OBJECTIVE: To delineate the clinical and genetic features of a Chinese girl harboring a rare de novo variant of SYNGAP1 associated with Mental retardation, autosomal dominant 5 (MRD5), and to conduct a comprehensive genotype-phenotype correlation analysis within the Chinese population through an extensive literature review. METHODS: A 5-year-old girl presenting with seizures without an obvious cause was enrolled in September 2020. Genomic DNA was extracted from the patient and her parents. Whole exome sequencing (WES) was performed on the proband to identify suspected pathogenic variants based on her clinical phenotype. Sanger sequencing was used for validation, followed by bioinformatic analysis of the variant. Additionally, data from 54 previously reported Chinese cases with SYNGAP1 variants were integrated to summarize the distribution of variant types and clinical characteristics. Ethical approval was obtained from the Ethics Committee of Kunming Children's Hospital (Ethics No.: 2021-03-055-K01). RESULTS: WES identified a heterozygous nonsense variant, SYNGAP1 c.725G>A (p.Trp242*), in the proband. Sanger sequencing confirmed it was a de novo variant. According to the ACMG guidelines, this variant was classified as pathogenic (PVS1+PS2). Based on the clinical manifestations, the patient was diagnosed with MRD5. Bioinformatic analysis suggested that this variant introduces a premature stop codon at tryptophan 242, disrupting the PH domain and leading to the loss of the C2, Ras-GAP, and C-terminal domains. The pooled analysis of Chinese cases revealed that nonsense (38.2%) and frameshift (36.4%) variants were the predominant types. Intellectual disability/developmental delay was present in 100.0% of patients, epilepsy in 83.6%, and autism spectrum disorder in 41.3%. The incidence of epilepsy differed significantly among variant types (P = 0.045). Exons 8 and 15 were identified as mutation hotspots. CONCLUSION This study has identified a SYNGAP1 c.725G>A variant in the Chinese population and confirmed it as a potential cause of MRD5, which expanded the mutational spectrum of this disorder.
Humans ; Female ; Child, Preschool ; Intellectual Disability/genetics* ; ras GTPase-Activating Proteins/genetics* ; Phenotype ; Exome Sequencing ; Genetic Association Studies

Objective: To investigate the prevalence of overweight and obesity among children and adolescents in Yangzhou City, and its association with screen behaviors, so as to provide scientific evidence for weight management among students. Methods: In May 2025, an electronic questionnaire survey was conducted among children and adolescents in Yangzhou City. A total of 3 722 participants were selected from grades 4 to 12 in 18 primary and secondary schools (108 classes) by using stratified cluster random sampling. The Chi square test was used to compare the differences in the detection rates of overweight and obesity among children and adolescents with 5 types of screen behaviors (watching TV, playing electronic games, scrolling short videos, screen based learning, electronic socializing) in different time groups each day (never, >0~<2 h, ≥2 h). Multivariate Logistic regression analysis was performed to examine the associations of five types of screen behaviors, presence of electronic devices in the bedroom, and screen use during meals on the weight status of children and adolescents. Results: The prevalence of overweight and obesity among children and adolescents was 37.3%. For all five types of screen behaviors, the differences in the distribution of overweight and obesity detection rates among children and adolescents across the three time spent categories were statistically significant ( χ 2=30.76- 70.78 , all P <0.01). After adjusting for confounding factors, multivariate Logistic regression analysis revealed that frequent or always using screens during meals( OR =1.63, 95％ CI =1.14~2.31), playing video games ( OR =1.28, 95% CI =1.11-1.48), browsing short videos ( OR =1.29, 95％ CI=1.09-1.54), and screen based learning ( OR =1.26, 95％ CI =1.10-1.44) were significantly associated with overweight and obesity among children and adolescents (all P <0.05). Conclusions Excessive screen use is positively correlated with the incidence of overweight and obesity in children and adolescents. Targeted interventions on screen behaviors among children and adolescents are therefore warranted.

