The composition of the Gut Microbiome(GM)is regulated by numerous factors,including geography,ethnicity,diet,and genetics.This review systematically synthesizes studies on the GM across different geographic regions and ethnic minority groups in China.It focuses on elucidating the impact of geographical factors and ethnic backgrounds on GM composition and structure and provides an in-depth discussion on the association between ethnicity-specific microbial taxa,their metabolic functions,and susceptibility to diseases.By systematically comparing microbial compositional differences in microbiota-related diseases among different populations,this review aims to uncover the underlying patterns.The findings are expected to provide a theoretical foundation for ethnicity-specific GM research,the elucidation of disease mechanisms,and the development of targeted prevention and control strategies.

Humans ; Glycated Hemoglobin ; Diabetes Mellitus, Type 1 ; Blood Glucose ; Diabetes Mellitus, Type 2

Objective To investigate the anti-inflammatory action of Celastrol in the ocular tissues of mice with ex-perimental autoimmune uveitis(EAU)and its effect on microglia polarization.Methods A total of 36 healthy B10.RⅢmice at 6-8 weeks of age were selected and randomly divided into the normal control group,EAU solvent control group and Celastrol intervention group,with 12 mice in each group.The interphotoreceptor retinoid-binding protein(IRBP)161-180 and Freund's complete adjuvant were mixed by thorough emulsification and injected subcutaneously into the bilateral thighs and tails of mice in the EAU solvent control group and the Celastrol intervention group with a total volume of 200 μL and 50 μg IRBP 161-180 in each mouse.On 7-14 days after immunization,mice in the Celastrol intervention group received a daily intraperitoneal injection of 0.5 mg·kg-1 Celastrol,and mice in the EAU solvent control group were injected with an equivalent dose of sterile Phosphate Buffered Saline solution.On the 14th day after immunization,the anterior segment of mice in each group was observed by slit-lamp microscope and Hematoxylin and Eosin(HE)staining of tissue sections was performed;the clinical and histopathological scores of mice in each group were obtained by reference to the Caspi grading standards;immunofluorescence staining was used to observe the activation of microglia in the eyes of mice;Western blot was used to detect the protein expression levels of inducible nitric oxide synthase(iNOS)and arginase-1(Argl)in the reti-na;quantitative real-time PCR was used to detect the relative mRNA expression of inflammatory factors in the retina,such as tumor necrosis factor(TNF)-α,interleukin(IL)-1β and IL-6.GraphPad Prism 9.0 was used for data analysis.Results On the 14th day after immunization,it was observed by the slit-lamp microscope that the anterior segment of mice in the EAU solvent control group was markedly congested with dilated iris blood vessels,corneal edema,and anterior chamber exudation;the inflammation in the anterior segment of mice in the Celastrol intervention group was markedly at-tenuated,and the iris blood vessels were seen to be mildly congested.Compared with the normal control group,the clini-cal scores of mice in the EAU solvent control group and the Celastrol intervention group were significantly elevated(both P＜0.05);the clinical scores of mice in the Celastrol intervention group were lower than those in the EAU solvent control group(P＜0.05).HE staining results showed that on the 14th day after immunization,mice in the EAU solvent control group showed severe retinal folds and detachment with diffuse infiltration of inflammatory cells,while mice in the Celastrol intervention group showed slight structural damage to the retina and a small amount of inflammatory cell infiltration.Com-pared with the normal control group,the histopathological scores of mice in the EAU solvent control group and the Celas-trol intervention group were significantly elevated(both P＜0.05);the histopathological scores of mice in the Celastrol in-tervention group were lower than those in the EAU solvent control group(P＜0.05).The intraocular Iba1+cell densities of mice in the normal control,EAU solvent control and Celastrol intervention groups were(1.00±0.12)％,(36.07± 4.57)％,and(1.83±0.36)％,respectively.Compared with the normal control group,the number of Iba1+cells in the eyes of mice in the EAU solvent control group and the Celastrol intervention group significantly increased(both P＜0.05);compared with the EAU solvent control group,the number of Iba1+cells in the eyes of mice in the Celastrol intervention group was significantly reduced(P＜0.05).Compared with the normal control group,the expression levels of iNOS and Arg1 proteins in the retinas of mice in the EAU solvent control group were significantly elevated(both P＜0.01);compared with the EAU solvent control group,the expression of iNOS protein in the retinas of mice in the Celastrol intervention group was significantly reduced(P＜0.01).Compared with the normal control group,the relative mRNA expressions of TNF-α.IL-1β,and IL-6 in the retinas of mice in the EAU solvent control group was significantly elevated(all P＜0.05);compared with the EAU solvent control group,the relative mRNA expressions of TNF-α,IL-1 β,and IL-6 in the retinas of mice in the Celastrol intervention group significantly decreased(all P＜0.05).Conclusion Celastrol inhibits Ml microglia activation and reduces the production of retinal inflammatory factors TNF-α,IL-1 β and IL-6 in EAU mice,thereby attenuating the in-flammatory reaction.

