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.Current quality status and management countermeasures of occupational health technical services in Zhejiang Province
Qiuliang XU ; Feng HAN ; Peng WANG ; Zhen ZHOU ; Fei LI ; Hongwei XIE ; Yong HU ; Weiming YUAN ; Lifang ZHOU ; Hua ZOU
Journal of Environmental and Occupational Medicine 2026;43(3):341-346
Background The quality of occupational health technical services is directly linked to the protection of workers' health rights and the efficacy of occupational disease prevention and control. However, the industry still faces critical challenges: sporadic instances of institutional non-compliance and persistent irregularities in professional practice continue to undermine overall service performance. Objective To assess the current quality status of occupational health technical services in Zhejiang Province and propose countermeasures for quality improvement, providing a scientific basis for policy optimization and service delivery quality enhancement. Methods A total of 69 occupational health technical service institutions in Zhejiang Province that obtained formal accreditation as of April 30, 2024, were sampled, including 3 public institutions and 66 private institutions (comprising 3 formerly Class-A, 28 formerly Class-B, 11 formerly Class-C, and 24 newly certified institutions). Following the Technical Protocol for Quality Monitoring of Occupational Health Technical Service in Zhejiang Province and the Technical Protocol for Proficiency Testing of Occupational Health Detection in Zhejiang Province, a quality assessment task force comprising national and provincial experts was established. Evaluation was conducted across four dimensions: qualification maintenance and compliance, standardization of technical services, authenticity of technical services, and proficiency testing, utilizing a combination of document review, on-site inspections, and technical skill assessments. Results The occupational health technical service institutions in Zhejiang Province were predominantly private entities (82.5%), with significant disparities in overall service quality. The pass rates for qualification maintenance and compliance, technical service standardization, technical service authenticity, and the excellence rate for laboratory proficiency testing were 81.5%, 80.7%, 97.3%, and 90.4%, respectively. Regarding qualification maintenance, the pass rates for "environmental conditions" (49.8%, 56.7%) and "instrumentation and equipment" (58.2%、65.6%) were significantly lower for formerly Class-C and newly certified institutions compared to other categories. In terms of technical standardization, "standardized on-site inspections" recorded the lowest pass rate (67.4%), with newly certified institutions at only 48.0%. Regarding technical service authenticity, formerly Class-C institutions exhibited issues such as missing raw chromatograms for blank samples (85.7% pass rate). In laboratory proficiency testing, public and formerly Class-A institutions achieved 100% excellence rates, but the performance of formerly Class-C and newly certified institutions was comparatively weak; specifically, the failure rate for organic analysis in formerly Class-C institutions reached 20%; the failure rate for dust testing items in newly certified institutions was 10.3%. Conclusion The overall quality of occupational health technical services in Zhejiang Province still requires significant improvement, particularly in basic institutional conditions, the standardization of on-site inspections, and laboratory proficiency in organic and dust analysis. Formerly Class-C and newly certified institutions should be the primary focus of quality management efforts. Differentiated regulatory strategies are recommended, alongside strengthening interim and ex-post supervision to gradually enhance the quality of occupational health technical services across all institutions.
