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.

Aim To explore the underlying molecular mechanism of Alisol A 24-acetate(24A)in improving oxygen-glucose deprivation/reoxygenation(OGD/R)injury in brain microvascular endothelial cells(BMECs)and its correlation with miR-98-5p/transi-ent receptor potential melastatin-2(TRPM2).Meth-ods The ischemia-reperfusion injury in brain micro-vascular endothelial cells(BMECs)was established u-sing bEnd.3 cells subjected to 8 h of oxygen-glucose deprivation followed by 16 h of re-oxygenation.The cells were intervened by miR-98-5p mimics and/or 18.77 μmol·L-1 24A for 24 h and divided into the control group,OGD/R group,OGD/R+24A group,OGD/R+24A+miR-98-5p mimics group and OGD/R+miR-98-5p mimics group.The mRNA levels of miR-98-5p and TRPM2 were detected by qPCR.IL-1 β and TNF-α levels were detected by ELISA.The expression levels of TRPM2,p-AKT,p-GSK3 β,AKT,GSK3 β,Bcl-2,Bax,ZO-1,Occludin,Claudin-5 were detected by Western blot.Apoptosis and reactive oxygen species(ROS)levels were detected by flow cytometry.The targeting relationship between miR-98-5p and TRPM2 was verified using dual luciferase assay.Results Compared with the control group,the apoptosis of OGD/R group was obvious,Bcl-2/Bax decreased,ZO-1,Occludin,Claudin-5 decreased,IL-1 β,TNF-α and ROS increased,miR-98-5p,p-AKT/AKT,p-GSK3β/GSK3β decreased but TRPM2 increased.But com-pared with the OGD/R group,except the control group,the other three groups showed the opposite trend in the above aspects;compared with the OGD/R+24A group,OGD/R+24A+miR-98-5p mimics group showed decreased apoptosis,decreased degradation of ZO-1,Occludin and Claudin-5,and decreased inflam-mation and ROS.miR-98-5p,p-AKT/AKT,p-GSK3β/GSK3β increased and TRPM2 decreased.However,compared with the OGD/R+24A+miR-98-5p mimics group,the OGD/R+miR-98-5p mimics group reversed this trend.Dual luciferase confirmed that miR-98-5p targeted regulation of TRPM2.Conclusion 24A in-hibits the expression of TRPM2 in BMECs through miR-98-5p,regulates AKT/GSK3β signal pathway,re-duces OGD/R inflammation and oxidative stress-medi-ated apoptosis,prevents the degradation of ZO-1,Oc-cludin and Claudin-5,and improves BBB permeability.

Objective To analyze the spatial distribution pattern of potential suitable habitats and the influencing factors of habitat spatial differentiation of Gastrodiae Rhizoma under current climate conditions.Methods Based on 137 distribution records of Gastrodiae Rhizoma sourced from the Global Biodiversity Information Facility and 104 environmental variables acquired from the WorldClim dataset,a predictive model for the potential suitable habitat of Gastrodiae Rhizoma was developed using the MaxEnt model.The geodetector was applied to quantitatively analyze the environmental factors influencing the spatial heterogeneity of the suitable habitats.Subsequently,an overlay analysis with land cover types was conducted to obtain the distribution characteristics of forest land and cultivated land in the potential suitable habitats.Results Under current climate conditions,key environmental factors affecting the distribution of Gastrodiae Rhizoma included precipitation in July,average temperature in the coldest quarter,precipitation in the warmest quarter,water vapor pressure in September,altitude,and solar radiation in December.The potential geographical distribution range of Gastrodiae Rhizoma was 1.64×106 km2.Considering land cover types,the actual potential suitable area for Gastrodiae Rhizoma was 1.33×106 km2,of which the forest land area was 8.56×105 km2 and the cultivated land area was 4.74×105 km2.The highly suitable forest areas were mainly located within the provinces of Guizhou,Sichuan,Shaanxi,Hubei,Hunan and Gansu.The cultivated land suitable areas are mainly located within the provinces of Guizhou,Sichuan,Yunnan,Shaanxi and Hubei.Conclusion The highly suitable habitats of Gastrodiae Rhizoma are mainly located in provinces such as Guizhou,Sichuan,Shaanxi and Hubei,and are affected by factors such as solar radiation,water vapor pressure,temperature and precipitation.The research results can provide reference for the protection of wild Gastrodiae Rhizoma resources,artificial nurturing and optimal selection of ecological planting areas.

