The pathogenesis of metabolic dysfunction-associated steatotic liver disease （MASLD） is fundamentally rooted in spleen deficiency and is closely associated with phlegm turbidity， damp-heat and blood stasis. Clinically， liver constraint with spleen deficiency and internal retention of damp turbidity represent the predominant traditional Chinese medicine （TCM） syndrome patterns. Researches have indicated intrinsic connections between the syndrome patterns and biological indicators such as gut microbiota and metabolic profiles. Regarding treatment， classical famous formulas， modern empirical formulas， and newly developed TCM drugs show positive effects in regulating glucose and lipid metabolism， improving insulin resistance， and alleviating metabolic inflammation， exhibiting multi-target mechanisms of action； acupuncture and other external therapies also provide adjunctive value. Nevertheless， current researches still have limitations such as the lack of high-quality clinical evidence and insufficient systematic elucidation of the uncerlying mechanisms. Future efforts should focus on conducting high-quality TCM clinical trials with hard endpoint outcomes such as hepatic histology outcomes， and utilizing modern technologies like multi-omics to elucidate TCM's mechanisms of action， thereby advancing the position of TCM as a first-line therapeutic strategy for MASLD.

Objective To analyze the effect of releasing the lower pulmonary ligament on right residual lung expansion after right upper lobe resection under different body mass index (BMI) levels. Methods The clinical data of patients who underwent thoracoscopic right upper lobe resection in the First Affiliated Hospital with Nanjing Medical University from 2021 to 2022 were retrospectively analyzed. Patients were divided into a group A (17 kg/m2＜BMI≤23 kg/m2), a group B (23 kg/m2＜BMI≤29 kg/m2) and a group C (BMI＞29 kg/m2) according to BMI. The presence of residual cavity was judged by chest X-ray at 7-10 days after operation, the degree of compensation change of the right main bronchus angle was measured, and the changes in lung volume were determined by CT three-dimensional reconstruction. Results A total of 157 patients who underwent thoracoscopic right upper lobe resection were included, including 71 males and 86 females, with an average age of (59.7±11.2) years. There were 50 patients in the group A, 75 patients in the group B, and 32 patients in the group C. In the group A, compared with those without releasing the lower pulmonary ligament, patients with releasing had a lower incidence of postoperative residual cavity (P=0.016), greater changes in bronchus angle (P<0.001), and smaller changes in lung volume (P<0.001). In the group B and C, there was no significant effect of releasing the lower pulmonary ligament on postoperative residual cavity, bronchus angle, and lung volume changes (P>0.05). Conclusion For patients with thin and long body shape and low BMI, releasing the lower pulmonary ligament is helpful to promote the expansion of the residual lung after right upper lobe resection and reduce the occurrence of postoperative residual cavity in patients.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

Pulmonary fibrosis（PF） is a progressive and life-threatening disease with limited therapeutic options， highlighting the urgent need for innovative drug discovery strategies. To address this challenge， the authors propose the formula-originated rational intelligent screening&translation（FIRST）， a systematic framework for developing anti-fibrotic monomers derived from classical traditional Chinese medicine（TCM）. The strategy integrates three key dimensions， including tissue-oriented intelligent screening of active compounds， structural optimization based on drug-target spatial interactions and plant biosynthetic pathways， and cross-scale validation of drug. We further highlight its applications in discovering tissue-oriented novel drugs from clinically validated TCM， the development and mechanistic elucidation of anti-fibrotic therapeutics， as well as the clinical translation and secondary development of candidate drugs. This strategy paves the way for first-in-class， formula-derived monomeric drugs with defined structures， clarified mechanisms， and proven safety， offering a transformative avenue to meet the urgent therapeutic needs of PF and setting a new paradigm for TCM-based drug innovation.

