The saliva secreted from submandibular gland (SMG) accounts for 60%-65%. It plays an important role in maintaining the human function of swallow, digestion, testing, speech, protection of oral mucosa, and prevention from dental carries. The SMG is frequently resected during the treatment for various kinds of oral and maxillofacial diseases, resulting in xerostomia and decreased quality of life. During the past 15 years, Research Center of Salivary Gland Diseases in Peking University School and Hospital of Stomatology conducted a series of studies on new techniques for preservation of SMG and achieved remarkable results. The clinicopathologic and imaging characteristics of IgG4-related sialadenitis (IgG4-RS) were clarified based on systematic studies. The results of studies on the pathogenesis of IgG4-RS showed that unbalance of inflammatory factors mediated the abnormality of secretion of SMG. IL-4 participates in occurring and development of glandular fibrosis of SMG. Regulation of tumor necrosis factor α (TNF-α) and cleaning of senescent cells might be taken as the targets for treatment of IgG4-RS. The combination of glucocorticoid and steroid-sparing agents showed effective results for treating IgG4-RS, clinical remission was achieved in all the patients, serum IgG4 levels decreased, and salivary gland secretion significantly increased. Sialoendoscopy-assisted sialolithectomy was applied in the treatment of about 1 000 cases with submandibular hilar calculi with a success rate of more than 90%. Transfer of SMG was used for prevention from radiation-induced xerostomia in the patients with head and neck carcinoma. SMG was transferred to the submental region before radiotherapy and was kept away from the ra-diation field. The results of prospective clinical controlled study showed this technique could effectively preserve the function of SMG and prevent from xerostomia. Based on the micro-anatomical study on the blood vessels and ducts of SMG, partial sialoadenectomy was applied for treatment of benign tumors in the SMG. A clinical controlled study confirmed its safety for control of the tumors and its advantage of preservation of SMG function. The studies on the involvement of SMG in oral squamous cell carcinoma (OSCC) provided the anatomical and histopathological basis for preservation of SMG during neck dissection for early cases with OSCC. A innovated surgical modality "four preservations including SMG" was used during the neck dissection for the early cases with OSCC. A prospective randomized clinical controlled study confirmed its safety, feasibility, effectiveness for control of the carcinoma, and advantages of preservation of SMG function.

Objective: To investigate the effects and mechanisms of Kindlin-2 on uterus development and reproductive capacity in female mice. Methods: Cdh16-Cre tool mice and Kindlin-2^flox/flox mice were used to construct the mouse model of uterus specific knockout of Kindlin-2, and the effects of Kindlin-2 deletion on uterine development and reproduction capacity of female mice were observed. High expression and knockdown of Kindlin-2 in endometrial cancer cell lines HEC-1 and Ish were used to detect the regulation of mammalian target of rapamycin (mTOR) signaling pathway. In addition, uterine proteins of the female mice with specific knockout of Kindlin-2 and female mice in the control group were extracted to detect the protein levels of key molecules of mTOR signaling pathway and Hippo signaling pathway. Results: The mouse model of uterine specific knockout of Kindlin-2 was successfully constructed. The knockout efficiency of Kindlin-2 in mouse uterus was identified and verified by mouse tail polymerase chain reaction (PCR), Western blot protein identification, immunohistochemical staining (IHC) and other methods. Compared with the control group, the female mice with uterus specific deletion of Kindlin-2 lost weight, seriously impaired reproductive ability, and the number of newborn mice decreased, but the proportion of the female mice and male mice in the newborn mice did not change. Hematoxylin eosin staining (HE) experiment showed that the endometrium of Kindlin-2 knockout group was incomplete and the thickness of uterine wall became thinner. In terms of mechanism, the deletion of Kindlin-2 in endo-metrial cancer cell lines HEC-1 and Ish could downregulate the protein levels of mTOR, phosphorylated mTOR, adenosine monophosphate-activated protein kinase (AMPK), phosphorylated AMPK and phosphorylated ribosomal protein S6 (S6), and the mTOR signal pathway was inhibited. It was found that the specific deletion of Kindlin-2 could upregulate the protein levels of Mps one binding 1 (MOB1) and phosphorylated Yes-associated protein (YAP) in the uterus of the female mice, and the Hippo signal pathway was activated. Conclusion: Kindlin-2 inhibits the development of uterus by inhibiting mTOR signal pathway and activating Hippo signal pathway, thereby inhibiting the fertility of female mice.

Objective: To investigate the clinicopathological features and prognosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2 -) breast cancer. Methods: In the study, 3 035 consecutive breast cancer patients diagnosed in Breast Disease Center, Peking University First Hospital from January 2008 to December 2017 were collected. The prognostic signi-ficance of important pathological factors in HR +/HER2 - patients with complete clinicopathological information was analyzed. Results: Within the 1 920 (63.26%) cases of HR +/HER2 - breast cancer, there were 1 624 cases with complete clinicopathological data, of which, 124 cases (7.64%) recurred and/or metastasized and 63 cases died of the disease, and the 5-year overall survival (OS) rate and disease-free survival (DFS) rate was 93.0% and 92.6% respectively. The stage of pT1-2 was 92.80%, while pN0 was 69.03%. 89.66% cases belonged to histologically non-specific type and 30.11%, 55.60%, 14.29% were credited to Grade 1, 2 and 3 respectively. The distribution of ER negative, low or high expression groups were 1.60%, 2.09% and 96.31%, while PR were 6.83%, 10.47%, 82.70%, respectively. The group of Ki67 index < 10% was 19.52%, ≥10% & < 20% for 32.02%, ≥20% for 48.46%. Survival analysis showed that cases with pT1 stage had lower risk of recurrence than those with pT3, while cases with pT2 and pT3 had shorter DFS than those with pT1, with higher risk of recurrence and metastasis. Analysis proved that both pN stage and histological grade were negatively correlated with DFS. The cases with pN0, pN1 and pN2 were lower risk of recurrence than those with pN3, while cases with Grade 1 and 2 had lower risk of recurrence than cases with Grade 3. And the group of Ki67 index ≥20% showed higher risk of recurrence and metastasis. The prognostic significance of ER expression in HR+/HER2- breast cancer was not significant. However, the negative/low PR expression groups showed higher risk of recurrence and metastasis, of which PR < 10% group had shortest DFS and OS, followed by 10%-60% group and then > 60% group. The most common site of metastasis was bone (55 cases, 44.35%), while cases with liver metastasis (30 cases, 24.20%) had the worst outcome. Conclusion: Our study revealed that pT, pN, Grade, HR expression level and Ki67 index were important prognostic factors for HR +/HER2 - breast cancer, although there are variables in prognostic value. Factors of pN and Grade showed independent prognostic significance. PR expression level had prognostic significance for the risk of recurrence and metastasis. The stratified level of PR expression (< 10%, 10%-60%, >60%) had independent prognostic value, showing successively longer DFS and OS, lower risk of recurrence. PR>60% group had the longest DFS and OS as well as the lowest risk of recurrence.

