specimens were prepared for each material. The specimen was fixed on a custom-made polishing apparatus and sequentially polished with Sof-Lex poli-shing disk system including medium disk (with abrasive particle sizes of 10-40 μm), fine disk (with abrasive particle sizes of 3-9 μm) and superfine disk (with abrasive particle sizes of 1-7 μm). Surface roughness (Ra value) and gloss value were measured every 10 seconds until the numerical values were no longer changed. Then the surface roughness, gloss value and polishing time were recorded and the specimen was moved to the next sequence of polishing. Finally, statistical analysis was performed using SPSS 24.0. Results: For all the restorative materials, the Ra values were significantly reduced (P < 0.05) and the gloss values were significantly increased (P < 0.05) after sequentially polishing with Sof-Lex disks. No significant difference was detected among Ra values of all the tested materials (P>0.05) after sequential polishing. The gloss values of LU [(68.1±4.5) GU] and BC [(68.2±5.8) GU] were significantly higher than those of VE [(48.1±8.1) GU] and BC [(53.2±5.8) GU], P < 0.05. To obtain optimal surface smoothness, VM cost the shortest polishing time [40 (30, 55) s] among all the restorative materials (P < 0.05). No significant differences in the total polishing time were observed among VE [140 (135, 145) s], LU [130 (120, 140) s], SB [140 (130, 150) s] and BC [130 (120, 140) s], P>0.05. Conclusion: The surface roughness of all CAD/CAM restorative materials were decreased after sequentially polishing with Sof-Lex disk system. To obtain the smoothest surface, different types of restorative materials might need different polishing times using Sof-Lex polishing disk system. For ceramic restorative material VM, we recommend polishing only with medium disk for 40 s. For hybrid restorative material VE and composite restorative material LU, SB and BC, we recommend polishing with medium disk, fine disk and superfine disk in sequence for 130-140 s in total.

Objective: To explore the feasibility of preparing compound tablets for the treatment of hypertension by fused deposition modeling (FDM) 3D printing technology and to evaluate the quality of the printed compound tablets in vitro. Methods: Polyvinyl alcohol (PVA) filaments were used as the exci-pient to prepare the shell of tablet. The ellipse-shaped tablets (the length of major axes of ellipse was 20 mm, the length of the minor axes of ellipse was 10 mm, the height of tablet was 5 mm) with two separate compartments were designed and printed using FDM 3D printer. The height of layer was 0.2 mm, and the thickness of roof or floor was 0.6 mm. The thickness of shell was 1.2 mm, and the thickness of the partition wall between the two compartments was 0.6 mm. Two cardiovascular drugs, captopril (CTP) and hydrochlorothiazide (HCT), were selected as model drugs for the printed compound tablet and filled in the two compartments of the tablet, respectively. The microscopic morphology of the tablets was observed by scanning electron microscopy (SEM). The weight variation of the tablets was investigated by electronic scale. The hardness of the tablets was measured by a single-column mechanical test system. The contents of the drugs in the tablets were determined by high performance liquid chromatography (HPLC), and the dissolution apparatus was used to measure the in vitro drug release of the tablets. Results: The prepared FDM 3D printed compound tablets were all in good shape without printing defects. The average weight of the tablets was (644.3±6.55) mg. The content of CTP and HCT was separately (52.3±0.26) mg and (49.6±0.74) mg. A delayed in vitro release profile was observed for CTP and HCT, and the delayed release time for CTP and HCT in vitro was 20 min and 40 min, respectively. The time for 70% of CTP and HCT released was separately 30 min and 60 min. Conclusion: CTP and HCT compound tablets were successfully prepared by FDM 3D printing technology, and the printed tablets were of good qualities.

Infective endocarditis in pregnancy is extremely rare in clinical practice. Guidelines addressing prophylaxis and management of infective endocarditis do not extensively deal with concomitant pregnancy, and case reports on infective endocarditis are scarce. Due to increased blood volume and hemodynamic changes in late pregnancy, endocardial neoplasms are easy to fall off and cause systemic or pulmonary embolism, respiratory, cardiac arrest and sudden death may occur in pregnant women, the fetus can suffer from intrauterine distress and stillbirth at any time, leading to adverse outcomes for pregnant women and fetuses. The disease is dangerous and difficult to treat, which seriously threatens the lives of mothers and babies. Early diagnosis and reasonable treatment can effectively improve the prognosis of patients. The most important method for the treatment of infective endocarditis requires early, adequate, long-term and combined antibiotic therapy. Moreover, surgical controversies regarding indication and timing of treatment exist, especially in pregnancy. In terms of the timing of termination of pregnancy, the timing of cardiac surgery, and the method of surgery, individualized programs must be adopted. A pregnant woman with 30⁺⁵ weeks of gestation is reported. She was admitted to hospital due to intermittent chest tightness, suffocation and fever, with grade Ⅲ cardiac insufficiency. Imaging revealed large mitral valve vegetation, 22.0 mm×4.1 mm and 22.0 mm×5.1 mm, respectively, and severe valve regurgitation. Mitral valve perforation was more likely, blood culture suggested Staphylococcus epidermidis infection, after antibiotic conservative treatment, the effect was poor. After the joint consultation including cardiology, neonatology, interventional vascular surgery, anesthesiology, and obstetrics, the combined operation of obstetrics and cardiac surgery was performed in time. The heart was blocked for 60 minutes, the bleeding was 1 200 mL, the newborn was mildly asphyxiated after birth, and the birth weight was 1 890 g. Nine days after the operation, the patient was discharged from the hospital, and the newborn was discharged with the weight of 2 020 g. Critical cases like this require a thorough weighing of risks and benefits followed by swift action to protect the mother and her unborn child. An optimal outcome in a challenging case like this greatly depends on effective interdisciplinary communication, informed consent of the patient, and concerted action among the specialists involved.