ObjectiveThe essence of syndrome manifestation recognition in traditional Chinese medicine (TCM) is to infer the body’s latent pathogenesis state from clinical observational information, rather than to perform simple label matching. However, previous studies have largely modeled this task as syndrome pattern classification within a fixed label space, which does not adequately reflect the cognition process of TCM syndrome differentiation centered on pathogenesis reasoning, and is also insufficient to capture the openness, semantic variability, and cross-disease reusability of syndrome manifestation expression. This study aimed to investigate whether introducing pathogenesis reasoning chain-of-thought (PR-CoT) supervision into large language models (LLMs) could improve the quality and cognitive consistency of syndrome manifestation recognition and support cross-disease transfer. MethodsSyndrome manifestation recognition was formulated as a conditional generation task under the framework of clinical observational information (X)→pathogenesis structure (Z)→syndrome pattern output (Y), where Z serves as an explicit intermediate structural variable linking the clinical evidence and syndrome judgment. Within this framework, a PR-CoT-supervised dataset for syndrome manifestation recognition was constructed based on medical case records of spleen-stomach disorders. After preprocessing, information extraction, manual proofreading, and data cleaning, the dataset comprised 4 800 training cases, 400 development cases, and 400 test cases. Each sample was annotated with a structured PR-CoT consisting of three progressive levels: clinical information summarization, comprehensive pathogenesis analysis, and syndrome pattern output. Supervised fine-tuning was conducted on open-source LLMs, with an end-to-end model serving as the baseline. Qwen3-32B was used as the primary experimental model, and Qwen3-14B as the scale comparison model. A progressive multidimensional evaluation framework was further established, comprising a structural parsing level, a semantic similarity level, and an expert blind review level. At the structural parsing level, syndrome pattern expressions were decomposed into structural elements and evaluated using Precision, Recall, F1 score, and Jaccard similarity. At the semantic similarity level, independent LLMs scored the theoretical proximity between predicted and reference syndrome patterns. At the expert blind review level, three TCM experts independently evaluated model outputs on two dimensions: syndrome differentiation consistency and terminology standardization of syndrome patterns. In addition, zero-shot cross-disease transfer evaluation was conducted on gynecological and heart-system disorder test sets. ResultsAt the structural parsing level, PR-CoT supervision did not lead to a stable improvement in the element-wise overlap of syndrome pattern structural components. Compared with the corresponding baselines, neither Qwen3-32B nor Qwen3-14B showed consistent advantages in structural matching metrics after the introduction of PR-CoT supervision. In contrast, at the semantic similarity level, PR-CoT supervision produced stable positive gains across different model scales and evaluation systems. The average semantic score of Qwen3-32B increased from 6.425 8 in the baseline model to 6.585 0 after PR-CoT supervision, and that of Qwen3-14B increased from 5.870 0 to 5.964 2. At the expert blind review level, the overall score of Qwen3-32B (PR-CoT) was 7.026 0±0.107 7, higher than 6.416 3±0.288 9 for its baseline. In zero-shot cross-disease testing, the PR-CoT model still showed advantages in semantic evaluation and expert evaluation on both gynecological and heart-system disorder test sets, indicating a certain degree of transferability. ConclusionThe benefits of PR-CoT supervision are mainly reflected in TCM semantic consistency and clinical plausibility, rather than in improved hard matching of structural elements. These findings support understanding syndrome manifestation recognition as a process of generating and expressing latent pathogenesis structures, rather than as a classification task within a traditional fixed label space. By introducing pathogenesis reasoning as an explicit intermediate structure into the modeling process and combining it with a progressive multidimensional evaluation framework, this study provides a methodological pathway for intelligent TCM syndrome differentiation that integrates theoretical alignment, interpretability, and multi-level evaluation.