Objective To analyze the spatial distribution pattern of the potential suitable habitats for the Tibetan medicinal plant Sinopodophyllum hexandrum under current climatic conditions and the factors influencing the spatial differentiation of the habitats.Methods Based on the maximum entropy model,a species distribution model was established using selected species distribution data and environmental variable data.The geographic detector and the interaction detector were applied to quantify the factors affecting the spatial differentiation of the suitable area.By overlaying the suitable area with land cover types,the distribution characteristics of potential arable land and forest land within the potential suitable area were quantified.Results Under the current climatic conditions,altitude,precipitation in July,precipitation during the warmest season,water vapor pressure in June,precipitation in December,and the highest temperature in February are the key environmental factors affecting the distribution of Sinopodophyllum hexandrum.Under the current climatic conditions,the potential geographical distribution range of Sinopodophyllum hexandrum covers an area of 1.30×106 km2.Considering land cover types,the actual suitable area for Sinopodophyllum hexandrum is 6.13×105 km2,including 4.25×105 km2 of forest land and 1.88×105 km2 of arable land.The highly suitable forest areas are mainly distributed in the Aba Tibetan and Qiang Autonomous Prefecture,Ganzi Tibetan Autonomous Prefecture of Sichuan Province,Diqing Tibetan Autonomous Prefecture,Nujiang Lisu Autonomous Prefecture of Yunnan Province and Linzhi City within the Tibet Autonomous Region.The highly suitable arable land areas are mainly distributed in the Linxia Hui Autonomous Prefecture,Dingxi City,Tianshui City,and Longnan City of Gansu Province,with sporadic belt-like distributions in Sichuan Province,Yunnan Province and the Tibet Autonomous Region.Conclusion The study can provide evidence for the protection of wild Sinopodophyllum hexandrum resources and the selection of optimal planting areas.

OBJECTIVE T o carry out the health economics evaluation and cost-benefit analysis of the type b Hae-mophilus influenzae(Hib)vaccination for the children who were hospitalized due to Hib infection so as to provide evidence for public health policies.METHODS The children who were diagnosed with Hib-related respiratory tract infections or meningitis and were hospitalized in respiratory medicine department,infection management depart-ment,emergency rooms and neurology department of Jiangxi Provincial Children's Hospital from Jan.1,2021 to Dec.31,2023 were recruited as the research subjects.Based on a 1∶1 matching condition,the matching variables included four items such as the same age for the admission to the hospital,same gender,same department and same grade of disease severity.The children for whom the primary immunization of Hib vaccination(including Hib monovalent vaccine and Hib-containing combination vaccine)were completed and the integrity of vaccination infor-mation could be checked out were assigned as the intervention group,while the children for whom the primary im-munization of Hib vaccination was not completed were chosen as the control group.The clinical data,vaccination data and the data such as length of hospital stay and hospitalization cost were collected from the children.The cost-benefit of the Hib vaccination among the children with Hib infection was observed.RESULTS A total of 622 hospi-talized children who were detected with Hib-positive respiratory tract infections or meningitis were enrolled in the study,and 73 children(20 children from infection management department,27 children from respiratory medi-cine department,26 children from emergency rooms)were finally included in the intervention group after matc-hing and multiple rounds of screening,73 children were chosen as the control group based on a 1∶1 matching con-dition.The male children accounted for 57.53％(42 cases)in both groups,and the female children accounted for 42.47％(31 cases)in both groups.With the respect to the length of hospital stay,it was 7.00(5.00,8.00)days in the intervention group,7.00(6.00,8.00)days in the control group(Z=-0.341,P=0.733).In terms of the hospitalization cost,it was 7 756.17(6 617.92,10 617.69)yuan in the intervention group,9 040.65(8 033.76,10 935.84)yuan in the control group(Z=-2.795,P=0.005).The cost of Hib vaccination was 343.03 yuan per capita in the intervention group,and the benefit-cost ratio(BCR)was 1∶3.74(343.03 yuan/1 284.48 yuan).CONCLUSIONS The Hib vaccination can save the hospitalization cost and has high cost effectiveness.It is sugges-ted that the Hib vaccination should be promoted and the coverage rate of Hib vaccination should be raised among the age-eligible children.

