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.Quercetin Ameliorates Gouty Arthritis in Rats via ROS/NLRP3/IL-1β Signaling Pathway
Baowei FENG ; Yan WANG ; Chang LI ; Yujing ZHANG ; Dingxing FAN ; Xin LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):145-153
ObjectiveTo investigate the effect of quercetin on acute gouty arthritis (GA) in rats by inhibiting the reactive oxygen species (ROS)/NOD-like receptor protein 3 (NLRP3)/interleukin-1β (IL-1β) signaling pathway. MethodsSixty SPF-grade male SD rats were randomized into normal, model, colchicine (0.3 mg·kg-1), and low-, medium-, and high-dose (25, 50, 100 mg·kg-1, respectively) quercetin groups (n=10). The rats in the dosing groups were administrated with the corresponding drugs (10 mL·kg-1) by gavage once a day for one week. An equal volume of normal saline was given by gavage to rats in normal and model groups. One hour after drug administration on day 5, an acute GA model was established in other groups except the control group via intra-articular injection of monosodium urate (MSU) suspension into the right posterior ankle joint cavity. The joint swelling and gait were scored at the time points of 6, 12, 24, 48 h after modeling. Histopathological alterations in the ankle joint tissue from each group were assessed by hematoxylin-eosin (HE) staining. Malondialdehyde (MDA), xanthine oxidase (XOD), and total superoxide dismutase (T-SOD) assay kits were used to assess the levels of MDA, XOD, and T-SOD in the serum. The levels of tumor interleukin-6 (IL-6), necrosis factor-α (TNF-α), and IL-1β in the rat serum, as well as ROS in the ankle joint tissue, were measured by enzyme-linked immunosorbent assay (ELISA). Western blot was performed to determine the protein levels of NLRP3, thioredoxin-interacting protein (TXNIP), apoptosis-associated speck-like protein containing a CARD domain (ASC), precursor cysteinyl aspartate-specific proteinase-1 (pro-Caspase-1), cleaved Caspase-1 (Caspase-1 p20), and IL-1β in the ankle joint tissue. Real-time PCR was employed to assess the mRNA levels of TXNIP, NLRP3, ASC, IL-1β, and TNF-α in the ankle joint tissue. ResultsCompared with the normal group, the model group exhibited decreased spontaneous activity, mental fatigue, increased ankle joint swelling and gait scores (P<0.01), aggravated synovial tissue edema and inflammatory cell infiltration (P<0.01), elevated levels of XOD, MDA, TNF-α, IL-1β, and IL-6 in the serum and ROS in the joint tissue (P<0.01), a declined level of T-SOD (P<0.01), up-regulated protein levels of NLRP3, TXNIP, ASC, pro-Caspase-1, Caspase-1 p20, and IL-1β in the ankle joint tissue (P<0.01), and up-regulated mRNA levels of NLRP3, TXNIP, ASC, IL-1β, and TNF-α in the ankle joint tissue (P<0.01). Compared with the model group, the medium- and high-dose quercetin groups showed improved general conditions, decreased gait scores (P<0.05, P<0.01), reduced joint swelling (P<0.01), alleviated synovial tissue edema and inflammatory cell infiltration (P<0.05, P<0.01), lowered levels of XOD, MDA, TNF-α, IL-1β, and IL-6 in the serum and ROS in the joint tissue (P<0.01), increased levels of T-SOD (P<0.01), down-regulated protein levels of TXNIP, NLRP3, ASC, pro-Caspase-1, Caspase-1 p20, and IL-1β in the ankle joint tissue (P<0.05, P<0.01), and down-regulated mRNA levels of TXNIP, NLRP3, ASC, IL-1β, and TNF-α in the ankle joint tissue (P<0.01). Low-dose quercetin also ameliorated some of the above parameters (P<0.05, P<0.01). ConclusionQuercetin exerts anti-GA effects by blocking the ROS/NLRP3/IL-1β signaling pathway, downregulating NLRP3 inflammasome activation, and inhibiting the production of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6.