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.Mechanism of Rehmannia glutinosa-medicated serum regulating BV2 microglia polarization to interfere with neuroinflammation
Ping TIAN ; Hongzhi AN ; Qian FEI ; Ruifeng LIANG ; Dan YANG ; Xuexia ZHANG ; Wenjing GE ; Yifei LIU ; Hongwei LI ; Deen HAN
China Pharmacy 2026;37(15):1979-1985
OBJECTIVE To study the mechanism of action of Rehmannia glutinosa-medicated serum (RG) in regulating lipopolysaccharide (LPS)-induced polarization of BV2 microglia to interfere with neuroinflammation. METHODS An in vitro neuroinflammation model of BV2 cells induced by LPS was established. Cells were divided into control group, LPS group, 10%RG group, 20%RG group, BAY 11-7082 [nuclear factor kappa B (NF-κB) inhibitor] group, and 20%RG+BAY 11-7082 group. Except for the control group, cells in all other groups were pretreated with corresponding drugs for 12 h and then stimulated with LPS for 24 h. The morphology of cells in each group was observed, and the fluorescence intensity of ionized calcium binding adaptor molecule 1 (Iba-1), inducible nitric oxide synthase (iNOS), CD206, the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, iNOS, IL-4, IL-10, transforming growth factor-β (TGF-β), arginase-1 (Arg-1), and the Toll-like receptor 4 (TLR4)/NF-κB/NOD-like receptor thermal protein domain associated protein 3 (NLRP3) signaling pathway-related protein expression were detected. RESULTS Compared with the control group, the LPS group showed significant changes in cell morphology, exhibiting a typical M1 activated morphology. The fluorescence intensity of Iba-1 and iNOS, the relative expression levels of TNF-α, IL-6, IL-1β, iNOS mRNA, the relative expression levels of TLR4, NLRP3, caspase-1 p20, IL-1β p17 protein, and the phosphorylation levels of NF-κB p65 and inhibitor of nuclear factor kappa B α were significantly increased (P<0.05). The fluorescence intensity of CD206 and the relative expression levels of IL-4, IL-10, TGF-β, and Arg-1 mRNA were significantly reduced (P<0.05). Compared with the LPS group, the changes in the above indicators in the cells of the 10%RG group, 20%RG group, BAY 11-7082 group, and 20%RG+BAY 11-7082 group were significantly reversed (P<0.05), and there was no statistically significant difference in the comparison of the last three groups (P>0.05). CONCLUSIONS RG can effectively inhibit the overall activation of microglia and correct their M1/M2 polarization imbalance, and its mechanism may be closely related to the inhibition of excessive activation of the TLR4/NF-κB/NLRP3 signaling pathway.
5.Mechanism of Shenling baizhu san in ameliorating ulcerative colitis via regulating flora metabolism-related proteins and TLR4/NF-κB/NLRP3 inflammatory axis
Jiajia XU ; Yu YOU ; Jiaoman WANG ; Yuhui LIU ; Shiyao CHANG ; Zhixian HE ; Ping LI ; Ziyan WANG ; Wei XIONG ; Fei HAN
China Pharmacy 2026;37(15):1992-1997
OBJECTIVE To investigate the mechanism of Shenling baizhu san (SLBZS) in ameliorating ulcerative colitis (UC). METHODS Mice were randomly divided into normal group, model group, and low-, medium-, high-dose SLBZS groups (3, 6, 12 g/kg), with 10 mice in each group. Except for the normal group, mice in other groups were given free access to 3% dextran sulfate sodium solution for 7 days to establish UC models. Simultaneously, mice in each group were intragastrically administered corresponding medicinal liquid or double-distilled water once a day for consecutive 7 days. After the last administration, the histopathological morphology of colon tissues was observed; the serum levels of inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-18 were detected; the total bile acid contents in liver, gallbladder and colon tissues were determined; the expression level of NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) in colon tissues was tested. The expression levels of flora metabolism-related proteins [G protein-coupled receptor 41(GPR41),GPR43,farnesoid X receptor (FXR), G protein-coupled bile acid receptor 1 (TGR5), flavin-containing monooxygenase 3 (FMO3), cytochrome P450 family 27 subfamily A member 1 (CYP27A1), CYP7A1] in liver or colon tissues, as well as the proteins related to Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB)/NLRP3 inflammatory axis [TLR4, NF-κB, phosphorylated NF-κB (p-NF-κB), myeloid differentiation factor 88 (MyD88), NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1] in colon tissues were measured. RESULTS Compared with the model group, the colon tissue injury and inflammatory cell infiltration were alleviated in medium- and high-dose SLBZS groups. The serum levels of TNF-α, IL-1β and IL-18, total bile acid contents in liver and colon tissues, as well as the protein expression levels of FMO3 and CYP7A1 in liver tissues, TLR4, p-NF-κB, NF-κB, MyD88, NLRP3, ASC and caspase-1 in colon tissues were significantly decreased (P<0.05). Meanwhile, the total bile acid content in gallbladder, the protein expression levels of GPR41 and GPR43 in colon tissues, along with CYP27A1, FXR and TGR5 in liver tissues were significantly increased (P<0.05). CONCLUSIONS SLBZS may relieve colonic inflammatory injury and ameliorate UC by regulating the expression of flora metabolism-related proteins and inhibiting the abnormal activation of TLR4/NF-κB/NLRP3 inflammatory axis.