This paper combs through the current situation and influencing factors of the application of action research in nursing undergraduate teaching reform, and puts forward its problems and suggestions, with a view to providing reference for nursing educators in China to carry out nursing undergraduate teaching action research.

Objective:To explore the experiences of nursing undergraduates with the blended teaching model in midwifery courses.Methods:This qualitative study employed purposive sampling to select 17 nursing undergraduates from the 2021 cohort who participated in the "Midwifery Theory and Skills 2" course in December 2023. Face-to-face semi-structured interviews were conducted, and the data were analyzed using Colaizzi's seven-step method.Results:Three main themes and eight subthemes were identified. First, the blended teaching model enhanced professional knowledge and skills in midwifery: online resources expanded professional knowledge; online demonstration videos improved operational skills; offline group collaboration strengthened communication skills. Second, it developed professional awareness and emotions in midwifery: systematic course learning enhanced professional identity; offline role-playing cultivated emotional perception; clinical experience sharing by teachers fostered a sense of responsibility in midwifery. Third, it optimized blended teaching resources: the user experience on online platforms was improved, and offline classroom settings were better designed.Conclusions:The blended teaching model aids in enhancing students' comprehensive knowledge and skills in midwifery and fosters professional emotions related to the field. It is recommended to further optimize blended teaching resources to improve the effectiveness of this teaching model in midwifery courses.

Objective To analyze the spatial distribution pattern of the potential suitable habitats for the Tibetan medicinal plant Sinopodophyllum hexandrum under current climatic conditions and the factors influencing the spatial differentiation of the habitats.Methods Based on the maximum entropy model,a species distribution model was established using selected species distribution data and environmental variable data.The geographic detector and the interaction detector were applied to quantify the factors affecting the spatial differentiation of the suitable area.By overlaying the suitable area with land cover types,the distribution characteristics of potential arable land and forest land within the potential suitable area were quantified.Results Under the current climatic conditions,altitude,precipitation in July,precipitation during the warmest season,water vapor pressure in June,precipitation in December,and the highest temperature in February are the key environmental factors affecting the distribution of Sinopodophyllum hexandrum.Under the current climatic conditions,the potential geographical distribution range of Sinopodophyllum hexandrum covers an area of 1.30×106 km2.Considering land cover types,the actual suitable area for Sinopodophyllum hexandrum is 6.13×105 km2,including 4.25×105 km2 of forest land and 1.88×105 km2 of arable land.The highly suitable forest areas are mainly distributed in the Aba Tibetan and Qiang Autonomous Prefecture,Ganzi Tibetan Autonomous Prefecture of Sichuan Province,Diqing Tibetan Autonomous Prefecture,Nujiang Lisu Autonomous Prefecture of Yunnan Province and Linzhi City within the Tibet Autonomous Region.The highly suitable arable land areas are mainly distributed in the Linxia Hui Autonomous Prefecture,Dingxi City,Tianshui City,and Longnan City of Gansu Province,with sporadic belt-like distributions in Sichuan Province,Yunnan Province and the Tibet Autonomous Region.Conclusion The study can provide evidence for the protection of wild Sinopodophyllum hexandrum resources and the selection of optimal planting areas.

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude