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.

Objective: To analyze the school tuberculosis (TB) outbreaks and preventive treatment in Hefei from 2022 to 2024, so as to provide reference for TB prevention and control in schools. Methods: Data were collected on all school based TB outbreaks occurring during 2022-2024 in Hefei, defined as ≥2 epidemiologically linked TB cases within the same school during a single semester. Statistical analyses were performed using the Chi square test. Results: Close contacts exhibited significantly higher TB incidence (2.88%) and latent mycobacterium tuberculosis infection (LTBI) rates (13.80%) in the school TB outbreaks, compared to non close contacts (0.12% and 2.63%, respectively). Among close contacts, secondary school students showed lower TB incidence (0.48%) and LTBI prevalence (3.42%) than both primary school or younger children (0.68%, 6.95%) and college students ( 0.78% , 6.50%), with statistically significant differences ( χ 2=360.91, 6.37; 791.71, 102.03, all P <0.05). The proportion of LTBI individuals recommended for preventive therapy was higher in primary school or younger groups (98.59%) than in secondary (95.25%) or college students (86.34%) ( χ 2=25.86, P <0.01). However, among those recommended, close contacts had higher uptake (85.82%) and completion rates (87.25%) of preventive therapy than non close contacts (69.63% and 70.57%); similarly, secondary school students demonstrated higher uptake (91.21%) and completion rates (86.45%) compared to primary school or younger (88.57%, 83.87%) and college students (57.28%, 64.08%) ( χ 2=30.52, 26.72; 125.17, 38.84, all P <0.01). Subsequent TB incidence among LTBI close contacts (13.30%) and among those who did not complete preventive therapy (22.73%) were significantly higher than among non close contacts (2.80%, 2.41%), respectively ( χ 2=32.19, 13.87, both P <0.05). Conclusions In school TB outbreaks, close contacts face higher LTBI prevalence and subsequent TB risk than non close contacts. College students show notably low adherence to preventive therapy. It is necessary to take targeted measures to improve the compliance of preventive measures among students.

Hepatocellular carcinoma (HCC) is a lethal cancer with high morbidity rates worldwide. It is a major threat to public health in China, due to the combination of known and new risk factors, such as endemic hepatitis B virus (HBV), dietary aflatoxin exposure, and the occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD). Although many methods for surveillance and multimodal therapies, such as surgery, local ablation, transarterial therapy, and new systemic agents, have been available, the survival rates of HCC remains poor. They have very limited durable responses, long post-treatment recurrence rates, and high resistance to treatment. This reflects an imperfect picture of the biological cause of the disease and a need for new mechanistic or targeted techniques. A significant characteristic of HCC, in common with other aggressive cancers, is the presence of reprogrammed, hyperactive cell metabolism. Tumor cells hijack metabolic pathways to promote their uncontrolled growth, stress survival, invasion and metastasis. While classical mechanisms such as the Warburg effect, lipid metabolism and glutamine utilization have been understood, the lysosome, which was once viewed as a static “waste disposal unit” to remove old organelles and proteins, is instead a dynamic signaling and metabolic core. The lysosomes incorporate nutrients, energy and stress signals by master regulators such as mTORC1 (activated on its surface) that balance anabolic growth and catabolic recycling to the cellular demands. In HCC, lysosomes are not passive, but are highly active and dysregulated. HCC cells upregulate lysosomes, which scavenge intracellular components via enhanced autophagy and engulf extracellular proteins via macropinocytosis, crucial for survival in the nutrient-poor, hypoxic tumor microenvironment. In addition to metabolism, lysosomes exhibit pro-invasive functions by secreting hydrolases to remodel the extracellular matrix, promote angiogenesis, and suppress stromal immune cells to foster a pro-tumor microenvironment. In a clinical context, lysosomes play an important role in therapeutic resistance: they sequester and inactivate chemotherapeutics via lysosomal sequestration, and enhanced autophagic flux protects the cell from therapy-induced damage, contributing to relapse, as lysosomal dysfunction is a key cause of treatment failure. This makes lysosomes promising yet challenging therapeutic targets in HCC. Recent preclinical and early clinical studies investigate multiple strategies to exploit the susceptibility of lysosomes: lysosome-specific agents, alkalinizing the lysosome lumen or inducing membrane permeabilization and lysosome-dependent cell death; pharmacological inhibition of key lysosomal enzymes or autophagy to impair nutrient recycling and stress adaptation; smart nanotherapeutic agents or antibody-drug conjugates, specifically activated in the acidic lysosomal environment or utilizing lysosomal pathways for efficient intracellular drug release; and combination strategies of lysosome-targeting agents with tyrosine kinase inhibitors or immunotherapy to overcome resistance and achieve synergistic antitumor effects. In summary, our review systematically presents the role of lysosomes in HCC, from metabolic reprogramming and microenvironmental adaptation to therapeutic resistance. By synthesizing the latest mechanistic insights and preclinical advances, this review highlights the indispensable role of lysosomes in the complex HCC biological network, emphasizing that an in-depth understanding of this dynamic organelle holds great promise for developing innovative, targeted therapies, offering new hope for improving the poor prognosis of global HCC patients.

ObjectiveThis study aims to elucidate the potential mechanism of Zuojinwan in improving liver fibrosis through hepatic tissue metabolomics analysis. MethodsTwenty-four mice were randomly allocated into normal group， model group ， positive drug group （silymarin， 100 mg·kg^-1）， and Zuojinwan group （Zuojinwan solution， 2.5 g·kg^-1）， with per group six mice. Liver fibrosis model was induced via intraperitoneal injection of olive oil solution with 10% carbon tetrachloride （CCl₄） （0.5 μL·g^-1， three times weekly for 8 weeks） in all groups except the normal group. During the final 4 weeks， the silymarin group received silymarin （100 mg·kg^-1） by gavage thrice weekly， while the Zuojinwan group was administered Zuojinwan solution （2.5 g·kg^-1） under the same regimen. After the last administration， the levels of liver fibrosis indicators and liver injury markers in serum were detected. The pathological morphological changes of the liver tissues were observed. The levels of liver fibrosis markers α-smooth muscle actin （α-SMA） and Collagen Ⅰ（ColⅠ） were detected. Metabolomics was analyzed on mice's liver tissues. The mice's serum was collected for metabolomics analysis. ResultsCompared with the model group， Zuojinwan significantly improved indicators related to liver fibrosis and liver injury. Compared with the normal group， the model group showed significantly elevated levels of fibrosis markers such as laminin （LN）， hyaluronic acid （HA）， procollagen typeⅢ （PC-Ⅲ）， and type Ⅳ Collagen （Ⅳ-C）， while liver injury indicators such as alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， alkaline phosphatase （ALP）， lactate dehydrogenase （LDH）， and total bilirubin （TBIL）， exhibited a marked upward trend （P<0.05）. Compared with the model group， the silymarin group showed a significant decrease in the aforementioned indicators （P<0.05）. Notably， compared with the model group， the Zuojinwan group exhibited a significant reduction in all these indicators （P<0.05）， with efficacy comparable to that of the silymarin group. Zuojinwan reduced mRNA and protein levels of α-SMA and ColⅠ in the liver tissue. Metabolomics results revealed that compared with the model group， Zuojiinwan significantly reduced levels of glucose metabolism-related metabolites such as D-fructose 1，6-bisphosphate （FBP）， nicotinamide adenine dinucleotide phosphate （NADPH）， sodium beta-D-fructose 6-phosphate （F6P）， dihydroxyacetone phosphate （DHAP）， fumaric acid， and D-glucose 6-phosphate （G6P） （P<0.05）. Serum enzyme-linked immunosorbent assay （ELISA） was used to detect glucose metabolism indicators and further validate the regulatory effect of Zuojinwan on glucose metabolism. ConclusionThese results suggest that Zuojinwan may improve liver fibrosis by regulating the dysregulated levels of glucose metabolism during the progression of liver fibrosis.