Objective: To explore the role of the microbiota in drug naïve first-onset schizophrenia patients and to seek evidence from multidimensional longitudinal analyses of the intestinal microbiome and clinical phenotype with antipsychotic drugs (APDs) therapy. Methods: In this study, 28 drug naïve first onset schizophrenia patients and age-, gender- and education-matched 29 healthy controls were included, and the patients were treated with APDs. We collected fecal and serum samples at baseline and after 6 weeks of treatment to identify the different microbiota strains and analyse their correlation with clinical symptoms and serum metabolites. The 16S rRNA genes of the gut microbiota were sequenced, and the diversity and relative abundance at the phylum and genus levels were analyzsed in detail. The PANSS score, BMI changed value, and serum metabolome were included in the data analyses. Results: A multiomics study found a potential connection among the clinical phenotype, microbiota and metabolome. The species diversity analyses revealed that the alpha diversity index (chao1, ACE, and goods_coverage) in the schizophrenia APDs group was significantly lower than that in the control group, and the schizophrenia group had clear demarcation from the control group. The microbiota composition analysis results showed that the relative abundance of the genera of Bacteroides, Streptococcus, Romboutsia, and Eubacterium ruminantium group significantly changed after APDs treatment in the schizophrenia patients. These strains could reflect the APDs treatment effect. More genera had differences between the patient and control groups. The LEfSe analysis showed that Prevotella_9 and Bacteroides were enriched in schizophrenia, while Blautia, Dialister, and Roseburia were enriched in the control group. The correlation analysis between microbiota and clinical symptoms showed that Bifidobacterium in schizophrenia was positively correlated with the PANSS reduction rate of the general psychopathology scale. The BMI changed value was positively correlated with the alteration of Clostridium_sensu_stricto_1 during treatment and the baseline abundance of Bacteroides. Moreover, metabolomic data analysis revealed a significant correlation between specific genera and metabolites, such as L-methionine, L-proline, homovanillic acid, N-acetylserotonin, and vitamin B6. Conclusion: Our study found some microbiota features in schizophrenia patients and healthy controls, and several strains were correlated with APDs effects. Furthermore, the multiomics analysis implies the intermediate role of microbiota between antipsychotic effects and serum metabolites and provides new evidence to interpret the difference from multiple levels in the pathogenesis and pharmacological mechanism of schizophrenia.

Objective: To analyze the distribution characteristics of hereditary peripheral neuropathy (HPN) pathogenic genes in Chinese Han population, and to explore the potential pathogenesis and treatment prospects of HPN and related diseases. Methods: Six hundred and fifty-six index patients with HPN were enrolled in Peking University Third Hospital and China-Japan Friendship Hospital from January 2007 to May 2022. The PMP22 duplication and deletion mutations were screened and validated by multiplex ligation probe amplification technique. The next-generation sequencing gene panel or whole exome sequencing was used, and the suspected genes were validated by Sanger sequencing. Results: Charcot-Marie-Tooth (CMT) accounted for 74.3% (495/666) of the patients with HPN, of whom 69.1% (342/495) were genetically confirmed. The most common genes of CMT were PMP22 duplication, MFN2 and GJB1 mutations, which accounted for 71.3% (244/342) of the patients with genetically confirmed CMT. Hereditary motor neuropathy (HMN) accounted for 16.1% (107/666) of HPN, and 43% (46/107) of HPN was genetically confirmed. The most common genes of HMN were HSPB1, aminoacyl tRNA synthetases and SORD mutations, which accounted for 56.5% (26/46) of the patients with genetically confirmed HMN. Most genes associated with HMN could cause different phenotypes. HMN and CMT shared many genes (e.g. HSPB1, GARS, IGHMBP2). Some genes associated with dHMN-plus shared genes associated with amyotrophic lateral sclerosis (KIF5A, FIG4, DCTN1, SETX, VRK1), hereditary spastic paraplegia (KIF5A, ZFYVE26, BSCL2) and spinal muscular atrophy (MORC2, IGHMBP, DNAJB2), suggesting that HMN was a continuum rather than a distinct entity. Hereditary sensor and autosomal neuropathy (HSAN) accounted for a small proportion of 2.6% (17/666) in HPN. The most common pathogenic gene was SPTLC1 mutation. TTR was the main gene causing hereditary amyloid peripheral neuropathy. The most common types of gene mutations were p.A117S and p.V50M. The symptoms were characterized by late-onset and prominent autonomic nerve involvement. Conclusion: CMT and HMN are the most common diseases of HPN. There is a large overlap between HMN and motor-CMT2 pathogenic genes, and some HMN pathogenic genes overlap with amyotrophic lateral sclerosis, hereditary spastic hemiplegia and spinal muscular atrophy, suggesting that there may be a potential common pathogenic pathway between different diseases.

Objective: KRAS gene is one of the most common mutations of proto-oncogenes in human tumors, G12V is one of the most common mutation types for KRAS. It's challenging to chemically acquire the targeted drug for this mutation. Recent studies reported that this mutation peptides can form a neoepitope for T cell recognition. Our study aims to clone the T cell receptor (TCR) which specifically recognizes the neoepitope for KRAS G12V mutation and constructs TCR engineered T cells (TCR-T), and to investigate if TCR-Ts have strong antitumor response ability. Methods: In this study, tumor infiltrating lymphocytes were obtained from one colorectal cancer patient carrying KRAS G12V mutation. Tumor-reactive TCR was obtained by single-cell RT-5′ rapid-amplification of cDNA ends PCR analysis and introduced into peripheral blood lymphocytes to generate TCR-Ts. Results: We obtained a high-affinity TCR sequence that specifically recognized the HLA-A^*11:01-restricted KRAS G12V_8-16 epitope: KVA11-01. KVA11-01 TCR-T could significantly kill various tumor cells such as PANC-1, SW480 and HeLa (overexpressing HLA-A^*11:01 and KRAS G12V), and secreting high levels of interferon-γ (IFN-γ). Non-specific killing experiments suggested KVA11-01 specifically recognized tumor cells expressing both mutant KRAS G12V and HLA-A^*11:01. In vivo assay, tumor inhibition experiments demonstrated that infusion of approximately 1E7 KVA11-01 TCR-T could significantly inhibit the growth of subcuta-neously transplanted tumors of PANC-1 and HeLa (overexpressing HLA-A^*11:01 and KRAS G12V) cells in nude mice. No destruction of the morphologies of the liver, spleen and brain were observed. We also found that KVA11-01 TCR-T could significantly infiltrate into tumor tissue and had a better homing ability. Conclusion: KVA11-01 TCR-T cells can effectively target a variety of malignant tumor cells carrying KRAS G12V mutation through in vitro and in vivo assay. KVA11-01 TCR-T cells have excellent biological activity, high specificity of target antigen and homing ability into solid tumor tissue. KVA11-01 TCR-T is expected to be an effective treatment for patients with KRAS G12V mutant solid malignancies.

