Objective: To develop a clinical decision and prescription generation system (CDPGS) specifically for diarrhea in traditional Chinese medicine (TCM), utilizing a specialized large language model (LLM), Qwen-TCM-Dia, to standardize diagnostic processes and prescription generation. Methods: Two primary datasets were constructed: an evaluation benchmark and a fine-tuning dataset consisting of fundamental diarrhea knowledge, medical records, and chain-of-thought (CoT) reasoning datasets. After an initial evaluation of 16 open-source LLMs across inference time, accuracy, and output quality, Qwen2.5 was selected as the base model due to its superior overall performance. We then employed a two-stage low-rank adaptation (LoRA) fine-tuning strategy, integrating continued pre-training on domain-specific knowledge with instruction fine-tuning using CoT-enriched medical records. This approach was designed to embed the clinical logic (symptoms → pathogenesis → therapeutic principles → prescriptions) into the model’s reasoning capabilities. The resulting fine-tuned model, specialized for TCM diarrhea, was designated as Qwen-TCM-Dia. Model performance was evaluated for disease diagnosis and syndrome type differentiation using accuracy, precision, recall, and F1-score. Furthermore, the quality of the generated prescriptions was compared with that of established open-source TCM LLMs. Results: Qwen-TCM-Dia achieved peak performance compared to both the base Qwen2.5 model and five other open-source TCM LLMs. It achieved 97.05% accuracy and 91.48% F1-score in disease diagnosis, and 74.54% accuracy and 74.21% F1-score in syndrome type differentiation. Compared with existing open-source TCM LLMs (BianCang, HuangDi, LingDan, TCMLLM-PR, and ZhongJing), Qwen-TCM-Dia exhibited higher fidelity in reconstructing the “symptoms → pathogenesis → therapeutic principles → prescriptions” logic chain. It provided complete prescriptions, whereas other models often omitted dosages or generated mismatched prescriptions. Conclusion By integrating continued pre-training, CoT reasoning, and a two-stage fine-tuning strategy, this study establishes a CDPGS for diarrhea in TCM. The results demonstrate the synergistic effect of strengthening domain representation through pre-training and activating logical reasoning via CoT. This research not only provides critical technical support for the standardized diagnosis and treatment of diarrhea but also offers a scalable paradigm for the digital inheritance of expert TCM experience and the intelligent transformation of TCM.

ObjectiveTo systematically compare the effects of diverse electromagnetic stimulation protocols on hand function and activities of daily living (ADL) in stroke patients using network meta-analysis (NMA), and screen the optimal stimulation strategy for post-stroke hand dysfunction rehabilitation. MethodsNMA was performed in accordance with the PRISMA-NMA statement. Databases of CNKI, Wanfang data, VIP, CBM, PubMed, Web of Science and Embase were searched from database inception to April, 2026 for eligible randomized controlled trials (RCTs) comparing different electromagnetic stimulation protocols for post-stroke hand impairment. The Cochrane Risk of Bias tool and PEDro scale were used to assess methodological quality of included studies, while the GRADE system was adopted to grade evidence quality of primary outcomes of Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and modified Barthel Index (MBI). After literature screening, data extraction and bias evaluation, RevMan 5.4 and Stata 17.0 were used for meta-analysis and NMA. ResultsA total of 22 RCT involving 17 electromagnetic stimulation protocols were finally included. The PEDro scores ranged from six to ten. The top five protocols for improving FMA-UE score were repetitive peripheral magnetic stimulation (rPMS) + repetitive transcranial magnetic stimulation (rTMS), intermittent theta-burst stimulation (iTBS) + rPMS, iTBS + transcranial direct current stimulation (tDCS), transcutaneous electrical acupoint stimulation (TEAS) and contralaterally controlled functional electrical stimulation (CCFES). tDCS was the most effective on MBI, followed by TEAS and iTBS+rPMS. Evidence quality for FMA-UE and MBI was moderate. Funnel plots suggested low risk of publication bias, and consistency tests verified good coherence between direct and indirect comparisons in network models. ConclusionElectromagnetic stimulation significantly facilitates upper limb and hand functional recovery, and improves ADL in stroke patients. The combined central-peripheral magnetic stimulation protocol may be the most effective on motor rehabilitation, whereas tDCS on ADL.

