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.Predictive Factors Associated With Dysphagia in Patients With Traumatic Brain Injury
Shu-Mei YANG ; Ting-Ju LAI ; Ya-Chu HSU ; Yu-Lin LU ; Hsing-Yu CHEN ; Hsiao-Ting TSAI ; Sheng-Hao CHENG ; Ming-Yen HSIAO ; Meng-Ting LIN
Annals of Rehabilitation Medicine 2026;50(2):117-128
Objective:
To identify early clinical predictors associated with dysphagia and delayed swallowing recovery in patients with traumatic brain injury (TBI).
Methods:
In this retrospective study, we enrolled adult TBI patients admitted to the rehabilitation unit of a tertiary medical center between June 2019 and June 2023. Data on baseline characteristics, neurological status, imaging findings, and rehabilitation-related variables were collected. Swallowing function was assessed using two indicators: (1) nasogastric (NG) tube retention and (2) the Functional Oral Intake Scale (FOIS) scores at 1, 4, and 12 weeks post-injury. Regression analyses were conducted to identify predictors associated with dysphagia and swallowing recovery.
Results:
A total of 160 patients were included. At 1 week post-injury, longer intensive care unit (ICU) stay, poor initial sitting balance and use of sedative medication in ICU were associated with NG tube retention. At 4 weeks, lower initial Rancho Los Amigos Scale (RLAS) scores, immobility-related complications, longer hospitalization, and temporal lobe hematomas were associated with persistent NG tube dependence. By 12 weeks, older age, delayed ability to follow commands, and poor initial sitting balance remained associated with NG tube retention. FOIS outcomes were also associated with older age, delayed time to follow commands, impaired initial sitting balance, prolonged ICU stay, temporal lobe hematomas, lower initial RLAS scores, immobility-related complications, prolonged endotracheal tube placement and extended hospital stays.
Conclusion
Impaired cognitive status, poor physical function, immobility-related complications, and temporal lobe hematomas were key factors associated with dysphagia and delayed oral intake in individuals with TBI.
4.Research progress on intelligent diagnosis of eye diseases based on facial photos
Hanwen XU ; Moxin CHEN ; Xiaoyi LIANG ; Qin SHU ; Wanqin NIE ; Xuefeng YANG ; Minxuan SHEN ; Xiaojing LI ; Yu CAO ; Lin LI
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(9):1249-1255
The number of patients with eye diseases in China is enormous,and the negative effects of these conditions,such as impaired visual function,psychological burdens,and restricted social participation,are becoming increasingly severe.Due to the limited and unevenly distributed ophthalmic resources,and the significant limitations of traditional diagnostic and therapeutic approaches in terms of accuracy and efficiency,there is an urgent need for more sensitive and efficient modalities.With the rapid advancement of artificial intelligence technology,ophthalmic diagnosis has entered a new stage of intelligent transformation.Facial photos,as a noninvasive and convenient medium,show unique advantages in eye disease diagnosis.Artificial intelligence systems based on facial photo analysis have been applied to the screening and diagnosis of conditions such as myopia,strabismus,ptosis,and thyroid eye disease,showing promising results.This review introduces the workflow of intelligent diagnosis for ocular diseases based on facial photographs,with a focus on recapitulating relevant research findings both domestically and internationally in recent years.It summarizes the innovative features and application advantages of intelligent diagnosis systems for eye diseases based on facial photos,analyzes the current technical bottlenecks and challenges in application,proposes corresponding countermeasures,and discusses future development directions,aiming to provide references and new insights for the intelligent screening and diagnosis of eye diseases.
5.Teaching Practice and Exploration of"Tutorial System"Based on The Cultivation of Scientific Research and Innovation Ability of Medical Students
Qiao ZHANG ; Yin-Feng YANG ; Yue-Li NI ; Zhuo-Ran TENG ; Wen-Jing LIU ; Jing WU ; Yan-Rui WU ; Yu DOU ; Ming HE ; Shu-De LI ; Ping GAN ; Fang YUAN ; Zhe YANG ; Xin-Wang YANG
Chinese Journal of Biochemistry and Molecular Biology 2025;41(3):470-480
The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.
6.Teaching Practice and Exploration of"Tutorial System"Based on The Cultivation of Scientific Research and Innovation Ability of Medical Students
Qiao ZHANG ; Yin-Feng YANG ; Yue-Li NI ; Zhuo-Ran TENG ; Wen-Jing LIU ; Jing WU ; Yan-Rui WU ; Yu DOU ; Ming HE ; Shu-De LI ; Ping GAN ; Fang YUAN ; Zhe YANG ; Xin-Wang YANG
Chinese Journal of Biochemistry and Molecular Biology 2025;41(3):470-480
The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.