ObjectiveThe essence of syndrome manifestation recognition in traditional Chinese medicine (TCM) is to infer the body’s latent pathogenesis state from clinical observational information, rather than to perform simple label matching. However, previous studies have largely modeled this task as syndrome pattern classification within a fixed label space, which does not adequately reflect the cognition process of TCM syndrome differentiation centered on pathogenesis reasoning, and is also insufficient to capture the openness, semantic variability, and cross-disease reusability of syndrome manifestation expression. This study aimed to investigate whether introducing pathogenesis reasoning chain-of-thought (PR-CoT) supervision into large language models (LLMs) could improve the quality and cognitive consistency of syndrome manifestation recognition and support cross-disease transfer. MethodsSyndrome manifestation recognition was formulated as a conditional generation task under the framework of clinical observational information (X)→pathogenesis structure (Z)→syndrome pattern output (Y), where Z serves as an explicit intermediate structural variable linking the clinical evidence and syndrome judgment. Within this framework, a PR-CoT-supervised dataset for syndrome manifestation recognition was constructed based on medical case records of spleen-stomach disorders. After preprocessing, information extraction, manual proofreading, and data cleaning, the dataset comprised 4 800 training cases, 400 development cases, and 400 test cases. Each sample was annotated with a structured PR-CoT consisting of three progressive levels: clinical information summarization, comprehensive pathogenesis analysis, and syndrome pattern output. Supervised fine-tuning was conducted on open-source LLMs, with an end-to-end model serving as the baseline. Qwen3-32B was used as the primary experimental model, and Qwen3-14B as the scale comparison model. A progressive multidimensional evaluation framework was further established, comprising a structural parsing level, a semantic similarity level, and an expert blind review level. At the structural parsing level, syndrome pattern expressions were decomposed into structural elements and evaluated using Precision, Recall, F1 score, and Jaccard similarity. At the semantic similarity level, independent LLMs scored the theoretical proximity between predicted and reference syndrome patterns. At the expert blind review level, three TCM experts independently evaluated model outputs on two dimensions: syndrome differentiation consistency and terminology standardization of syndrome patterns. In addition, zero-shot cross-disease transfer evaluation was conducted on gynecological and heart-system disorder test sets. ResultsAt the structural parsing level, PR-CoT supervision did not lead to a stable improvement in the element-wise overlap of syndrome pattern structural components. Compared with the corresponding baselines, neither Qwen3-32B nor Qwen3-14B showed consistent advantages in structural matching metrics after the introduction of PR-CoT supervision. In contrast, at the semantic similarity level, PR-CoT supervision produced stable positive gains across different model scales and evaluation systems. The average semantic score of Qwen3-32B increased from 6.425 8 in the baseline model to 6.585 0 after PR-CoT supervision, and that of Qwen3-14B increased from 5.870 0 to 5.964 2. At the expert blind review level, the overall score of Qwen3-32B (PR-CoT) was 7.026 0±0.107 7, higher than 6.416 3±0.288 9 for its baseline. In zero-shot cross-disease testing, the PR-CoT model still showed advantages in semantic evaluation and expert evaluation on both gynecological and heart-system disorder test sets, indicating a certain degree of transferability. ConclusionThe benefits of PR-CoT supervision are mainly reflected in TCM semantic consistency and clinical plausibility, rather than in improved hard matching of structural elements. These findings support understanding syndrome manifestation recognition as a process of generating and expressing latent pathogenesis structures, rather than as a classification task within a traditional fixed label space. By introducing pathogenesis reasoning as an explicit intermediate structure into the modeling process and combining it with a progressive multidimensional evaluation framework, this study provides a methodological pathway for intelligent TCM syndrome differentiation that integrates theoretical alignment, interpretability, and multi-level evaluation.

Introduction: The 2021 IDF-DAR risk calculator had been previously evaluated in multiple studies and subsequently widely accepted and applied in clinical practice as a practical standardized tool for patient risk stratification. Recently updated, the 2026 IDF-DAR Risk calculator enables a more individualized, evidence-related evaluation of patientrelated and disease-related risk factors, incorporating modern diabetes technologies, including continuous glucose monitoring (CGM), automated insulin delivery (AID) systems, and advanced insulin formulations to enhance risk stratification. This tool allows medical professionals to tailor Ramadan practices based on overall factors toward promoting safe fasting. Methodology: This prospective multicentre observational study recruited adults with Type 1 and Type 2 diabetes attending public hospitals nationwide. People with diabetes (PwD) intending to perform Ramadan fasting were invited to participate and assessed using the 2026 IDF-DAR Risk Calculator in the 6-week pre-Ramadan period between 30th January and 19th March 2026. Results: A total of 458 PwD were evaluated and stratified into low (15.7%), moderate (41%), and high risk (43.3%) categories. Most participants had Type 2 diabetes (83.6%), with 60.3% having a disease duration exceeding 10 years and 43% exhibiting poor glycemic control (hemoglobin A1c >9%). Insulin therapy was used by 76.4% of participants, including two individuals with Type 1 diabetes using AID systems. Most participants reported no recent hypoglycemia (76.4%), 81.0% performed glucose monitoring, and 3.3% used CGM. Severe comorbidities were uncommon, with 1.1% having unstable macrovascular disease and 4.4% advanced chronic kidney disease (estimated glomerular filtration rate <30). Notably, 72.2% received structured Ramadan education. Conclusion Majority of PwD attending tertiary diabetes clinics were in the moderate- to high-risk category and intended to fast despite medical advice against fasting in some cases. Although most participants were on insulin therapy, hypoglycemia was low in the pre-Ramadan period. Integration of modern technologies, advanced insulin therapies, and structured education may support safer fasting practices.
Risk Assessment ; Diabetes Mellitus ; Hospitals ; Fasting

