Objective: To explore the association between CDKAL1 rs35261542, FAIM2 rs 3205718, and VGLL4 rs 2574704 polymorphisms with childhood obesity and related metabolic phenotypes to provide evidence for personalized prevention and management strategies. Methods: Based on the 2023 Long term Nutritional Health Effects of Early Childhood Nutrition Package Intervention project, the study enrolled 1 078 children aged 5-7 years from four counties in Henan (Songxian and Ruyang countries) and Guizhou (Guiding and Fuquan countries) provinces. Using BMI Z scores, 87 overweight and obese(OVOB) children were selected and matched by sex, age, and BMI Z score with 117 normal weight controls. Participants were further stratified into four metabolic phenotype groups: metabolically healthy normal weight (MHNW, n =51), metabolically unhealthy normal weight (MUNW, n =66), metabolically healthy obesity (MHO, n =31) and metabolically unhealthy obesity (MUO, n =56) based on four conventional cardiometabolic risk factor (CR) criteria. Data were collected through questionnaires, anthropometric measurements, serum biochemical tests, and KASP genotyping. The distribution of three genetic polymorphisms ( CDKAL1 rs35261542, FAIM2 rs3205718, VGLL4 rs 2574704) across metabolic subgroups was analyzed. Multivariate Logistic regression models assessed associations between these polymorphisms and obesity/metabolic phenotypes. Results: Multivariate Logistic regression analysis showed that Homozygous mutant AA genotype of CDKAL1 rs 35261542 was positively associated with OVOB( OR =3.63), MHO ( OR =11.04), MUO ( OR = 4.88 ) ( P <0.05). Homozygous TT genotype of FAIM2 rs 3205718 increased OVOB risk ( OR =4.44, P <0.05) but showed no association with metabolic phenotypes ( P >0.05). Homozygous mutant TT of VGLL4 rs 2574704 reduced the risks of MHO and MUO ( OR = 0.30, 0.24， P <0.05). Cumulative genetic effects analysis demonstrated carriers of 1 or 2 risk genotypes of rs 35261542 and rs 3205718 had progressively higher OVOB risk ( OR =2.53, 20.79), and the combination of rs 35261542 and rs 2574704 increased risks for both MHO ( OR =8.50) and MUO ( OR =5.00) ( P <0.05). Conclusions The AA genotype of rs 35261542 ( CDKAL1 ) positively correlates with childhood obesity and metabolic abnormalities. The TT genotype of rs 3205718 ( FAIM 2) increases obesity risk but not metabolic phenotypes. The TT genotype of rs 2574704 ( VGLL 4) shows protective effects against metabolic dysfunction. Risk genotypes exhibit dosedependent cumulative effects on obesity and metabolic outcomes.

In order to solve the problems of difficult test, high cost and long cycle in the development of large-scale airborne negative pressure isolation system, the simulation analysis of negative pressure response characteristics is carried out around various aviation conditions such as aircraft ascending, leveling and descending, especially rapid decompression, based on the computational fluid dynamics (CFD) method. The results showed that the isolation cabin could achieve -50 Pa pressure difference environment and form a certain pressure gradient. The exhaust air volume reached the maximum value in the early stage of the aircraft's ascent, and gradually decreased with the increase of altitude until it was level flying. In the process of aircraft descent, the exhaust fan could theoretically maintain a pressure difference far below -50 Pa without working; Under the special condition of rapid pressure loss, it was difficult to deal with the rapid change of low pressure only by the exhaust fan, so it was necessary to design safety valve and other anti-leakage measures in the isolation cabin structure. Therefore, the initial stage of aircraft ascent is the key stage for the adjustment and control of the negative pressure isolation system. By controlling the exhaust air volume and adjusting parameters, it can adapt to the change of low pressure under normal flight conditions, form a relatively stable negative pressure environment, and meet the needs of biological control, isolation and transport.
Aircraft ; Computer Simulation ; Aviation/instrumentation* ; Humans ; Hydrodynamics ; Air Pressure ; Equipment Design ; Pressure