7.Study on the correlation between cardiac implantable electronic device electrode leads and tricuspid regurgitation
Yu-yang JIN ; Jian-hua WANG ; Jian XU ; Shu-feng LI ; Wei CAO
Chinese Journal of Interventional Cardiology 2025;33(3):141-149
Objective To investigate the effect of operation mode,thickness,and number of implanted electrode leads on tricuspid regurgitation.Methods This was a single-center retrospective study.Patients who received their first cardiac implantable electronic device at the Second Affiliated Hospital of Harbin Medical University from January 2019 to January 2024 and were followed up within(10±4)months were continuously enrolled.General clinical data,preoperative and outpatient follow-up echocardiography,and other indicators were collected.According to the different operation modes,patients were divided into delivery sheath group,support wire group,and delivery sheath combined support wire group.Under the premise of only one electrode wire crossing the tricuspid valve,according to the different thicknesses of the electrode wire,they were divided into 3830 69 group(4.1 F),5076 58/Solia S60 group(7 F),and 6935M-65cm defibrillator group(9 F).The number of electrode wires was divided into 3830 69 subgroup and 6935M-65cm defibrillator subgroup under the premise of balanced operation mode and electrode material.The changes in tricuspid valve regurgitation were compared in each group.Results A total of 219 patients,aged(65.92±12.04)years,were enrolled.There was no difference in tricuspid valve regurgitation in the 6935M-65cm defibrillator subgroup before implantation(all P>0.05).In the 3830 69 subgroup,there was a higher proportion of severe regurgitation in the two-electrode group before implantation(P=0.013).In comparison with the change in tricuspid valve regurgitation before electrode wire implantation and during follow-up,the regurgitation of the tricuspid valve in the 6935M-65cm defibrillator subgroup with≥2 electrodes was unexpectedly improved compared to that in the group with one electrode,and the regurgitation of the valve in the group with one electrode was more severe than that in the group with ≥ 2 electrodes implantation(P=0.019).Conclusions The operation mode and thickness of the implanted electrode lead did not cause significant differences in tricuspid valve regurgitation.Single implantation of a 6935M-65cm defibrillator electrode will lead to increased tricuspid regurgitation,and the effect brought by combination with physiological pacing will offset the adverse effects of electrode leads on the valve,providing directional evidence for future implantation strategy selection.
8.Clinical effects of Yifei Tongluo Decoction combined with azithromycin on patients with childern severe Mycoplasma pneumoniae pneumonia due to Toxic Heat Blocking Lung
Shu-ling WANG ; Yu-qing GUO ; Xiao-yang TANG ; Yan ZHANG ; Yan-rong GUO ; Xiao-song CHEN
Chinese Traditional Patent Medicine 2025;47(4):1162-1167
AIM To investigate the clinical effects of Yifei Tongluo Decoction combined with azithromycin on patients with childern severe Mycoplasma pneumoniae pneumonia due to Toxic Heat Blocking Lung.METHODS One hundred and fifty-six patients were randomly assigned into control group(78 cases)for 7-day administration of azithromycin,and observation group(78 cases)for 7-day administration of both Yifei Tongluo Decoction and azithromycin.The changes in clinical effects,disappearance time of local symptoms,mycoplasmas,pulmonary imaging score,Toxic Heat Blocking Lung score,pulmonary function indices(PEF,VPTEF,MMF,TPTEF),inflammatory factors(sB7-H3,Cgp-39,sICAM-1,CCL5),immune function indices(RBC-C3bR,RBC-ICR,CD3+,CD4+)and safety indices were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05),along with shorter disappearance time of local symptoms(P<0.05).After the treatment,the two groups displayed decreased mycoplasmas,pulmonary imaging score,Toxic Heat Blocking Lung score,inflammatory factors,RBC-ICR(P<0.05),and increased pulmonary function indices,RBC-C3bR,CD3+,CD4+(P<0.05),especially for the observation group(P<0.05).No obvious difference in incidence of adverse reactions was found between the two groups(P>0.05).CONCLUSION For the patients with childern severe Mycoplasma pneumoniae pneumonia due to Toxic Heat Blocking Lung,Yifei Tongluo Decoction combined with azithromycin can safely and effectively alleviate clinical symptoms,improve pulmonary functions,and reduce body inflammatory responses.
9.Pathogenic analysis of suspected food poisoning due to Clostridium perfringens through whole genome sequencing
Shu-kun YU ; Zi-yan CUI ; Lang LIU ; Ya-xin TAN ; Zhou-ying CUI ; Zhi-yang TAO
Chinese Journal of Zoonoses 2025;41(1):61-66
This study was aimed at tracing the molecular typing and drug resistance characteristics of a suspected food poi-soning event caused by Clostridium perfringens in a district of Wuhan City.The FilmArray detection system and multiple fluo-rescence quantitative PCR methods were used to rapidly screen for pathogens in samples from the poisoning event.According to the initial screening results,bacteria were isolated,cultured,and identified by mass spectrometry.Fluorescence PCR was used to detect six virulence genes of the isolated Clostridium perfringens strains.On the basis of whole genome sequencing results,we conducted virulence genes,resistance genes,and whole genome single nucleotide polymorphism genetic evolution(wgSNPs)analyses.Antibiotic sensitivity testing was conducted with the agar dilution method.A total of ten strains of Clos-tridium perfringens were isolated,including eight strains from seven anal swab samples,one strain from fecal samples,and one strain from food samples.Food with suspected contamination had a Clostridium perfringens count of 7.8×106 CFU/g.The PLC(a)toxin gene was detected in all ten gas producing capsule isolation strains,but no other 5 tox-in genes such as CPE were detected,thus confirming that all were type A bacteria producing capsule Clostridium.All strains were 100%resistant to clindamycin and almost completely sensitive to antibiotics such as vancomycin,cefoxitin,and meropenem.Ten strains of Clos-tridium perfringens carried resistance genes such as tetB(P),tetA(P),and mprF,followed by ermQ(70%),ant(6)-Ⅰb(10%),and LnuP(10%).Genetic evolution analysis of wgSNPs indicated that the four outbreak strains clustered together and belonged to an independent subbranch with the suspected food sourcestrains,thus indicating close genetic relationships.In con-clusion,this food poisoning incident might have been be caused by hand torn chickens contaminated with Clostridium perfrin-gens,and the molecular types of the strains revealed high genetic diversity.No multiple drug resistance was observed,but all strains were resistant to clindamycin,an aspect requiring further clinical attention.
10.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.

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