Objective:To subdivide clinical classification of refractory atlantoaxial dislocation, and evaluate the reliability of new subdivide clinical classification of refractory atlantoaxial dislocation.Methods:From January 2010 to December 2018, 48 patients with refractory atlantoaxial dislocation were treated, including 19 males and 29 females, aged 16 to 65 years, with an average of 39.2±13.3 years. According to the changes of relative anatomical position of C 1 and C 2 under general anesthesia with heavy traction of 1/6 body weight, subdivide clinical classification of refractory atlantoaxial dislocation were proposed, and refractory atlantoaxial dislocation was divided into traction loosening type (atlantoaxial angle≥5°) and traction stabilization type (atlantoaxial angle<5°). The traction loosening type was directly reduced by posterior atlantoaxial screw-rod fixation and fusion without anterior or posterior soft tissue release. For traction stabilization type, transoral soft tissue release was performed first, and then transoral anterior reduction plate fixation and fusion or posterior atlantoaxial screw-rod fixation and fusion were performed. Atlantodental interval (ADI) and atlantoaxial angle (AAA) were measured and collected before and after surgery to evaluate atlantoaxial reduction. The space available for the spinal cord (SAC) were measured to evaluate spinal cord compression. Visual analogue score (VAS) was used to evaluate the neck pain levels, and Japanese Orthopaedic Association (JOA) scores was used to evaluate the neurological function. American Spinal Cord Injury Association impairment scale (AIS) was used to evaluate the degree of spinal cord injury. One week, 3, 6, 12 months postoperatively and the annual review of the X-ray and CT scan were checked, in order to evaluate the reduction, internal fixation and bone graft fusion. Results:Among all 48 cases, 22 cases were traction loosening type, of which posterior atlantoaxial screw-rod fixation and fusion were performed in 16 cases and occipitocervical fixation and fusion in 6 cases. 26 cases were traction stabilization type, and they all underwent anterior transoral release, and then, anterior TARP fixation and fusion were performed in 24 cases and posterior screw-rod fixation and fusion in the other 2 cases. X-ray, CT and MRI images and of all patients 1 week after surgery showed good atlantoaxial reduction and decompression of spinal cord. In each of the two types, there was one case lost to follow-up. For 46 cases in follow-up, the follow-up time ranged from 6 to 72 months, with an average of 38.0±17.2 months. Among 46 cases, 21 cases of traction loosening type showed that, ADI reduced from preoperative 9.9±2.2 mm to 2.3±0.9 mm at 3 months after surgery and 2.3±1.0 mm at the last follow-up, AAA increased from preoperative 57.9°±12.3° to 91.0°±2.2° at 3 months after surgery and 90.9°±2.2° at the last follow-up, SAC increased from preoperative 9.8±1.3 mm to 15.1±0.7 mm at 3 months after surgery and 14.9±0.7 mm at the last follow-up, VAS score reduced from preoperative 1.5±2.1 to 0.7±1.0 at 3 months after surgery and 0.3±0.6 at the last follow-up, and JOA score increased from preoperative 10.2±1.7 to 13.3±1.3 at 3 months after surgery and 14.9±1.5 at the last follow-up. Twenty-five cases of traction stabilization type presented that, ADI reduced from preoperative 9.7±2.0 mm to 2.1±1.4 mm at 3 months after surgery and 2.1±1.3 mm at the last follow-up, AAA increased from preoperative 55.8°±9.2° to 90.9°±1.4° at 3 months after surgery and 90.9°±1.3° at the last follow-up, SAC increased from preoperative 10.5±1.0 mm to 15.4±0.5 mm at 3 months after surgery and 14.8±2.8 mm at the last follow-up, VAS score reduced from preoperative 1.7±2.1 to 0.7±0.9 at 3 months after surgery and 0.3±0.5 at the last follow-up, and JOA score increased from preoperative 10.1±1.3 to 12.9±1.5 at 3 months after surgery and 14.4±1.3 at the last follow-up. In the traction loosening type, all the 10 grade D patients were improved to grade E at the last follow-up. In the 2 grade C patients of traction stabilization type before surgery, 1 patient was improved to grade E, 1 patient was improved to grade D, and all 11 patients with grade D were improved to grade E at the last follow-up. Bony fusion was obtained in all patients from 3 to 6 months, with an average of 4.4±1.5 months. During follow-up period, no looseness of internal fixation or redislocation happened.Conclusion:Refractory atlantoaxial dislocation can be divided into traction loosening type and traction stabilization type. For traction loosening type, satisfactory reduction can be achieved by using posterior atlantoaxial screw-rod system without soft tissue release. For traction stabilization type, anterior release is preferable, and then anterior TARP or posterior screw-rod can be used to achieve satisfactory reduction.

