1.Clinical decision and prescription generation for diarrhea in traditional Chinese medicine based on large language model
Jiaze WU ; Hao LIANG ; Haoran DAI ; Hongliang RUI ; Baoli LIU
Digital Chinese Medicine 2026;9(1):13-30
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.
2.Polypeptide-based Nanocarriers for Oral Targeted Delivery of CAR Genes to Pancreatic Cancer
Feng XIN ; Jian REN ; Zhao-Zhen LI ; Quan FANG ; Rui-Jing LIANG ; Lan-Lan LIU ; Lin-Tao CAI
Progress in Biochemistry and Biophysics 2026;53(2):431-441
ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.
3.Polypeptide-based Nanocarriers for Oral Targeted Delivery of CAR Genes to Pancreatic Cancer
Feng XIN ; Jian REN ; Zhao-Zhen LI ; Quan FANG ; Rui-Jing LIANG ; Lan-Lan LIU ; Lin-Tao CAI
Progress in Biochemistry and Biophysics 2026;53(2):431-441
ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.
4.TCM Syndrome Distribution Patterns and Clinical Characteristics in Patients with Chronic Hepatitis B Comorbid with Metabolically Associated Fatty Liver Disease
Dingqi LI ; Liang HUANG ; Baixue LI ; Rui ZHAO ; Zhenglong ZHENG ; Yichen PENG ; Yu LIANG ; Caiying HE ; Jingdong CUI ; Zilin XIONG ; Xiyang LIU ; Quansheng FENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):259-270
ObjectiveThis paper aims to investigate the distribution patterns of traditional Chinese medicine syndromes in patients with chronic hepatitis B (CHB) comorbid with metabolically associated fatty liver disease (MAFLD) and analyze their correlation with clinical characteristics and the progression of liver fibrosis. MethodsA cross-sectional study method was employed, and 506 patients with CHB comorbid with MAFLD who attended the Hepatology Outpatient Department of Public Health Clinical Center of Chengdu from June 2024 to December 2024 were enrolled. General information, traditional Chinese medicine syndromes information, laboratory indicators, and imaging examination results were collected using case report forms (CRF). Tongue images of patients were acquired using a tongue diagnosis instrument, and tongue feature parameters were extracted using computer image processing technology. Frequency analysis, factor analysis, and cluster analysis, and other methods were used to explore syndrome categories and distribution patterns. Non-parametric tests were used to compare the differences in clinical characteristics among different syndromes. Univariate and multivariate logistic regression analyses were performed to investigate the correlation between traditional Chinese medicine syndromes and the progression of liver fibrosis. ResultsThe main traditional Chinese medicine syndromes in patients with CHB comorbid with MAFLD were mainly dominated by damp-heat accumulation syndrome, liver stagnation and spleen deficiency syndrome, and phlegm-blood stasis syndrome, with damp-heat accumulation syndrome accounting for the highest proportion (41.89%). Compared with those without damp-heat accumulation syndrome, patients with damp-heat accumulation syndrome had significantly lower tongue proper H value, tongue coating H value, and tongue coating a* value (P<0.05), significantly higher tongue coating b* value (P<0.05), significantly increased levels of white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB), and glucose (GLU), increased CAP values (P<0.05), a higher proportion of males (P<0.05), and a younger age (P<0.05). Univariate and multivariate logistic regression analyses show that age, hepatitis B surface antigen (HBsAg), diabetes, and damp-heat accumulation syndrome are independent risk factors for liver fibrosis (P<0.05), and that damp-heat accumulation syndrome is predominantly distributed in liver fibrosis stage F0-F1. ConclusionDamp-heat accumulation syndrome is a typical syndrome in patients with CHB comorbid with MAFLD, which is significantly associated with enhanced inflammatory response, metabolic disorders, and early liver fibrosis, and is a key link in disease progression. Clinical attention and early intervention are needed.
