1.Sipeimine inhibits the proliferation of human gastric adenocarcinoma AGS cells by modulating the cyclin D1-mediated CDK4/6-Rb-E2F1 signaling axis
LIU Xue1 ; LI Zhihan1 ; YANG Xia2, ; ZHANG Zhaopeng2 ; CHEN Huidan2 ; LI Yiquan2 ; HAN Jicheng2 ; ZHU Yilong2 ; ZHU Guangze2,3
Chinese Journal of Cancer Biotherapy 2026;33(5):528-536
[摘 要] 目的:探究西贝素通过调控Cyclin D1介导的CDK4/6-Rb-E2F1信号轴对人胃腺癌细胞(AGS)的增殖抑制效果及其分子机制。方法:利用不同浓度的西贝素处理AGS和人正常胃黏膜上皮细胞(GES-1),通过CCK-8检测和结晶紫染色实验确定西贝素的最适抑制剂量和作用时间;采用划痕实验和Transwell迁移实验与侵袭实验检测西贝素对AGS细胞迁移与侵袭能力的影响;利用流式细胞术和WB检测西贝素对AGS细胞周期及细胞周期相关蛋白表达的影响;利用质粒过表达Cyclin D1,并通过WB检测、结晶紫染色实验、划痕实验和Transwell迁移实验与侵袭实验进一步明确西贝素的抑制机制;构建AGS移植瘤裸鼠模型,采用免疫荧光染色法和免疫组化检测Cyclin D1、CDK4、CDK6、Rb、p-Rb、E2F1的表达水平。结果:与对照组相比,西贝素药物浓度为100 μg/mL时,对GES-1细胞的增殖无影响(P > 0.05),但能够显著性抑制AGS细胞增殖、迁移和侵袭能力(P < 0.01),并诱导AGS细胞周期G0/G1期阻滞,显著抑制周期相关蛋白Cyclin D1、CDK4、CDK6、p-Rb、E2F1的表达水平(P < 0.05或P < 0.01);Cyclin D1过表达能够显著降低西贝素对AGS细胞的抑制效果(P < 0.05或P < 0.01);荷瘤裸鼠实验结果显示,西贝素能够抑制AGS移植瘤的增殖,影响肿瘤组织中Cyclin D1、CDK4、CDK6、p-Rb、E2F1的表达(P < 0.01)。结论:西贝素可能通过下调Cyclin D1介导的CDK4/6-Rb-E2F1信号轴活化抑制AGS增殖。
2.WANG Xixing's Clinical Experience in Treating Immune Checkpoint Inhibitor-Related Pneumonitis Based on the Theory of "Cough Attributed to the Five Zang (脏) Organs"
Xue QI ; Xi YANG ; Xinyue WANG ; Dongxin ZHANG ; Yuxing MAO ; Yuankun HAN ; Wenbo ZHAI ; Boyang LYU ; Yifang LI ;
Journal of Traditional Chinese Medicine 2026;67(5):477-481
This paper summarizes Professor WANG Xixing's clinical experience in treating immune checkpoint inhibitor-related pneumonitis (CIP) based on the theory of "cough attributed to the five zang (脏) organs". Cough is a common predominant symptom of CIP. According to the theory of "cough attributed to the five zang organs", drug toxicity triggers cancer toxin, leading to disharmony among the five zang organs, and then lung failing to diffuse and govern descent as the core pathogenesis. Therefore, treatment should focus on harmonizing the five zang organs to restore the normal function of lung qi to diffuse and govern descent. In clinical practice, CIP can be classified into four syndrome patterns, including lung yin depletion, deficiency of both the lung and the spleen with phlegm-dampness, liver fire harassing the lung, and lung-kidney yin deficiency. Correspondingly, Chaimai Jinluo Runfei Decoction (柴麦金络润肺汤) is used to nourish yin and moisten the lung; Qigui Peitu Huayin Decoction (芪桂培土化饮汤) is used to fortify the spleen and tonify the lung, resolve dampness and dispel phlegm; Chaidan Shuyu Runjin Decoction (柴丹疏郁润金汤) is used to drain liver and clear the lung; and Dimai Jinshui Xiangsheng Decoction (地脉金水相生汤) is used to nourish the kidney and moisten the lung.
3.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.
4.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.
5.Bidirectional association between metabolic associated fatty liver disease and the risk of atherosclerotic cardiovascular disease
Yanan ZHAO ; Qi QI ; Xinyu WU ; Quanle HAN ; Jing YANG ; Boheng ZHANG ; Xuyang LI ; Lei LI ; Yun ZHANG ; Shouling WU ; Kangbo LI
Journal of Clinical Hepatology 2026;42(4):856-865
ObjectiveTo investigate the association between metabolic associated fatty liver disease (MAFLD) and the risk of atherosclerotic cardiovascular disease (ASCVD), and to provide data support for the prevention and treatment of such metabolic-associated diseases in clinical practice. MethodsAn observation cohort was established for the workers of Kailuan who underwent physical examination for the first time from June 2006 to October 2007 and had complete liver assessment data, without the history of malignant tumor, MAFLD or ASCVD. According to the presence or absence of MAFLD, the patients were divided into non-MAFLD group with 67 565 patients and MAFLD group with 29 004 patients, and according to the presence or absence of ASCVD, the patients were divided into non-ASCVD group with 69 141 patients and ASCVD group with 481 patients. The group t-test or the Wilcoxon rank-sum test was used for comparison of continuous data between the two groups. The
6.Research on quality control of the potential allergic ingredient scutellarin in Shuganning Injection
HE Feng ; CAO Lu ; YANG Cuiping ; LI Jing ; ZHANG Quan ; WANG Jinjin ; L& ; #252 Yanni ; HAN Shengli
Drug Standards of China 2026;27(1):0037-0042
Objective: Scutellarin in Shuganning injection has potential allergenicity and is prone to causing anaphylactoid reactions. There is an urgent need to establish a simple and rapid chromatographic quantitative method to achieve the limit control of scutellarin in Shuganning injection.
Methods: For scutellarin, HPLC method was used in the quantitative analysis using a Shim-pack GIS C18 (2.1 mm×150 mm, 5 μm) column. The mobile phase was a blend of 0.1% trifluoroacetic acid in water and acetonitrile, and gradient elution progress was applied for the whole process. The flow rate was 0.3 mL·min-1 and the column temperature was maintained at 37 ℃. The detecting wavelength was 320 nm.
Results: The linear regression equation was y=51 456x-27 352, the correlation coefficient r=0.999 8, namely the calibration curve was linear in the range of 1.02-102.00 μg·mL-1; the average recovery was 103.76%; the detection and quantification limit for determining scutellarin was 0.16 μg·mL-1 and 0.57 μg·mL-1, respectively; the injection sample was stable at room temperature for 48 h.
Conclusion: This method is easy to operate, reproducible and has high accuracy, thus can be used for quality control of Shuganning injection.
7.Advances in perioperative nutritional management for patients with esophageal cancer
Zuyu ZHANG ; Bo YANG ; Rong NIU ; Jijun XUE ; Jian CHEN ; Dong LI ; Wentao ZHAO ; Wenfeng HAN ; Yue BAI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(01):157-162
Esophageal cancer is a prevalent malignant tumor of the digestive tract in China, and radical surgery remains the cornerstone of its comprehensive treatment. However, multifactorial challenges such as postoperative gastrointestinal tract reconstruction, traumatic stress, and tumor-related metabolic disturbances render esophageal cancer patients highly susceptible to malnutrition. Perioperative nutritional support therapy plays a crucial role in enhancing surgical safety, improving clinical outcomes, and elevating patients' quality of life by regulating metabolic homeostasis, preserving organ function, and optimizing the immune microenvironment. This article reviews the mechanisms underlying malnutrition in esophageal cancer, methods for nutritional status assessment, and precision intervention pathways based on multi-omics evaluations. The aim is to strengthen clinicians' awareness of standardized perioperative nutritional management for esophageal cancer patients and promote its clinical implementation, thereby facilitating postoperative recovery and improving long-term quality of life.