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

ObjectiveThis study aims to develop a prediction model for the compatibility of Chinese medicinal pairs based on Graph Convolutional Networks （GCN）， named HC-GCN. The model integrates the properties of herbs with modern pharmacological mechanisms to predict pairs with specific therapeutic effects. It serves as a demonstration by applying the model to predict and validate the efficacy of blood-activating herb pairs. MethodsThe training dataset for herb pair prediction was constructed by systematically collecting commonly used herb pairs along with their characteristic data， including Qi， flavor， meridian tropism， and target genes. Integrating traditional characteristics of herb with modern bioinformatics， we developed an efficacy-oriented herb pair compatibility prediction model （HC-GCN） using graph convolutional networks （GCN）. This model leverages machine learning to capture the complex relationships in herb pair compatibility， weighted by efficacy features. The performance of the HC-GCN model was evaluated using accuracy （ACC）， recall， precision， F1 score （F1）， and area under the ROC curve （AUC）. Its predictive effectiveness was then compared to five other machine learning models： eXtreme Gradient Boosting （XGBoost）， logistic regression （LR）， Naive Bayes， K-nearest neighbor （KNN）， and support vector machine （SVM）. ResultsUsing herb pairs with blood-activating effects as a demonstration， a prediction model was constructed based on a foundational dataset of 46 blood-activating herb pairs， incorporating their Qi， flavor， meridian tropism， and target gene characteristics. The HC-GCN model outperforms other commonly used machine learning models in key performance metrics， including ACC， recall， precision， F1 score， and AUC. Through the predictive analysis of the HC-GCN model， 60 herb pairs with blood-activating effects were successfully identified. Among of these potential herb pairs， 44 include at least one herb with blood-activating effects. ConclusionIn this study， we established an efficacy-oriented compatibility prediction model for herb pairs based on GCN by integrating the unique characteristics of traditional herbs with modern pharmacological mechanisms. This model demonstrated high predictive performance， offering a novel approach for the intelligent screening and optimization of traditional Chinese medicine prescriptions， as well as their clinical applications.

Objective To investigate effect of cassava RS3 resistant starch(Ce-RS3)on serum homocysteine(Hcy)level in patients with atherosclerotic cerebral infarction(ACI)during the recovery period.Methods A total of 55 patients with ACI at the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from October 2023 to October 2024 were selected as subjects.They were devieded into observation group(n=28)and control group(n=27)using a random number table.The control group received atorvastatin calcium,phospholipids,and aspirin,while the observation group received atorvastatin calcium,phospholipids,aspirin,and Ce-RS3.After 12 weeks of treatment,homocysteine(Hcy)levels,carotid plaque diameter,National Institutes of Health stroke scale(NIHSS)scores,Barthel index(BI)scores,and traditional Chinese medicine(TCM)syndrome scores were compared between two groups.Results After treatment,the serum Hcy levels decreased and carotid plaque size reduced in both groups,with the NIHSS scores and TCM syndrome scores also decreased,and observation group was lower than control group(P＜0.05).After treatment,the BI score increased,with observation group higher than control group(P＜0.05).Conclusion The use of Ce-RS3 in the recovery phase of patients with ACI can effectively improve neurological function and enhance treatment efficacy.

Objective:To explore the clinical features and genetic characteristics of three patients with Infantile liver failure syndrome type 2 (ILFS2).Methods:Three children who were diagnosed with ILFS2 at the Children′s Hospital Affiliated to Zhengzhou University from February 2023 to February 2024 were selected as the study subjects. Clinical data of the children were collected. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing (WES). Candidate variants of the NBAS gene were verified by Sanger sequencing. This study was approved by the Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No. 2024-k-069). Results:The three children had presented with fever-triggered recurrent acute liver failure. All of them were found to harbor compound heterozygous variants of the NBAS gene, including c. 3596G>A and c.1181A>T in child 1, c.2617C>T and c. 2T>C in child 2, and c. 3596G>A and c. 2817_2818insT in child 3. Among these, the c. 1181A>T and c. 2817_2818insT variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), they were respectively classified as variants of uncertain significance (PM2_Supporting+ PM3+ PP3) and pathogenic (PVS1+ PM2_Supporting+ PM3). Conclusion:Combined with the patient′s clinical phenotype, the compound heterozygous variants of the NBAS gene probably underlay the pathogenesis of ILFS2 in the three children. For children with fever-related acute liver failure of unknown causes, the possibility of this disease should be suspected, and genetic testing may facilitate the diagnosis. Early diagnosis and timely intervention can significantly improve the prognosis. Discoveries of the c. 1181A>T and c. 2817_2818insT variants have enriched the mutational spectrum of the NBAS gene.