Objective: To identify whether naringenin plays a protective role during thoracic aneurysm formation in Marfan syndrome. Methods: To validate the effect of naringenin, Fbn1^C1039G/+ mice, the mouse model of Marfan syndrome, were fed with naringenin, and the disease progress was evaluated. The molecular mechanism of naringenin was further investigated via in vitro studies, such as bioluminescence resonance energy transfer (BRET), atomic force microscope and radioligand receptor binding assay. Results: Six-week-old Fbn1^C1039G/+ mice were fed with naringenin for 20 weeks. Compared with the control group, naringenin significantly suppressed the aortic expansion [Fbn1^C1039G/+ vs. Fbn1^C1039G/++naringenin: (2.49±0.47) mm, n=18 vs. (1.87±0.19) mm, n=22, P < 0.05], the degradation of elastin, and the expression and activity of matrix metalloproteinase 2 (MMP2) and MMP9 in the ascending aorta of Fbn1^C1039G/+ mice. Besides, treatment with naringenin for 6 weeks also attenuated the disease progress among the 20-week-old Fbn1^C1039G/+ mice with established thoracic aortic aneurysms [Fbn1^C1039G/+ vs. Fbn1^C1039G/++naringenin: (2.24±0.23) mm, n=8 vs. (1.90±0.17) mm, n=8, P < 0.05]. To understand the underlying molecular mechanisms, we examined the effects of naringenin on angiotensin Ⅱ type 1 receptor (AT1) signaling and transforming growth factor-β (TGF-β) signaling respectively, which were the dominant signaling pathways contributing to aortopathy in Marfan syndrome as previously reported. The results showed that naringenin decreased angiotensin Ⅱ (Ang Ⅱ)-induced phosphorylation of protein kinase C (PKC) and extracellular regulating kinase 1/2 (ERK1/2) in HEK293A cell overexpressing AT1 receptor. Moreover, naringenin inhibited Ang Ⅱ-induced calcium mobilization and uclear factor of activated T-cells (NFAT) signaling. The internalization of AT1 receptor and its binding to β-arrestin-2 with Ang Ⅱ induction were also suppressed by naringenin. As evidenced by atomic force microscope and radioligand receptor binding assay, naringenin inhibited Ang Ⅱ binding to AT1 receptor. In terms of TGF-β signaling, we found that feeding the mice with naringenin decreased the phosphorylation of Smad2 and ERK1/2 as well as the expression of TGF-β downstream genes. Besides, the serum level of TGF-β was also decreased by naringenin in the Fbn1^C1039G/+ mice. Furthermore, we detected the effect of naringenin on platelet, a rich source of TGF-β, both in vivo and in vitro. And we found that naringenin markedly decreased the TGF-β level by inhibiting the activation of platelet. Conclusion: Our study showed that naringenin has a protective effect on thoracic aortic aneurysm formation in Marfan syndrome by suppressing both AT1 and TGF-β signaling.

Objective: Jingfang Granules have been recommended for the prevention and treatment of corona virus disease 2019 (COVID-19). Through chemical analysis and bioactivity evaluation, this study aims to elucidate the potential effective components of Jingfang Granules. Methods: The inhibitory acti-vities of Jingfang Granules extract against 3-chymotrypsin-like protease (3CL^pro), papain like protease (PL^pro), spike protein receptor-binding domain (S-RBD) and human cyclooxygenase-2 (COX-2) were evaluated using enzyme assay. The antitussive effects were evaluated using the classical ammonia-induced cough model. The chemical constituents of Jingfang Granules were qualitatively and quantitatively analyzed by liquid chromatography-mass spectrometry (LC/MS). The 3CL^pro and PL^pro inhibitory activities of the major compounds were determined by enzyme assay, molecular docking, and site-directed mutagenesis. Results: Jingfang Granules exhibited 3CL^pro and PL^pro inhibitory activities, as well as COX-2 inhibitory and antitussive activities. By investigating the MS/MS behaviors of reference standards, a total of fifty-six compounds were characterized in Jingfang Granules. Sixteen of them were unambiguously identified by comparing with reference standards. The contents of the 16 major compounds were also determined, and their total contents were 2 498.8 μg/g. Naringin, nodakenin and neohesperidin were three dominating compounds in Jingfang Granules, and their contents were 688.8, 596.4 and 578.7 μg/g, respectively. In addition, neohesperidin and naringin exhibited PL^pro inhibitory activities, and the inhibition rates at 8 μmol/L were 53.5% and 46.1%, respectively. Prim-O-glucosylcimifugin showed significant inhibitory activities against 3CL^pro and PL^pro, and the inhibitory rates at 8 μmol/L were 76.8% and 78.2%, respectively. Molecular docking indicated that hydrogen bonds could be formed between prim-O-glucosylcimifugin and amino acid residues H163, E166, Q192, T190 of 3CL^pro (binding energy, -7.7 kcal/mol) and K157, D164, R166, E167, T301 of PL^pro(-7.3 kcal/mol), respectively. Site-directed mutagenesis indicated amino acid residue K157 was a key active site for the interaction between prim-O-glucosylcimifugin and PL^pro. Conclusion: Prim-O-glucosylcimifugin, neohesperidin, and naringin as the major compounds from Jingfang Granules could inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus proteases 3CL^pro and PL^pro. The results are valuable for rational clinical use of Jingfang Granules.

Objective: To better understand and revise the natural history and disease progression of chronic hepatitis B virus (HBV) infection through analysis of a single-center large-scale cohort of indivi-duals with chronic HBV infection. Methods: Patients with chronic HBV infection who had undergone liver biopsy in the Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital from January 2014 to October 2020 were retrospectively recruited. Based on patient's hepatitis B e antigen (HBeAg) states and pathologic diagnosis, they were categorized into four disease progression statuses (or phases according to the old-terminology in the updated guidelines of chronic hepatitis B (CHB), such as European Association for the Study of the Liver (EASL) 2017, Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection: HBeAg-positive chronic HBV infection (immune tolerance), HBeAg-positive CHB (immune active HBeAg positive), HBeAg-negative chronic HBV infection (inactive carrier), and HBeAg-negative CHB (immune reactive HBeAg negative). Then the demographic, laboratory tests and liver histological results of the patients in different disease progression stages were compared. Age differences between the two groups were evaluated using Mann-Whitney U test. Results: A total of 760 eligible patients with a median age of 29 (interquartile range: 16-39) years were enrolled. Among them, 197 were underage individuals (age < 18 years) and 563 were adults; and 456 were males and 304 females. According to the pathological diagnosis, the patients were classified, and in each of the above four natural disease phases there were 173, 329, 95, and 163 individuals, respectively. Further comparison of the ages of the patients of the four disease progression statuses revealed that patients of HBeAg-negative CHB had a median age at 37 years, which was reasonably higher than those with HBeAg-positive CHB in immune active phase (37 vs. 24 years, P < 0.001), but was relatively younger than those with HBeAg-negative chronic HBV infection (37 vs. 39 years, P= 0.240). Conclusion: According to this study, it could be speculated that HBeAg-negative CHB patients probably not all reactivate from individuals of HBeAg-negative chronic HBV infection. Instead, certain HBeAg-negative CHB patients may also come from HBeAg-positive CHB patients who have undergone HBeAg clearance or seroconversion and still remain in the immune active state.

