ObjectiveThis paper aims to conduct the feature analysis and correlation analysis on the ocular collateral features and differential metabolites in patients with chronic hepatitis B （CHB） complicated by glucose metabolism disorder （GMD），particularly those with the damp-heat syndrome type，by integrating shadowless scleral imaging and metabolomics technologies. MethodsA total of 313 patients were recruited from the Hepatology and Endocrinology Outpatient Departments of Public Health Clinical Center of Chengdu according to the inclusion/exclusion criteria，and they were divided into a CHB group and a CHB complicated by GMD groups （damp-heat syndrome group and non-damp-heat syndrome group）. All patients underwent high-definition ocular image acquisition and feature extraction using an intelligent analysis system for shadowless scleral imaging to analyze the differences in the counting of morphological feature scores of ocular collaterals among groups. By using a digital sampling method，24 patients from each group were randomly selected，along with 20 healthy volunteers，for untargeted metabolomic analysis of peripheral serum. Differential metabolites were identified，statistically analyzed，and subjected to potential biomarker analysis and pathway enrichment. Spearman method was performed to conduct the correlation analysis on the differential ocular collateral features and differential metabolites，followed by correlation network construction. ResultsCompared with those in the CHB group，patients with CHB complicated by GMD showed significant changes in ocular collateral feature scores such as "hillock"，"blood vessels"，and "pale dusky coloration" （P<0.05）. In comparison with those in the healthy group，metabolites including N-acetylglucosamine，acetylhomoserine，and myo-inositol （AUC>0.7） were identified as potential biomarkers for the disease. Compared with those in the CHB complicated by GMD group with non-damp-heat syndrome，patients with damp-heat syndrome exhibited significant changes in feature scores of "plaques"，"yellow coloration"，"spleen"，and "gallbladder" （P<0.05）. In comparison with those in the healthy group，metabolites such as O²′-4a-cyclic tetrahydrobiopterin，theobromine，xanthurenic acid，and L-glutamic acid 5-phosphate （AUC>0.7） were identified as potential biomarkers for the damp-heat syndrome type. The Spearman correlation analysis reveals weak to moderate linear correlations between the differential scleral collateral features and metabolites. By constructing a "disease-syndrome" network of ocular diagnosis and metabolites，"xanthurenic acid-gallbladder" and "theobromine-plaque/yellow coloration" were identified as specific molecular-phenotypic correlated biomarker clusters for CHB complicated by GMD with dampness-heat syndrome. ConclusionPatients with CHB complicated by GMD demonstrate differential ocular diagnostic features and serum metabolites corresponding to disease states and dampness-heat syndrome. These objective biomarkers can guide both clinical syndrome differentiation and medication. The macro-micro integration based on ocular feature clusters and potential metabolic biomarkers offers an innovative approach to a combined traditional Chinese and Western medicine diagnosis and treatment model for this disease.

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Objective To construct an evaluation index system of organizational resilience of county medical alliance,and to propose countermeasures and suggestions for the enhancement of organizational resilience and operational effectiveness of county medical alliance.Methods The initial evaluation index system was constructed based on literature research and semi-structured interviews.Two rounds of Delphi expert consultation combined with critical value method refined the evaluation indexs.Evaluation index weights were determined via analytic hierarchy process and multiplicative weighting.The system was empirically tested using Zhejiang Province data.Results 21 experts completed consultations.Then the evaluation index system of county medical alliance organizational resilience was formed,which contains 5 first-level indexes,15 second-level indexes and 43 third-level indexes,containing 19 subjective and 24 objective evaluation indexs.The overall evaluation score of the organizational resilience of county medical alliance in Zhejiang Province was 73.97,which was at the average level of resilience.Conclusion The evaluation index system of organizational resilience of county medical alliance fits in with the national development plan to promote the construction of county high-quality,efficient and integrated medical and healthcare service system,and can provide effective measurement tools and theoretical references for the organizational capacity of county medical alliance and their maturity evaluation.

Objectives:This study aimed to explore the association between perceived mental stress (MS), lymphocyte subset variations, and coronary lesion severity in patients with coronary artery disease (CAD).Methods:Patients with CAD were enrolled in this study from September 2023 to May 2024. Perceived Stress Scale-14 (PSS-14) was used to evaluate MS during the last 1 month. Lymphocyte subsets were analyzed, including the percentage and absolute counts of CD3 +, CD3 +CD4 +, CD3 +CD8 +, CD3 -CD19 +, CD3 -CD56 +16 +, and the Th/Ts ratio. Statistical analysis was conducted using SPSS 24.0. Results:This study recruited patients with 323 CAD, with an average age of 61 (56, 68) years, including 203 males and 120 females. According to the PSS-14, a score of 14-42 and 43-70 were categorized as normal and increased MS, respectively. Patients with CAD with increased MS had significantly higher Gensini scores than those with normal MS [37(19,64) vs. 28(12,50), Z=-2.19, P=0.029]. Male CAD patients with increased MS exhibited significantly higher Gensini scores [39(20, 58) vs. 26(12, 45), Z=-2.37, P=0.018], levels of CD3 +CD8 +%[28.3%(23.6%,36.6%) vs. 25.9%(21.0%,32.4%), Z=-2.05, P=0.041], and CD3 +CD8 +absolute value [485 (346, 675) vs. 396 (309, 510) cells/μl, Z=-2.55, P=0.011] than those with normal MS. In male patients with CAD, a positive correlation was observed between Gensini scores (correlation coefficient: 0.181, P=0.011), PSS-14 scores, and CD3 +CD8 +absolute value (correlation coefficient: 0.162, P=0.038). Conclusion:This study reveals a positive correlation between MS and coronary stenosis severity, with notable sex differences. In male patients with CAD, higher levels of MS are associated with more severe coronary stenosis. The potential underlying mechanism may involve the regulation of lymphocyte subsets .