ObjectiveTo investigate the effect of folic acid-modified crebanine polyethylene glycol-polylactic acid hydroxyacetic acid copolymer（PEG-PLGA） nanoparticles（FA-Cre@PEG-PLGA NPs， hereinafter referred to as NPs） combined with ultrasonic irradiation on subcutaneous tumor of liver cancer in Kunming（KM） mice. MethodsEighty-four healthy male KM mice were utilized to establish a subcutaneous tumor model of mouse hepatocellular carcinoma with H22 cells， then mice were randomly divided into model group， placebo group， hydroxycamptothecin group（8 mg∙kg^-1）， low， medium and high dose crebanine raw material groups（2， 2.5， 3 mg∙kg^-1， hereinafter referred to as the low， medium and high dose crebanine groups， respectively）， low， medium and high dose NPs groups（2， 2.5， 3 mg∙kg^-1）， and low， medium and high dose NPs combined with ultrasonic irradiation groups（2， 2.5， 3 mg∙kg^-1， hereinafter referred to as the low， medium and high dose combination groups， respectively）. The corresponding doses of drugs were administered via tail vein injection， the model group received no treatment， while the placebo group was injected with an equivalent amount of normal saline. Dosing was conducted for a total of 10 times on alternate days. The body mass of the mice was monitored， and parameters such as body mass change rate， thymus index， spleen index， tumor volume， tumor weight， relative tumor growth rate（T/C）， and tumor inhibition rate（TGI） were calculated. Pathological changes in liver and kidney tissues as well as the tumor were observed by hematoxylin-eosin（HE） staining. Additionally， the levels of aspartate aminotransferase（AST）， alanine aminotransferase（ALT）， blood urea nitrogen（BUN） and creatinine（CREA） in serum of mice were detected by biochemical method. Furthermore， the effect of ultrasound on the distribution of NPs in subcutaneous tumors of mouse hepatocellular carcinoma was observed by in vivo imaging technique. ResultsAmong different treatment methods， the combination of NPs and ultrasound irradiation had the best therapeutic effect. Compared with the model group， the body mass growth rates of mice in the medium and high combination groups decreased， while the thymus index and spleen index increased， but there was no statistically significant difference in serum AST， ALT， BUN and CREA levels， indicating that NPs combined with ultrasound irradiation had little effect on the normal physiological state of the body， oth groups had TGI>40% and T/C<60%， indicating a clear anti-tumor effect. Pathological analysis showed that compared with the NPs groups， the combination groups exhibited varying degrees of necrosis in tumor cells， accompanied by less damage to the liver and kidneys. In vivo imaging of small animals showed that compared with the high dose NPs group， the high dose combination group had stronger tumor targeting ability（P<0.01）. ConclusionNPs combined with ultrasonic irradiation can not only effectively targeted the drug to the tumor site， inhibit the subcutaneous tumor growth of mouse liver cancer， but also decrease damage to liver and kidney tissues.

Objective: To investigate the seroepidemiological characteristics of hepatitis B among outpatients in medical institutions in Jiaxing City, Zhejiang Province, so as to provide a reference for formulating region-specific hepatitis B prevention and control strategies. Methods: From April to June 2024, outpatients were selected as study subjects from sentinel medical institutions in Jiaxing City. Information such as gender and age was collected. Venous blood samples were obtained and serological markers including hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B e antigen (HBeAg), hepatitis B e antibody (HBeAb), and hepatitis B core antibody (HBcAb) were tested. Positive rates of hepatitis B virus (HBV) serological markers were analyzed by genders and ages. Results: A total of 1 468 outpatients were included, among whom 721 were males (49.11%) and 747 were females (50.89%). The mean age was (46.41±19.66) years. The positive rates of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb were 7.29%, 44.75%, 1.84%, 23.50%, and 42.03%, respectively. The HBcAb positive rate in males was significantly higher than in females (46.05% vs. 38.15%, P<0.05), while no statistically significant gender differences were observed in the positive rates of other four HBV serological markers (all P>0.05). Except for HBsAb, the positive rates of the other four HBV serological markers showed statistically significant differences across different age groups (all P<0.05). Pairwise comparisons results showed that the HBsAg positive rates in age groups of 20-<40 years and 40-<60 years were 9.48% and 9.57%, respectively, which were higher than those in age groups of <20 years (1.43%) and ≥60 years (2.75%) (all P<0.05). A total of 17 HBV serological marker patterns were observed, among which the proportion of all markers negative was the highest, at 39.65%. The proportions of "small three positive" (HBsAg+, HBeAb+, HBcAb+) and "large three positive" (HBsAg+, HBeAg+, HBcAb+) patterns were 4.77% and 1.50%, respectively. Among HBsAg-positive individuals, the proportions of the "small three positive" pattern across age groups were 0, 45.45%, 90.00%, and 81.82%, while those of the "large three positive" were 0, 36.36%, 5.00%, and 0, with statistically significant differences across age groups (both P<0.05). Conclusions The positive rate of HBsAg among outpatients in medical institutions in Jiaxing City is relatively high, with a notable proportion of individuals showing either no immunity or non-response to vaccination. It is recommended to strengthen hepatitis B immunization efforts among the population aged 20-<60 years, and to enhance monitoring and interventional treatment for "small three positive" and "large three positive" patterns.

