1.Pathogenesis Reasoning Chain-of-thought Supervision for Large Language Models: Syndrome Manifestation Recognition and Multidimensional Evaluation in Spleen-stomach Disorders
Shu-Han YANG ; Yu-Xin HU ; Xin-Yu YU ; Yu-Ying TU ; Yi-Chang ZANG ; Pan-Fei LI
Progress in Biochemistry and Biophysics 2026;53(5):1240-1263
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.
2.Pathogenesis Reasoning Chain-of-thought Supervision for Large Language Models: Syndrome Manifestation Recognition and Multidimensional Evaluation in Spleen-stomach Disorders
Shu-Han YANG ; Yu-Xin HU ; Xin-Yu YU ; Yu-Ying TU ; Yi-Chang ZANG ; Pan-Fei LI
Progress in Biochemistry and Biophysics 2026;53(5):1240-1263
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.
3.Cost–utility analysis of lecanemab and donanemab for early Alzheimer’s disease in China
Wei SHAO ; Fei YU ; Ying LIU ; Lixin SHU ; Dan HAN
Journal of Pharmaceutical Practice and Service 2026;44(7):376-382
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.
4.Bufotaline Enhances the Sensitivity of Pancreatic Cancer Cells to Adriamycin Treatment by Inhibiting DNA Damage Repair
Ming-Wen YIN ; Shu-Ting HAN ; Jiao XUE ; Jun-Jie MIAO ; Shi-Ying ZHAO ; Ze YU ; Jing JIN
Chinese Journal of Biochemistry and Molecular Biology 2025;41(10):1410-1420
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.
5.Application of teamwork cooperation model of encephalopathy discipline group in clinical teaching of Neurology
Ying BIAN ; Bao QIU ; Shu LI ; Junping RAO ; Hongzhong SONG ; Lisheng YU
Journal of Shenyang Medical College 2025;27(1):91-95
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.
6.NLRP3-COX-2 signaling pathway activating microglia mediates breast cancer-related depression
Song YANG ; Ying HE ; Yuan-shan HAN ; Man-shu ZOU ; Hai-xia HE ; Yu-HONG WANG
Chinese Pharmacological Bulletin 2025;41(9):1754-1761
Aim To investigate the effects of breast cancer-related depression model on microglial activa-tion and neuronal function via the NLRP3-COX-2 sig-naling pathway.Methods In the cell experiment,BV2 and HT22 cells were co-cultured to observe the polarization of BV2 cells and the injury of HT22 cells.In the animal experiment,behavioral experiments were used to evaluate the depressive behaviors of mice.HE staining and tumor weight were used to evaluate the changes of axillary tumors.ELISA was used to detect the contents of CA153,CA125,CEA,as well as the changes in the contents of 5-HT,DA and others in the serum and hippocampus.RT-qPCR and immunohisto-chemistry were used to detect the mRNA and protein expression of IL-1 β,IL-18 and other indicators,re-spectively.Immunofluorescence was used to detect CD1 1b and Iba-1.Nissl staining and transmission elec-tron microscopy were used to observe the hippocampal neurons.Results The results of cell experiments showed that compared with the model group,the pro-tein contents and mRNA expression levels of NLRP3,COX-2,and IL-1 β in the NLRP3 knockdown group were all decreased.The results of animal experiments showed that compared with the model group,the be-havioral performance of the experimental group was im-proved,and the mRNA and protein expression levels of IL-1 β,IL-18,and NLRP3 were decreased.Conclu-sion BCRD may mediate the polarization of microglia and the injury of hippocampal neurons through the NL-RP3-COX-2 signaling pathway.
7.Effects of Japan Tallow on Alleviating Liver Injury and Modulating Gut Microbiota in Type 2 Diabetic Mice
Kai-ya XIE ; Xin YU ; En-ya LI ; Li-ping HUA ; Xiao-man LI ; Ying-zhen SU ; Meng-chun SHU ; Yi-jian YANG
Progress in Modern Biomedicine 2025;25(19):3041-3047
Objective:To investigate the effects of Japan tallow(JT)on liver injury and gut microbiota regulation in type 2 diabetes mellitus(T2DM)mice,thereby providing a theoretical basis for developing therapeutic edible oils for diabetes treatment.Methods:T2DM animal model was established through a combined approach of nutritional intervention and chemical induction.Experimental animals were first fed a high-fat diet(HFD)for 6 weeks,followed by intraperitoneal injection of freshly prepared streptozotocin(STZ).After successful model establishment,the mice were divided into five groups(n=6 per group):control group without any intervention;T2DM group;HFD reversion to standard chow group;metformin group;and JT intervention group,which received respective treatments for 4 weeks.At the endpoint,fresh fecal samples were collected from all groups,and the gut microbiota composition was analyzed using 16s rDNA high-throughput sequencing.Liver histopathological changes were examined using histological methods.Results:Compared with the normal control(ND),T2DM mice showed significantly increased fasting blood glucose(FBG)levels,with evident hepatocyte lipid accumulation,steatosis,inflammatory cell infiltration,and widespread vacuolar and fatty degeneration.After Japan tallow(JT)intervention,FBG levels decreased significantly,liver color approximated normal appearance,and pathological morphology improved noticeably.16s rDNA sequencing analysis demonstrated that JT treatment could effectively regulate the intestinal microbiota structure in T2DM mice.Increased microbial α-diversity indices(Chao1,observed_species,Faith_pd,Simpson);At the phylum level,increased Verrucomicrobia abundance while decreased Proteobacteria were detected;At the family level,elevated Bifidobacteriaceae and reduced Porphyromonadaceae were seen;At the genus level,Bifidobacterium was promoted and Akkermansia proliferat while Escherichia and Klebsiella were downregulated.Conclusions:Japan tallow exhibits significant effects in alleviating liver tissue damage and regulating intestinal microbiota disorders in T2DM mice,our study indicated new theoretical basis for the research and development of potential strategy for diabetes.