Objective To evaluate the cost–utility of lecanemab and donanemab in the treatment of early Alzheimer’s disease （AD） in China. Methods A Markov model was developed from a societal perspective to compare standard of care （SOC）, lecanemab plus SOC, and donanemab plus SOC in terms of costs, quality-adjusted life years （QALY）, and incremental cost–utility ratios （ICUR）. Deterministic and probabilistic sensitivity analyses were conducted to assess parameter uncertainty. Results Both intervention strategies increased QALY compared with SOC but were associated with substantially higher costs, and neither was cost-effective under the current willingness-to-pay threshold. Conclusion Lecanemab and donanemab may be more appropriately considered within a multi-tiered healthcare reimbursement framework in China rather than relying solely on basic medical insurance.

With the rapid advancement of medical technology and the increasing complexity of clinical environments, competence in clinical ethical decision-making has become an indispensable core competency for exemplary physicians. However, traditional medical ethics education has long been confronted with the persistent challenges of theory-practice dissociation and the disconnect between pedagogical settings and clinical realities. Thus, how to construct a "Clinical Ethics" curriculum that aligns with the objectives of training high-caliber medical professionals has emerged as a critical and challenging issue in current medical education reform. To effectively address this challenge, the Office of Education at Peking University Third Hospital, since 2021, has assembled a multidisciplinary "Clinical Ethics" teaching and management team comprising faculty from Peking University School of Humanities and key clinical specialists from the hospital. In 2022, the "Clinical Ethics" elective course was formally launched for fourth-year students in the eight-year MD program who had completed coursework in "Medical Ethics" and organ-system-based curricula, with the aim of exploring and operationalizing a pre-clinical ethics education model tailored for senior medical students. The course employs a modular instructional design encompassing "theoretical review-case-based deliberation-clinical workshop", which effectively facilitates the deep integration of medical humanities with clinical practice.Following four years of iterative refinement through the "plan-act-observe-reflect" cycle, the course has demonstrated positive outcomes in enhancing students' ethical awareness and decision-making capabilities, and has preliminarily established a sustainable collaborative mechanism among the multidisciplinary faculty team. This article systematically delineates the course development background, pedagogical model and methodological innovations, and the multidisciplinary collaborative framework, alongside reflections and summaries based on implementation outcomes, with the intent of providing references for the future development of "Clinical Ethics" curricula.

