Objective: To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation. Methods: Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method. Results: Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years. Conclusion Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.

Objective: To investigate the barrier membrane fixation performance and enhanced guided bone regeneration (GBR) capability of a thermosensitive adhesive containing bioactive glass nanoparticles in order to provide a novel solution for membrane fixation during GBR procedures. Methods: M2NP@BGN (methoxyethyl acrylate-co-N-isopropylacrylamide-co-protocatechuic acid@Bioactive glass nanoparticle), a thermosensitive adhesive, was synthesized via free radical polymerization by compositing methoxyethyl acrylate, N-isopropylacrylamide, and protocatechuic acid into a basic adhesive that was modified with bioactive glass nanoparticle (BGN). The successful fabrication of basic adhesive M2NP was characterized by attenuated total reflection-Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The thermosensitive adhesive M2NP@BGN (BGN concentration of 1 mg/mL) was characterized by scanning electron microscopy and a rheometer. By adjusting the BGN concentration (0.1 mg/mL, 0.5 mg/mL, 1 mg/mL, and 2 mg/mL), the adhesive and mechanical strengths were investigated with a universal testing machine. Biocompatibility was evaluated with a cell counting kit-8 assay and hemolysis test to identify the optimal formulation. The optimal material’s extract was co-cultured with mouse bone marrow mesenchymal stem cells, and its osteogenic activity was examined in vitro by quantitative real-time PCR, alkaline phosphatase, and alizarin red S staining. The rat mandibular defect model was established, filled with bone graft, and divided into 3 groups based on membrane fixation method: M2NP@BGN (BGN concentration of 1 mg/mL) fixation group (M2NP@BGN), titanium nail fixation group (Nail), and unfixed control group (Negative). Bone regeneration was analyzed after 8 weeks by micro computed tomography and histological staining. Results: M2NP@BGN (BGN concentration of 1 mg/mL) was successfully synthesized and demonstrated rapid gelation under warm, humid conditions. The adhesive with a BGN concentration of 1 mg/mL exhibited the highest adhesive strength (P < 0.001) and significantly enhanced mechanical strength (P < 0.001) under 37℃ wet conditions. All formulations showed excellent biocompatibility, with cell viability > 80% and hemolysis ratio < 5%. M2NP@BGN (BGN concentration of 1 mg/mL) significantly upregulated the expression of Runx2 and Col I (P < 0.001) and enhanced the activity of osteogenic differentiation markers (P < 0.05). In the animal model, the M2NP@BGN group (BGN concentration of 1 mg/mL) achieved significantly higher bone volume fraction and better bone maturity compared to the negative and nail groups (P < 0.05). Conclusion M2NP@BGN (BGN concentration of 1 mg/mL) combines excellent wet adhesion with potent osteogenic activity, enhances the bone augmentation efficacy of membranes, and presents a novel fixation strategy with significant clinical translation potential for GBR therapy.

[摘 要] 目的：探究着丝粒蛋白M（CENPM）在脑胶质瘤中的表达特征、临床预后价值及其对肿瘤恶性生物学行为的调控机制，为脑胶质瘤的精准治疗提供潜在靶点。方法：基于中国胶质瘤基因组图谱（CGGA）和癌症基因组图谱（TCGA）数据库分析CENPM在胶质瘤中的表达及其与患者临床病理特征和预后的相关性。通过基因本体论（GO）分析、京都基因与基因组百科全书（KEGG）富集分析和单细胞转录组分析探索CENPM的生物学功能和作用机制。WB法检测CENPM在胶质瘤细胞（LN-18、LN-229、U-138MG、U-251MG）和正常胶质细胞（HEB）中的表达；构建CENPM敲低细胞后，通过CCK-8、集落形成、Transwell和划痕实验评估恶性表型改变。结果：CENPM在WHO高级别胶质瘤中呈高表达（P < 0.05），与肿瘤恶性程度正相关。高表达组患者总体生存期显著短于低表达组（P < 0.01），Cox回归证实CENPM是影响胶质瘤患者预后的独立危险因素（P < 0.05）。功能富集分析结果显示CENPM相关基因主要富集于细胞周期调控、PI3K-Akt通路和免疫相关过程。单细胞分析结果显示CENPM主要在CD8⁺ T细胞高表达，并通过PTN-PTPRZ1/NCL配受体调控细胞通信。体外实验证实CENPM在胶质瘤细胞表达高于正常胶质细胞（LN-18：P < 0.01，LN-299：P < 0.05）；敲低CENPM显著抑制迁移（P < 0.05），但增强集落形成，提示其在肿瘤进展中的双重调控作用。结论：CENPM作为胶质瘤独立预后危险因子，通过调控细胞周期、PTN通路和免疫微环境驱动肿瘤进展，其差异化调控机制（抑制迁移、促进增殖）具有潜在的临床转化价值，可作为分子分型和靶向治疗候选标志物。

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Changes in biliary system dynamics are closely associated with the development and progression of related diseases， and with the in-depth interdisciplinary research on medical sciences and engineering， the value of biliary biomechanics in clinical diagnosis and treatment has become increasingly important. This article systematically reviews the characteristics of changes in biliary system dynamics under pathological conditions and explores the application value of technologies such as biliary manometry， hydrodynamic evaluation， and experimental simulation in clinical diagnosis， treatment， and postoperative management， so as to deepen the understanding of existing diagnostic and therapeutic modes and provide new ideas for promoting precision medicine for biliary tract diseases.

The digitization of traditional Chinese medicine (TCM) has generated vast amounts of data. However, these data are characterized by significant heterogeneity and complex semantic structures, posing substantial challenges for systematic integration and intelligent analysis, and limiting its potential for modern clinical and computational research. To address the challenges posed by the high heterogeneity and complex structure in TCM data, we designed and developed the TCM Data Hub platform, which is powered by the YiYuan large language models (LLMs). This platform aims to enhance intelligent data processing capabilities and unlock the potential for clinical application of TCM data through systematic integration and efficient utilization, thereby bridging the gap between traditional knowledge and modern computational research. This study first analyzed the heterogeneity and complexity of TCM information with respect to data types, structures, and semantics. A standardized data framework was constructed to enhance data integration and interoperability. Based on the TCM Intelligent Computing Platform of the China Academy of Chinese Medical Sciences, we trained the YiYuan LLMs to acquire domain-specific semantic understanding of TCM, thereby improving the platform’s comprehension of specialized terminology and knowledge systems. Leveraging the natural language processing capabilities of the LLMs, we developed a human-in-the-loop data processing system to enable efficient extraction, cleansing, and structured organization of TCM data. In addition, utilizing Vue and Java technologies, we developed multiple LLM-powered intelligent agents and systems, including a human-in-the-loop data processing system, as well as automated prescription mining and network pharmacology analysis agents. Task-specific agents tailored to TCM data processing were developed to enhance the model’s effectiveness in clinical knowledge discovery. System functionality and platform infrastructure were implemented using Java and Vue technologies.The TCM Data Hub platform has completed system construction and core functionality implementation. It supported integrated management and efficient access to 8 key types of TCM data: prescriptions, materia medica, ingredients, targets, diseases (Western medicine), diseases (TCM), syndromes, and therapeutic methods. The human-in-the-loop data processing system achieved an accuracy of 95.34% in structuring TCM data and supported annotation for data requiring manual labeling. The intelligent agent-driven big-data analytics module enabled 1-click, end-to-end workflows for TCM prescription mining, herb-syndrome association analysis, network pharmacology, and molecular biology research, completing a full data mining task in approximately 30 minutes. Users can interact with and manipulate data through a visual front-end interface. The system demonstrated stable performance, strong scalability, and a user-friendly experience. Empowered by the YiYuan LLMs, the TCM Data Hub platform significantly improves the accessibility, usability, and intelligence of TCM data. It effectively bridges traditional TCM knowledge with modern intelligent technologies, providing robust data support and intelligent tools for TCM research and clinical applications.

Objective To explore the application value of metagenomic next-generation sequen-cing(mNGS)technology in the diagnosis of spinal tuberculosis.Methods A total of 129 patients with suspected spinal tuberculosis admitted from January 2021 to January 2023 were selected as study subjects.Lesion tissue samples were collected intraoperatively and subjected to conventional microbio-logical testing(CMT),Mycobacterium tuberculosis DNA(MTB-DNA)amplification testing,and mNGS testing.The diagnostic efficacy of different testing methods was compared using results of com-prehensive clinical diagnosis as the gold standard.Results Among 129 patients,101(78.29％)were confirmed to have spinal tuberculosis,and 28(21.71％)had other spinal infections.Using clinical results as the diagnostic gold standard,the sensitivity of mNGS was 94.06％(95/101),and specificity was 89.29％(25/28);the sensitivity of MTB-DNA amplification was 90.10％(91/101),and specificity was 89.29％(25/28);the sensitivity of CMT was 86.14％(87/101),and specifici-ty was 85.71％(24/28).Compared with MTB-DNA amplification and CMT,mNGS showed the highest consistency with clinical results,and its consistency in detecting different lesion sites was also optimal,with statistically significant differences(P＜0.05).Conclusion mNGS testing has high diagnostic value for spinal tuberculosis and can provide a reference for clinical diagnosis,thereby guiding clinical decision-making.

