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.Study on Spatial Distribution Characteristics and Influencing Factors of the Potential Suitable Habitats for Cremastrae Pseudobulbus Pleiones Pseudobulbus Based on Maximum Entropy Model Combined with Geographical Detector
Shaoyang XI ; Gonghan TU ; Huaqian GONG ; Fei CHEN ; Xudong GUO ; Ling JIN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(2):7-13
Objective To analyze the spatial distribution patterns of the potential suitable habitats for Cremastrae Pseudobulbus Pleiones Pseudobulbus,including Cremastra appendiculata(D.Don)Makino,Pleione bulbocodioides(Franch.)Rolfe and Pleione yunnanensis Rolfe under current climatic conditions,and the factors influencing the spatial differentiation of their habitats.Methods Based on the maximum entropy(MaxEnt)model,a species distribution model was established using the screened species distribution data and environmental variable data.The factor detection and interaction detection of geographical detector were applied to quantify the factors influencing the spatial differentiation of the suitable areas.By overlaying the suitable areas with land cover types,the distribution characteristics of forest land and arable land in the potential suitable areas were quantified.Results Under the current climatic scenario,environmental variables such as solar radiation intensity,precipitation and temperature were closely related to the spatial distribution of Cremastrae Pseudobulbus Pleiones Pseudobulbus.The potential suitable areas for Cremastra appendiculata(D.Don)Makino,Pleione bulbocodioides(Franch.)Rolfe and Pleione yunnanensis Rolfe were 2.20×106 km2,2.75×106 km2 and 7.22×105 km2,respectively.Considering land cover types,the actual possible suitable areas for Cremastra appendiculata(D.Don)Makino,Pleione bulbocodioides(Franch.)Rolfe and Pleione yunnanensis Rolfe were 1.86×106 km2,2.20×106 km2 and 5.77×105 km2,respectively.Among these,the area of forest land was 1.17×106 km2,1.34×106 km2 and 3.67×105 km2,respectively,and the area of arable land was 6.95×105 km2,8.64×105 km2 and 2.10×105 km2,respectively.Conclusion This study can provide a basis for the protection and sustainable utilization of wild resources of the original plant materials of Cremastrae Pseudobulbus Pleiones Pseudobulbus.
4.Spatial Distribution Characteristics and Influencing Factors of Suitable Habitats of Codonopsis pilosula(Franch.)Nannf.Based on Maximum Entropy Modeling and Geographical Detector
Shaoyang XI ; Gonghan TU ; Huaqian GONG ; Fei CHEN ; Xudong GUO ; Ling JIN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(5):1-6
Objective To investigate the spatial distribution pattern of the suitable habitats for Codonopsis pilosula(Franch.)Nannf.and the factors influencing the spatial differentiation of its habitat under current climatic conditions in China.Methods Based on maximum entropy(MaxEnt)model,a species distribution model was established with filtered species occurrence data and environmental variable data.The geographical detector was applied to quantify the factors influencing the spatial differentiation of the suitable areas,employing both factor detection and interaction detection functionalities.Additionally,an overlay analysis with land cover types was conducted to quantify the distribution characteristics of arable land and forest land within the potential suitable areas for Codonopsis pilosula(Franch.)Nannf..Results Based on the contribution rate of environmental factors and the Jackknife method,average solar radiation intensity in December,precipitation in July,and highest temperature in December were identified as key environmental factors affecting the suitability of Codonopsis pilosula(Franch.)Nannf.habitats,which were further validated by the geographical detector.The total suitable area for Codonopsis pilosula(Franch.)Nannf.in China under current climatic conditions was approximately 4.46×106 km2,with the areas of high,moderate,and low suitability being 1.08×106 km2,1.70×106 km2,and 1.68×106 km2,respectively.After overlaying with arable and forest lands,the potentially suitable total forest area for Codonopsis pilosula(Franch.)Nannf.was 1.55×106 km2,and the arable land area was 1.63×106 km2.Conclusion This study provides reference for the optimization of cultivation areas for Codonopsis pilosula(Franch.)Nannf.and the conservation of its wild resources.
5.Simulation and Quantitative Analysis of the Suitable Habitats for Cordyceps Based on Habitat Characteristics,Biological Traits,and Ecological Niche Overlap
Shaoyang XI ; Xudong GUO ; Fei CHEN ; Huaqian GONG ; Gonghan TU ; Ling JIN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(6):1-7
Objective To analyze the spatial distribution pattern of the potential suitable habitats for Cordyceps under current climatic conditions in China based on space characteristics and biological traits;To explore the key environmental factors affecting the spatial differentiation of its habitats.Methods The Maximum Entropy model was utilized as a predictive tool to synthesize the distribution data of Cordyceps and its associated species Polygonum viviparum and Polygonum macrophyllum,along with environmental variable data.Factor detectors and interaction detectors of geographic detectors were used to conduct geographic exploration of spatial differentiation factors in the suitable habitats of Cordyceps.Furthermore,by overlaying the potential suitable habitats of Cordyceps with surface cover types and the suitable areas of Polygonum viviparum and Polygonum macrophyllum,the specific distribution range of the potential suitable habitats for Cordyceps was refined.Results Under the current climatic conditions,altitude,the precipitation amount of the warmest season,the highest temperature in February,and the precipitation in July are the key environmental factors influencing the distribution of Cordyceps.The potential suitable habitats for Cordyceps reaches 1.18×106 km2,and considering surface cover types,the actual potential suitable habitats for Cordyceps is 7.33×105 km2.Taking into account the associated relationships between species,the actual potential suitable habitats for Cordyceps is 7.27×105 km2.Conclusion The results of this study can reflect the ecological needs of Cordyceps,promote its sustainable utilization of resources,and provide reference for maintaining biodiversity and ecosystem integrity.
6.Analysis on Geographical Distribution Pattern Simulation and Influencing Factors of Potential Suitable Areas for Cynomorium songaricum Rupr
Gonghan TU ; Shaoyang XI ; Xudong GUO ; Huaqian GONG ; Fei CHEN ; Tiantian ZHU ; Li LIU ; Ling JIN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(9):1-6
Objective To investigate the geographical distribution patterns and influencing factors of suitable habitats for the desert medicinal plant Cynomorium songaricum Rupr under current climatic conditions;To provide a basis for its resource conservation and sustainable utilization.Methods The MaxEnt model was used to analyze potential suitable habitats for Cynomorium songaricum Rupr.Geographical Detector model was used to identify key environmental factors affecting habitat suitability.Surface cover data were overlaid to assess the distribution of sandy and Gobi regions within suitable habitats,enabling a quantitative evaluation of actual potential suitable areas.Results Model predictions indicated a total suitable habitat area of approximately 2.98×106 km2,representing 30.99%of China's mainland area.Highly suitable habitats are concentrated in desert and Gobi regions of Gansu,Xinjiang,Inner Mongolia,Qinghai and Ningxia.Among climatic factors,precipitation of the coldest quarter(bio19),solar radiation in August(srad8),and mean temperature of the coldest quarter(bio11)significantly influence Cynomorium songaricum Rupr distribution.The interaction between temperature and solar radiation intensity exhibited the highest explanatory power for habitat distribution patterns(q=0.82).Overlay analysis with surface cover data estimated the actual potential suitable area at approximately 9.70×105 km2,with sandy regions comprising 5.73×105 km2 and Gobi regions 3.98×105 km2.Conclusion By integrating multi-source data and modeling approaches,this study delineates the potential suitable habitats for Cynomorium songaricum Rupr across China and evaluates the spatial distribution characteristics and influencing factors of suitable habitats in Cynomorium songaricum Rupr.These findings offer a foundation for conserving wild Cynomorium songaricum Rupr resources,optimizing ecological planting regions,and promoting sustainable industry development.