Pancreatic cancer has emerged as one of the most challenging malignancies worldwide,with its high resistance to chemotherapy being the primary cause of treatment failure.Therefore,enhancing the chemosensitivity of pancreatic cancer has become a major focus of current research.In this study,we in-vestigated how Bufotaline,a bufadienolide extracted from the traditional Chinese medicine toad venom,exhibits its antitumor activity.Specifically,we explored the potential of Bufotaline to enhance the chemo-sensitivity of pancreatic cancer cells to Adriamycin and elucidated its underlying molecular mechanisms.Using CCK-8 and colony formation assays,we demonstrated that Bufotaline enhances the inhibitory effect of Adriamycin on the survival of pancreatic cancer cell lines Patu-8988T,Aspc-1,and Patu-8988S.No-tably,Bufotaline treatment reduced the IC50 of Adriamycin in drug-resistant pancreatic cancer cells to lev-els comparable to those in non-resistant cells.Results from Western blot,immunofluorescence,comet as-say,and TUNEL assays revealed that Bufotaline promotes Adriamycin-induced DNA damage in pancreatic cancer cells.RNA-seq analysis of Patu-8988T cells treated with Adriamycin alone or in combination with Bufotaline showed significant changes in gene expression,and qRT-PCR analysis further confirmed that Bu-fotaline downregulates the expression of DNA damage repair proteins NBS1 and RAD50.Moreover,Western blot analysis revealed that Bufotaline reduces the levels of DNA damage response repair proteins,and Im-munofluorescence experiments indicated that Bufotaline inhibits the activation of the ATM/CHK2 signaling pathway.Finally,in a subcutaneous xenograft mouse model,the combination of Adriamycin and Bufotaline treatment significantly suppressed pancreatic cancer cell growth.In conclusion,Bufotaline enhances Adria-mycin-induced chemosensitivity in pancreatic cancer cells;the combination of Adriamycin and Bufotaline downregulates the expression of DNA damage response repair proteins NBS1 and RAD50,and inhibits the ATM/CHK2-mediated DDR signaling pathway,thereby delaying DNA damage repair.

Objective To explore the clinical and pathological characteristics of medullary thyroid carcinoma(MTC)combined with papillary thyroid carcinoma(PTC),and to improve the detection rate of mixed thyroid tumors.Methods A retrospective analysis was conducted on the clinicopathological data of 11 cases of MTC combined with PTC diagnosed in the Department of Pathology,Jiangsu Province Hospital on Integration of Chinese and Western Medicine from April 2010 to April 2025,and analysis.Results Among the 11 patients,there were 4 males and 7 females with a median age of 57 years.The preoperative puncture pathology of 11 cases was not diagnosed as MTC combined with PTC.All patients underwent intraoperative rapid pathological diagnosis.Among them,5 cases were MTC combined with PTC,3 cases were PTC combined with thyroid follicular neoplasm,and the rest were diagnosed with single tumor(PTC or MTC).Conventional pathology diagnosed that all 11 patients had MTC combined with PTC,among which 2 cases were mixed MTC-PTC,and 6 cases were combined with multinodular goiter,and 3 cases combined with chronic lymphocytic thyroiditis.The histological morphology of MTC and PTC was diverse,presenting in arrangements such as papillary,island,follicular or solid.MTC cells are round,oval,spindle-shaped or plasma cell-like,with indistinct boundaries.The cytoplasm is eosinophilic,bicolotropic or transparent.The nucleus is round,irregular or spindle-shaped,with rough chromatin that does not have the characteristics of PTC cell nuclei.Amyloid deposits are seen in the interstitium.Immunohistochemistry expresses calcitonin(CT)and carcinoembryonic antigen(CEA),but does not express thyroglobulin(Tg).Special staining shows Congo red as brick red,and under a polarizing microscope,it appears as a refractive apple green.The nuclei of PTC cells are round or oval,and the cytoplasm is eosinophilic or bicolotropic.The nuclei are enlarged and arranged in a crowded manner.Nuclear grooves and pseudo-inclusions within the nucleus can be seen.Immunohistochemistry expressed thyroid transcription factor-1,paired box gene 8,and mesothelial cell membrane protein protenin mesothelial cell membrane protenin-1,Tg,galectin-3,cytokeratin are not expressed.CT and CEA are not expressed.Special staining is negative for Congo red.Conclusion MTC combined with PTC is relatively rare.There are no special manifestations in clinical features and imaging examinations.Preoperative puncture pathology and intraoperative rapid pathology are difficult to make a clear diagnosis.Clinicians and pathologists should avoid missed diagnoses or misdiagnoses.

Objective:To observe the applying effect of teamwork cooperation model of encephalopathy in the clinical teaching of Neurology.Methods:Sixty undergraduate students who practiced in our hospital were randomly divided into the control group and the experimental group,with 30 students in each group.The control group was arranged for internship according to the traditional department-based model,while the experimental group was arranged according to the teamwork cooperation model of encephalopathy discipline group.The theoretical examination scores and clinical skills scores of the two groups were compared,and the Mini-Clinical Evaluation Exercise(Mini-CEX)scale was used for dual evaluation by teachers and students from seven aspects:inquiry skills,physical examination skills,humanistic care,clinical judgment,communication skills,organizational effectiveness,and overall clinical competence.Result:There were statistically significant differences between the experimental group and the control group in theoretical examination scores,clinical skills scores,and dual evaluation by teachers and students(P＜0.05).Conclusion:Compared with the traditional teaching model,the teamwork cooperation model of encephalopathy discipline group has achieved better results in the clinical teaching of Neurology.