Objective: To evaluate the type of wound healing following modified crown lengthening surgery in dog model to provide a biological basis for its clinical application. Methods: Flap surgery, traditional crown lengthening procedure and modified crown lengthening procedure were performed on the right maxillary central incisor, the left maxillary central incisor and the left maxillary first lateral incisor respectively of five male beagle dogs. The right maxillary first lateral incisors with no surgical intervention were used as controls. Thirty-six weeks after the experimental procedure, tissue blocks were harvested and prepared for histological examination and analysis. Results: Histometric examination of buccolingual sections stained with hematoxylin-eosin demonstrated that the type of wound healing in the flap surgery group was re-attachment, similar to the control group. For the traditional crown lengthening surgery group, all of the five beagle dogs had lamellar cementum defects on root surface, the wound healing of four beagle dogs was new attachment accompanied by new cementum formation at cementum defect areas and the suprac-restal connective tissue was functionally oriented perpendicular to the new cementum. The wound healing of the other beagle dog was long junctional epithelial attachment, in which the junctional epithelium extended to the apical terminus of the cementum defect. In the modified crown lengthening surgery group, four beagle dogs had cementum defects on root surface (two lamellar cementum defects and two shallow platform-like cementum defects), the wound healing of three beagle dogs was new attachment, however, the supracrestal connective tissue was parallel to the root surface. The type of wound healing of another one beagle dog was long junctional epithelial attachment. Wound healing of one beagle dog in this group could not be characterized due to incomplete dissection. Conclusion: Wound healing in the modified crown lengthening surgery group was similar to the traditional crown lengthening surgery group, and two types of wound healing were observed: new attachment and long junctional epithelium attachment. Neither type of root treatment procedure (root planing or root reshaping) nor root surface defect pattern (the lamellar cementum defect or shallow platform-like cementum defect) influenced the observed type of wound healing.

Objective: To analyze the efficacy and prognosis of fertility-sparing therapy of the patient with complex atypical hyperplasia (CAH) and endometrial cancer (EC). Methods: Clinical data of 191 EC and CAH patients who received fertility-sparing therapy in Peking University People's Hospital between January 2009 and September 2021 were recruited retrospectively. Outcomes of remission, recurrence and pregnancy were analyzed. Results: (1) Efficacy and efficacy-related factors: The complete response (CR) rate was 86.1% (161/187) for all the patients, and the CR rate of the CAH patients were higher than that of the EC patients (92.7% vs. 79.1%, P=0.007), the CR rate was significant higher in the CAH patients (OR=2.786, P=0.035). (2) The recurrence rate was 19.3% (31/161), and the recurrence rate of the EC patients were much higher than that of the CAH patients (26.4% vs. 13.5%, P=0.039). The median recurrence time was 22.5 (9.0, 50.0) months. (3) The high risk factors of recurrence were pathological type of EC (χ²=4.880, P=0.027), without the use of metfor-min (χ²=7.075, P=0.008), longer time to complete remission (>7 months) (χ²=6.204, P=0.013), and no pregnancy (χ²=6.765, P=0.009). (4) Results of pregnancy and related factors: Among the patients who achieved CR, 108 patients had fertility willing with the pregnancy rate of 41.7% (45/108), and the live birth rate was 34.3% (37/108). The live birth rate was lower in EC than that in the CAH patients (28.6% vs. 42.4%, P=0.045). The median time to achieve pregnancy was 10.50 (5.75, 33.25) months. The pregnancy rate was significant higher in the patients with pregnancy history (OR=9.468, P < 0.001) and in those who received assisted reproductive therapy (OR=7.809, P < 0.001). Conclusion: Fertility-sparing therapy of CAH and EC patients is effective resulting in high disease remission and certain pregnancy. However, the high recurrence rate and low pregnancy rate are still key problems for EC and CAH patients, therefore close monitoring and follow-up are indicated.

Objective: To evaluate the feasibility and effectiveness of fetal reduction by transabdominal intracranial KCl injection for multifetal pregnancies in the early second trimester. Methods: The data of 363 patients who underwent transabdominal fetal reduction in the Reproductive Medical Center of Peking University Third Hospital from January 2006 to December 2019 were analyzed retrospectively. According to the location of fetal reduction, they were divided into two groups: Intracranial injection group (n=196) and intrathoracic injection group (n=167). The process of fetal reduction and pregnancy outcome of the two groups were compared. Results: There was no significant difference between the two groups in the average age and the proportion of type of infertility before assisted reproductive technology, conception method, indication for fetal reduction, starting number of fetuses, reduced number of fetuses, and finishing number of fetuses (P>0.05). There was no significant difference between the two groups in the proportion of the number of puncture ≥ 2 times (12.1% vs. 8.6%, P=0.249) and the incidence of replacing puncture site (10.7% vs. 6.4%, P=0.161). The next day after fetal reduction, color Doppler ultrasound was rechecked. In the intracranial injection group and intrathoracic injection group, the incidence of fetal heartbeat recovery [3.6% (8/224) vs. 1.1% (2/187), P=0.188], the volumes of KCl used [(2.6±1.0) mL vs. (2.8±1.1) mL, P=0.079], and the abortion rate within 4 weeks after fetal reduction (1.0% vs. 0.6%, P=0.654) were of no significant difference. In addition, there was no significant difference in the total abortion rate after fetal reduction, premature delivery rate, cesarean section rate, delivery gestational week and neonatal birth weight between the two groups (P>0.05). Conclusion: Intracranial KCl injection can be an effective alternative to intrathoracic KCl injection for multifetal pregancy reduction.