4.Association between takeout fast foods and sugar sweetened beverage consumption with co-occurrence of anxiety and depressive symptoms among first year junior high school students in Yunnan Province
HU Dongyue, ZHANG Zhengwu, XU Zenglei, TAO Lei, ZENG Anna, GUAN Liao, CHANG Litao,〖JZ〗 HUANG Xin, CHEN Weiwei, LI Jiangli, XU Honglü ;
Chinese Journal of School Health 2026;47(1):23-26
Objective:
To explore the association between takeout fast foods and sugar sweetened beverage consumption with co-occurrence of anxiety and depressive symptoms among first year junior high school students in Yunnan Province, so as to provide theoretical basis for the prevention of anxiety and depressive symptoms co-occurrence among adolescents.
Methods:
A random cluster sampling involving 8 500 first year junior high school students in 11 counties in Yunnan Province was conducted by a questionnaire survey from October to December 2022. The Depression Anxiety Stress Scale-21 (DASS-21) was applied to assess anxiety and depressive symptoms in first year junior high school students. Chi-square test was used to compare the anxiety-depression co-occurrence symptoms of first year junior high school students with different demographic characteristics. The association between takeout fast foods and sugar sweetened beverage consumption with co-occurrence of anxiety and depressive symptoms of adolescents was analyzed by binary Logistic regression models.
Results:
The detection rate of co-occurrence of anxiety and depression symptoms among first year junior high school students in Yunnan Province was 26.92%. After controlling for demographic variables and other confounders, takeout fast foods and sugar sweetened beverage consumption( OR=1.50, 95%CI =1.27-1.77) was associated with anxiety-depression co-occurrence symptoms among first year junior high school students in Yunnan Province ( P <0.01). Stratified analysis showed that both Han ( OR=1.37, 95%CI =1.07-1.77) and ethnic minorities ( OR=1.60, 95%CI =1.29-2.00) exhibited statistically significant associations between takeout fast foods and sugar sweetened beverage consumption with co-occurrence of anxiety and depressive symptoms(both P <0.05).
Conclusions
Takeout fast foods and sugar sweetened beverage consumption increases the risk of co-occurrence of anxiety and depressive symptoms among first year junior high school students in Yunnan Province. It is recommended to strengthen guidance on the consumption of such products among junior high school students to prevent co-occurrence of anxiety and depressive symptoms.
5.The first record of Anopheles messeae (Diptera: Culicidae) parasitized by water mites in China
Xue-ru CHEN ; Wen-zhen YAO ; Yu-hao LI ; Gui-chang LI ; Tao MENG ; Qun-ling FENG ; Xin-hui LIU ; Li-hong QIAO ; Xiang-ting WU ; Xue-feng ZHANG ; Cheng-lin LI ; Xue-cheng DONG ; Da-wei WANG ; Xiao-yan SI ; Yu-hong GUO
Acta Parasitologica et Medica Entomologica Sinica 2026;33(1):53-57
Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.