BACKGROUND:The most common complication of traumatic femoral neck fractures after internal fixation is femoral head necrosis.Currently,many studies have reported on the risk factors that affect the occurrence and development of postoperative femoral head necrosis,but there is still a lack of tools to predict the risk of femoral head necrosis after internal fixation of femoral neck fractures.OBJECTIVE:To develop a predictive model that estimates the risk of femoral head necrosis shortly after patients with femoral neck fractures receive cannulated screw internal fixation.METHODS:A retrospective analysis reviewed clinical records of 172 patients who underwent cannulated screw internal fixation for femoral neck fractures at Department of Orthopedics of Mianyang Central Hospital from January 2013 to June 2023.Patients were categorized into two groups based on the presence or absence of femoral head necrosis within one year post-operation:the necrosis group and the non-necrosis group.Univariate analysis,Lasso regression,and multivariate Logistic regression techniques were employed to identify the determinants of femoral head necrosis.A nomogram prediction model was constructed using R language's"rms"package,version 4.0.The receiver operating characteristic curve was used to evaluate the discriminatory ability of the model.The Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model,and the decision curve analysis was used to determine its clinical application benefits.Internal validation of the study was conducted using the Bootstrap method,involving 1 000 repeated samplings.To delve deeper into the primary factors influencing femoral head necrosis post-internal fixation of the femoral neck,this paper employed the SHAP method for data set analysis.RESULTS AND CONCLUSION:(1)The risk factors leading to femoral head necrosis in the short term after cannulated screw fixation of femoral neck fractures include:smoking,diabetes,Garden classification,fracture line location,reduction quality,age,and operation time.(2)The prediction model demonstrated robust performance,evidenced by an area under the curve of 0.940(95％Confidence Interval:0.903 to 0.977),indicating a high level of prediction accuracy.The model achieved a sensitivity of 90.2％and a specificity of 87.6％,indicating that its diagnostic performance was stable.The Hosmer-Lemeshow goodness-of-fit test yielded a chi-square value of 6.593 with a P-value of 0.581,confirming that the model's predictions closely align with the observed outcomes.(3)The calibration curve of the model also performed well,and its overall trend was very close to the ideal curve,further proving the high accuracy of the model.(4)The internal validation was carried out by the Bootstrap method with 1 000 repeated samplings,and the area under the curve of the model internal validation was still as high as 0.939,proving that the model had good stability.(5)Through the decision curve,it is found that within the probability threshold range of 1％to 92％,the model can obtain the maximum net benefit value.(6)The SHAP analysis results show that among the risk factors analyzed in this study,the location of the fracture line serves as the most significant predictor of femoral head necrosis following internal fixation with cannulated screws in femoral neck fractures,and subcapital fractures are extremely prone to femoral head necrosis after surgery.(7)It is concluded that the validated prediction model demonstrates strong discriminative power and reliability,offering practical clinical utility.It serves as a useful reference tool for short-term risk assessment of femoral head necrosis following internal fixation of femoral neck fractures.

BACKGROUND:The most common complication of traumatic femoral neck fractures after internal fixation is femoral head necrosis.Currently,many studies have reported on the risk factors that affect the occurrence and development of postoperative femoral head necrosis,but there is still a lack of tools to predict the risk of femoral head necrosis after internal fixation of femoral neck fractures.OBJECTIVE:To develop a predictive model that estimates the risk of femoral head necrosis shortly after patients with femoral neck fractures receive cannulated screw internal fixation.METHODS:A retrospective analysis reviewed clinical records of 172 patients who underwent cannulated screw internal fixation for femoral neck fractures at Department of Orthopedics of Mianyang Central Hospital from January 2013 to June 2023.Patients were categorized into two groups based on the presence or absence of femoral head necrosis within one year post-operation:the necrosis group and the non-necrosis group.Univariate analysis,Lasso regression,and multivariate Logistic regression techniques were employed to identify the determinants of femoral head necrosis.A nomogram prediction model was constructed using R language's"rms"package,version 4.0.The receiver operating characteristic curve was used to evaluate the discriminatory ability of the model.The Hosmer-Lemeshow test was used to evaluate the goodness of fit of the model,and the decision curve analysis was used to determine its clinical application benefits.Internal validation of the study was conducted using the Bootstrap method,involving 1 000 repeated samplings.To delve deeper into the primary factors influencing femoral head necrosis post-internal fixation of the femoral neck,this paper employed the SHAP method for data set analysis.RESULTS AND CONCLUSION:(1)The risk factors leading to femoral head necrosis in the short term after cannulated screw fixation of femoral neck fractures include:smoking,diabetes,Garden classification,fracture line location,reduction quality,age,and operation time.(2)The prediction model demonstrated robust performance,evidenced by an area under the curve of 0.940(95％Confidence Interval:0.903 to 0.977),indicating a high level of prediction accuracy.The model achieved a sensitivity of 90.2％and a specificity of 87.6％,indicating that its diagnostic performance was stable.The Hosmer-Lemeshow goodness-of-fit test yielded a chi-square value of 6.593 with a P-value of 0.581,confirming that the model's predictions closely align with the observed outcomes.(3)The calibration curve of the model also performed well,and its overall trend was very close to the ideal curve,further proving the high accuracy of the model.(4)The internal validation was carried out by the Bootstrap method with 1 000 repeated samplings,and the area under the curve of the model internal validation was still as high as 0.939,proving that the model had good stability.(5)Through the decision curve,it is found that within the probability threshold range of 1％to 92％,the model can obtain the maximum net benefit value.(6)The SHAP analysis results show that among the risk factors analyzed in this study,the location of the fracture line serves as the most significant predictor of femoral head necrosis following internal fixation with cannulated screws in femoral neck fractures,and subcapital fractures are extremely prone to femoral head necrosis after surgery.(7)It is concluded that the validated prediction model demonstrates strong discriminative power and reliability,offering practical clinical utility.It serves as a useful reference tool for short-term risk assessment of femoral head necrosis following internal fixation of femoral neck fractures.

