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.Application of CRISPR/Cas System in Precision Medicine for Triple-negative Breast Cancer
Hui-Ling LIN ; Yu-Xin OUYANG ; Wan-Ying TANG ; Mi HU ; Mao PENG ; Ping-Ping HE ; Xin-Ping OUYANG
Progress in Biochemistry and Biophysics 2025;52(2):279-289
Triple-negative breast cancer (TNBC) represents a distinctive subtype, characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). Due to its high inter-tumor and intra-tumor heterogeneity, TNBC poses significant chanllenges for personalized diagnosis and treatment. The advant of clustered regular interspaced short palindromic repeats (CRISPR) technology has profoundly enhanced our understanding of the structure and function of the TNBC genome, providing a powerful tool for investigating the occurrence and development of diseases. This review focuses on the application of CRISPR/Cas technology in the personalized diagnosis and treatment of TNBC. We begin by discussing the unique attributes of TNBC and the limitations of current diagnostic and treatment approaches: conventional diagnostic methods provide limited insights into TNBC, while traditional chemotherapy drugs are often associated with low efficacy and severe side effects. The CRISPR/Cas system, which activates Cas enzymes through complementary guide RNAs (gRNAs) to selectively degrade specific nucleic acids, has emerged as a robust tool for TNBC research. This technology enables precise gene editing, allowing for a deeper understanding of TNBC heterogeneity by marking and tracking diverse cell clones. Additionally, CRISPR facilitates high-throughput screening to promptly identify genes involved in TNBC growth, metastasis, and drug resistance, thus revealing new therapeutic targets and strategies. In TNBC diagnostics, CRISPR/Cas was applied to develop molecular diagnostic systems based on Cas9, Cas12, and Cas13, each employing distinct detection principles. These systems can sensitively and specifically detect a variety of TNBC biomarkers, including cell-specific DNA/RNA and circulating tumor DNA (ctDNA). In the realm of precision therapy, CRISPR/Cas has been utilized to identify key genes implicated in TNBC progression and treatment resistance. CRISPR-based screening has uncovered potential therapeutic targets, while its gene-editing capabilities have facilitated the development of combination therapies with traditional chemotherapy drugs, enhancing their efficacy. Despite its promise, the clinical translation of CRISPR/Cas technology remains in its early stages. Several clinical trials are underway to assess its safety and efficacy in the treatment of various genetic diseases and cancers. Challenges such as off-target effects, editing efficiency, and delivery methods remain to be addressed. The integration of CRISPR/Cas with other technologies, such as 3D cell culture systems, human induced pluripotent stem cells (hiPSCs), and artificial intelligence (AI), is expected to further advance precision medicine for TNBC. These technological convergences can offer deeper insights into disease mechanisms and facilitate the development of personalized treatment strategies. In conclusion, the CRISPR/Cas system holds immense potential in the precise diagnosis and treatment of TNBC. As the technology progresses and becomes more costs-effective, its clinical relevance will grow, and the translation of CRISPR/Cas system data into clinical applications will pave the way for optimal diagnosis and treatment strategies for TNBC patients. However, technical hurdles and ethical considerations require ongoing research and regulation to ensure safety and efficacy.
4.Analysis of the influencing factors of early enteral nutrition-related diarrhea in severe patients with temporary ileostomy
Jia-Jia HU ; Lu-Lu GU ; Cui-Li WU ; Xiang-Hong YE ; Yan JIANG ; Xin-Ying WANG
Parenteral & Enteral Nutrition 2025;32(1):48-53
Objective:To investigate the influencing factors of diarrhea during early enteral nutrition(EEN)therapy in severe patients with temporary ileostomy.Method:A total of 154 patients with temporary ileostomy who received EEN in the Department of General Surgery,Jinling Hospital from November 2019 to November 2023 were included in this study.All patients were divided into two groups:the diarrhea group(n=43)and the non-diarrhea group(n=111).The clinical data of the patients were retrospectively collected and analyzed,and univariate analysis was performed to compare the differences between groups.The indicators with significant differences were subjected to multivariate logistic regression analysis to determine the influencing factors of diarrhea during EEN therapy in severe patients with temporary ileostomy.Result:Among the 154 patients,43 developed diarrhea during EEN therapy,with an incidence of 27.9%.Multivariate logistic regression analysis showed that enteral nutrition(EN)infusion rate(OR=6.342,P=0.001,95%CI:2.055~19.572),antibiotics type(OR=8.342,P=0.013,95%CI:1.577~44.119),mechanical ventilation(OR=7.011,P=0.001,95%CI:2.272~21.629),EN formulation type(OR=6.497,P=0.001,95%CI:2.177~19.392),and diabetes(OR=3.321,P=0.036,95%CI:1.080~10.215)were closely associated with EN-related diarrhea in severe patients with temporary ileostomy.Conclusion:There was a high incidence of diarrhea in severe patients with temporary ileostomy who received EEN.EN infusion rate,antibiotics use,mechanical ventilation,EN formulation type and diabetes were the influencing factors for presence of EEN-related diarrhea in the patients.Our data could provide a reference for preventing EEN-related diarrhea in severe patients with temporary ileostomy after surgery.
5.2022 incidence and mortality of gastric cancer globally and in China
Zerui HU ; Xiaoqiong ZHU ; Wangshuqi GE ; Minchan GAO ; Ao JIANG ; Xin ZHANG ; Wenwen YING ; Cunxi ZHAO
Academic Journal of Naval Medical University 2025;46(6):767-774
Objective To analyze the incidence and mortality of gastric cancer in countries and territories with different human development index(HDI)levels in 2022,and to understand the burden of gastric cancer globally and in China.Methods Data on gastric cancer incidence and mortality were collected from GLOBOCAN 2022 and HDI data for all countries were obtained from the Human development report 2022.Spearman correlation was applied to examine the associations between the age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),mortality-to-incidence ratio(M/I),and HDI for gastric cancer.The Wilcoxon rank-sum test was used to assess the differences in ASIR and ASMR between males and females.Results In 2022,gastric cancer ranked the 5th in both incidence and mortality among all cancer types globally.In China,gastric cancer ranked the 5th in incidence and the 3rd in mortality among all cancer types.The ASIR and ASMR of gastric cancer showed a descending trend from high,very high,medium to low HDI countries and territories.The ASIR of gastric cancer was positively correlated with HDI(rs=0.256,P=0.001),while ASMR showed no significant correlation with HDI(rs=-0.008,P=0.918).The M/I was negatively correlated with HDI(rs=-0.831,P<0.001).The ASIR and ASMR of gastric cancer in males were significantly higher than those in females globally,in China,and across all HDI groups(all P<0.05).Globally,both ASIR and ASMR of gastric cancer remained relatively stable before the age of 45,but showed a consistently rising trend after the age of 45.In China,the ASIR and ASMR of gastric cancer exceeded global average level across all age groups.Conclusion The burden of gastric cancer incidence and mortality is higher in very high and high HDI countries and territories compared to medium and low HDI countries and territories.In China,the burden of gastric cancer incidence and mortality is above the global average,highlighting the need for targeted prevention and control measures.
6.Expert consensus on visualized tele-round and quality control management based on the improvement of clinical practice ability
Wanhong YIN ; Xiaoting WANG ; Ran ZHOU ; Dawei LIU ; Yan KANG ; Yaoqing TANG ; Xiaochun MA ; Jianguo LI ; Zhenjie HU ; Haitao ZHANG ; Wei HE ; Lixia LIU ; Wenjin CHEN ; Ran ZHU ; Jun WU ; Hongmin ZHANG ; Lina ZHANG ; Wenzhao CHAI ; Shihong ZHU ; Wangbin XU ; Rongqing SUN ; Xiangyou YU ; Tianjiao SONG ; Ying ZHU ; Hong REN ; Ai SHANMU ; Qing ZHANG ; Wei FANG ; Xiuling SHANG ; Liwen LYU ; Shuhan CAI ; Xin DING ; Heng ZHANG ; Guang FENG ; Lipeng ZHANG ; Bo HU ; Dong ZHANG ; Weidong WU ; Feng SHEN ; Xiaojun YANG ; Zhenguo ZENG ; Qibing HUANG ; Xueying ZENG ; Tongjuan ZOU ; Milin PENG ; Yulong YAO ; Mingming CHEN ; Hui LIAN ; Jingmei WANG ; Yong LI ; Feng QU ; Gang YE ; Rongli YANG ; Xiukai CHEN ; Suwei LI ; Juxiang WANG ; Yangong CHAO
Chinese Journal of Internal Medicine 2025;64(2):101-109
Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.
7.Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury (version 2025)
Aijun XU ; Shuixia LI ; Bo CHEN ; Mengyuan YE ; Lejiao LANG ; Ning NING ; Lin ZHANG ; Changqing LIU ; Zhonglan CHEN ; Weihu MA ; Weishi LI ; Xiaoning WANG ; Dongmei BIAN ; Jiancheng ZENG ; Xin WANG ; Yuan GAO ; Yaping CHEN ; Jiali CHEN ; Yun HAN ; Xiuting LI ; Yang ZHOU ; Xiaojing SU ; Qiong ZHANG ; Tianwen HUANG ; Ping ZHANG ; Hua LIN ; Xingling XIAO ; Ruifeng XU ; Fanghui DONG ; Bing HAN ; Luo FAN ; Yanling PEI ; Suyun LI ; Xiaoju TAN ; Rongchen GUO ; Yefang ZOU ; Xiaoyun HAN ; Junqin DING ; Yi WANG ; Shuhua DENG ; Jinli GUO ; Yinhua LIANG ; Yuan CEN ; Xiaoqin LIU ; Junru CHEN ; Haiyang YU ; Lunlan LI ; Ying REN ; Yunxia LI ; Jianli LU ; Ying YING ; Lan WEI ; Yin WANG ; Qinhong XU ; Yanqin ZHANG ; Yang LYU ; Shijun ZHANG ; Sui WENJIE ; Sanlian HU ; Shuhong YANG ; Guoqing LI ; Jingjing AN ; Baorong HE ; Leling FENG
Chinese Journal of Trauma 2025;41(6):530-541
Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.