7.Status quo of general practice postgraduate researches: a visualized analysis of master′s theses
Xiuqing CHEN ; Jing TU ; Zhaoxiang YU ; Fei GAO
Chinese Journal of General Practitioners 2025;24(2):176-183
Objective:To understand the status quo of general practice postgraduate researches through visualized analysis of masters′ theses.Methods:The master′s theses in general medicine from January 2007 to December 2022 were retrieved from China Knowledge and Wanfang databases. The number and regional distribution of theses, the degree-granting institutions were analyzed; the performed keywords were visualizde with CiteSpace and VOSviewer softwares.Results:A total of 1 688 master′s theses in general practice were included in the analysis. The highest number of theses ( n=345) were published in 2022. The theses from institutions in the eastern, central and western regions of China accounted for 45.67% (771/1 688), 22.16% (374/1 688) and 32.17% (543/1 688), respectively, and those in Shaanxi Province accounted for the highest proportion at 13.68% (231/1 688). A total of 3 755 keywords were included in the theses, and the top three were diabetes mellitus (115/3 755), risk factors (77/3 755) and clinical efficacy (71/3 755). The results of keyword clustering and timeline mapping showed that the research topics were mainly clustered around five themes: clinical treatment and drug efficacy/safety for diabetes mellitus, training of general practitioners and evaluation of general practice services, risk factors related to common chronic diseases in the community, risk factors and cognitive changes in cerebrovascular diseases, and pathogenic mechanisms of cardiovascular diseases. The results of the emergent words showed that recent research hotspots mainly included obesity, older adults, and cognitive function. Conclusions:The number of general practice master′s theses published in China is increasing rapidly with an uneven regional distribution; and the research topics are diverse, mainly focusing on the diagnosis and treatment of chronic diseases and analysis of related risk factors.
8.Single-position O-arm X-ray navigation assisted oblique lateral interbody fusion combined with minimally invasive percutaneous pedicle nail internal fixation for lumbar spondylolisthesis.
Kai-Kai TU ; Hui FEI ; Yu-Liang LOU ; Can-Feng WANG ; Chang-Ming LI ; Li-Shen ZHOU ; Feng HONG
China Journal of Orthopaedics and Traumatology 2025;38(5):447-453
OBJECTIVE:
To investigate the early clinical efficacy of single-position O-arm navigation-assisted oblique lateral interbody fusion(OLIF) combined with minimally invasive percutaneous pedicle screw fixation(PPS) in the treatment of lumbar spondylolisthesis.
METHODS:
A retrospective analysis was conducted on 22 patients with lumbar spondylolisthesis who underwent OLIF-PPS surgery including 11 males and 11 females with a mean age of (64.6±1.5) years old ranging from 49 to 80 years old between April 2021 and June 2023. All patients presented with lumbosacral pain, lower limb radiating pain, numbness, and had poor responses to conservative treatment. Surgical time, intraoperative blood loss, hospital stay, and postoperative complications were recorded. Clinical outcomes were evaluated using the visual analogue scale(VAS) and Oswestry disability index(ODI) preoperatively at 3 days after operation and the final follow-up. Standing lumbar anteroposterior and lateral X-rays were performed to measure disc height(DH), slippage degree, vertebral reduction rate, pedicle screw accuracy, and cage subsidence.
RESULTS:
All surgeries were successfully completed with a mean follow-up of (27.1±2.2) months (range 18 to 36 months). The mean surgical time was (76.1±12.2) min (range 60 to 93 min), intraoperative blood loss was (86.3±32.2) ml (range 40 to 113 ml), and hospital stay was (7.1±1.2) days. Postoperative VAS significantly improved from (7.2±0.7) preoperatively to (2.3±0.5) at 3 days after operation and (1.7±0.2) at the final follow-up (P<0.05). ODI decreased from (68.5±7.2)% preoperatively to (30.3±3.1)% at 3 days after operation and (16.6±1.6)% at the final follow-up (P<0.05). DH increased from (8.5±1.7) mm preoperatively to (18.1±1.4) mm at 3 days after operation and (17.2±1.1) mm at the final follow-up (P<0.05). Slippage degree improved from (24.1±4.6)% preoperatively to (10.3±4.2)% at 3 days after operation and (10.1±3.2)% at the final follow-up (P<0.05). A total of 88 pedicle screws were implanted with an excellent rate of 98% (86/88). Complications included transient left hip flexion weakness (2 cases) and left anteromedial thigh pain (1 case), all resolved during follow-up. No incision hematoma, infection, screw loosening, or cage subsidence occurred.