ObjectiveTo investigate the therapeutic effect of sitravatinib on carbon tetrachloride （CCl₄）-induced liver fibrosis in mice. MethodsA total of 30 male C57BL/6J mice， aged 8 weeks， were randomly divided into control group， CCl₄ model group， and low- （5 mg/kg）， middle- （10 mg/kg）， and high-dose （20 mg/kg） sitravatinib groups. All mice except those in the control group were given intraperitoneal injection of CCl₄ for 4 consecutive weeks to induce liver fibrosis， and since the first day of modeling， the mice in the low-， middle-， and high-dose sitravatinib groups were given sitravatinib at the corresponding dose by gavage every day. The serum levels of total cholesterol （TC）， triglyceride （TG）， and alanine aminotransferase （ALT） were measured for the mice in each group； hepatic hydroxyproline content was measured； HE staining， Masson staining， and Sirius Red staining were used to observe liver histopathological changes； quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression levels of α-smooth muscle actin （α-SMA） and collagen type I alpha 1 （Col1a1） in liver tissue. The therapeutic effect of sitravatinib was assessed based on the above results. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group， the model group had significant increases in the levels of TC， TG， and ALT （all P<0.05）， and there were no significant differences in the levels of TC， TG， and ALT between the model group and the low-， middle-， and high-dose sitravatinib groups （all P>0.05）. Hepatic hydroxyproline content decreased after sitravatinib intervention， with a significant difference between the middle-/high-dose sitravatinib groups and the CCl₄ model group （both P<0.05）. Histopathological staining showed that the sitravatinib treatment groups had a reduction in collagen deposition， along with thinning and fragmentation of fibrous septa， and in the high-dose sitravatinib group， 4 mice had a fibrosis stage of S0—S1 and 2 mice had a fibrosis stage of S2—S3， suggesting a certain degree of alleviation of liver fibrosis degree compared with the CCl₄ model group （mainly S3—S4）. The measurement of related molecules showed that sitravatinib downregulated the mRNA and protein expression levels of α-SMA and Col1a1 （all P<0.05）. ConclusionSitravatinib can effectively alleviate CCl₄-induced liver fibrosis in mice， possibly by inhibiting hepatic stellate cell activation and collagen synthesis.

ObjectiveTo analyze the current research status, hotspots and future trends of the application of digital health technology (DHT) in the rehabilitation of upper limb motor function after stroke. MethodsRelevant literature on the application of DHT in upper limb motor rehabilitation for stroke patients published between January, 2015 and December, 2025 was retrieved from Web of Science Core Collection, CNKI and Wanfang database. CiteSpace 6.4.R1 was used for visualized bibliometric analysis. ResultsA total of 1 295 publications were included, comprising 454 in Chinese and 841 in English. The annual number of publications generally showed an upward trend. China ranked first in publication output in English literature. The institutions with the highest numbers of publications were Huashan Hospital Affiliated to Fudan University and Swiss Federal Institute of Technology in Zurich. Both Chinese and English keywords formed ten clustering groups. Chinese clusters mainly involved occupational therapy, neural mechanisms and home-based rehabilitation, whereas English clusters focused on virtual reality, brain-computer interfaces and machine learning. High-frequency keywords included virtual reality, brain-computer interface, machine learning and deep learning. Chinese keywords with a strong burst included rehabilitation training, while deep learning showed a strong burst in English keywords. Stroke was the most frequently cited journal. Highly cited journals covered multiple disciplines, including rehabilitation medicine, neuroscience and computer science, reflecting the interdisciplinary characteristics of this field. ConclusionResearches on DHT for upper limb motor function rehabilitation in stroke are increasing annually, focusing on core interaction technologies, neural mechanism and artificial intelligence. Future research trends may include inter-disciplinary integration of artificial intelligence with core rehabilitation technologies, neuroimaging-guided targeted interventions, optimisation of home-based rehabilitation systems, and development of multidimensional quantitative assessment models.