Objective: To investigate the clinical characteristics, treatment, and prognosis of seizures in children with acute lymphoblastic leukemia (ALL) during chemotherapy. Methods: Children with ALL with seizures during chemotherapy admitted to the Department of Pediatrics, Peking University People's Hospital from January 2010 to March 2022 were retrospectively analyzed. Clinical data including the incidence of seizure, time at seizure onset, causes, management, and prognosis were collected retrospectively. Results: A total of 932 children with ALL were admitted during the study period, of whom, 75 (8%) were complicated with seizures during the period of chemotherapy. There were 40 males and 35 females, with a median age of 7.5 (1-17) years, and 43 cases (57.3%) occurred within the first 2 months of chemotherapy. The underlying diseases were reversible posterior encephalopathy syndrome (n=15), cerebral hemorrhage (n=10, one of whom was complicated with venous sinus thrombosis), intrathecal or systemic methotrexate administration (n=11), brain abscess (n=7, fungal infection in 3 cases, and bacterial in 4), viral encephalitis (n=2), febrile seizure (n=7), hyponatremia (n=7), hypocalcemia (n=2), and unknown cause (n=14). Sixty-four children underwent neuroimaging examination after seizure occurrence, of whom 37 (57.8%) were abnormal. The electroencephalograhpy (EEG) was performed in 44 cases and was abnormal in 24 (54.4%). Fifty-five patients remained in long-term remission with regular chemotherapy, 8 patients received hematopoietic stem cell transplantation, 9 died and 3 lost to follow-up. Symptomatic epilepsy was diagnosed in 18 cases (24%), and was well controlled in 16 with over 1 year of seizure-free. Whereas 2 cases were refractory to anti-seizure medications. Conclusion: Seizures are relatively common in children with ALL, most commonly due to reversible posterior encephalopathy syndrome, methotrexate-related neurotoxicity, and cerebral hemorrhage. Seizures occurred within 2 months of chemotherapy in most cases. Neuroimaging and EEG should be performed as soon as possible after the first seizure onset to identify the etiology and to improve the treatment regimen. Some cases developed symptomatic epilepsy, with a satisfactory outcome of seizure remission mostly after concurrent antiseizure medication therapy.

Objective: To analyze the disease spectrums underlying orthostatic intolerance (OI) and sitting intolerance (SI) in Chinese children, and to understand the clinical empirical treatment options. Methods: The medical records including history, physical examination, laboratory examination, and imagological examination of children were retrospectively studied in Peking University First Hospital from 2012 to 2021. All the children who met the diagnostic criteria of OI and SI were enrolled in the study. The disease spectrums underlying OI and SI and treatment options during the last 10 years were analyzed. Results: A total of 2 110 cases of OI and SI patients were collected in the last 10 years, including 943 males (44.69%) and 1 167 females (55.31%) aged 4－18 years, with an average of (11.34±2.84) years. The overall case number was in an increasing trend over the year. In the OI spectrum, postural tachycardia syndrome (POTS) accounted for 826 cases (39.15%), followed by vasovagal syncope (VVS) (634 cases, 30.05%). The highest proportion of SI spectrum was sitting tachycardia (STS) (8 cases, 0.38%), followed by sitting hypertension (SHT) (2 cases, 0.09%). The most common comorbidity of OI and SI was POTS coexisting with STS (36 cases, 1.71%). The highest proportion of treatment options was autonomic nerve function exercise (757 cases, 35.88%), followed by oral rehydration salts (ORS) (687 cases, 32.56%), metoprolol (307 cases, 14.55%), midodrine (142 cases, 6.73%), ORS plus metoprolol (138 cases, 6.54%), and ORS plus midodrine (79 cases, 3.74%). The patients with POTS coexisting with VVS were more likely to receive pharmacological intervention than the patients with POTS and the patients with VVS (41.95% vs. 30.51% vs. 28.08%, χ²= 20.319, P < 0.01), but there was no significant difference in the proportion of treatment options between the patients with POTS and the patients with VVS. Conclusion: POTS and VVS in children are the main underlying diseases of OI, while SI is a new disease discovered recently. The number of children with OI and SI showed an increasing trend. The main treatment methods are autonomic nerve function exercise and ORS. Children with VVS coexisting with POTS were more likely to take pharmacological treatments than those with VVS or POTS only.

Objective: To explore and analyze the relationship between early onset of puberty and different types of obesity in children, by combining large sample cross-sectional survey data with long-term longitudinal cohort data, so as to provide clues for further clarifying the health hazards of early onset of puberty and obesity prevention and control. Methods: The research data were from the cross-sectional survey data of seven provinces(autonomous regions, municipalities) in China and the cohort data of adolescent development in Xiamen. The study first found the association between early onset of puberty and obesity by Logistic regression on the cross-sectional data, and then used Poisson regression to analyze the association between early puberty initiation and various types of obesity risk. Results: In the study, 43 137 and 1 266 children were included in the cross-sectional survey and cohort survey respectively. The cross-sectional study found that among the girls aged 10-13 years, compared with the girls of the same age who did not start puberty, the body mass index (BMI)-Z score of the girls in the puberty start group was 0.5-0.8 higher, and the waist circumference Z score was 0.4-0.7 higher, and the risk of various types of obesity was higher. At the same time, the early onset of puberty was positively correlated with simple obesity, central obesity and compound obesity, the OR (95%CI) were 1.86 (1.42-2.44), 1.95 (1.65-2.32) and 1.86 (1.41-2.45), respectively. No significant association was found in boys. According to the cohort data, in girls, the risk of simple obesity was 6.00 times [RR (95%CI): 6.00 (1.07-33.60)], the risk of central obesity was 3.30 times [RR (95%CI): 3.30 (1.22-8.92)], and the risk of compound obesity was 5.76 times [RR (95%CI): 5.76 (1.03-32.30)], compared with the group without early puberty initiation, while no association between early puberty initiation and obesity was found in boys. Conclusion: Based on the cross-sectional survey and longitudinal cohort survey, it is confirmed that the early onset of puberty in girls may increase the risk of simple obesity, central obesity and compound obesity, while there is no significant correlation between puberty onset and obesity in boys.

Objective: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). Methods: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). Results: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. Conclusion: Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.

