Objective: To develop QingNangTCM, a specialized large language model (LLM) tailored for expert-level traditional Chinese medicine (TCM) question-answering and clinical reasoning, addressing the scarcity of domain-specific corpora and specialized alignment. Methods: We constructed QnTCM_Dataset, a corpus of 100 000 entries, by integrating data from ShenNong_TCM_Dataset and SymMap v2.0, and synthesizing additional samples via retrieval-augmented generation (RAG) and persona-driven generation. The dataset comprehensively covers diagnostic inquiries, prescriptions, and herbal knowledge. Utilizing P-Tuning v2, we fine-tuned the GLM-4-9B-Chat backbone to develop QingNangTCM. A multi-dimensional evaluation framework, assessing accuracy, coverage, consistency, safety, professionalism, and fluency, was established using metrics such as bilingual evaluation understudy (BLEU), recall-oriented understudy for gisting evaluation (ROUGE), metric for evaluation of translation with explicit ordering (METEOR), and LLM-as-a-Judge with expert review. Qualitative analysis was conducted across four simulated clinical scenarios: symptom analysis, disease treatment, herb inquiry, and failure cases. Baseline models included GLM-4-9B-Chat, DeepSeek-V2, HuatuoGPT-II (7B), and GLM-4-9B-Chat (freeze-tuning). Results: QingNangTCM achieved the highest scores in BLEU-1/2/3/4 (0.425/0.298/0.137/0.064), ROUGE-1/2 (0.368/0.157), and METEOR (0.218), demonstrating a balanced and superior normalized performance profile of 0.900 across the dimensions of accuracy, coverage, and consistency. Although its ROUGE-L score (0.299) was lower than that of HuatuoGPT-II (7B) (0.351), it significantly outperformed domain-specific models in expert-validated win rates for professionalism (86%) and safety (73%). Qualitative analysis confirmed that the model strictly adheres to the “symptom-syndrome-pathogenesis-treatment” reasoning chain, though occasional misclassifications and hallucinations persisted when dealing with rare medicinal materials and uncommon syndromes. Conclusion Combining domain-specific corpus construction with parameter-efficient prompt tuning enhances the reasoning behavior and domain adaptation of LLMs for TCM-related tasks. This work provides a technical framework for the digital organization and intelligent utilization of TCM knowledge, with potential value for supporting diagnostic reasoning and medical education.

Chronic heart failure （CHF） is the terminal stage of various heart diseases， with high morbidity， mortality， and hospitalization rate. According to the theory of collateral diseases， the core pathogenesis of CHF is blood stasis of collaterals， water retention and stagnation， and pathogen accumulation in collaterals. Accordingly， the treatment should focus on reinforcing healthy Qi to warm Yang， activating blood to dredge collaterals， and excreting water to alleviate edema. On this basis， Qili Qiangxin capsules （QLQX） are created. This prescription can effectively treat chronic heart failure. Modern studies have shown that QLQX contains a variety of pharmacological components such as flavonoids， alkaloids， terpenoids， phenylpropanoids， phenolic acids， and cardiac glycosides. QLQX can improve the cardiac function， inhibit myocardial fibrosis， improve hemodynamics， mitigate inflammation， reduce cardiomyocyte apoptosis， and regulate the nervous system， with mild adverse reactions. This study analyzed the etiology and pathogenesis of CHF based on the theory of collateral diseases， explored the relationship between the prescription and syndrome， and delved into the material basis and mechanism of QLQX in the treatment of CHF， aiming to provide reference for the clinical application and scientific research of QLQX.

This paper summarizes Professor SHI Zaixiang's clinical experience in treating high fever caused by sepsis using Chaihu Guizhi Ganjiang Decoction （柴胡桂枝干姜汤）. He holds that the key pathogenesis of sepsis involves constrained heat in the shaoyang and internal accumulation of water and fluids. The clinical manifestations such as high fever， chills， and alternating sensations of cold and heat are attributed to pathogenic heat constrained in the shaoyang. Meanwhile， soft tissue edema and serous cavity effusions are due to shaoyang dysfunction and internal water retention. In clinical practice， treating sepsis-related high fever requires addressing both the shaoyang-constrained heat and the associated edema and effusions. The therapeutic approach focuses on harmonizing the shaoyang and resolving internal fluids， using Chaihu Guizhi Ganjiang Decoction as the base formula with flexible modifications. Professor SHI emphasizes that this formula shows a rapid antipyretic effect， particularly in cases where multiple anti-infective treatments have failed.