Objective A non-targeted metabolomics analysis of vitreous fluid from patients with proliferative diabetic retinopathy(PDR)is conducted to explore the"metabolic map"of PDR.This approach aims to deepen the understanding of the disease,identify potential biomarkers.Methods From 35 PDR patients and 30 fresh rhegmatogenous retinal de-tachment(RRD)patients,10 PDR patients with vitreoretinal abnormal adhesions were selected as the experimental group(PDR group),and 10 fresh RRD patients were chosen as the control group(RRD group).Using ultra-high-performance liq-uid chromatography-mass spectrometry non-targeted metabolomics technology,the metabolic profiles of vitreous fluid were analyzed to obtain metabolic spectra.One-dimensional and multidimensional statistical methods were used to analyze the differences in metabolites and metabolic pathways between the PDR and RRD groups.Results A total of 165 differential metabolites were identified in the vitreous humor samples of patients in the PDR and RRD groups,these differential metab-olites were significantly enriched in 21 metabolic pathways(P＜0.05),Among these pathways,those with at least 5 differ-ential metabolites include:methionine and cysteine metabolism;glycine,serine,and threonine metabolism;ascorbic acid and aldose metabolism;amino acid biosynthesis;and central carbon metabolism in cancer.Pyruvate,serine,D-2-phospho-glycerate,threonine,phosphoserine,and high serine are present in multiple metabolic pathways,the areas under the curve are 0.96,0.82,0.85,0.78,0.40,and 0.31,respectively.Conclusion There are 21 significantly different metabolic pathways between PDR and RRD patients.Pyruvate stands out in multiple pathways,potentially serving as a biomarker for PDR diagnosis.

BACKGROUND: The effect of air pollution on annual change rates in grip strength and body composition in the elderly is unknown. OBJECTIVES: This study evaluated the effects of long-term exposure to ambient air pollution on change rates of grip strength and body composition in the elderly. METHODS: In the period 2016-2020, grip strength and body composition were assessed and measured 1-2 times per year in 395 elderly participants living in the Taipei basin. Exposure to ambient fine particulate matters (PM_2.5), nitric dioxide (NO₂), and ozone (O₃) from 2015 to 2019 was estimated using a hybrid Kriging/Land-use regression model. In addition, long-term exposure to carbon monoxide (CO) was estimated using an ordinary Kriging approach. Associations between air pollution exposures and annual changes in health outcomes were analyzed using linear mixed-effects models. RESULTS: An inter-quartile range (4.1 µg/m³) increase in long-term exposure to PM_2.5 was associated with a faster decline rate in grip strength (-0.16 kg per year) and skeletal muscle mass (-0.14 kg per year), but an increase in body fat mass (0.21 kg per year). The effect of PM_2.5 remained robust after adjustment for NO₂, O₃ and CO exposure. In subgroup analysis, the PM_2.5-related decline rate in grip strength was greater in participants with older age (>70 years) or higher protein intake, whereas in skeletal muscle mass, the decline rate was more pronounced in participants having a lower frequency of moderate or strenuous exercise. The PM_2.5-related increase rate in body fat mass was higher in participants having a lower frequency of strenuous exercise or soybean intake. CONCLUSIONS Among the elderly, long-term exposure to ambient PM_2.5 is associated with a faster decline in grip strength and skeletal muscle mass, and an increase in body fat mass. Susceptibility to PM_2.5 may be influenced by age, physical activity, and dietary protein intake; however, these modifying effects vary across different health outcomes, and further research is needed to clarify their mechanisms and consistency.
Humans ; Hand Strength ; Aged ; Male ; Female ; Environmental Exposure/adverse effects* ; Follow-Up Studies ; Taiwan ; Air Pollution/adverse effects* ; Particulate Matter/adverse effects* ; Muscle, Skeletal/drug effects* ; Air Pollutants/adverse effects* ; Ozone/adverse effects* ; Aged, 80 and over ; Adipose Tissue/drug effects* ; Body Composition/drug effects* ; Nitrogen Dioxide/adverse effects*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Tauopathies, including Alzheimer's disease (AD), are a series of neurodegenerative diseases characterized by pathological accumulation of the microtubule-associated protein tau. Since the abnormal modification and deposition of tau in nerve cells are crucial for tauopathy etiology, methods for reducing tau levels, such as promoting tau degradation, may become effective strategies for disease treatment. Herein, we identified that sorafenib significantly reduced total tau and phosphorylated tau levels through screening FDA-approved drugs. We showed that sorafenib treatment attenuated cognitive deficits and tau pathologies in PS19 tauopathy model mice. Mechanistically, we found that sorafenib inhibited multiple kinases involved in tau phosphorylation and promoted autophagy. Importantly, we further demonstrated that sorafenib also promoted the expression of the E3 ubiquitin ligase FBXW7, which could bind tau and mediate tau degradation through the ubiquitin-proteasome pathway. Finally, we showed that FBXW7 expression decreased in the brains of AD patients and tauopathy model mice, and that overexpression of FBXW7 in the hippocampus attenuated cognitive deficits and tau pathologies in PS19 mice. These results suggest that sorafenib may be a promising treatment option for tauopathies by promoting tau degradation and reducing tau phosphorylation, and that targeting FBXW7 could also serve as an alternative therapeutic strategy for tauopathies.