CONCLUSION
Single-position O-arm navigation-assisted OLIF combined with PPS demonstrates satisfactory early clinical efficacy for lumbar spondylolisthesis, with advantages including minimal invasiveness, significant pain relief, effective vertebral reduction, and low complication rates.
Humans
;
Male
;
Female
;
Spondylolisthesis/diagnostic imaging*
;
Middle Aged
;
Aged
;
Spinal Fusion/methods*
;
Lumbar Vertebrae/diagnostic imaging*
;
Minimally Invasive Surgical Procedures/methods*
;
Pedicle Screws
;
Aged, 80 and over
;
Retrospective Studies
9.Alginate lyase immobilized Chlamydomonas algae microrobots: minimally invasive therapy for biofilm penetration and eradication.
Xiaoting ZHANG ; Huaan LI ; Lu LIU ; Yanzhen SONG ; Lishan ZHANG ; Jiajun MIAO ; Jiamiao JIANG ; Hao TIAN ; Chang LIU ; Fei PENG ; Yingfeng TU
Acta Pharmaceutica Sinica B 2025;15(6):3259-3272
Bacterial biofilms can make traditional antibiotics impenetrable and even promote the development of antibiotic-resistant strains. Therefore, non-antibiotic strategies to effectively penetrate and eradicate the formed biofilms are urgently needed. Here, we demonstrate the development of self-propelled biohybrid microrobots that can enhance the degradation and penetration effects for Pseudomonas aeruginosa biofilms in minimally invasive strategy. The biohybrid microrobots (CR@Alg) are constructed by surface modification of Chlamydomonas reinhardtii (CR) microalgae with alginate lyase (Alg) via biological orthogonal reaction. By degrading the biofilm components, the number of CR@Alg microrobots with fast-moving capability penetrating the biofilm increases by around 2.4-fold compared to that of microalgae. Massive reactive oxygen species are subsequently generated under laser irradiation due to the presence of chlorophyll, inherent photosensitizers of microalgae, thus triggering photodynamic therapy (PDT) to combat bacteria. Our algae-based microrobots with superior biocompatibility eliminate biofilm-infections efficiently and tend to suppress the inflammatory response in vivo, showing huge promise for the active treatment of biofilm-associated infections.
10.The technology of fecal microbiota transplantation and its application progress
Shuo YUAN ; Yi-fan ZHANG ; Peng GAO ; Jun LEI ; Ying-yuan LU ; Peng-fei TU ; Yong JIANG
Acta Pharmaceutica Sinica 2025;60(1):82-95
Fecal microbiota transplantation (FMT) technology originated in China during the Eastern Jin Dynasty and has rapidly developed over the past two decades, becoming a primary method for studying the causal relationship between gut microbiota and the occurrence and progression of diseases. At the same time, the therapeutic effects of FMT in the field of gastrointestinal diseases have gained widespread recognition and are gradually expanding into other disease areas. The FMT procedure is relatively complex, and there is currently no standardized method; its success is influenced by various factors, including the donor, recipient, processing of the fecal material, and the method of implantation. Given the increasingly recognized relationship between gut microbiota and various diseases, FMT has become a research hotspot in both scientific studies and clinical applications, achieving a series of significant advancements. To help researchers better understand this technology, this paper will outline the development history of FMT, summarize common operational methods in research and clinical settings, review its application progress, and look forward to future development directions.

Result Analysis
Print
Save
E-mail