OBJECTIVE To study the chemical components， components migrating to the blood and metabolites of Sanhua decoction in rats. METHODS Male Wistar rats were divided into administration group and blank group， with 6 rats in each group. The rats in the administration group were given 13.3 g/kg of Sanhua decoction lyophilized powder solution by gavage once a day in the morning and evening， and the rats in the blank group were given an equal volume of saline by gavage once a day in the morning and evening， both for 3 consecutive days. Plasma samples were collected from the two groups of rats after the last administration. The chemical components， prototype components migrating to the blood and metabolites of Sanhua decoction were analyzed by UHPLC-Q-TOF/MS technique. The structures were identified combined with the self-built natural product high- resolution mass spectrometry database and relevant literature. RESULTS & CONCLUSIONS Totally 69 compounds were identified from the lyophilized powder of Sanhua decoction， including 29 components from Rheum officinale， 16 components from Magnoliae Officinalis Cortex， 22 components from Aurantii Fructus Immaturus， and 10 components from Notopterygii Rhizoma et Radix. Among them， 3 components （citric acid， L-tyrosine， adenosine） were present in all 4 medicinal herbs. Another component （feruloylgluconic acid） still needed to be specifically attributed. A total of 43 prototype components migrating to the blood were identified， including flavonoids， phenols， anthraquinones， phenylpropanoids， alkaloids and triterpenoids. A total of 61 metabolites were identified， predominantly consisting of flavonoids， anthraquinones and phenylpropanoids. The metabolic pathways mainly involved phase Ⅰ metabolic reactions such as demethylation and phase Ⅱ metabolic reactions like sulfation and glucuronidation.

Abstract Modern western medicine typically focuses on treating specific symptoms or diseases, and traditional Chinese medicine (TCM) emphasizes the interconnections of the body’s various systems under external environment and takes a holistic approach to preventing and treating diseases. Phenomics was initially introduced to the field of TCM in 2008 as a new discipline that studies the laws of integrated and dynamic changes of human clinical phenomes under the scope of the theories and practices of TCM based on phenomics. While TCM Phenomics 1.0 has initially established a clinical phenomic system centered on Zhenghou (a TCM definition of clinical phenome), bottlenecks remain in data standardization, mechanistic interpretation, and precision intervention. Here, we systematically elaborates on the theoretical foundations, technical pathways, and future challenges of integrating digital medicine with TCM phenomics under the framework of “TCM phenomics 2.0”, which is supported by digital medicine technologies such as artificial intelligence, wearable devices, medical digital twins, and multi-omics integration. This framework aims to construct a closed-loop system of “Zhenghou–Phenome–Mechanism–Intervention” and to enable the digitization, standardization, and precision of disease diagnosis and treatment. The integration of digital medicine and TCM phenomics not only promotes the modernization and scientific transformation of TCM theory and practice but also offers new paradigms for precision medicine. In practice, digital tools facilitate multi-source clinical data acquisition and standardization, while AI and big data algorithms help reveal the correlations between clinical Zhenghou phenomes and molecular mechanisms, thereby improving scientific rigor in diagnosis, efficacy evaluation, and personalized intervention. Nevertheless, challenges persist, including data quality and standardization issues, shortage of interdisciplinary talents, and insufficiency of ethical and legal regulations. Future development requires establishing national data-sharing platforms, strengthening international collaboration, fostering interdisciplinary professionals, and improving ethical and legal frameworks. Ultimately, this approach seeks to build a new disease identification and classification system centered on phenomes and to achieve the inheritance, innovation, and modernization of TCM diagnostic and therapeutic patterns.

Objective: To construct an index system of public health risk assessment for air pollution emergency, so as to provide a tool of evaluating the public health risks of air pollution emergency. Methods: Index system of public health risk assessment for air pollution emergency was established through literature review and group discussions. The index system was determined through two rounds of Delphi expert consultations involving specialists in environmental health, toxicology, epidemiology, health emergency response, and atmospheric monitoring. The effectiveness of the consultation was evaluated by positive coefficient, authority coefficient and coordination coefficient. The weights of index were determined using a combination weighting method of the expert scoring method and the entropy weight method. Results: Fifteen experts participated in the consultation, including 11 males and 4 females. There were 8 experts with a doctor degree, 6 experts with a master degree, 1 experts with a bachelor degree. A total of 11 experts with senior professional titles, and 4 experts with associate senior professional titles. The average work experience was (23.73±10.48) years. The expert positive coefficients for the two rounds of consultations were 83.33% and 100%, respectively. The expert authority coefficients were 0.794 and 0.811, respectively. The coefficients of variation for the importance, feasibility, and sensitivity scores of each index in the two rounds of comsultations were 0.097 to 0.352, 0.078 to 0.478, 0.115 to 0.388, and 0.049 to 0.133, 0.052 to 0.153, 0.049 to 0.178, respectively. The Kendall's coefficients of concordance were 0.237 and 0.440 (both with P<0.05) for the two rounds of consultations. The constructed assessment index system included "likelihood" "hazard" "vulnerability" "controllability" with comprehensive weights of 0.206 7, 0.059 6, 0.378 1, and 0.355 5, respectively. Among the 13 second indicators, "monitoring capability" had the highest comprehensive weight of 0.192 6. Among the 40 tertiary indicators, "real-time monitoring of atmospheric pollutants" "retrospective evaluation of early forecasting results" "types, quantities, and combined effects of atmospheric pollutants" "exposure modes of the population to atmospheric pollutants" had relatively high comprehensive weights of 0.089 5, 0.043 1, 0.041 1 and 0.040 3, respectively. Conclusion The constructed index system of public health risk assessment for air pollution emergency can be applied to the public health risk assessment for air pollution emergencies.

[摘 要] 目的：构建胆管癌（CCA）患者来源癌组织类器官（PDO）模型，并评估其在检测顺铂与吉西他滨单药及联合用药敏感性中的应用价值。方法：收集4例经病理确诊、术前未行系统治疗的胆管癌患者的肿瘤组织，采用基质胶三维培养法构建PDO模型，并通过苏木精-伊红（H-E）染色法、免疫组化（IHC）法及全外显子组测序（WES）验证其与原发肿瘤的组织学形态及遗传特征一致性。对稳定传代的PDO采用三磷酸腺苷（ATP）法进行药物敏感性检测，拟合剂量-反应曲线计算IC50；并通过Chou-Talalay方法计算联合指数（CI）评估协同作用。结果：成功构建3例可稳定传代超过7代的CCA的PDO模型，H-E和IHC结果显示PDO模型与原代肿瘤组织高度一致，WES显示配对PDO保留了其来源组织约78.4%的遗传变异。3例PDO对顺铂的IC50分别为 （277.50 ± 4.056）、（9.129 0 ± 1.012）及（115.50 ± 3.034） μmol/L；对吉西他滨的IC50分别为（0.581 8 ± 0.020）、（0.012 1 ± 0.008）及（0.048 9 ± 0.004） μmol/L，显示显著个体差异。联合用药实验中，PDO#1表现为显著协同作用（CI = 0.116~0.573）；PDO#2在低剂量出现拮抗，部分中等剂量呈协同；PDO#3在低剂量出现拮抗，在中剂量呈协同，而在高剂量再次出现拮抗（最高组CI ≈ 1.99），表明该药物组合的协同作用仅限定于一个剂量范围内。结论：本研究构建的CCA的PDO模型能再现原代肿瘤组织的形态学及遗传学特征，有效模拟患者肿瘤的药物反应异质性，为临床个性化治疗方案的选择和优化提供了高效、可靠的检测平台。

BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged