ObjectiveTo explore the effects of Jingui Shenqiwan （JSW） and Liuwei Dihuangwan （LDW） on the reproductive ability and brain function of normal mice and compare the actions of the two medications. MethodsSeven groups of female and male mice were divided at a ratio of 2∶1. Except for the control group， the other six groups were as follows： a group of both males and females receiving JSW （3.0 g·kg^-1）， a group of both males and females receiving LDW （4.5 g·kg^-1）， a group of males receiving water and females receiving JSW， a group of males receiving water while females receiving LDW， a group of females receiving water while males receiving JSW， and a group of females receiving water while males receiving LDW. Each group was administered the drug for 14 days and then caged together at a 2∶1 （female∶male） ratio to detect the number of pregnant mice and calculate the pregnancy rate. Pregnant mice continued receiving the drug until they naturally gave birth， which was followed by the observation of newborn mice， calculation of their average number， and the measurement of the offspring's preference for sugar water and neonatal recognition index. At the end of the experiment， the weights of the thymus and spleen were measured to calculate the organ coefficients， and mRNA or protein expression was analyzed in the brain and testes or ovaries. A 1% sucrose solution was used to examine the euphoria of their brain reward systems， while novel object recognition test （NOR） was applied to assess their memory capabilities. mRNA expression was detected using real-time quantitative polymerase chain reaction （Real-time PCR） assay， and protein expression was analyzed with Western blot. ResultsCompared with the control group， oral administration of JSW to both male and female mice for 14 days significantly increased the pregnancy rate of female mice on day 2 after being caged together （P<0.05）， while LDW showed a trend but no statistical significance. Additionally， compared with the control group， JSW could upregulate the gene expression of gonadotropin-releasing hormone （GnRH） in the thalamus， as well as reproductive stem cell factor （SCF） and tyrosine kinase receptor （c-Kit） in the testes and reproductive stem cell marker mouse vasa homologue （MVH） in the ovaries， upregulate the expression of proteins influencing neuronal functional activity， such as brain-derived neurotrophic factor （BDNF）， in hippocampal neurons （P<0.05）， and enhance sucrose preference in male mice （P<0.05）. Compared with the control group， JSW significantly increased sucrose preference and novel object recognition index in offspring mice （P<0.05）， which was related to the upregulation of hippocampal dopamine D1 receptor （D1R） and N-methyl-D-aspartate receptor （Nmdar） gene expression. Compared with the control group， both JSW and LDW could upregulate the protein expression of glucocorticoid receptor （GR）， BDNF， and tyrosine kinase receptor B （TrkB） in the hippocampus of offspring mice （P<0.05）. ConclusionJSW significantly enhances the reproductive ability of normal mice， which is not only related to the release of gonadotropin but also associated with its regulation of brain function. Additionally， JSW has a certain regulatory effect on the brain function of the offspring mice.

This paper outlines the development of artificial intelligence （AI） and its applications in traditional Chinese medicine （TCM） research， and elucidates the roles and advantages of large language models， knowledge graphs， and natural language processing in advancing syndrome identification， prescription generation， and mechanism exploration. Using spleen-stomach diseases as an example， it demonstrates the empowering effects of AI in classical literature mining， precise clinical syndrome differentiation， efficacy and safety prediction， and intelligent education， highlighting an upgraded research paradigm that evolves from data-driven and knowledge-driven approaches to intelligence-driven models. To address challenges related to privacy protection and regulatory compliance in cross-institutional data collaboration， a "trusted federated evidence-based analysis platform for TCM spleen-stomach diseases" is proposed， integrating blockchain-based smart contracts， federated learning， and secure multi-party computation. The deep integration of AI with privacy-preserving computing is reshaping research and clinical practice in TCM spleen-stomach diseases， providing feasible pathways and a technical framework for building a high-quality， trustworthy TCM big-data ecosystem and achieving precision syndrome differentiation.

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.

[摘 要] 目的：探究肌动蛋白样蛋白6A（ACTL6A）通过调控铁死亡参与弥漫大B细胞淋巴瘤（DLBCL）细胞多柔比星（DOX）耐药的机制。方法：培养亲本DLBCL细胞SU-DHL-4与耐药细胞SU-DHL-4/DOX，qPCR和WB法检测ACTL6A表达变化；通过转染携带靶向ACTL6A干扰序列（sh-ACTL6A）及其阴性对照（sh-NC）的质粒，构建敲减ACTL6A的SU-DHL-4/DOX，qPCR和WB法检测转染后细胞中ACTL6A、铁死亡相关蛋白谷胱甘肽过氧化酶4（GPX4）、溶质载体家族7成员11（SLC7A11）、长链酰基辅酶A合成酶4（ACSL4）的表达水平，染色质免疫沉淀（ChIP）、双萤光素酶报告基因实验验证ACTL6A与GPX4间的靶向结合与调控作用。将SU-DHL-4/DOX细胞分为对照组、sh-NC组、sh-ACTL6A组、sh-NC + oe-GPX4组和sh-ACTL6A + oe-GPX4组，用转染试剂将相应质粒转染至细胞中，qPCR和WB法检测各组细胞中ACTL6A和GPX4表达水平，CCK-8法检测不同浓度DOX处理后各组细胞存活率，FerroOrange探针检测各组细胞中亚铁离子（Fe2+）水平，Liperfluo探针检测各组细胞中脂质过氧化物水平，DCFH-DA探针检测各组细胞中活性氧（ROS）水平，比色法检测各组细胞中谷胱甘肽（GSH）和丙二醛（MDA）含量。结果： 与SU-DHL-4细胞相比，SU-DHL-4/DOX细胞中ACTL6A mRNA和蛋白均呈高表达（均P < 0.05）；ACTL6A与GPX4间存在靶向结合关系；敲减ACTL6A后SU-DHL-4/DOX细胞中ACTL6A和GPX4 mRNA及其蛋白表达水平均明显下降（均P < 0.05），表明ACTL6A可调控GPX4的表达；敲减ACTL6A可抑制SU-DHL-4/DOX细胞的存活率，促进细胞内Fe2+、脂质过氧化物、ROS、MDA的生成，抑制GSH生成（均P < 0.05）；而在敲减ACTL6A的同时过表达GPX4可上调SU-DHL-4/DOX细胞中GPX4的mRNA及其蛋白表达水平（均P < 0.05），并提高细胞存活率，抑制细胞内Fe2+、脂质过氧化物、ROS、MDA的生成，并增加GSH生成（均P < 0.05）。结论：ACTL6A在DOX耐药DLBCL细胞中高表达，通过调控GPX4表达抑制铁死亡，促进DLBCL细胞耐药。

The crystalline lens of the eye is recognized as one of the most radiosensitive tissues in the human body. While the International Commission on Radiological Protection (ICRP) has classified ionizing radiation (IR)-induced cataracts as a tissue reaction (deterministic effect) and subsequently reduced the occupational equivalent dose limit for the lens, significant uncertainties remain regarding the precise dose threshold and the complex biological pathways driving lens opacification. This review provides a comprehensive synthesis of current knowledge concerning radiation-induced lens damage, integrating epidemiological exposure characteristics with dose-response modeling and mechanistic molecular insights. First, we analyze exposure characteristics through four epidemiological dimensions: dose, time, space, and population. Clinical evidence suggests that radiation cataracts—particularly posterior subcapsular opacities—exhibit a distinct latency period that is inversely correlated with dose. We highlight that risk is not confined to acute high-dose scenarios (such as in atomic bomb survivors) but is increasingly relevant in chronic low-dose occupational settings (e.g., interventional radiology) and medical diagnostics (e.g., CT scans). Crucially, individual susceptibility is modified by genetic background, age, and environmental co-factors, complicating risk assessment. Second, we critically examine the dose-effect relationship. Although the ICRP suggests a threshold of 0.5 Gy, emerging data challenge the traditional threshold model, with some studies advocating for a linear non-threshold (LNT) relationship. We further discuss the critical roles of radiation quality and dose rate. High linear energy transfer (LET) radiation demonstrates a significantly higher relative biological effectiveness (RBE) for cataractogenesis compared to low-LET radiation. Paradoxically, and unlike many other tissues, the lens may exhibit an “inverse dose-rate effect,” where fractionated or protracted exposures potentially enhance biological damage—a finding that challenges classical radiobiological paradigms. Third, drawing upon the “cataractogenic load” hypothesis and the unique physiological constraints of the lens, this review elucidates the multidimensional molecular mechanisms driving radiation-induced opacification. Key mechanisms include four aspects. (1) DNA damage and repair: IR induces DNA double-strand breaks (DSBs) that, due to the lens’ limited repair capacity (modulated by genes such as ATM, Ptch1, and Ercc2), lead to the accumulation of damage. (2) Antioxidant defense system: dysfunction of the Nrf2/HO-1 antioxidant axis results in redox imbalances, triggering NF-κB-mediated inflammation and protein aggregation. (3) Cell proliferation and senescence: IR disrupts cell cycle regulation, causing a dichotomy of effects—driving premature senescence in some cell populations (evidenced by ATM nuclear foci) while inducing aberrant proliferation via growth factor upregulation (FGF2, TGFβ) in others. (4) Cell migration and adhesion: activation of the Wnt/β‑catenin pathway and alterations in the E-cadherin complex promote the abnormal migration of epithelial cells to the posterior capsule, a hallmark of radiation-induced cataracts. In conclusion, radiation-induced cataractogenesis is a multifactorial process in which genetic susceptibility and environmental stressors converge to overwhelm the lens’ homeostatic thresholds. Future research must prioritize longitudinal cohort studies to refine dose thresholds and employ multi-omics approaches to map the crosstalk between DNA damage responses and matrix remodeling. Establishing a robust mechanistic model is essential for developing targeted radioprotective strategies and optimizing radiation protection standards for occupational and medical safety.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