Objective: Critically ill patients with solid tumors complicated with paraneoplastic pemphigus are usually treated in intensive care units (ICU) for perioperative management after surgical treatment. In this study, the clinical characteristics and predictors of long-term prognosis of these critically ill patients were analyzed. Methods: the clinical and laboratory data of 63 patients with solid tumors complicated with paraneoplastic pemphigus admitted to ICU from 2005 to 2020 were retrospectively analyzed, and the survival status of the patients were followed up. Results: Among the 63 patients, 79.4% had Castleman disease as the primary tumor, and 20.6% with other pathological types; 69.8% had severe-extensive skin lesions, and 30.2% had other skin lesions; the patients with bronchiolitis obliterans accounted for 44.4%, and 55.6% were not merged. Postoperative fungal infection occurred in 23.8% of the patients, and 76.2% without fungal infection. The median follow-up time was 95 months, and 25 patients died during the study period. The 1-year, 3-year and 5-year survival rates were 74.6% (95%CI 63.8%-85.4%), 67.4% (95%CI 55.6%-79.2%) and 55.1% (95%CI 47.9%-62.3%), respectively. The log-rank univariate analysis showed that the patients had age>40 years (P=0.042), preoperative weight loss>5 kg (P=0.002), preoperative albumin < 30 g/L (P < 0.001), paraneoplastic pemphigus complicated with bronchiolitis obliterans (P=0.002), and perioperative fungal infection (P < 0.001) had increased mortality. Cox univariate analysis showed that preoperative weight loss >5 kg (P=0.005), preoperative albumin < 30 g/L (P < 0.001), paraneoplastic pemphigus complicated with bronchiolitis obliterans (P=0.009), preoperative bacterial pulmonary infection (P=0.007), prolonged surgical time (P=0.048), postoperative oxygenation index (P=0.012) and low albumin (P=0.010) and hemoglobin concentration (P=0.035) in ICU, acute physiology and chronic health evaluation (APACHE Ⅱ) score (P=0.001); sequential organ failure assessment (SOFA) score (P=0.010), and postoperative fungal infection (P < 0.001) were risk factors for long-term survival. Cox regression model for multivariate analysis showed that preoperative weight loss > 5 kg (HR 4.44; 95%CI 1.47-13.38; P=0.008), and preoperative albumin < 30 g/L (HR 4.38; 95%CI 1.72-11.12; P=0.002), bronchiolitis obliterans (HR 2.69; 95%CI 1.12-6.50; P=0.027), and postoperative fungal infection (HR 4.85; 95%CI 2.01-11.72; P < 0.001) were independent risk factors for postoperative mortality. Conclusion: The 5-year survival rate of critically ill patients undergoing surgery for paraneoplastic pemphigus combined with solid tumors is approximately 55.1%, with preoperative weight loss > 5 kg, albumin < 30 g/L, bronchiolitis obliterans and postoperative fungal infection were associated with an increased risk of near- and long-term postoperative mortality.

Objective: To analyze the feasibility of using vascular plaque quantification (VPQ) to evaluate carotid atherosclerotic plaques and to observe the effect of statins on carotid atherosclerotic plaques. Methods: Patients with carotid plaques from January 2016 to September 2018 in Peking University First Hospital Neurology Department were recruited and underwent three-dimonsional ultrasound (3DUS). Their gray scale median (GSM) and other parameters of carotid plaques were measured with VPQ. The patients were divided into low GSM group (GSM < 40) and high GSM group (GSM≥40). The clinical characteristics and plaque characteristics of the patients in the two groups were compared to analyze the stability of plaques. According to whether taking statins or not, the patients were further divided into statin group and non-statin group, plaque GSM and other parameters of their carotid plaques were measured and the changes of carotid plaques at the end of 3 months and 2 years were observed. Results: A total of 120 patients were enrolled, including 79 males and 41 females, with an average age of (65.39±9.11) years. The patients were divided into low GSM group (31 cases) (GSM < 40) and high GSM group (89 cases) (GSM≥40). The stenosis of the lumen in the low GSM group was more severe (the area stenosis rate was 41.32%±21.37% vs. 29.79%±17.16%, P < 0.05). The nor-malized wall index (NWI) of plaque in low GSM group was significantly higher than that in high GSM group (0.61 ±0.14 vs. 0.52±0.12, P < 0.01). A total of 77 patients, including 51 males and 26 females, aged (64.96±9.58) years, were enrolled to observe the statin effects on carotid plaque. They were divided into statin group (n=56) and non-statin group (n=21) according to whether taking statins or not. At the baseline and 3-month follow-up, there were no significant differences in carotid plaque volume, area, degree of luminal stenosis and GSM between the two groups (P>0.05). At the end of the 2-year follow-up, GSM increased in the statin group [median 10.00 (2.00, 28.00)] but decreased in the non-statin group [median －7.00 (－11.00, 5.50)], with a statistically significant difference between the two groups (P < 0.01). There was no significant increase in carotid plaque volume in the statin group, while there was a slight increase in the non-statin group, but there was no significant difference between the two groups [median increase in plaque volume was 0.00 (－30.00, 40.00) mm³ in the statin group and 30.00 (10.00, 70.00) mm³ in the non-statin group, P>0.05]. Conclusion: The VPQ technology of 3DUS can be used to evaluate carotid atherosclerotic plaques. Patients with low GSM (GSM < 40) have more severe vascular stenosis and higher normalized wall index. VPQ technology can also be used to observe the effect of statins on carotid plaque, the GSM of plaques increase in patients who are taking moderate-intensity statin treatment for two years.

Objective: To evaluate the effect of photobiomodulation (PBM) on the drainage of brain interstitial fluid (ISF) and to investigate the possible mechanism of the positive effect of PBM on Alzheimer's disease (AD). Methods: Twenty-four SD male rats were randomly divided into PBM group (n=12), sham PBM group (n=6), and negative control group (n=6). According to the injection site of tracer, the PBM group was further divided into PBM-ipsilateral traced group (n=6) and PBM-contralateral traced group (n=6). Rats in the PBM group and the sham PBM group were exposed to the dura minimally invasively on the skull corresponding to the frontal cortical area reached by ISF drainage from caudate nucleus region. The PBM group was irradiated by using 630 nm red light (5-6 mW/cm²), following an irradiation of 5 min with a 2 min pause, and a total of 5 times; the sham PBM group was kept in the same position for the same time using the light without power. The negative control group was kept without any measure. After PBM, tracer was injected into caudate nucleus of each group. The changes of ISF drainage in caudate nucleus were observed according to the diffusion and distribution of tracer molecule by tracer-based magnetic resonance imaging, and the structural changes of brain extracellular space (ECS) were analyzed by diffusion rate in ECS-mapping (D_ECS-mapping) technique. Finally, parameters reflecting the structure of brain ECS and the drainage of ISF were obtained: volume fraction (α), tortuo-sity (λ), half-life (T_1/2), and D_ECS. The differences of parameters among different groups were compared to analyze the effect of PBM on brain ECS and ISF. One-Way ANOVA post hoc tests and independent sample t test were used for statistical analysis. Results: The parameters including T_1/2, D_ECS, and λ were significantly different among the PBM-ipsilateral traced group, the PBM-contralateral traced group, and the sham PBM group (F=79.286, P < 0.001; F=13.458, P < 0.001; F=10.948, P=0.001), while there was no difference in the parameter α of brain ECS among the three groups (F=1.217, P=0.324). Compared with the sham PBM group and the PBM-contralateral traced group, the PBM-ipsilateral traced group had a significant decrease in the parameter T_1/2 [(45.45±6.76) min vs. (76.01±3.44) min, P < 0.001; (45.45±6.76) min vs. (78.07±4.27) min, P < 0.001], representing a significant acceleration of ISF drainage; the PBM-ipsilateral traced group had a significant increase in the parameter D_ECS [(4.51±0.77)×10^-4 mm²/s vs. (3.15±0.44)×10^-4 mm²/s, P < 0.001; (4.51±0.77)×10^-4 mm²/s vs. (3.01±0.38)×10^-4 mm²/s, P < 0.001], representing a significantly increased molecular diffusion rate of in the brain ECS; the PBM-ipsilateral traced group had a significant decrease in the parameter λ (1.51±0.21 vs. 1.85±0.12, P=0.001; 1.51±0.21 vs. 1.89±0.11, P=0.001), representing a significant decrease in the degree of tortuosity in the brain ECS. Conclusion: PBM can regulate the brain ISF drainage actively, which may be one of the potential mechanisms of the effect of PBM therapy on AD. This study provides a new method for enhancing the brain function via ECS pathway.