This article reports the diagnosis and treatment of a patient with diffuse large B-cell lymphoma (DLBCL) initially manifested as acquired von Willebrand syndrome (AvWS), along with a literature review. The patient, a 22-year-old male, was diagnosed with hereditary von Willebrand disease at the initial stage due to repeated mucosal bleeding, and was later diagnosed with DLBCL (non germinal center type, Ann Arbor stage Ⅳ) due to chest wall mass. Through chemotherapy combined with autologous hematopoietic stem cell transplantation and zebutinib maintenance therapy, the patient achieved sustained complete remission, and the coagulation function returned to normal. This case provides an important reference for the diagnosis and treatment of lymphoma associated AvWS, and highlights the importance of early recognition of basic diseases.

This paper analyzes current issues in general practitioners (GP) education (e.g., inadequate systems, faculty shortages, misaligned training with community needs, low workforce attractiveness) and proposes strategies for reform in the new development era. Key recommendations include: strengthening academic discipline building in general practice within medical universities; innovating curricula to integrate prevention with treatment and emphasize practical skills; leveraging institutional resources to foster clinician-educator-researcher roles; tailoring training pathways to regional contexts; deepening collaboration between medical education and healthcare delivery systems; and building a robust lifelong learning framework for GPs. Furthermore, the paper details the comprehensive reform initiatives undertaken by Guangzhou Medical University (GMU). These include establishing integrated education platforms spanning university, hospital, and community settings. GMU′s experience offers valuable insights for enhancing GP training quality and scalability in China.

Objective:To comprehensively evaluate the cost and cost-effectiveness of the colorectal cancer screening program for key populations in Zhejiang Province from 2020 to 2022, and provide reference for optimizing colorectal cancer screening strategies.Methods:Based on the colorectal cancer screening program for key populations in Zhejiang Province from 2020 to 2022, parameters such as initial screening positivity rates, colonoscopy compliance rates, and detection rates for colorectal-related lesions among residents aged 50-74 were obtained. Questionnaire surveys assessed program costs and direct medical costs associated with colorectal cancer-related lesions. From a health system perspective, the cost-effectiveness ratio was calculated using the Early Detection Cost Index (EDCI) and the cost per detected case, followed by sensitivity analysis.Results:A total of 5 881 364 screenings were completed from 2020 to 2022. The initial screening positive rate (positive for either questionnaire or fecal immunochemical testing ) was 16.83%, with a colonoscopy compliance rates of 33.96% ( n=336 150). Detection rates for non-advanced adenomas, advanced adenomas, and colorectal cancer were 24.83% ( n=83 453), 11.91% ( n=40 033), and 1.01% ( n=3 397), respectively. Initial screening positivity rates and detection rates increased with age, while colonoscopy compliance rates decreased with age. Cost analysis showed a total project investment of 378 730 457 yuan, with initial screening costing 146 633 103 yuan (38.72%) and diagnostic colonoscopy 232 097 354 yuan (61.28%). The average cost per initial screening and diagnostic colonoscopy was 24.93 and 690.46 yuan, respectively. Direct medical costs for non-advanced adenomas, advanced adenomas, and colorectal cancer at stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ were 4 921, 8 380, 42 547, 62 156, 66 720, and 72 334 yuan, respectively. Cost-effectiveness analysis indicated that screening needed to detect one case of colorectal cancer required 1 731 people and cost 111 490 yuan; the cost per detected advanced adenoma was 9 460 yuan, and the EDCI was 0.09. Costs decreased with increasing age per detected colorectal lesion. Sensitivity analysis showed that increasing colonoscopy compliance could reduce the cost-effectiveness ratio. Conclusions:The colorectal cancer screening program for key populations in Zhejiang Province demonstrates cost-effectiveness. Improving colonoscopy compliance can enhance overall screening effectiveness and economic benefits.