Objective To investigate the efficacy of varying doses of methylprednisolone(MP)on mice with acute exacerbations of chronic obstructive pulmonary disease(AECOPD)induced with influenza A virus(IAV).Methods Mouse model of COPD was established using LPS combined with smoking for 12 weeks,and then these COPD mice were treated with administration of 40 μL IAV via nasal drip to establish a AECOPD model.A total of 15 AECOPD mice were randomly divided into low-,medium-and high-dose MP groups,oseltamivir group and blank group.The body weight and survival time were monitored within 10 d after IAV infection.On days 1,3,and 5 post-treatment,lung function was assessed using whole-body plethysmography(WBP),inflammatory factors in bronchoalveolar lavage fluid(BALF)were quantified with ELISA,viral titers in BALF were determined using plaque assays,and colony-forming units were evaluated with blood agar plates.Immunofluorescence analysis:① Pulmonary immunofluorescence assay:Mice were randomly categorized into(n=4):LPS 1-day group,LPS 3-day group,and LPS+MP treatment group.All groups received an initial dose of LPS via atomization;subsequently,the LPS+MP treatment group received a single gavage dose of MP.Lung tissues were harvested from the 1-day LPS group on 1 d post-treatment,and from the 3-day LPS and LPS+MP groups on 3 d for immunofluorescence staining.② Cellular immunofluorescence assay:Mouse bone marrow neutrophils were classified into blank control(no intervention),LPS stimulation(LPS group),MP intervention with LPS stimulation(LPS+MP group),and MP intervention alone(MP group).The above cells were collected in 4 h after corresponding interventions for subsequent cellular immunofluorescence analysis.Results ①The medium-dose MP group demonstrated the most significant improvement in survival rate,weight recovery,and lung function when compared to other groups(P＜0.05).② Treatment of medium-dose MP obviously reduced the levels of IL-6 and neutrophil extracellular traps(NETs)(P＜0.05),while,elevated inflammatory factors and NETs were observed in the high-dose MP group on day 5 post-treatment.③ Notable decline in the lung injury score was found in the medium-dose MP group than the other groups(P＜0.05).④The high-dose MP group exhibited substantial bacterial proliferation and delayed viral clearance since day 5 after treatment.Conclusion Medium-dose MP shows best efficacy in treatment of IAV-induced AECOPD,and the dose neither delays viral clearance nor increases the risk of bacterial infection following viral infection.

Objective:Constructing efficacy evaluation index of TCM in treating kidney-yang deficiency syndrome based on three-dimensional hybrid method.Methods:The outcome index list of kidney-yang deficiency syndrome was preliminarily constructed through literature research, questionnaire survey and expert interview. The core indicators of kidney-yang deficiency syndrome were screened by Delphi questionnaire, and the expert consensus meeting was held to determine the core outcome of kidney-yang deficiency syndrome.Results:The TCM symptoms of kidney-yang deficiency syndrome: 7 items: frequent urination at night, waist pain, low libido, chills, fatigue, diarrhea and mental malaise. Related core indicators of kidney-yang deficiency syndrome: Level quality of life score (scale), sex life level (sexual self satisfaction, sexual life log, etc.)two entries, objective indicators in the core index and stronger correlation disease, curative effect evaluation, can be combined with clinical research involves the related diseases, used to supplement the curative effect, as recommendations, not as the main body of kidney-yang deficiency syndrome curative effect evaluation content.Conclusion:This study refers to the clinical trial of the TCM core outcome to develop technical specifications, in the development process and methods, through the "combination of qualitative and quantitative research methods" "combination of subjective and objective indicators" "combination of doctor-patient evaluation" three dimensions of mixed research methods, formation of kidney-yang deficiency syndrome curative effect evaluation of the core outcome, for the kidney-yang deficiency syndrome curative effect evaluation standard of prophase research foundation, to provide ideas and methods for the evaluation of curative effect of syndrome.

OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.

This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

Objective To evaluate the gap between China's top-tier medical institutions and top-tier international medical institutions,and to provide references for the construction of first-class medical science discipline in China.Methods Using globally recognized rankings of medical institutions,we selected 24 top-tier international medical institutions and 11 top-tier Chinese medical institutions.Publicly available,general,and comparable data on indicators were collected to analyze the performance and gaps between top-tier international and Chinese medical institutions in human resources development,talent cultivation,scientific research,social services,and discipline construction.Results In the field of medicine,the largest gap between top-tier international and Chinese medical institutions was in high-level talent.Specifically,the average numbers of individuals who are Clarivate Analytics'Highly Cited Researchers,who are Nobel Prize laureates in Physiology or Medicine,and who serve on advisory boards or editorial boards of top medical journals,and who rank among the Top 2 000 Medicine Scientists were 1.00,0.09,0.45 and 4.00,respectively,among top-tier Chinese medical institutions,while those of the top-tier international medical institutions were 131.46,118.25,9.72,and 6.76 times,respectively,those of the Chinese medical institutions.The second largest gap was in social services and medical innovation.The average proportion of industrial collaboration papers and the number of clinical trials of China's top-tier medical institutions were 1.51％and 1 851,respectively,while those of international top-tier medical institutions were 3.62 and 1.87,times,respectively,those of top-tier Chinese medical institutions.However,the average number of(untranslated)patents held by top-tier international medical institutions was only 15％ of that of China's top-tier medical institutions.The third largest gap was in scientific research.The average number of papers published in New England Journal of Medicine,Journal of the American Medical Association,The Lancet,and British Medical Journal,the percentage of hot papers in papers included in Web of Science,the percentage of highly cited papers,the percentage of international collaboration papers,the total number of citations per paper,category normalized citation impact(CNCI),and the number of publications of top-tier Chinese medical institutions were 78,0.03％,1.39％,22.55％,19.61,1.26,30 706,while those of the top-tier international medical institutions were 6.96,2.66,2.57,2.15,1.83,1.58 and 1.54 times those of the Chinese medical institutions,respectively.However the average percentage of zero-citation papers of top-tier international medical institutions was only 71％of that of China's top-tier medical institutions.Furthermore,in discipline development,the average overall scores of the Times Higher Education(THE)and QS rankings for medicine-related disciplines of top-tier Chinese medical institutions were 72.84 and 69.30,respectively,while those of top-tier international medical institutions were 1.38 and 1.21 times those of the Chinese medical institutions.However,in terms of talent cultivation,the average number of students of China's top-tier medical institutions was 10724,which is roughly double that of international institutions.Conclusion Currently,China's top-tier medical institutions are still in a basic stage that emphasizes the quality of talent cultivation and medical services.There is considerable room for development and potential for catching up in multiple aspects,especially in high-level talent,medical research,and innovation.It is recommended that the construction experience of top-tier international medical institutions should be fully utilized to build China's first-class medical science discipline.

ObjectiveTo evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) for muscle atrophy in patients with immobilization after surgical fixation of foot and ankle fractures.MethodsThis was a two-arm randomized controlled trial wherein 80 patients were recruited and divided into control (n = 40) and intervention (n = 40) groups. The control group received conventional orthopedic treatment, whereas the intervention group received TEAS and conventional treatment. The intervention group received TEAS 3 times a week for 30 min each time for 8 weeks. The primary outcomes were muscle thickness (MT) and cross-sectional area (CSA) of the rectus femoris and gastrocnemius muscles, whereas the secondary outcome measure was echo intensity (EI). Data were collected before the fixation operations (baseline assessment) and 4 and 8 weeks after intervention.ResultsCompared with baseline, the MT and CSA were reduced in both groups by the end of treatment, whereas EI increased in both groups. At week 4, the reduction in the rectus femoris CSA in the intervention group was significantly lower than that in the control group (P = .02); however, the between-group differences in the MT and EI (all P .05) were not significant. No serious adverse events were observed in either group.ConclusionOur study showed that TEAS can improve muscle atrophy by attenuating the decline in the muscle CSA. Because this was only a pilot trial, subsequent studies will need longer follow-ups and larger sample sizes.