Objective: To investigate the surgical strategy for large and giant recurrent meningiomas near the middle and posterior third part of the superior sagittal sinus with extracranial invading. Methods: The clinical data of 16 patients with large and giant recurrent meningioma in the middle and posterior third part of the superior sagittal sinus with extracranial invasion who underwent surgery in the Department of Neurosurgery of Peking University Third Hospital from May 2019 to May 2022 were retrospectively analyzed. All the patients underwent brain-enhanced magnetic resonance imaging (MRI), magnetic resonance venography (MRV), computed tomography angiography (CTA) and three-dimensional skull computed tomography (CT) before, to evaluate the extent of tumor invasion, the edema of brain tissue, the degree of skull damage, the blood supply of the tumor, and the degree of compression of the superior sagittal sinus, etc, and to formulate an individualized surgical plan. The neurological function of the patients was evaluated 1 week, 1 month, and 3 months after the operation, and the tumor condition was evaluated by brain-enhanced MRI 3 months, 6 months, and 1 year after the operation. Results: The tumors in the 16 patients were all located in the middle and posterior 1/3 part of the superior sagittal sinus and invaded extracranially. Among them, 8 cases were operated for the second time, 6 cases for the third time, and 2 cases for the fourth time; In the last operation, the bone flap was used to repair the skull in 4 cases, and the titanium mesh was used in 12 cases; Tumor arterials of 3 cases were embolized under digital subtraction angiography (DSA). Tumors of 10 cases were resected at Simpson grade Ⅰ, and 6 cases at Simpson grade Ⅱ; 2 cases underwent decompressive craniectomy during operation, and 14 cases underwent cranioplasty at the same time; scalp incisions of 14 cases were directly sutured, and flap transposition was used in 14 cases. When evaluating nerve function after operation, the limb muscle strength was improved compared with that before operation, and the Karnofsky performance scale (KPS) score reached 100 points 3 months after operation. During the follow-up, 1 patient's tumor recurred after 1 year and received Gamma Knife treatment, and the rest of the patients had no recurrence during the follow-up period. Conclusion: Surgical treatment is the first choice for large and giant recurrent meningiomas near the middle and posterior third part of the superior sagittal sinus with extracranial invading. It is a safe and effective surgical method to take individualized surgical plan after detailed preoperative assessment of cerebral edema, tumor blood supply, venous sinus compression, and scalp invasion.

Objective: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). Methods: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ² test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ² test, Bonferroni correction was used for the level of significance test. Results: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. Conclusion: Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.

Objective: To analyze the effect of short-segment circumferential decompression and the nerve function improvement in 30 cases of multilevel thoracic OPLL assisted by intraoperative ultrasound. Methods: A total of 30 patients with multilevel thoracic OPLL from January 2016 to January 2021 were enrolled, all of whom were located by intraoperative ultrasound and underwent circumferential decompression. There were 14 males and 16 females, with an average age of (49.3±11.4) years. The initial symptoms were mainly numbness and weakness of lower limbs (83.3%), and the mean duration of symptoms was (33.9±42.9) months (1-168 months). Neurological function was assessed by the Modified Japanese Orthopedic Association (mJOA) score (0-11) preoperative and at the last follow-up, in which the rate of neurological improvement was calculated by the Harabayashi method. The patients were divided into excellent improved group and poor improved group according to the improvement of neurological function. The age, body mass index (BMI), duration of symptoms, operation time, blood loss, mJOA score, surgical level, and cerebrospinal fluid leakage of the two groups were collected and analyzed for statistical differences. The factors influencing the improvement of neurological function were analyzed by univariate and multivariate Logisitic regression analysis. Results: The mean operation time was 137.4±33.8 (56-190) min, and the mean blood loss was (653.7±534.2) mL (200－3 000 mL). The preoperative mJOA score was 6.0±2.1 (2－9), and the last follow-up mJOA score was 7.6±1.9 (4－11), which was significantly improved in all the patients (P < 0.001). The average improvement rate of neurological function was 38.1%±24.4% (14.3%－100%), including 75%－100% in 4 cases, 50%－74% in 3 cases, 25%－49% improved in 14 cases, and 0%－24% in 9 cases. There was significant difference in intraoperative blood loss between the excellent improved group and the poor improved group (P=0.047). Intraoperative blood loss was also an independent risk factor in regression analysis of neurological improvement. Conclusion: Thoracic circumferential decompression assisted with intraoperative ultrasound can significantly improve the neurological function of patients with multilevel OPLL and achieve good efficacy. The improvement rate of nerve function can be improved effectively by controlling intraoperative blood loss.

Objective: To study the rate and characteristics of H-type hypertension in Chinese hypertensive population, and to compare them with the relevant data from the United States. Methods: Observational studies on the prevalence of H-type hypertension in Chinese population published before April 30, 2022 were searched in several Chinese and English databases (PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Databases, and Chinese Biome-dical Literature Database). Study selection, date extraction and quality evaluation were conducted. Random effect model was used to estimate the rate of H-type hypertension in hypertensive patients and the pooled prevalence of H-type hypertension. Stratified analysis was used to explore the distribution characteristics of H-type hypertension in China. We made meta-regression to search the source of heterogeneity. The National Health and Nutrition Examination Survey (NHANES) population from 1999 to 2006 in the United States was divided into four stages according to the time of data collection. Basic information of the participants was acquired from the database and the rate and prevalence of H-type hypertension analyzed. Results: This study was finally comprised of 33 studies, involving 78 470 patients with hypertension, among whom 59 842 patients were with H-type hypertension. The rate of H-type hypertension in hypertensive population in China was 73.1% (95%CI: 69.3%-76.9%, I²=99.4%, P < 0.001), and the prevalence of H-type hypertension in general population was 26.9% (95%CI: 21.1%-32.8%, I²=99.8%, P < 0.001). In the stratified analysis, the rate of H-type hypertension was higher among the elderly over 65 years, males, ethnic minorities, and residents in the inland, western, northern, and rural areas. During the decade from 2011 to 2020, the rate of H-type hypertension in China declined slowly (2011-2013: 79.2% vs. 2014-2016: 70.4% vs. 2017-2020: 66.6%, P < 0.001). Meta-regression showed that area was the source of heterogeneity. The rate of H-type hypertension in the United States increased over time, reaching a high value in 2003-2004 and then declining in 2005-2006. The rate of H-type hypertension in hypertensive patients and the prevalence of H-type hypertension in general population in the United States was lower than that in China. Conclusion: Although the rate of H-type hypertension in Chinese hypertensive patients has a downtrend, it still far exceeds that in the United States, especially in the elderly, males, ethnic minorities, and residents in the inland, western, northern, and rural areas. Understanding the epidemiology of H-type hypertension provides scientific evidence for further prevention of cardiovascular and cerebrovascular diseases.