OBJECTIVE To investigate the clinical characteristics of drug-induced liver injury （DILI） induced by glucagon- like peptide-1 receptor agonists （GLP-1RAs）， and to provide a reference for safe clinical medication. METHODS Using search terms such as “GLP-1”“GLP-1RAs”“semaglutide” “drug-induced liver injury”， relevant studies from PubMed， Embase， the Cochrane Library， CNKI， Wanfang Data and VIP were retrieved. Descriptive analysis was performed on cases of DILI induced by GLP-1RAs. RESULTS A total of 11 studies， comprising 11 patients， were included. Among them， 4 were male （36.4%） and 7 were female （63.6%）. Patient ages ranged from 17 to 64 years； 5 patients （45.5%） were between 50 and 65 years old. Six patients were treated for diabetes， and five for weight loss. Ten patients had underlying diseases. The shortest time to the onset of DILI was 5 days after medication， while the longest was approximately 180 days. The DILIs induced by GLP-1RAs were mainly hepatocellular injury type （6 cases）； severity levels included severe （3 cases）， moderate （6 cases）， and mild （2 cases）. Gastrointestinal symptoms and jaundice were the most common clinical manifestations. The association between DILI and GLP- 1RAs was assessed as “probable” in 10 cases and “possible” in 1 case. All 11 patients improved after drug discontinuation and （or） corresponding treatment. CONCLUSIONS DILI induced by GLP-1RAs is relatively concentrated in patients aged 50-65， with a higher incidence in females. The risk may be further increased in patients with underlying diseases. Clinical use of these agents should enhance pharmaceutical care， including identification of high-risk populations and patient education （especially symptom recognition）. When relevant symptoms appear， the drug should be discontinued immediately， with liver-protective therapy initiated when necessary， to ensure patient safety of drug use.

ObjectiveTo explore the effectiveness of feedforward control mode on improving occupational burnout among operating room nurses through theoretical research and clinical practice， with a view to promoting their physical and mental health and enhancing the quality of surgical nursing. MethodsA total of 440 operating room nurses from different regions， scales， and nursing experiences in Shaanxi Province from November 2023 to December 2023 were randomly divided into an experimental group and a control group， with 220 nurses in each group. While the control group received routine intervention measures， the experimental group introduced a feedforward control mode based on the control group， with “emotional exhaustion，” “depersonalization，”and“personal achievement” as observation indicators. ResultsThe incidence of occupational burnout in the experimental group was 11.4%， while that in the control group was 20.0%. The experimental group showed a significantly lower incidence than the control group （P=0.013）. ConclusionThe feedforward control mode can significantly alleviate nurses’ sense of job burnout， promote the improvement of surgical nursing quality， as well as continuously improve the scientific rigor， advancement， and humanistic nature of nursing services， which is conducive to building a harmonious and efficient nursing team. The spirit of teamwork， reflected in mutual support， mutual trust， and joint efforts for surgical success and patient health， has become an important component of nurses’ professional ethics.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