5.Mid- and long-term efficacy of mitral valve plasty versus replacement in the treatment of functional mitral regurgitation: A 10-year single-center outcome
Hanqing LIANG ; Qiaoli WAN ; Tao WEI ; Rui LI ; Zhipeng GUO ; Jian ZHANG ; Zongtao YIN ; Jinsong HAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):108-113
Objective To compare the mid- and long-term clinical results of mitral valve plasty (MVP) and mitral valve replacement (MVR) in the treatment of functional mitral regurgitation (FMR). Methods Patients with FMR who underwent surgical treatment in the Department of Cardiovascular Surgery of the General Hospital of Northern Theater Command from 2012 to 2021 were collected. The patients who underwent MVP were divided into a MVP group, and those who underwent MVR into a MVR group. The clinical data and mid-term follow-up efficacy of two groups were compared. Results Finally 236 patients were included. There were 100 patients in the MVP group, including 53 males and 47 females, with an average age of (61.80±8.03) years. There were 136 patients in the MVR group, including 72 males and 64 females, with an average age of (61.29±8.97) years. There was no statistical difference in baseline data between the two groups (P>0.05). There was no statistical difference between the two groups in the extracorporeal circulation time, aortic occlusion time, postoperative hospital and ICU stay, intraoperative blood loss, or hospitalization death (P>0.05), but the time of mechanical ventilation in the MVP group was significantly shorter than that in the MVR group (P=0.022). The total follow-up rate was 100.0%, the longest follow-up was 10 years, and the average follow-up time was (3.60±2.55) years. There were statistical differences in the left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and cardiac function between the two groups compared with those before surgery (P<0.05). The postoperative left ventricular ejection fraction in the MVP group was statistically higher than that before surgery (P=0.002), but there was no statistical difference in the MVR group before and after surgery (P=0.658). The left atrial diameter in the MVP group was reduced compared with the MVR group (P=0.026). The recurrence rate of mitral regurgitation in the MVP group was higher than that in the MVR group, and the difference was statistically significant (10.0% vs. 1.5%, P=0.003). There were 14 deaths in the MVP group and 19 in the MVR group. The cumulative survival rate (P=0.605) and cardiovascular events-free survival rate (P=0.875) were not statistically significant between the two groups by Kaplan-Meier survival analysis. Conclusion The safety, and mid- and long-term clinical efficacy of MVP in the treatment of FMR patients are better than MVR, and the left atrial and left ventricular diameters are statistically reduced, and cardiac function is statistically improved. However, the surgeon needs to be well aware of the indications for the MVP procedure to reduce the rate of mitral regurgitation recurrence.
6.Current research status and application prospects of mesenchymal stem cell-derived exosomes in islet transplantation
Rui LI ; Dianxiang WANG ; Zhaowei LIANG ; Bing HAN ; Hao LIAN
Organ Transplantation 2025;16(1):163-168
Type 1 diabetes mellitus is a chronic autoimmune disease caused by the destruction of pancreatic islet β cells. Pancreatic islet transplantation provides a treatment method for patients with type 1 diabetes mellitus to restore endogenous insulin secretion. However, some problems limit the widespread application of islet transplantation, such as the shortage of donors and post-transplantation rejection damage. Mesenchymal stem cell-derived exosome (MSC-Exo) has become a potential tool for islet transplantation therapy due to their immunomodulatory and tissue repair capabilities. MSC-Exo shows great promise for application, because of low immunogenicity, easily being stored and transported, and the potential as drug delivery vehicles. However, challenges such as preparation, purification, standardization and safety verification need to be overcome before converting MSC-Exo into clinical practice. Therefore, this article reviews the application and potential advantages of MSC-Exo in islet transplantation, aiming to providing more effective and safer treatment options for patients with type 1 diabetes mellitus.
7.Value of DCE-MRI quantitative parameters in differential diagnosis of brain metastases from non-small cell lung cancer
Rui-peng LIANG ; Yong-long LI ; Hao-tian WANG ; Dan SU ; Xiu-fu ZHANG ; Jun ZHOU
Chinese Medical Equipment Journal 2025;46(5):54-59
Objective To evaluate the value of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)in differentiating histopathological types of brain metastases from non-small cell lung cancer(NSCLC).Methods Sixty-eight patients with brain metastases confirmed by pathology were collected,including 47 lung adenocarcinoma patients divided into a lung adenocarcinoma group and 21 lung squamous cell carcinoma patients into a lung squamous cell carcinoma group.The two groups were compared in terms of the DCE-MRI derived parameters including volume transfer constant(Ktrans),extra vascular extracellular volume fraction(Ve)and plasma volume fraction(Vp);ROC curves were used to assess the diagnostic efficacy of different quantitative parameters for the pathologic types of brain metastases from lung adenocarcinoma group or lung squamous cell carcinoma.SPSS 22.0 software was used for statistical analysis.Results The lung adenocarcinoma group had the values of Ktrans,Ve,Vp and Ve+Vp higher than those of the lung squamous cell carcinoma group,with the differences being statistically significant(all P<0.05).ROC curve analysis results showed that Ktrans,Vp and Ve had high differential diagnosis values for the pathologic types of brain metastases from lung adenocarcinoma group or lung squamous cell carcinoma,with the AUC being 1.000,0.998 and 0.875,the optimal Youden index being 0.183 min-1,0.039 and 0.270,the sensitivity being 100.00%,100.00%and 80.56%and the specificity being 100.00%,97.06%and 80.88%,respectively.Conclusion The quantitative parameters of DCE-MRI gain advantages in the differential diagnosis of NSCLC brain metastases,and provide references for the diagnosis and treatment of brain metastases of lung cancer.[Chinese Medical Equipment Journal,2025,46(5):54-59]