ObjectiveTo analyze the potential risk of infection sources during the consolidation phase of schistosomiasis elimination in Lushan County (a mountainous region) of Sichuan Province, and to provide prevention and control strategies for the consolidation of schistosomiasis elimination achievements in mountainous areas. MethodsIn 2024, one to two villages with historically severe epidemics were selected in the heavily endemic townships of Lushan County as monitoring sites to carry out monitoring for wild animal feces, domestic animals, wild rats, free-roaming dogs, local residents, and mobile populations. Follow-up monitoring for previously infected individuals was carried out in Caoping Village of Siyan Town. Statistical analyses were performed to assess the risks associated with infection sources. ResultsA total of 115 fecal samples from 13 species of wildlife were incubated, with all negative. Blood tests were conducted on 492 cattle, 34 sheep, and 261 dogs, with all negative. A total of 2 520 rodent traps were set, capturing 67 wild rats with a capture rate of 2.66%, and no positive wild rats were found upon dissection. The activity track of 25 loose dogs was 2 212 meters at the farthest, 236 meters at the nearest, and 744 meters on average. a total of 68 wild droppings (all dog feces) were picked up along the way, with all negative. Blood tests were performed on 3 540 local population, yielding 39 blood-positive cases with a blood positive rate of 1.1%. Fecal examinations were conducted on 193 individuals, with all negative. A total of 315 blood tests were performed on the mobile population, identifying 1 positive case with a blood-positive rate of 0.32%. One person received a fecal examination, with zero positive. A follow-up survey of 505 previously infected individuals revealed 5 blood-positive cases, with a positive rate of 0.99%. Fecal examinations were conducted on 15 individuals, with all negative. ConclusionIn this investigation, no local or imported sources of schistosomiasis transmission were found. However, there was a wide variety and a large number of potential sources of infection in the local area. It is necessary to actively explore regional monitoring models for schistosomiasis elimination flexibly adjust prevention and control strategies according to local conditions, achieve precise prevention and control, and consolidate the achievements of elimination.

Objective To develop and validate a machine learning model based on preoperative clinical characteristics, laboratory indices, and radiological features for the non-invasive prediction of spread through air spaces (STAS) in patients with early-stage lung adenocarcinoma. Methods Preoperative data from patients with early-stage lung adenocarcinoma who underwent surgical resection at Northern Jiangsu People's Hospital between January 2020 and August 2025 were retrospectively collected. The data included clinical characteristics, laboratory indices, and radiological features. Patients were divided into a STAS-positive and a STAS-negative group based on postoperative pathological findings. The dataset was randomly split into a training set and a testing set at a 7 : 3 ratio. Feature variables were selected using the maximum relevance and minimum redundancy (mRMR) algorithm and the least absolute shrinkage and selection operator (LASSO) regression. Five machine learning models were constructed: logistic regression (LR), random forest (RF), support vector machine (SVM), light gradient boosting machine (LightGBM), and extreme gradient boosting (XGBoost). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). The shapley additive explanations (SHAP) method was employed to interpret the optimal prediction model. Results A total of 377 patients were included, comprising 177 (46.9%) males and 200 (53.1%) females, with a mean age of (63.31±9.73) years. There were 261 patients in the training set and 116 patients in the testing set. In the training set, statistically significant differences were observed between the STAS-positive group (n=130) and STAS-negative group (n=131) across multiple features, including age, sex, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), clinical T stage, and maximum solid component diameter (P<0.05). A final set of 10 feature variables was selected by combining mRMR and LASSO regression, and five machine learning models (LR, RF, SVM, LightGBM, XGBoost) were developed. The XGBoost model demonstrated optimal performance in both the training and testing sets, achieving AUCs of 0.947 [95%CI (0.920, 0.975)] and 0.943 [95%CI (0.894, 0.993)], respectively. DCA indicated that the XGBoost model provided a high net clinical benefit across a wide range of threshold probabilities. SHAP analysis revealed that the vessel convergence sign, clinical T stage, age, consolidation-to-tumor ratio (CTR), and MLR were the features with the highest contributions to STAS prediction. Conclusion The XGBoost model effectively predicts preoperative STAS status in early-stage lung adenocarcinoma, exhibiting excellent discriminative performance and good clinical interpretability. Key predictors such as the vessel convergence sign, clinical T stage, age and CTR provide a crucial reference for preoperative risk assessment and the individualized selection of surgical strategies, ultimately benefiting patients.