8.Clinical efficacy and safety of Octocog alfa in Chinese patients with hemophilia A: One-year follow-up results from the Antihemophilic Factor Hemophilia A Outcome Database (AHEAD) study
Runhui WU ; Zhenyu LI ; Jing SUN ; Xin DU ; Xinsheng ZHANG ; Ying WANG ; Qun HU ; Rongfu ZHOU ; Joan GU ; Randy GUERRA ; Renchi YANG
Chinese Journal of Hematology 2025;46(8):705-712
Objective:To evaluate the long-term efficacy and safety of recombinant coagulation factor Ⅷ (Octocog alfa) in Chinese patients with hemophilia A (HA) enrolled in the International Antihemophilic Factor Hemophilia A Outcome Database (AHEAD) study (NCT02078427) .Methods:Enrollment of Chinese patients in the AHEAD study was completed by January 2021, and data were collected up to July 15, 2022. This study primarily assessed patients in terms of the Gilbert score, global gait score within the Hemophilia Joint Health Score (HJHS), annualized bleeding rate (ABR), annualized joint bleeding rate, and adverse events.Results:A total of 168 male patients were included in this study, of which 113 received prophylactic treatment and 53 received on-demand treatment. The average age of the patients was 21.4±13.37 years. Compared with baseline, the global gait score within HJHS significantly decreased during the 1-year follow-up in patients with moderately severe HA in the prophylactic treatment group ( P=0.01) and on-demand treatment group ( P=0.008). The mean reduction in Gilbert score was greater in the prophylactic treatment group than in the on-demand treatment group (28.6% vs 8.2%). The average ABR decreased significantly during the 1-year follow-up (3.70 vs 7.78, P=0.01) in the prophylactic treatment group, particularly in patients with severe HA (2.14 vs 8.98, P=0.006) and pediatric patients (2.1 vs 4.73, P=0.03). The ABR score also decreased significantly in the moderate-dose prophylactic treatment group ( P=0.015). During the 1-year follow-up, 25 patients (14.9%) reported 39 adverse events, with only one patient developing treatment-related F Ⅷ inhibitor. Conclusion:Joint mobility improved in patients receiving either prophylactic or on-demand Octocog alfa. Bleeding episodes significantly reduced in patients receiving prophylactic treatment, particularly in pediatric patients and those with severe HA.
9.Research status of insulin resistance mechanisms and the improvement of insulin resistance by active ingredients of dark plum
Zhen-ni ZHANG ; Wen-fang JIN ; Hu-gang JIANG ; Xin-qiang WANG ; Kai LIU ; Ying-dong LI ; Xin-ke ZHAO
The Chinese Journal of Clinical Pharmacology 2025;41(2):274-278
Dark plum can be used to treat symptoms such as consumptive thirst due to deficiency-heat and chronic cough due to lung deficiency.Its active ingredients have auxiliary effects on lowering blood glucose,antibacterial and anti-inflammatory activities.Insulin resistance is mainly characterized by the weakening of the physiological effects of insulin in the body,with a relatively complex mechanism that can lead to various metabolic-related diseases and seriously affect health.The active ingredients of dark plum can improve insulin resistance by regulating insulin signaling pathways,endoplasmic reticulum stress,antioxidant stress,inflammatory signaling pathways,levels of related inflammatory mediators,and free fatty acid levels.By reviewing the relevant literature on the improvement of insulin resistance by the active ingredients of dark plum,this article summarizes and analyzes its mechanism of action,aiming to provide new ideas and scientific evidence for in-depth research on insulin resistance and the development and application of drugs.
10.Research progress of exoskeleton robot for lower limb medical rehabilitation
Hua-jun WANG ; Lian-xin HU ; Ze-feng WANG ; PEYRODIE LAURENT ; Ying NIE ; Shi-jia HU ; Xin-xin NI
Chinese Medical Equipment Journal 2025;46(1):88-100
The exoskeleton robot for lower limb medical rehabilitation in foreign countries and China was introduced in terms of the research status,structure and working principle,and analysis was carried out over its key technologies.It's pointed out the exoskeleton robot for lower limb medical rehabilitation would be enhanced in energy endurance,safety and comfort,individualized and intelligent control,modularity and lightweight design.[Chinese Medical Equipment Journal,2025,46(1):88-100]

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