OBJECTIVE: To elucidate the molecular mechanisms underlying sepsis-induced injury in mouse intestinal organoids and investigate the possible mechanisms or potential drug targets of myeloid differentiation factor 88 inhibitor [TJ-M2010-5 (TJ5)] on this condition. METHODS: Small intestinal organoids from C57BL/6 mice aged 6-8 weeks were established and characterized using immunofluorescence for cell growth and proliferation marker nuclear antigen Ki-67, goblet cell marker mucin-2 (MUC-2), epithelial cell marker E-cadherin, and Paneth cell marker lysozyme (Lyz). Small intestinal organoids after 3 days of passaging were divided into different groups: a normal control group treated with culture medium containing 0.2% dimethyl sulfoxide (DMSO) for 10 hours, a lipopolysaccharide (LPS) group treated with culture medium containing 200 mg/L LPS and 0.2% DMSO for 10 hours, and a TJ5 group pre-treated with 10 mmol/L TJ5 for 2 hours followed by treatment with culture medium containing 200 mg/L LPS for 10 hours. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to measure the expression levels of interleukin-6 (IL-6) and zonula occludens-1 (ZO-1) in the small intestinal organoids. RNA transcriptome sequencing was performed on the small intestinal organoids from each group to analyze differentially expressed genes between groups, and significant enrichment was analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS: By the 7th day of primary culture, mature organoids had formed, and their growth rate increased after passaging. Immunofluorescence identification showed expressions of Ki-67, MUC-2, E-cadherin, and Lyz, indicating that the mouse small intestinal organoids maintained their cellular composition and functional characteristics under in vitro culture conditions. RT-qPCR results showed that compared with the normal control group, the mRNA expression of IL-6 in the small intestinal organoids of the LPS group was significantly increased (2^-ΔΔCT: 1.83±0.16 vs. 1.02±0.28, P < 0.05), while the mRNA expression of ZO-1 was significantly decreased (2^-ΔΔCT: 0.53±0.11 vs. 1.01±0.18, P < 0.05). In contrast, the mRNA expression trends of both IL-6 and ZO-1 were reversed in the TJ5 group, showing statistically significant differences as compared with the LPS group (2^-ΔΔCT: IL-6 mRNA was 1.24±0.01 vs. 1.83±0.16, ZO-1 mRNA was 1.97±0.29 vs. 0.53±0.11, both P < 0.05). RNA transcriptome sequencing showed 49 differentially expressed genes in the LPS group compared to the normal control group, with 42 upregulated and 7 downregulated. Compared to the LPS group, the TJ5 group showed 84 differentially expressed genes, with 47 upregulated and 37 downregulated. GO enrichment analysis of these differentially expressed genes showed that the significantly enriched biological processes of the differentially expressed genes between the normal control group and the LPS group included responses to LPS, responses to molecule of bacterial origin and responses to bacterium. The significantly enriched biological processes of the differentially expressed genes between the LPS group and the TJ5 group included glutathione metabolic processes, responses to stress cellular and responses to chemical stimulus. In molecular function groups, glutathione binding and oligopeptide binding were significantly enriched by the differentially expressed genes. In cellular component classifications, the enrichment of the differentially expressed genes was mainly observed in the cytoplasm, endoplasmic reticulum, and microsomes. KEGG pathway enrichment analysis indicated that the differentially expressed genes between the normal control group and LPS group were enriched in IL-17 signaling pathways, tumor necrosis factor (TNF) signaling pathways, viral protein interactions with cytokines and cytokine receptors signaling pathways, and cytokine-cytokine receptor interaction signaling pathways. In contrast, the differentially expressed genes between the LPS and TJ5 groups were mainly enriched in atherosclerosis signaling pathways, ferroptosis signaling pathways, glutathione metabolism signaling pathways, and cytochrome P450-mediated drug metabolism signaling pathways. CONCLUSIONS Mouse small intestinal organoids were successfully extracted and cultured. TJ5 may exert its protective effects by regulating gene expression and related signaling pathways (fluid shear stress and atherosclerosis, ferroptosis, glutathione metabolism, cytochrome P450 drug metabolism, etc.) in sepsis-injured mouse small intestinal organoids. These genes and signaling pathways may be key targets for treating sepsis-induced intestinal injury.
Animals ; Mice ; Sepsis/genetics* ; Organoids/drug effects* ; Mice, Inbred C57BL ; Intestine, Small/metabolism* ; Gene Expression Profiling ; Transcriptome ; Lipopolysaccharides