8.Exploring the pathogenesis and treatment methods of irritable bowel syndrome from the
Yan XU ; Fang YANG ; Rongshi SHAO ; Huili SUN ; Juan LI ; Xin CHEN ; Jing HAN
Journal of Beijing University of Traditional Chinese Medicine 2026;49(1):10-15
This article adopts Professor CHEN Chaozu′s " sanjiao composed by membrane-striae" theory as its foundation to explore the relationship between irritable bowel syndrome and functional/structural abnormalities of the membrane-striae. Sanjiao encompasses both the tangible membrane and the intangible striae. These striae permeate the entire body,and their pathological changes comprehensively reflect qi,body fluids,and fasciae. Based on the physiological function of the membrane-striae in regulating qi and fluids,the pathogenesis of irritable bowel syndrome is characterized by a disharmony of membrane-striae and an imbalance of the qi-fluid interactions. In the early stage,external pathogens,emotional factors,or dietary stimuli often cause membrane-striae constriction and disordered qi-fluid circulation. In the middle stage,stagnant fluids gradually transform into phlegm retention,leading to membrane-striae obstruction. In the late stage,deficiency of vital qi becomes predominant,manifesting as laxity of membrane-striae with impaired control or weakened conduction. The treatment of irritable bowel syndrome should adopt " unblocking" as the guiding principle. In the early stage,therapy should focus on eliminating pathogenic factors and soothing membrane-striae to promptly restore qi-fluid circulation,thereby attaining unblocking through spasm relief. In the middle stage,treatment should focus on resolving tangible obstructions in membrane-striae,achieving unblocking via dredging. In the late stage,the emphasis should shift to reinforcing healthy qi,particularly by strengthening spleen-kidney yang qi,and achieving unblocking through supplementation. Concurrently,throughout the entire treatment process,the regulation of mental state and easing of emotional tension should be integrated to alleviate patient′s anxiety,achieving the goal of holistic treatment of both body and mind.
9.Expert consensus on the clinical application of parenteral direct thrombin inhibitors in special populations
Xin YAO ; Yuan BIAN ; Lizhu HAN ; Qinan YIN ; Yang LEI ; Zimeng WAN ; Luyao HUANG ; Danjie ZHAO ; Yu YAN ; Qin LI ; Baorong HU
China Pharmacy 2026;37(8):965-975
OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors (DTIs) in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital(the Affiliated Hospital of UESTC), a multidisciplinary working group was formed comprising experts from multiple fields, including clinical pharmacy, cardiac surgery, obstetrics, pediatrics and evidence-based medicine. Through literature review and the Delphi method, clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” (PICO) framework;systematic searches were conducted in CJFD, PubMed, Embase and other databases. Relevant evidence from randomized controlled trials,cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment,Development and Evaluation (GRADE) approach, and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected (with a consensus rate exceeding 90%), resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations, including children, pregnant women, patients with hepatic or renal impairment, patients with mesenteric venous thrombosis, and individuals with thrombophilia. These recommendations clarify the preferred agents, dosing ranges, monitoring parameters, and safety management strategies for parenteral DTIs in these special populations. This expert consensus, which is formulated based on the best available evidence, provides evidence-based guidance for standardized and individualized use of parenteral DTIs in special populations.
10.Dilemmas and challenges for parasitology teachers at shortage of clinicalmedical sciences knowledge background in medical colleges and universities
Su HAN ; Yang CHENG ; Chao DENG ; Youyi LIU ; Yuhong LI
Chinese Journal of Schistosomiasis Control 2026;38(1):69-73
Medical parasitology, as a course bridging basic medical sciences and clinical medicine, has an important disciplinary value in the medical education system. This study investigated the composition of parasitology teachers from multiple medical colleges and universities across China. The results showed that there was a significant difference in the proportion of teachers with clinical medicine background knowledge, and there was common dilemma that there were insufficient clinical medicine knowledge reserves among teachers in some medical colleges and universities, who encountered severe teaching challenges. Based on this issue, this study constructed a basic-clinical medicine collaborative problem-based learning (PBL) teaching model. This model integrated theoretical teaching, case analyses, and experimental operations, and combined transdisciplinary team building and multidimensional teacher training, which significantly improved the clinical teaching capability among parasitology teachers, and effectively compensated the impact of insufficient clinical medicine knowledge reserves on teaching. Following teaching reform, students' scores significantly improved, and their case analysis capability enhanced. This study provides a practical path to address the shortage of clinical medicine background knowledge among parasitology teachers, which facilitates the progress of educational reform of medical parasitology and improvement of teaching quality.


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