Objective: To determine the potential genetic causal relationship between sleep related phenotypes and female pubertal onset using the two sample Mendelian randomization approach. Methods: Genetic instrumental variables for sleep and age at menarche were sourced from FinnGen, IEU Open GWAS and GWAS Catalog three publicly available Genome Wide Association Study databases. Causal effects were estimated using the inverse variance weighted method, supplemented by sensitivity analyses and tests for heterogeneity, pleiotropy, and direction. Results: Genetically predicted sleep duration was positively associated with age at menarche ( β =0.61, 95% CI =0.30-0.91, P <0.01). Conversely, overall sleep problems ( β =-0.13, 95% CI =-0.20 to -0.07 ), two specific types of sleep disorders (sleep apnea: β =-0.10, 95% CI =-0.16 to -0.03; insomnia: β =-0.40, 95% CI = -0.69 to -0.11) were causally associated with earlier age at menarche (all P <0.01). Sensitivity analyses confirmed the robustness of these findings with consistent effect directions and no evidence of significant directional pleiotropy. Conclusions The study reveales a genetic causal relationship between sleep and pubertal onset. Adequate sleep duration appears to have a protective effect. These findings suggest that sleep may have a critical regulatory role in the initiation of pubertal development.

OBJECTIVE To explore the effect and mechanism of berberine in ameliorating asthma in mice by regulating glycolysis via the hypoxia inducible factor-1α （HIF-1α）/pyruvate dehydrogenase kinase-1 （PDHK1） pathway.METHODS Mice were randomly divided into blank control group， model group， low- and high-dose berberine groups （100， 200 mg/kg， intragastric administration）， dimethyloxalylglycine （DMOG， HIF-1α agonist） group （2 mg， intranasal instillation）， and berberine+DMOG group （intragastric administration of 200 mg/kg berberine plus intranasal instillation of 2 mg DMOG）， with 12 mice in each group. Except for the blank control group， mice in the remaining groups were subjected to ovalbumin-induced sensitization and challenge to establish the asthma model. During the challenge period， mice were given corresponding drugs or normal saline once a day for 6 consecutive days. At 24 h after the last challenge， pulmonary function and airway reactivity of mice were determined； the content of ovalbumin-specific immunoglobulin E （OVA-sIgE） in serum was detected； inflammatory cells in bronchoalveolar lavage fluid （BALF） were counted； bronchial inflammation and goblet cell hyperplasia were histologically evaluated； the levels of inflammatory cytokines [interleukin-4 （IL-4）， IL-5， IL-13]， contents of glycolytic products [lactic acid， pyruvic acid， adenosine triphosphate （ATP）]， as well as mRNA and protein expressions related to the HIF-1α/PDHK1 pathway in lung tissue were measured.RESULTS Compared with the model group， the low- and high-dose berberine groups exhibited significantly elevated or increased dynamic lung compliance， peak expiratory flow， forced vital capacity （FVC）， forced expiratory volume in 0.1 second （FEV 0.1 ）， and FEV 0.1 /FVC （ P ＜0.05）， accompanied by significantly decreased airway resistance and enhanced pause value （ P ＜0.05）. Moreover， serum OVA-sIgE content， counts of white blood cell， neutrophil， lymphocyte， monocyte， eosinophil and basophil in BALF， scores for bronchial inflammation and goblet cell hyperplasia， levels of pulmonary inflammatory cytokines and contents of glycolytic products， as well as mRNA and protein expressions of HIF-1α， PDHK1， pyruvate kinase M2 and lactate dehydrogenase A were all significantly reduced （ P ＜0.05）. DMOG pretreatment obviously reversed the protective effects of high-dose berberine in asthmatic mice （ P ＜0.05）.CONCLUSIONS Berberine can inhibit the HIF-1α/PDHK1 pathway to decrease glycolytic level， so as to ameliorate airway inflammation and airway hyperresponsiveness in asthmatic mice.