Objective:To compare the efficacy and safety of radium-223 in the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients with and without homologous recombination repair (HRR) gene mutation.Methods:The clinical data of 27 patients with mCRPC bone metastases who received radium-223 therapy from April 2021 to November 2022 in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine were retrospectively analyzed. Among the 27 mCRPC patients, 18 patients carrying HRR gene mutations belonged to the HRD(+ ) group, and 9 patients without HRR gene mutation belonged to the HRD(-) group. The age of patients in HRD(+ ) group was 69.5 (63.8, 77.0) years old, alkaline phosphatase (ALP) was 243.0 (82.8, 301.3) U/L, prostate specific antigen (PSA) was 71.6 (7.3, 329.8) ng/ml, pain score was 3.0 (1.0, 5.0) points. Eastern Cooperative Oncology Group (ECOG) score ranged from 0 to 1 points in 7 cases, and 2 points in 11 cases. In the HRD(-) group, the median age was 72.0 (64.5, 76.5) years old, ALP was 88.0 (67.5, 260.6) U/L, PSA was 19.1 (1.1, 117.8) ng/ml, and pain score was 2.0 (0, 4.5) points. The ECOG score ranged from 0 to 1 in 4 cases, and 2 in 5 cases in the HRD(-) group. There was no significant difference in the above general data between the two groups ( P>0.05). All patients received radium-223 treatment every 4 weeks, no more than 6 times. The changes of ALP, PSA, pain score and hematological adverse reactions were compared between the two groups. Results:In the HRD(+ ) group, the median number of radium-223 treatment was 4.5 (3.0, 5.3) couses, 4 patients (22.2%) completed 6 courses, and 6 patients died of prostate cancer during follow-up. In the HRD(-) group, the median number of radium treatment was 4.0 (2.5, 6.0) couses, 3 patients (33.3%) completed 6 courses, and 1 patient died of prostate cancer during follow-up. There was no significant difference in the number of radium treatment courses between the two groups ( P=0.320). ALP in HRD(+ ) group was 101.8 (61.3, 147.0) U/L after radium-223 treatment, which was significantly lower than that before treatment ( P=0.002). ALP in HRD(-) group was 73.0 (64.0, 113.5) U/L after radium-223 treatment, and it was not significantly different from that before treatment ( P=0.327). The rate of ALP response (ALP decrease >10%) in HRD(+ ) group was significantly higher than that in HRD(-) group [83.3% (15/18) vs. 44.4% (4/9), P=0.037]. PSA was 105.9(5.2, 798.4) ng/ml in HRD (+ ) group after radium-223 treatment, and was 25.6(0.8, 1 031.0) ng/ml in HRD(-) group, and they were not significantly different from that before treatment ( P=0.145, P=0.386). There were no significant differences in the rate of PSA response (PSA decrease>10%) between HRD(+ ) group and HRD(-) group [38.9% (7/18) vs. 22.2% (2/9), P=0.386]. The median pain score of HRD(+ ) group was 3.0 (0, 4.0) points after treatment, which was significantly lower than that before treatment ( P=0.028). The pain score of HRD(-) group was 1.0(0, 3.0) points after treatment, and it was not significantly different from that before treatment ( P=0.129). There was no significant difference in pain relief rate between HRD(+ ) group and HRD(-) group [66.7% (12/18) vs. 44.4% (4/9), P=0.411]. The incidence of at least one hematological adverse event during radium-223 treatment in the HRD(+ ) group was higher than that in the HRD(-) group [77.8% (14/18) vs. 33.3% (3/9), P=0.039]. There was no significant difference in the incidence of grade 1-2 hematological adverse events between the two groups [72.2%(13/18) vs. 33.3%(3/9), P=0.097]. Only 1 patient in the HRD(+ ) group experienced grade 3 anemia during treatment which was recovered after blood transfusion. Conclusions:Compared to mCRPC patients without HRR gene mutation, patients with HRR gene mutations had better ALP response and bone pain relief after radium-223 treatment. The overall incidence of adverse events in the HRD(+ ) group is higher than that in HRD(-) group, and there was no significant difference in grade 1-2 hematological adverse events between the two goups. It is necessary to expand the sample size to further verify the conclusion.