6.Economic evaluation of risdiplam in the treatment of pediatric spinal muscular atrophy under health insurance scenarios
Dan HAN ; Fei YU ; Xintong ZHU ; Yue WU ; Wei SHAO ; Ruimin LI
Journal of Pharmaceutical Practice and Service 2026;44(8):431-436
Objective To evaluate the cost-utility of risdiplam in the treatment of pediatric spinal muscular atrophy (SMA) and analyze changes in patients’ out-of-pocket economic burden under the medical insurance scenarios. Methods A Markov model was developed from the healthcare system perspective to compare the long-term costs and quality-adjusted life years (QALYs) of risdiplam treatment versus conventional therapy. The incremental cost-utility ratio (ICUR) was calculated. One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to assess the robustness of the model. On this basis, health insurance scenarios were simulated to evaluate patients’ individual economic burden. Results Base-case analysis showed that risdiplam treatment generated additional health benefits but substantially increased medical costs. The resulting ICUR did not demonstrate a clear cost-utility advantage under the current willingness-to-pay threshold. Sensitivity analyses indicated that the model results were relatively robust, with drug costs and key utility parameters being the main drivers of economic outcomes. Health insurance scenario analysis demonstrated that increasing reimbursement levels and reducing patient copayment rates could significantly alleviate patients’ financial burden. Conclusion Risdiplam for pediatric SMA faces economic challenges under the current health insurance payment framework in China. However, optimizing health insurance reimbursement policies and developing multi-tiered healthcare security mechanisms may improve its affordability and accessibility.
7.Concept analysis of care-resistant behavior in dementia patients
Han LI ; Yingqi HUANG ; Fei DU ; Qiushi ZHANG ; Yongxia MEI ; Hui XU
Chinese Journal of Nursing 2025;60(15):1818-1823
Objective To analyze and clarify the concept and connotation of care-resistant behavior in dementia patients,so as to provide references for the evaluation and practice of care-resistant behavior in clinical dementia patients.Methods PubMed,Scopus,Web of Science,Cochrane Library,Embase,CINAHL,CNKI,VIP,Wanfang database and Chinese Biomedical Literature Database were systematically searched for the literature on care-resistant behavior in dementia patients.The search time limit was from the establishment of the database to December 2024.Walker and Avant's classical concept analysis method was used to analyze the literature.Results The care-resistant behav-ior in dementia patients included 5 conceptual attributes,including nursing background,perceived threat,unmet needs,lack of understanding and multi-dimensional performance.The antecedent factors include patient factors,care-giver factors,environmental factors and organizational factors.Post-impact includes the impact on patients and the impact on caregivers.Conclusion This study clarified the conceptual attributes,antecedents and post-effects of care-resistant behavior in dementia patients through concept analysis.In the future,researchers should combine the connotation of dementia patients' care-resistant behavior,develop localized assessment tools for dementia patients' care-resistant behavior,and construct targeted intervention programs,so as to improve the quality of nursing staff and enhance the care experience of dementia patients.
8.2024 Update of Chinese Guidelines for the Management of Hyperuricemia and Gout Part Ⅱ: Recommendations for Patients with Common Comorbidities
Changgui LI ; Mingshu SUN ; Zhen LIU ; Detian LI ; Changqian WANG ; Zibin TIAN ; Yuxiang DAI ; Zhe FENG ; Chengfu XU ; Dongbao ZHAO ; Feng WEI ; Bo BAN ; Chao XIE ; Zhenmei AN ; Jia LIU ; Zhuo LI ; Yuwei HE ; Xinde LI ; Fei YAN ; Lin HAN ; Lidan MA ; Xiaoyu CHENG ; Tian LIU ; Xufei LUO ; Lingling CUI ; Ying GONG ; Can WANG ; Yaolong CHEN ; Zhaohui LYU ; Yip Ronald ML ; Jiajun ZHAO
Chinese Journal of Endocrinology and Metabolism 2025;41(11):918-929
The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.