8.Research Progress in Chinese Materia Medica Regulating Ferroptosis for the Treatment of Atherosclerosis
Huiying WANG ; Shaona WANG ; Liang ZHANG ; Haixin FU ; Rui LAN ; Jitao WU
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(1):192-196
Atherosclerosis is a chronic vascular disease caused by lipid deposition in the inner wall of blood vessels.Ferroptosis is a non-apoptotic form of cell death characterized by iron dependence and lipid reactive oxygen accumulation.Recent studies have shown that ferroptosis is closely related to the occurrence and development of atherosclerosis.This article explained the correlation between ferroptosis and atherosclerosis from the aspects of foam cell formation,endothelial cell death,vascular smooth muscle proliferation and calcification,and believed that ferroptosis runs through its pathological process.By combing the current research status of the mechanism of Chinese materia medica regulating ferroptosis to treat atherosclerosis,it can be seen that TCM monomers and compounds can reduce endothelial cell dysfunction and inflammatory response,slow down oxidative stress levels,and reduce the accumulation of oxidized lipids under the intima of arterial blood vessels by regulating ferroptosis p53,Nrf2 signaling pathway,amino acid metabolism,lipid metabolism,etc.,so that the blood vessels reach homeostasis,which can provide a reference for the exploration of clinical treatment strategies for atherosclerosis.
9.Evaluation of the protective effect of acellular DPT vaccine for booster immunization in 6-year-old children
Xuewen TANG ; Yao ZHU ; Rui YAN ; Yaping CHEN ; Hui LIANG ; Hanqing HE
Chinese Journal of Preventive Medicine 2025;59(11):1861-1866
Objective:To evaluate the epidemiological protective effect of a booster dose of acellular DTP vaccine (DTaP) against pertussis in 6-year-old children.Methods:A retrospective cohort study was conducted to compare the incidence of pertussis in 6-year-old children who received DTaP versus DT vaccine boosters in 2023 over a two-year period from May 2023 to May 2025. The protective effect of the fifth dose of DTaP against pertussis in 6-year-old children was evaluated.Results:A total of 960 participants were enrolled in this study, including 480 children in the experimental group who received the fifth dose of DTaP vaccine and 480 children in the control group who received the DT vaccine booster. Baseline characteristics were balanced between the two groups. There were six confirmed cases of pertussis in the experimental group, with a reported incidence rate of 1.25%. In the control group, 14 pertussis cases were reported, with a reported incidence rate of 2.92%. The protective effectiveness(VE) of the DTaP vaccine against pertussis was 57.14% (95% CI:-10.59%-83.39%). For 6-year-old children who completed the booster immunization, the incidence data of pertussis were collected from the 14 th day after vaccination (i.e., the study day 0). Based on the annual cumulative incidence rate, the VE of DTaP against pertussis at 6, 12, 18, and 24 months after vaccination was 100%, 63.80% (95% CI:-14.49%-88.55%), 64.59% (95% CI: 1.17%-87.31%), and 57.60% (95% CI:-10.80%-83.78%), respectively. In the DTaP group, the annual cumulative incidence rate of 12 to 24 months did not show a significant upward or downward trend ( Z=-0.995, P=0.320). Conclusion:Boosting 6-year-old children with the DTaP vaccine provides measurable protection against pertussis. The protective efficacy is significant in the early stage (0 to 6 months) after vaccination, and it still remains effective at 12 to 24 months.
10.Advances in the integrated Chinese and Western medicine approach to managing septic acute lung injury
Rui FAN ; Han LIU ; Qun LIANG ; Shuai LIU ; Yang YANG ; Boyang ZHENG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2025;32(3):369-372
Septic acute lung injury(ALI),a life-threatening complication of sepsis,has garnered significant attention due to its high mortality rate.Despite advances in Western medicine,including anti-infective therapy and lung-protective ventilation strategies,managing inflammatory storm and alveolar-capillary barrier repair remain critical challenges with Western medicine alone,leading to suboptimal patient outcomes.Traditional Chinese medicine,with its emphasis on holistic regulation,has unique advantages in inhibiting excessive inflammation,protecting lung function,alleviating clinical symptoms,and improving the quality of life of patients,and integrated Chinese and Western integrative therapy has demonstrated improved clinical outcomes.This article systematically reviews recent research on Traditional Chinese medicine for septic ALI,focusing on single herbal medicines,traditional Chinese medicine injections,compound formulas,acupuncture,and herbal enemas.It also analyzes research gaps,aiming to inform clinical practice and promote the standardization of integrated Chinese and Western integrative therapy approaches,thus offering new therapeutic strategies for patients with septic ALI.

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