Objective:To investigate the protective effects and underlying mechanisms of carbon monoxide-releasing molecule-3 (CORM-3) against hypoxia-reoxygenation-induced injury in Caco-2 cells.Methods:A hypoxia-reoxygenation injury model was established in Caco-2 cell monolayers by culturing cells under glucose-free, serum-free hypoxic conditions (1% O 2) for 8 hours, followed by reoxygenation with glucose and serum restoration for 4 hours. Experimental groups included: blank control (Control), hypoxia-reoxygenation model (HR), and HR with 300 μmol/L (HR_C1), 400 μmol/L (HR_C2), or 500 μmol/L CORM-3 (HR_C3), plus HR with 500 μmol/L inactive iCORM-3 (HR_iC). CORM-3/iCORM-3 was administered during the hypoxic phase. Assessments included: cell viability (CCK-8 assay), apoptosis/necrosis rates (flow cytometry), monolayer permeability (sodium fluorescein), tight junction protein distribution (ZO-1, Occludin, Claudin2 immunofluorescence), protein expression (Western blot), and transcriptomic analysis of differentially expressed genes. Results:Compared to controls, HR group showed significantly reduced cell viability ( P<0.05), increased apoptosis/necrosis rates, elevated sodium fluorescein permeability (both P<0.05), disrupted tight junction structure, decreased Occludin and increased Claudin2 expression (both P<0.05). CORM-3 treatment significantly improved viability ( P<0.05), reduced apoptosis/necrosis rates and permeability (both P<0.05, concentration-dependent), mitigated tight junction damage, showed a non-significant trend toward increased Occludin, and significantly decreased Claudin2 expression ( P<0.05). Transcriptomics identified 25 differentially expressed genes, with KEGG analysis revealing 14 significant pathways (including MAPK signaling, inflammatory bowel disease, and cellular senescence). GO analysis highlighted immune-inflammatory responses and cell membrane barrier components, with TGFB3 as the primary immune-related gene. Conclusions:CORM-3 effectively reduces apoptosis/necrosis, preserves tight junctions, and mitigates hypoxia-reoxygenation injury in Caco-2 cells, potentially through MAPK signaling regulation and immune-inflammatory response modulation.

Objective To investigate the levels of radionuclides in food in Beijing, China, and assess the committed effective dose to local residents from food intake. Methods From 2021 to 2022, a total of 65 food samples across 7 categories were collected in Beijing. The activity concentrations of radionuclides, including ¹³⁷Cs, ²¹⁰Pb, ²³⁸U, ²²⁸Ra, ²²⁶Ra, ⁴⁰K, ⁹⁰Sr, ²¹⁰Po, ³H and ¹⁴C, were measured using gamma spectrometry and radiochemical methods. By combining the monitoring results with dietary consumption data of Beijing residents and the internal dose coefficients for Chinese reference adult phantom, the committed effective dose was estimated. Results The levels of radionuclides in food in Beijing were within the normal background range, consistent with related surveys in China and abroad, with activity concentrations below national standard limits. No significant differences were found in the activity concentrations of ¹³⁷Cs, ²³⁸U, ²²⁸Ra, ²²⁶Ra and ⁴⁰K between food samples collected from key areas and those from control areas (P > 0.05). The committed effective doses calculated according to internal dose coefficients for Chinese reference adult male phantom and GB 18871-2002 were 0.26 mSv and 0.19 mSv, respectively. Based on the Chinese reference adult male phantom, the majority of the committed effective dose was attributed to ²¹⁰Pb (45.1%), ²²⁸Ra (37.1%), ²¹⁰Po (12.3%), and ²²⁶Ra (4.7%). Conclusion The levels of radionuclides in food in Beijing fluctuated within the background range, resulting in a low radiation dose burden to the population.

This study aims to investigate the characteristics of chitosan-loaded miR-146a nanoparti-cles and explore their protective effect against acute liver cell injury induced by LPS in vitro.Galac-tosylated arginine chitosan(GCA)nanoparticles were successfully synthesized,prepared and used to further prepare GCA-miR-146a nanoparticles with different mass ratios by ion cross-linking method.The binding efficiency of miR-146a by GCA nanoparticles was detected by gel retardation experiment.Particle size,morphology and potential were observed and detected by transmission e-lectron microscopy and Zetasizer NanoZS90 respectively.The cytotoxicity of GCA nanoparticles on HepG2 cells was detected by CCK-8 kit.Cellular uptake was assayed by fluorescence microscopy to select the optimum ratio for the further study.The LPS induced acute liver cell injury were evalua-ted by real-time fluorescence quantitative PCR.The results showed that the mass ratio of GCA-miR-146a was 5∶1.Encapsulation efficiency and drug loading efficiency of the nanoparticles reached 97.11％and 20.08％,respectively.The 100 nm nanoparticles with 1.15 mV surface charge showed uniform morphology.The GCA-miR-146a nanoparticles had no cytotoxicity and had high transfection efficiency on HepG2 cells.The study demonstrated that GCA-miR-146 ananoparticles could significantly increase the expression of miR-146a in HepG2 cells and reduce the mRNA ex-pression levels of IL-6 and TNF-α in vitro.The prepared GCA nanoparticles loaded with miR-146a had high loading efficiency and could protect LPS-induced acute liver cell injury in vitro.