ObjectiveTo establish a C-C motif chemokine receptor 6 （CCR6） homozygous knockout mouse model in order to provide a crucial animal model foundation for subsequent in vivo functional studies. MethodsCcr6^-/- mice were generated using CRISPR-Cas9 technology. Genomic DNA was extracted from mouse tails， with genotyping performed by PCR and agarose gel electrophoresis. Pathological morphology of major organs （heart， liver， lung， kidney） was assessed through HE staining. Western blot was used to analyze CCR6 protein expression in blood， spleen， and bone marrow. To analyze the impact of CCR6 gene knockout on the proportion of major immune cell populations， the ratio of T cells and macrophages in the mouse spleen was detected using flow cytometry. ResultsThe results of agarose gel electrophoresis demonstrated that mice exhibiting a single specific band at the 307 bp position upon primer-based identification were confirmed as Ccr6^-/- mice. HE staining revealed no significant histopathological differences between Ccr6^+/+and Ccr6^-/- mice. Western blot demonstrated near-complete absence of CCR6 protein in target tissues. Flow cytometry results demonstrated that CCR6 gene deletion significantly increased the proportion of CD8⁺T cells， while the ratios of both CD4⁺T cells and macrophages remained unaltered. ConclusionA Ccr6^-/- mouse model is established using CRISPR-Cas9 technology， serving as an essential tool for elucidating CCR6′s regulatory role in tumor proliferation.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is higher among individuals with inflammatory bowel disease (IBD) than in the general population. Emerging evidence indicates that the development of MASLD in patients with IBD may occur independently of traditional metabolic risk factors, suggesting a unique pathophysiological mechanism distinct from conventional MASLD pathways. Bile acids (BAs), which act as critical signaling molecules in enterohepatic circulation, play an essential role in maintaining gastrointestinal homeostasis through bidirectional gut–liver axis communication. These molecules are increasingly recognized as pivotal regulators in the progression of both MASLD and IBD. While previous studies have characterized the dynamics of BA in blood or fecal samples under both conditions, a comprehensive understanding of their metabolic profiles and the associated interactions within the gut–liver axis is still lacking. This review synthesizes current evidence from studies employing BA metabolomics to investigate IBD and MASLD. By focusing on BA signatures, we summarize conserved alterations between these two conditions and their potential mechanisms of disease progression. Our review advances understanding of BA-mediated pathways in IBD and MASLD, providing a foundation for assessing their roles in contributing to the pathogenesis of MASLD in patients with IBD.

There is a substantial unmet need for treatments in the field of pediatric rare diseases, and investigator initiated trial(IIT) provide a critical pathway for testing and developing new drugs or treatment strategies. However, healthcare institutions, when conducting such research, must address compliance risks related to project approval, contract management, data protection, and conflict of interest management. This study aims to analyze the particularities and challenges of IIT in pediatric rare diseases, review relevant regulations and regulatory requirements, and provide healthcare institutions with a reference framework for compliance risk management to maximize the benefits of IIT. Based on literature review, analysis of laws and regulations, practical work experience, and frameworks from other institutions, we summarize the unique aspects of pediatric rare disease IIT in terms of participant characteristics, innovative technologies, and organizational structures.On this basis, targeted compliance management recommendations are proposed, which include establishing a risk rating and full-cycle risk monitoring mechanism, a consent and ethical review mechanism tailored to pediatric participants, a robust contract management mechanism, a comprehensive data security management mechanism, and a multidisciplinary team and multi-channel compensation mechanism. The study concludes that healthcare institutions, funders, and other collaborating entities should implement compliance management in line with the characteristics of IIT to ensure the safety and effectiveness of research and facilitate innovation and development in the treatment of pediatric rare diseases.

Objective To analyze the levels of serum CTCs and ctDNA in NSCLC patients receiving first-line EGFR-TKI treatment, and to explore the clinical value of CTCs and ctDNA detection in assessing the efficacy of treatment for advanced lung cancer. Methods A total of 109 NSCLC patients receiving first-line EGFR-TKI treatment were enrolled. Serum tumor markers CEA, CTCs, and ctDNA were detected at baseline and after one month of treatment. Chest CT scans were performed, and treatment efficacy was evaluated based on RECIST1.1 criteria. CTCs were counted by enrichment-staining-computational algorithm to analyze malignant features, while ctDNA was assessed using digital PCR. Results Survival rate was low in patients with abnormal CEA and ctDNA tests at baseline and in patients with reduced serum CTCs after treatment. In the SD subgroup of patients with brain metastases and advanced stage, the PFS benefit was low. Conclusion Patients in the SD subgroup have significantly higher recurrence risks than those in the PR or CR subgroups. Therefore, CTC and ctDNA testing should be applied to patients in the SD subgroup to identify high-risk patients with poor response to EGFR-TKI treatment, intervene with additional treatment promptly, and obtain long progression-free survival.