Objective To develop a novel type of transparent simulation manikin as a surgical training model to meet the surgical treatment demand on the medical train.Methods A transparent manikin was developed with the steps of basic data collection,motherboard design and manufacture and module production and assembly.Firstly,basic data collection was carried out with reference to standardized human anatomy and parameters.Secondly,some software such as UG NX7.5 was used to construct the motherboard of the manikin.Finally,module production and assembly were performed with the materials of acrylic,transparent rubber,silicone and hydrogel and the technology of silicone infusion.Results The transparent manikin developed had its anatomy structure close to that of the real body and high visuality for its internal and external components,which simulated a variety of war wounds and thus could be integrated with the surgical training scenarios on the medical train effectively.Conclusion The transparent manikin developed is characterized by high visuality,modularity and blood flow,and meets the demands for surgical training on the medical train.[Chinese Medical Equipment Journal,2025,46(6):111-115]

Objective:To develop a deep learning-based system for real-time recognition and classification of portal hypertensive gastropathy (PHG) and evaluate its ability to assist junior endoscopists.Methods:A total of 2 848 gastroscopy images from 832 patients with liver cirrhosis were selected from Digestive Endoscopy Center databases of Renmin Hospital of Wuhan University, Wuhan Hospital of Traditional Chinese and Western Medicine, and the Second Hospital of Jingzhou from January 2015 to October 2023. This system referred to 3 endoscopic features of Baveno Ⅱ scoring system. Three models were developed respectively for gastric antral vascular ectasia (GAVE), mosaic-like pattern (MLP), and red marks (RM). The specific classification references were as follows: (1) GAVE model: 0 no, 1 yes; (2) MLP model: 0 no, 1 mild, 2 severe; (3) RM model: 0 no, 1 isolated, 2 fused. The classification results for endoscopic characteristics of PHG of 3 endoscopy experts were taken as the gold standard. The yolov8-m model was used for training. The training dataset, validation dataset, and test dataset were allocated at a ratio of 8∶1∶1. The test dataset was used to evaluate the performance of models and their auxiliary effects on endoscopists. The accuracy, recall, precision, specificity and Kappa coefficient were calculated. Results:The accuracy, recall, specificity of GAVE model were 96.0% (48/50), 87.5% (7/8) and 97.6% (41/42). There was no significant difference between its accuracy and the gold standard ( χ2=316.226, P=1.000). The precision of GAVE1 and GAVE0 were 87.5% (7/8) and 97.6% (41/42) respectively. The accuracy of MLP model was 84.1% (132/157), and there was no significant difference compared with the gold standard ( χ2=3.286, P=0.193). The precision and recall of MLP2 were 88.2% (15/17) and 75.0% (15/20). The precision and recall of MLP1 were 77.9% (60/77) and 88.2% (60/68). The precision and recall of MLP0 were 90.5% (57/63) and 82.6% (57/69). The accuracy of RM model was 87.9% (123/140), and there was no significant difference compared with the gold standard ( χ2=2.891, P=0.409). The precision and recall of RM2 were 94.7% (18/19) and 78.3% (18/23). The precision and recall of RM1 were 72.2% (26/36) and 81.3% (26/32). The precision and recall of RM0 were 92.9% (79/85) and 92.9% (79/85). The mean accuracy of the three junior endoscopists, with and without the assistance of the GAVE model, MLP model, and RM model, respectively increased from 95.3% to 99.3%, from 83.9% to 91.9%, and from 81.9% to 83.1%. The overall consistency analysis of the 3 junior endoscopists with the gold standard indicated that the consistency of the GAVE model before and after assistance was extremely strong (both an overall Kappa of 1.000); the consistency before assistance of the MLP model was moderate (with an overall Kappa of 0.601), which increased to extremely strong after assistance (with an overall Kappa of 0.964); and the consistency of the RM model before and after assistance was also relatively strong (with an overall Kappa of 0.792 before and 0.798 after). Conclusion:The deep learning system accurately identifies and classifies PHG features and significantly enhances diagnostic performance of junior endoscopists.