8.Risk prevention and control and quality efficiency improvement of medical equipment procurement
Quan-quan LI ; Ming QIU ; Shu-ying LI ; Xin-yi HUANG ; Yu ZHENG ; Zhi-ling WANG ; Ke MA
Chinese Medical Equipment Journal 2025;46(3):81-85
Objective To investigate the impact of risk prevention and control on the quality efficiency of medical equipment procurement.Methods The medical equipment procurement projects with enhanced risk prevention measures during 2023(119 items)were assigned to an observation group,while those without strengthened risk control during 2022(118 items)were enrolled into a control group.The two groups were compared in terms of bid failure/rejection rates,procurement completion cycles(including procurement execution cycle and total procurement cycle)and procurement satisfaction.Statistical analysis was performed using SPSS 20.0 software.Results The observation group demonstrated significantly lower bid failure/rejection rates when compared with the control group(≥2 occurrences:5.88%vs.15.25%,P<0.05).The procurement execution cycle was notably shorter in the observation group((69.16±78.65)d vs.(97.67±49.84)d,P<0.05),though no significant difference was observed in total procurement cycle(P>0.05).The observation group behaved better significantly than the control group in procurement efficiency,equipment performance,procedural compliance and post-purchase service satisfaction(all P<0.05).Conclusion Risk prevention and control measures in medical equipment procurement effectively reduce bid failure/rejection risks while enhancing procurement quality efficiency.[Chinese Medical Equipment Journal,2025,46(3):81-85]
9.Eye Movement and Gait Variability Analysis in Chinese Patients With Huntington’s Disease
Shu-Xia QIAN ; Yu-Feng BAO ; Xiao-Yan LI ; Yi DONG ; Zhi-Ying WU
Journal of Movement Disorders 2025;18(1):65-76
Objective:
Huntington’s disease (HD) is characterized by motor, cognitive, and neuropsychiatric symptoms. Oculomotor impairments and gait variability have been independently considered as potential markers in HD. However, an integrated analysis of eye movement and gait is lacking. We performed multiple examinations of eye movement and gait variability in HTT mutation carriers, analyzed the consistency between these parameters and clinical severity, and then examined the associations between oculomotor impairments and gait deficits.
Methods:
We included 7 patients with pre-HD, 30 patients with HD and 30 age-matched controls. We collected demographic data and assessed the Unified Huntington’s Disease Rating Scale (UHDRS) score. Examinations, including saccades, smooth pursuit tests, and optokinetic (OPK) tests, were performed to evaluate eye movement function. The parameters of gait include stride length, walking velocity, step deviation, step length, and gait phase.
Results:
HD patients have significant impairments in the latency and velocity of saccades, the gain of smooth pursuit, and the gain and slow phase velocities of OPK tests. Only the speed of saccades significantly differed between pre-HD patients and controls. There are significant impairments in stride length, walking velocity, step length, and gait phase in HD patients. The parameters of eye movement and gait variability in HD patients were consistent with the UHDRS scores. There were significant correlations between eye movement and gait parameters.
Conclusion
Our results show that eye movement and gait are impaired in HD patients and that the speed of saccades is impaired early in pre-HD. Eye movement and gait abnormalities in HD patients are significantly correlated with clinical disease severity.
10.Eye Movement and Gait Variability Analysis in Chinese Patients With Huntington’s Disease
Shu-Xia QIAN ; Yu-Feng BAO ; Xiao-Yan LI ; Yi DONG ; Zhi-Ying WU
Journal of Movement Disorders 2025;18(1):65-76
Objective:
Huntington’s disease (HD) is characterized by motor, cognitive, and neuropsychiatric symptoms. Oculomotor impairments and gait variability have been independently considered as potential markers in HD. However, an integrated analysis of eye movement and gait is lacking. We performed multiple examinations of eye movement and gait variability in HTT mutation carriers, analyzed the consistency between these parameters and clinical severity, and then examined the associations between oculomotor impairments and gait deficits.
Methods:
We included 7 patients with pre-HD, 30 patients with HD and 30 age-matched controls. We collected demographic data and assessed the Unified Huntington’s Disease Rating Scale (UHDRS) score. Examinations, including saccades, smooth pursuit tests, and optokinetic (OPK) tests, were performed to evaluate eye movement function. The parameters of gait include stride length, walking velocity, step deviation, step length, and gait phase.
Results:
HD patients have significant impairments in the latency and velocity of saccades, the gain of smooth pursuit, and the gain and slow phase velocities of OPK tests. Only the speed of saccades significantly differed between pre-HD patients and controls. There are significant impairments in stride length, walking velocity, step length, and gait phase in HD patients. The parameters of eye movement and gait variability in HD patients were consistent with the UHDRS scores. There were significant correlations between eye movement and gait parameters.
Conclusion
Our results show that eye movement and gait are impaired in HD patients and that the speed of saccades is impaired early in pre-HD. Eye movement and gait abnormalities in HD patients are significantly correlated with clinical disease severity.

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