ObjectiveIn the context of the digital transformation of education, this study aims to construct a triadic interactive teaching model for surgical animal surgery in clinical medicine using modern information technology. It explores the effectiveness of different teaching methods in improving students' practical skills, aseptic awareness, and teamwork abilities, providing a reference for the reform of clinical practice education. MethodsA quasi-experimental research design was adopted. A total of 80 students from the eight-year clinical medicine program at Nanjing University were selected, including the Class of 2020 (control group, n=40) and the Class of 2021 (experimental group, n=40). The control group received traditional teaching methods, while the experimental group implemented the "Teacher-Student-AI" triadic interactive teaching model. This model utilized a smart teaching platform for personalized pre-class preparation , as well as data-driven post-class review and feedback throughout the entire teaching process. The "assessment indicators and scoring criteria for the surgical animal surgery course" were used to evaluate teaching effectiveness, with independent samples t-tests used for statistical analysis. ResultsPre-course assessments revealed no statistically significant differences in baseline theoretical knowledge or practical skills between the two groups (P>0.05). Upon completion of the course, the experimental group achieved higher scores than the control group across three key dimensions: practical skills (47.98±1.34 vs 46.92±2.51, P=0.022), aseptic awareness (17.84±1.16 vs 16.94±2.29, P=0.029), and teamwork (16.82±1.44 vs 15.95±1.22, P=0.004). However, no statistically significant difference was observed in the scores for humane care awareness between the two groups (8.24±0.70 vs 8.16±0.53, P=0.589). ConclusionThe AI-based triadic interactive teaching model can, to some extent, address the limitations of traditional surgical animal surgery education. It plays a positive role in enhancing medical students' surgical skills, aseptic awareness, and collaborative abilities. This model facilitates the transition from traditional to personalized teaching and offers a practical framework for the digital reform of clinical practice education.

OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of five children with Lamb-Shaffer syndrome (LAMSHF). METHODS: Five children with LAMSHF diagnosed at the Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital from April 2021 to December 2024 were selected as study subjects. Clinical data of the children was collected. Genomic DNA was extracted from peripheral blood samples of the children and their parents. Whole exome sequencing (WES) was carried out to screen for variants. This study was approved by the Medical Ethics Committee of the Chinese PLA General Hospital (Ethics No.: S2025-411-01). RESULTS: All five children had presented with global developmental delay. Among them, two had manifestations of autism spectrum disorder, two had abnormal electroencephalogram findings, four had abnormal MRI results, and two had ocular abnormalities. WES has detected five novel variants in the SOX5 gene. Among these, c.1771G>C (p.Gly591Arg) was unreported previously. Sanger sequencing confirmed that none of the parents had carried the same variants, suggesting that they were all de novo variants. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG), two nonsense variants and one missense variant were classified as pathogenic, whilst two missense variants were classified as likely pathogenic. CONCLUSION This study has clarified the correlation between the clinical phenotypes of five children with LAMSHF and variants of the SOX5 gene, which expanded the mutational spectrum of the SOX5 gene and provided a basis for the clinical diagnosis and genetic counseling.
Humans ; Male ; Female ; Phenotype ; Child, Preschool ; Child ; SOXD Transcription Factors/genetics* ; Exome Sequencing ; Mutation ; Infant

Objective:To explore the clinical, genetic, and therapeutic prognostic characteristics of two pediatric cases of Lesch-Nyhan syndrome (LNS) in order to enhance understanding of this disease and investigate more effective treatment strategies.Methods:Clinical data were collected from two children clinically diagnosed with LNS who were treated at Anhui Provincial Children′s Hospital from April 2023 to January 2024. Data were collected retrospectively and included clinical manifestations (symptoms, signs, laboratory and imaging findings), treatment course, and follow-up results. Peripheral venous blood samples (2 mL each) were obtained from children 1 and his parents. Whole-exome sequencing (WES) was performed. Candidate variants were validated by Sanger sequencing to confirm the genetic etiology.Standard bioinformatic analysis of the raw WES data was conducted, including quality control, alignment, variant calling, and annotation. Candidate pathogenic variants were filtered using population frequency databases (e.g., gnomAD), disease databases (e.g., OMIM, ClinVar), and multiple in silico pathogenicity prediction tools (e.g., SIFT, PolyPhen-2, CADD). Phenotype matching was integrated using Human Phenotype Ontology (HPO) terms. Pathogenicity classification of variants was performed according to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants (2015). This study was approved by the Medical Ethics Committee of Anhui Children′s Hospital, Children′s Hospital of Fudan University (Approval No.: EYLL-2014-027).Results:Case 1, a 4-year-old boy presented with "developmental delay for over 3 years, accompanied by abnormal postures and involuntary lip-biting". Physical examination revealed limb dystonia, anxious expression, lower lip damage, and communication difficulties. Laboratory tests showed hyperuricemia and renal stones. Genetic testing identified a hemizygote variant in the HPRT1 gene, c. 135G>T (p.Arg45Ser), inherited from an asymptomatic carrier mother, confirming the diagnosis of LNS. This variant was absent from population databases (gnomAD, 1000 Genomes, dbSNP). Protein function prediction tools consistently indicated pathogenic or likely pathogenic variant (SIFT, PolyPhen-2, CADD, and REVEL scores all reached pathogenic thresholds). Protein structural modeling revealed that the mutation disrupts the hydrogen-bonding network, compromising tetramer stability. ACMG classification designated it as likely pathogenic (PM1 + PM2_Supporting + PM5 + PP3). The patient was treated with benhaxol hydrochloride, baclofen, and clonazepam to improve neurological symptoms, and also received treatment with febuxostat in the nephrology department to manage purine metabolism. After one year of follow-up, the patient′s abnormal posture showed slight improvement, self-injurious behavior persisted but was managed with protective gloves, blood uric acid levels normalized, and renal stones decreased. Case 2, a 13-year-old boy was hospitalized in the nephrology department due to a urinary tract infection. Following successful infection treatment, his limb dystonia worsened, leading to his transfer to the neurology ward. The patient had a history of delayed motor and language development, abnormal postures, and lip-biting self-injurious behavior, with elevated blood uric acid levels, leading to an LNS diagnosis. The parents declined genetic testing due to financial constraints. Following discharge, the patient did not adhere to the prescribed medication regimen or attend scheduled outpatient visits. The patient had died by the time of the 4-month follow-up contact. Conclusion:HPRT1 gene variants are the genetic cause of LNS in children, and the HPRT1 gene is the only known pathogenic gene for LNS. Early genetic diagnosis, strict adherence to multidisciplinary comprehensive treatment, and intensive intervention for self-injurious behaviors are crucial for improving the quality of life and prolonging survival in children with LNS.

Objective To investigate the correlation between arterial stiffness(AS)and incident chronic kidney disease(CKD)among the elderly individuals taking health checkup.Methods A retrospective study was conducted on 857 elderly individuals without CKD at baseline who taking physical exams in our medical center from December 2009 to May 2021.Their clinical and labora-tory data were collected.Brachial-ankle pulse wave velocity(baPWV)was used to assess the se-verity of AS,and then the subjects were divided into normal elasticity group(201 cases),and moderate(490 cases)and severe AS group(166 cases).Kaplan-Meier curves were plotted to dis-play cumulative incidence rates of incident CKD across different AS groups.Restricted cubic splines(RCS)and Cox regression models were applied to analyze the correlation of baPWV and incident CKD risk.Results The severe AS group had significantly advanced age,greater ratio of hypertension,larger waist circumference,higher HR,SBP and DBP,increased urinary albumin/creatinine ratio(UACR),elevated levels of TG and fasting blood glucose,and baPWV than the normal elasticity group(P＜0.05).During the follow-up period,37 participants developed CKD.The incidence of CKD was obviously higher in the severe AS group than the normal arterial elas-ticity group(9.04％vs 3.48％).RCS analysis revealed a U-shaped relationship between baPWV and incident CKD risk.When baPWV ≥1 400 cm/s,each standard deviation increase in baPWV indicates the risk of incident CKD increasing by 71％(HR=1.71,95％CI:1.30-2.25,P＜0.01).Regardless of adjustment for covariates or not,baPWV remained positive correlation with inci-dent CKD risk(P＜0.05).Conclusion Among the elderly individuals undergoing health check-up,increased AS severity is significantly associated with higher risk of incident CKD when baP-WV ≥1400 cm/s.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

This document targets digital human metabolic chamber platforms and specifies construction standards and testing protocols covering the full lifecycle of " build-test-operate." It encompasses chamber engineering and environmental control, digital platform and cybersecurity architecture, metabolic measurement and multimodal data acquisition, as well as quantitative system performance and data quality indicators with verifiable acceptance tests. By standardizing architecture, interfaces, and quality control, the specification enables multicenter data interoperability and harmonized quality management, providing high-quality, verifiable, and traceable infrastructure to support precision metabolism research and clinical translation in China.