Objective:To investigate the trajectory of frailty in elderly patients on maintenance hemodialysis(MHD)following SARS-CoV-2 infection and its associated risk factors.Methods:This prospective cohort study focused on elderly patients who underwent baseline frailty assessment(T0)during hemodialysis treatment at Beijing Friendship Hospital for over 3 months between December 1st, 2022, and December 31th, 2022, and were diagnosed with SARS-CoV-2 infection.The Fried Frailty Phenotype was evaluated at 1 month(T1), 3 months(T2), and 6 months(T3)post-infection.Frailty trajectory after infection was analyzed using repeated measurement ANOVA.Patients were divided into stable/improvement or exacerbation groups based on their frailty status at T0 and T3, with logistic regression analysis employed to identify risk factors for different frailty trajectories.Results:A total of 130 elderly maintenance hemodialysis patients, with a median age of 66 years(range: 63-71 years)and 62 males(47.7%), were included in the study.Six months after the infection, a majority of surviving patients saw their frailty scores return to baseline levels.Specifically, 72 patients(55.4%)either maintained or improved to robust or pre-frail states, while 9 patients(6.9%)progressed to a pre-frail state, 18 patients(13.8%)progressed to a frail state, and 31 patients(23.8%)remained in a frail state.Results from multivariate logistic regression analysis indicated that low grip strength( OR: 6.30, 95% CI: 1.48-26.73)and all-cause hospitalization( OR: 5.01, 95% CI: 1.19-21.03)were identified as risk factors for non-frail patients transitioning to frailty( P<0.05). Conclusions:The majority of elderly maintenance hemodialysis patients who survived SARS-CoV-2 infection returned to their baseline level of frailty or showed improvement within 6 months.Non-frail patients with low grip strength or those who were hospitalized were more likely to deteriorate towards frailty.

OBJECTIVE To explore the clinical characteristics and risk factors for refractory drug-resistant Pseudo-monas aeruginosa infection and evaluate the prognosis so as to provide theoretical bases for effective prevention and control of the refractory drug-resistant P.aeruginosa infection.METHODS A total of 95 patients who were di-agnosed with refractory drug-resistant P.aeruginosa infection and were treated in People's Hospital of Guangdong Province from Jan.2019 to Dec.2023 were assigned as the infection group.Meanwhile,95 patients who did not have drug-resistant P.aeruginosa infection,matched by the age and hospitalization period,were chosen as the non-infection group in a case-control(1∶1 ratio).The basic information and clinical data were collected from the two groups of patients.The characteristics and risk factors for the drug-resistant P.aeruginosa infection were ana-lyzed,and the prognosis of the patients was evaluated.RESULTS Among the clinical isolates of drug-resistant P.aeruginosa,78 were isolated from respiratory secretions;there were 59 patients from intensive care unit(ICU),13 patients from respiratory medicine department and 8 patients from geriatrics department.Fever,dyspnea,moist rales and cough were the major clinical manifestations.The proportions of patients with history of respirato-ry tract disease(P＜0.001),renal disease(P=0.008),nervous system disease(P=0.005),diabetes mellitus(P=0.017),hepatic disease(P=0.007),previous utilization rate of aminoglycosides(P=0.002)and previous u-tilization rate of no less than 3 types of antibiotics were higher in the infection group than in the non-infection group.Multivariate analysis showed that the history of respiratory tract disease(OR=2.813,95％CI:1.366 to 5.792,P=0.005),history of diabetes mellitus(OR=2.465,95％CI:1.129 to 5.382,P=0.024)and history of nervous system disease(OR=2.386,95％CI:1.151 to 4.944,P=0.019)were the risk factors for the drug-resist-ant P.aeruginosa infection.The mortality rate of the infection group was 30.53％,higher than 6.32％of the non-infection group(x2=18.527,P＜0.001).CONCLUSIONS The mortality rate of the patients with drug-resistant P.aeruginosa infection is high.The history of respiratory tract disease,history of diabetes mellitus and history of nervous system disease are the major risk factors for the infection.It is necessary for the hospital to strengthen the awareness of prevention of the drug-resistant P.aeruginosa infection so as to curb the hospital-associated infection.