Objective To investigate the clinical efficacy of Modified Yinhuo Guiyuan Huayu Formula(MYGHF)in diabetic retinopathy(DR)patients with yin deficiency and blood stasis syndrome and to observe its regulatory effects on the nuclear factor κB(NF-κB)signaling pathway.Methods A total of 100 DR patients(200 eyes)with yin deficiency and blood stasis syndrome admitted to the Fourth People's Hospital of Hengshui from January 2019 to April 2020 were equally randomized into a control group(50 cases,100 eyes)and an observation group(50 cases,100 eyes)using a random number table.Both groups were required to conduct intensive glycemic control.The control group was treated with conventional western medicine of lecithin-bound iodine,while the observation group received additional MYGHF for 3 months.Parameters of traditional Chinese medicine(TCM)syndrome scores,key components of NF-κB signaling pathway[NF-κB p65,inhibitor of kappa B kinase(IKK),inhibitor kappa B(IκB)],angiogenesis-related factors[fibroblast growth factor 21(FGF21),vascular endothelial growth factor(VEGF),angiopoietin 2(Ang2)],and efficacy indicators[glycated hemoglobin(HbA1c),fasting blood glucose(FBG),homeostasis model assessment of insulin resistance(HOMA-IR),visual field grayscale value,and best-corrected visual acuity(BCVA)]in the two groups were evaluated before treatment and 1 and 3 month(s)after treatment.After treatment,the clinical efficacy and safety of the two groups were assessed.Results(1)After 3 months of treatment,the total effective rate was 88.00%(44/50)in the observation group versus 70.00%(35/50)in the control group,demonstrating significantly superior therapeutic effects of TCM syndrome differentiation in the observation group(tested by chi-square test,P＜0.05).(2)At 1 and 3 month(s)after treatment,both groups showed reduced scores for TCM symptoms of blurred vision,dizziness and tinnitus,soreness and weakness of waist and knees,and feverish sensation in the palms and soles compared to the baseline levels(all P＜0.05).The observation group exhibited significantly greater reductions in these symptom scores than the control group at both time points(all P＜0.05).(3)The protein expression levels of NF-κB p65,IKK were decreased and IκB was increased in both groups at 1 and 3 month(s)after treatment compared to the baseline levels(all P＜0.05),and the observation group demonstrated more pronounced improvement of these key pathway components compared to the control group(all P＜0.05).(4)The levels of angiogenesis-related factors of FGF21,Ang2,and VEGF were significantly reduced in both groups at 1 and 3 month(s)compared to the baseline levels(all P＜0.05),and the observation group showed superior decreases compared to the control group(all P＜0.05).(5)The efficacy indicators of HbA1c,FBG,HOMA-IR,visual field grayscale values,and BCVA were improved in both groups at post-treatment 1 and 3 month(s)compared to the baseline levels(all P＜0.05),and the observation group achieved significantly superior improvement in all indicators compared to the control group(all P＜0.05).(6)The total incidence of adverse reactions was 2.00%(1/50)in the observation group versus 8.00%(4/50)in the control group,with no statistically significant difference between groups(P＞0.05).Conclusion MYGHF effectively alleviates clinical symptoms in patients with DR of yin deficiency and blood stasis type,and is effective on modulating angiogenesis-related factors and suppressing NF-κB signaling pathway activation,demonstrating satisfactory efficacy and good safety profile.

ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back， and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group， with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes， three times per week； the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement， as the primary outcome， was assessed using the Global Pain Scale （GPS） at baseline， after 2 weeks of treatment， and again 2 weeks post-treatment. To explore potential mechanisms， a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration， the between-group mean difference was -8.8 ［95% CI （-18.2， -0.7）， P＜0.05］. Part of the therapeutic effect was mediated by changes in deep muscle elasticity， with a mediation effect size of -1.5 ［95% CI （-2.0， -0.9）， P = 0.024］， accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back， partly through a mediating effect of improved deep muscle elasticity.