Objective: To evaluate the efficacy of plasma exchange therapy on crescentic IgA nephropathy (IgAN). Methods: A retrospective analysis was performed in a cohort of patients with crescentic IgAN from January 2012 to September 2020 at 9 sites across China. Clinical and pathological data, as well as therapeutic regimens, were collected. In order to minimize the effect of potential confounders in baseline characteristics, propensity score matching using a 1 ∶1 ratio nearest neighbor algorithm was performed between the adjunctive plasma exchange therapy group and the intensive immunosuppressive therapy group. The primary outcome was end-stage of kidney disease (ESKD). Kaplan-Meier method was used to compare the difference in renal survival between the two groups. Results: A total of 95 crescentic IgAN patients with acute kidney disease were included in this study, including 37 (38.9%) patients receiving adjunctive plasma exchange therapy, and 58 (61.1%) patients receiving intensive immunosuppressive therapy. In the whole cohort, the baseline eGFR was 12.77 (7.28, 21.29) mL/(min·1.73 m²), 24-hour urinary protein quantification was 5.9 (4.0, 8.9) g, and crescent percentage was 64.71% (54.55%, 73.68%). In the study, 23 patients in each group were matched after propensity score matching The median follow-up time was 7 (1, 26) months. As a whole, 29 patients (63.0%) reached ESKD, including 16 patients (69.6%) in the adjunctive plasma exchange therapy group and 13 (56.5%) patients in the intensive immunosuppressive therapy group.. There were no stastical difference between the two groups in terms of baseline eGFR [14.30 (9.31, 17.58) mL/(min·1.73 m²) vs. 11.45 (5.59, 20.79) mL/(min·1.73 m²)], 24-hour urinary protein (7.4±3.4) g vs. (6.6±3.8) g, crescent percentage 64.49%±13.23% vs. 66.41%±12.65% and the proportion of patients received steroid therapy[23 (100.0%) vs. 21 (91.3%)] (All P>0.05). Kaplan-Meier survival analysis demonstrated that there was no significant difference in renal survival rate between the two groups (Log-rank test, P=0.933). Conclusion: The adjunctive plasma exchange therapy in addition to conventional intense immunosuppressive therapy did not additionally improve the prognosis of crescentic IgA nephropathy.

Objective: To investigate the potential effect of modification of antihypertensive medications on the association of nitrogen dioxide (NO₂) long-term exposure and chronic kidney disease (CKD). Methods: Data of the national representative sample of adult population from the China National Survey of Chronic Kidney Disease (2007-2010) were included in the analyses, and exposure data of NO₂ were collected and matched. Generalized mixed-effects models were used to analyze the associations between NO₂ and CKD, stratified by the presence of hypertension and taking antihypertensive medications. The stratified exposure-response curves of NO₂ and CKD were fitted using the natural spine smoothing function. The modifying effects of antihypertensive medications on the association and the exposure-response curve of NO₂ and CKD were analyzed. Results: Data of 45 136 participants were included, with an average age of (49.5±15.3) years. The annual average exposure concentration of NO₂ was (7.2±6.4) μg/m³. Altogether 6 517 (14.4%) participants were taking antihypertensive medications, and 4 833 (10.7%) participants were identified as having CKD. After adjustment for potential confounders, in the hypertension population not using antihypertensive medications, long-term exposure to NO₂ was associated with a significant increase risk of CKD (OR: 1.38, 95%CI: 1.24-1.54, P < 0.001); while in the hypertension population using antihypertensive medications, no significant association between long-term exposure to NO₂ and CKD (OR: 0.96, 95%CI: 0.86-1.07, P=0.431) was observed. The exposure-response curve of NO₂ and CKD suggested that there was a non-linear trend in the association between NO₂ and CKD. The antihypertension medications showed significant modifying effects both on the association and the exposure-response curve of NO₂ and CKD (interaction P < 0.001). Conclusion: The association between long-term exposure to NO₂ and CKD was modified by antihypertensive medications. Taking antihypertensive medications may mitigate the effect of long-term exposure to NO₂ on CKD.

Objective: To understand the current state and problem of screening and management of chronic kidney disease (CKD) in the community, and to explore the improving strategies. Methods: We established a community-CKD integrated data science platform based on medical information from 79 community health centers, in Xicheng District, Beijing. Patients who referred to 79 community health centers from 21 June 2015 to 20 November 2021 were retrospectively included in this study using the CKD data platform. The monitoring of the indicator of kidney injury, risk factor control, medicine use and device configuration in community were assessed in the study. Results: In the study, 70.6% of the population were identified with high risk of CKD in the total 374 498 individuals who referred to the community health centers. Hypertension (62.3%), coronary heart disease (43.3%) and diabetes (30.4%) were the most common risk factors in high-risk CKD population. Only 17.2% of the patients with high risk of CKD were screened for kidney injury including at least one serum creatine (Scr) or albuminuria test, among which 10 992 (24.2%) individuals were defined as CKD. 22.7% (11 338/49 908) of the total patients with kidney screening in community were defined as CKD, of whom, 42.6% and 46.1% were identified by estimated glomerular filtration rate (eGFR) < 60 mL/(min·1.73 m²) and abnormalities of urinary proteins, respectively. The overall CKD detection rate in the community was 5.2% (19 299/374 498), and the miss-diagnosis rate of CKD was 38.1%. Of the 79 community health centers, 13 (16.5%) were equipped with ACR testing device, and eGFR was reported directly in 66 (83.5%) centers. Altogether 60.3% and 99.7% of the community CKD patients achieved glucose control and blood pressure control, respectively, and 59.3% of the CKD patients who had proteinuria was treated with renin-angiotensin-aldosterone system (RAAS) inhibitors. Conclusion: High-risk CKD population account for a substantial proportion of patients who refer to the community. Early screening, prevention and management of CKD in the community are of great importance to improve the prognosis and decrease the burden of CKD. It's essential to establish a screening and monitoring system, strengthen standardized management and clinician training for improving the ability of CKD management in the community.