Objective:To analyze the relationship between early-life famine exposure and the risk of metabolic syndrome in Chinese population.Methods:Relevant literature on the relationship between early-life famine exposure and the risk of metabolic syndrome in the Chinese population was retrieved from databases such as CNKI, Wanfang, VIP, CBM, Web of Science, and PubMed. The search was conducted from the inception of the databases up to October 2022. Two researchers independently extracted and systematically evaluated the data from the literature, and meta-analysis was performed using Stata 16.0 software. Results:A total of 12 publications met the inclusion criteria, including 71 470 study subjects. Meta-analysis results showed that early-life famine exposure increased the risk of metabolic syndrome in the Chinese population( OR=1.28, 95% CI 1.16-1.40). Subgroup analysis showed that both fetal famine exposure( OR=1.25, 95% CI 1.03-1.52) and childhood famine exposure( OR=1.29, 95% CI 1.15-1.45) increased the risk of developing metabolic syndrome compared to the non-exposed group, and this significant association was only found in the female population. Conclusion:Early-life exposure to famine may increase the risk of developing metabolic syndrome in adulthood in the Chinese population, particularly among females.

Objective:To evaluate the diagnostic for classification of newly diagnosed diabetes patients and assess the application of the screening tests recommended by the 2022 Chinese Expert Consensus on Diabetes Classification.Methods:Retrospective case series study. The data from the electronic medical record system of patients with new-onset diabetes mellitus (within 1 year of disease onset) who attending the Diabetes Specialist Outpatient Clinic at the Second Xiangya Hospital of Central South University from January 1, 2018 to December 31, 2021 were collected for the analysis. Based on the consensus, patients were categorized according their age of onset, body mass index (BMI), and suspicion of type 1 diabetes mellitus (T1DM). The chi-square statistic was used to compare key classifier indicators, including C-peptide, islet autoantibodies, and genetic markers, in the subgroups. The diagnosis in suspected T1DM patients was also evaluated. The screening strategy recommended in the consensus was further assessed using a logistic regression model and the area under the receiver-operating curve (AUC).Results:A total of 3 384 patients with new-onset diabetes were included. The average age of disease onset was (46.3±13.9) years, and 61.0% (2 065/3 384) of the patients were male. The proportions of patients who completed C-peptide and glutamic acid decarboxylase antibody (GADA) tests were 36.6% (1 238/3 384) and 37.5% (1 269/3 384), respectively. There were no significant differences in C-peptide test results among the subgroups (all P>0.05). In contrast, the GADA detection rate was higher in patients with young age of onset (<30 years old), in those who were non-obese (BMI<24 kg/m 2), and in those clinically suspected of T1DM (all P<0.05). According to the diagnostic pathway proposed by the consensus, only 57.4% (1 941/3 384) of patients could be subtyped. For a definitive diagnosis, the remaining patients needed completion of C-peptide, islet autoantibody, genetic testing, or follow-up. Furthermore, among patients with clinical features of suspected T1DM, the antibody positivity rate was higher than in non-suspected T1DM patients [24.5% (154/628) vs. 7.1% (46/646), P<0.001]. When the clinical features of suspected T1DM defined in the consensus were taken as independent variables and antibody positivity was considered the outcome variable in the logistic regression model, young onset, non-obese onset, and ketosis onset could enter the model. Based on AUC analysis, the accuracy of the diagnostic model was 0.77 (95% CI 0.73-0.81), suggesting that the clinical features of suspected T1DM in the consensus have good clinical diagnostic value for this patient subgroup. Conclusions:There was a significant discrepancy between the clinical practice of diabetes classification and the process recommended by the consensus, which was specifically reflected in the low proportions of both subtyping indicator testing and definitively subtyped diabetes patients. Attention should be pay to the classification diagnosis process proposed in the consensus and the clinical detection rate of key diabetes subtyping indicators such as C-peptide and islet autoantibodies for diabetes classification should be improved. Noteworthy, the screening strategy for T1DM proposed by the consensus showed good clinical application value.

Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R² = 0.033; P = 0.018), followed by acute kidney injury (AKI; R² = 0.032; P = 0.011) and plasma MIP-1β level (R² = 0.027; P = 0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients' lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.
Acute Kidney Injury/complications* ; Bacteria/classification* ; Chemokine CCL4/blood* ; Community-Acquired Infections/microbiology* ; Humans ; Lung ; Microbiota/genetics* ; Pneumonia, Bacterial/diagnosis* ; Prognosis ; RNA, Ribosomal, 16S/genetics*

The accumulation of protein sequence and structure data allows researchers to obtain large amount of descriptive information, simultaneously it poses an urgent need for researchers to extract information from existing data efficiently and apply it to downstream tasks. Protein design enables the development of novel proteins that are no longer restricted by experimental conditions, which is of great significance for drug target prediction, drug discovery, and material design. As an efficient method for data feature extraction, deep learning can be used to model protein data, and further add a priori information to design novel proteins. Therefore, protein design based on deep learning has become a promising approach despite of many challenges. This review summarizes the deep learning-based modeling and design methods of protein sequence and structure data, highlighting the strategies, principle, scope of application and case studies, with the aim to provide a valuable reference for relevant researchers.
Amino Acid Sequence ; Deep Learning ; Drug Development ; Proteins

BACKGROUND: Osteoporosis is a systemic bone disease characterized by decreased bone density and deterioration of bone microstructure, leading to an increased probability of fragility fractures. Once segmental bone defect occurs, it is easy to cause delayed union and nonunion. METHODS: The aim of this study is to investigate the efficacy of extracorporeal shock wave (ESW) and teriparatideloaded hydrogel (T-Gel) combined strategy on the cell activity and differentiation of osteoporosis derived bone marrow mesenchymal stem cells (OP-BMSCs) in vitro and bone regeneration in osteoporotic segmental bone defects in vivo. RESULTS: In vitro, the strategy of combining ESW and T-Gel significantly enhanced OP-BMSCs proliferation, survival, migration, and osteogenic differentiation by up-regulating the alkaline phosphatase activity, mineralization, and expression of runt-related transcription factor-2, type I collagen, osteocalcin, and osteopontin. In the segmental bone defect models of osteoporotic rabbits, MicroCT evaluation and histological observation demonstrated this ESW-combined with T-Gel injection significantly induced bone healing by enhancing the osteogenic activity of the local microenvironment in osteoporotic defects. CONCLUSION In conclusion, ESW-combined with T-Gel injection could regulate the poor osteogenic microenvironment in osteoporotic defects and show potential for enhancing fragility fractures healing.