9.Evaluation of clinical effectiveness of retrograde recanalization of occluded radial artery via distal transradial approach
Xiao-fei XIE ; Sheng-xin ZUO ; Jin-peng XU ; Xiao-liang HAN ; Gang-cheng SUN ; Liang LI
Chinese Journal of Interventional Cardiology 2025;33(3):135-140
Objective Radial artery occlusion(RAO)is one of the common complications following coronary intervention via the traditional radial artery approach.This study aims to evaluate the clinical effectiveness of retrograde recanalization of occluded radial arteries through the distal transradial approach(dTRA)approach.Methods A total of 35 patients with RAO admitted to the cardiovascular department of the Anhui Chest hospital between December 2022 and April 2024,who were scheduled to undergo coronary intervention and had attempted recanalization of RAO via dTRA approach were selected.The primary result was the success rate of recanalizing RAO via dTRA.The secondary results included factors influencing the failure of recanalization via dTRA,postoperative puncture complications,and the patency rate at the 3-month follow-up.Results This study divided the patients into a successful group(29 cases,82.9%)and a failed group(6 cases,17.1%)based on whether the distal radial artery was successfully opened and occluded.The proportion of smoking(100.00%vs.17.24%,P=0.040),history of diabetes(100.00%vs.10.34%,P=0.025),and chronic total occlusion of coronary artery(83.33%vs.17.24%,P=0.030)in the failure group were higher than those in the success group,and the difference was statistically significant.The application rate of balloon tracking assisted technology in the failed group(16.67%vs.58.62%,P=0.045),and the diameter of the radial artery at 3 days after surgery[(1.63±0.13)mm vs.(2.13±0.32)mm,P=0.021]and the peak radial artery blood flow velocity at 3 days postoperatively[(0.10±0.78)m/s vs.(0.50±0.13)m/s,P<0.001]were all lower in the successful group,and the differences were statistically significant.Logistic regression analysis 3 days after surgery showed that chronic complete occlusion of the coronary artery was an independent risk factor for surgical opening failure(OR 0.042,95%CI 0.004-0.438,P=0.008).After 3 months of follow-up,the patency rate of the successful group was 55.2%.Conclusions Retrograde recanalization of RAO via dTRA is safe and feasible,but its long-term patency rate is not high.
10.Effects of sacubitril/valsartan on myocardial fibrosis induced by abdominal aortic constriction in rats
Songhai LI ; Jun HAN ; Fei OUYANG ; Hongsheng GANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(3):364-369
Objective To investigate the effects of SAC/VAL on myocardial fibrosis and miR-21 expression in rats induced by AAC.Methods A total of 72 SPF SD male rats were randomly di-vided into sham operation group,AAC group,low-and high-dose SAC/VAL groups,high-dose SAC/VAL+agomiR-NC group,and high-dose SAC/VAL+miR-21 agomiR group,with 12 rats in each group.Echocardiography was used to test cardiac function.HE staining and Masson staining were applied to observe the pathological changes in myocardial tissues and myocardial tissue fi-brosis,respectively.Immunohistochemical assay was employed to detect the expression of α-SMA and COL-l in myocardial tissue.Real-time fluorescence quantitative polymerase chain reaction was conducted to detect miR-21 level.Results Compared with the sham operation group,the AAC group had thicker and broken myocardial fibers in disordered arrangement,hypertrophic myocar-dial cells with condensed and deeply stained nuclei,and extensive infiltration of inflammatory cells,and obvious myocardial fibrosis,increased LVEDD and LVESD values,and up-regulated miR-21,α-SMA and COL-1 expression,but decreased LVEF and LVFS levels(P<0.05).Low-and high-dose SAC/VAL treatment resulted in well-arranged less broken myocardial fibers in uniform distribution,relatively normal myocardial cells,less inflammatory cell infiltration,and reduced severity of myocardial fibers,lower LVEDD and LVESD values,decreased miR-21,α-SMA and COL-1 levels,but increased LVEF and LVFS levels when compared to the AAC group(P<0.05).When compared to the high dose SAC/VAL+agomiR NC group,the high-dose SAC/VAL+miR-21 agomiR group had disorderly-arranged myocardial fiber with thickening and breakage,aberrant myocardial cells,obvious infiltration of inflammatory cells,and intensified my-ocardial fibrosis,higher LVEDD and LVESD values and miR-21,α-SMA and COL-1 expression levels,and lower LVEF and LVFS levels[7.11±0.45 mm vs 6.05±0.38 mm,P<0.05;5.58±0.35 mm vs 4.01±0.28 mm,P<0.05;2.57±0.14 vs 0.98±0.10,P<0.05;0.62±0.06 A vs 0.41±0.04 A,P<0.05;0.79±0.08 A vs 0.53±0.05 A,P<0.05;(58.26±2.61)%vs(80.24±2.87)%,P<0.05;(24.52±1.03)%vs(33.72±1.25)%,P<0.05].Conclusion SAC/VAL inhibits AAC-induced myocardial fibrosis in rats,which is related to its regulation of miR-21 expression.

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