6.A multicenter,randomized,control clinical trial comparing the efficacy and safety of recombinant staphylokinase and alteplase in the treatment of acute ST-segment elevation myocardial infarction
Xin-gang WANG ; Guo-feng CHANG ; Rui-ping ZHAO ; Xiao-Li GAO ; Fang-Fang FAN ; Yan-jun GONG ; Jie JIANG ; Yong HUO
Chinese Journal of Interventional Cardiology 2025;33(6):319-326
Objective To evaluate the efficacy and safety of recombinant staphylokinase in patients with acute ST-segment elevation myocardial infarction(STEMI)by a multi-center,randomized,position-controlled,parallel post-marketing clinical trial.Methods This study was a multi-center,randomized,positive drug parallel control,non-inferiority clinical trial.From July 2019 to June 2022,a total of 251 patients with STEMI were enrolled in 31 hospitals.Patients were randomly assigned to receive intravenous staphylokinase or alteplase in a ratio of 1∶1.Vascular recanalization was evaluated by clinical indicators 30 minutes,60 minutes and 120 minutes after the initiation of thrombolysis.Coronary angiography was performed 90 to 120 minutes after the initiation of thrombolysis.The proportion of infarct-related artery(IRA)with thrombolysis in myocardial infarction(TIMI)grade Ⅱ and Ⅲ,corrected TIMI frame count(CTFC)and TIMI myocardial perfusion grade(TMPG)were analyzed Major adverse cardiac events(MACE,including all-cause death,rehospitalization,reinfarction,urgent target vessel revascularization)and bleeding events were followed up at 30 days(±2 days)after thrombolysis.Results After excluding 7 subjects who did not use thrombolytic drugs,244 subjects were finally eligibled from 31 hospitals(117 in trial group and 127 in control group),and 232 subjects completed the follow-up(111 in trial group and 121 in control group).The vascular recanalization rate evaluated by clinical indicators at 120 minutes after thrombolysis was 85.6% in trial group and 83.5% in control group(P=0.657).The difference between the two groups was 2.11(95%CI-7.19-11.41).Given that the lower confidence limit of the 95%CI was greater than-12%,the non-inferiority of the vascular recanalization rate was established based on clinical judgment.Coronary angiography showed that the total patency rate of IRA(TIMIⅡ-Ⅲ)was 77.5% in trial group and 77.7% in control group(P=0.970).The difference between the two groups was-0.21(95%CI-10.95-10.54),with the lower bound of the 95%CI exceeding-12%.Therefore,the non-inferiority of the TIMI blood flow grade was confirmed,indicating that the total patency rate of IRA in the trial group was not inferior to that in the control group.The CTFC was(32.7±17.6)frames in trial group and(37.6±16.6)frames in control group,with no statistically significant difference between the two groups(P=0.054).The difference between the two groups was-4.9(95%CI-10.0-0.1).As the lower limit of the 95%CI exceeded-12%,the noninferiority of CTFC was successfully demonstrated.The proportions of TMPG 0-Ⅲ were 20.7%,6.3%,2.7%and 69.4%in trial group,and 22.3%,4.1%,6.6% and 66.9% in control group,respectively.There was no significant difference in TIMI myocardial perfusion grade between the two groups(P=0.086).The incidence of MACE was 7.7% in trial group and 7.1% in control group within 30 days after the initiation of thrombolysis,and there was no significant difference between the two groups(P=0.857).Further analysis showed that there was no significant difference in cardiovascular mortality(3.4% vs.4.7%,P=0.751).All 244 subjects were included in the safety analysis set.There was no significant difference in the total incidence of bleeding events between the two groups(22.2% vs.15.0%,P=0.144).There was no significant difference in the incidence of major bleeding(1.7% vs.0.8%,P=0.609).Conclusions Recombinant staphylokinase is simple to use and has a rapid onset of action.The efficacy and safety of recombinant staphylokinase are not inferior to alteplase in the treatment of acute STEMI.
7.Astragaloside Ⅳ inhibits LPS-induced RAW 264.7 macrophage polarization and regulates their migration via cGAS/STING/NF-κB pathway
Chang-chao YANG ; Guo-ting LI ; Lin LIU ; Zi-xian ZHAO ; Wei-kang LI ; Qing-xin SUN ; Yu-ying ZHAO ; Jing-shan ZHAO
Chinese Pharmacological Bulletin 2025;41(7):1290-1297
Aim To explore the effect of astragalosideⅣ(AS-Ⅳ)on lipopolysaccharide(LPS)-induced po-larization and migration of RAW 264.7 macrophages and the underlying mechanism.Methods 1 mg·L-1 LPS was used to construct cell migration model.Scratch assay was utilized to determine cell migration rate.Immunofluorescence staining was utilized to de-tect the expression and location of F4/80,iNOS and Arg-1.CCK-8 assay was used to determine the viabili-ty of RAW 264.7 cells.Griess assay was used to measure NO content.Molecular docking was used to analyze the interaction between AS-Ⅳ and the core tar-gets such as cGAS and STING protein.Western blot was employed to detect the expression of iNOS,Arg-1,cGAS,STING,NF-κB p65 and p-NF-κB p65 protein.Results AS-Ⅳ significantly inhibited the migration and M1 polarization of RAW 264.7 cells induced by LPS.Moreover,AS-Ⅳ could interact with cGAS and STING protein,especially cGAS.Further Western blot assay showed that AS-Ⅳ significantly downregulated the expression of iNOS,cGAS,STING and p-NF-κB p65 protein.Conclusions AS-Ⅳ could promote mac-rophage M1 to M2 polarization,thereby inhibited mac-rophage migration through restraining the cGAS/STING/NF-κB signaling pathway,which provides a new therapeutic target for AS-Ⅳ to improve the early inflammatory response of AS.
8.PD-L1 inhibits and regulates liver CD8+IFN-γ+ T cells to damage liver function and participate in atherosclerosis
Xiao LIU ; Xin WU ; Zi-yi ZHEN ; Jia-ying ZHANG ; Qi LI ; Chang CHEN
Chinese Pharmacological Bulletin 2025;41(4):638-645
Aim To study the effect of anti-PD-L1 monoclonal antibody on high-fat diet-induced athero-sclerosis in ApoE-/-mice.Methods Twenty-four ApoE-/-mice were randomly divided into the normal group,high-fat group,and high-fat+anti-PD-L1 mAb group.After 70 days,the blood samples were harves-ted.Blood vessels(aortic root to abdominal aorta)and liver from each groups were stained with Oil Red O.Hematoxylin-eosin staining(HE)was employed to vis-ualize structural changes in liver.Enzyme-linked im-munosorbent assay(ELISA)was applied to detect the serum levels of total cholesterol(CHO),triglyceride(TG),high-density lipoprotein(HDL-c),low-density lipoprotein(LDL-c)and inflammatory factors(IFN-γ,TNF-α,IL-1 β).Flow cytometry was used to detect the proportion of lymphocytes(CD4 and CD8).RT-PCR was utilized to assess the expressions of IFN-γ,TNF-α,IL-1 β,CD4 and CD8 in liver.Results Compared with the high-fat group,the treatment with anti-PD-L1 monoclonal antibody promoted vascular wall and liver lipid accumulation,and also up-regulated serum and liver content of cholesterol(CHO),triglyceride(TG)and high-density lipoprotein(HDL-c).Treatment with anti-PD-L1 monoclonal antibody up-regulated the con-tent of alanine aminotransferase(GPT)and aspartate aminotransferase(GOT)in serum and liver,but not al-kaline phosphatase(AKP).ELISA test indicated that treatment with anti-PD-L1 monoclonal antibody stimu-lated the serum level of IFN-γ,TNF-α and IL-1 β.Fur-thermore,the mRNA level of IFN-γ,TNF-α and IL-1 βin liver was also up-regulated after treatment with anti-PD-L1 monoclonal antibody.With flow cytometry,we observed that treatment with anti-PD-L1 monoclonal antibody promoted hepatic CD8+T and CD8+IFN-γ+T cell activation,but had no effect on CD4+IFN-γ+T cell activation under high-fat feeding conditions.Con-clusions Anti-PD-L1 monoclonal antibody adminis-tered under high-fat feeding conditions can damage liv-er function and aggravate atherosclerosis by activating liver CD8+IFN-γ+T cells.
9.A multicenter,randomized,control clinical trial comparing the efficacy and safety of recombinant staphylokinase and alteplase in the treatment of acute ST-segment elevation myocardial infarction
Xin-gang WANG ; Guo-feng CHANG ; Rui-ping ZHAO ; Xiao-Li GAO ; Fang-Fang FAN ; Yan-jun GONG ; Jie JIANG ; Yong HUO
Chinese Journal of Interventional Cardiology 2025;33(6):319-326
Objective To evaluate the efficacy and safety of recombinant staphylokinase in patients with acute ST-segment elevation myocardial infarction(STEMI)by a multi-center,randomized,position-controlled,parallel post-marketing clinical trial.Methods This study was a multi-center,randomized,positive drug parallel control,non-inferiority clinical trial.From July 2019 to June 2022,a total of 251 patients with STEMI were enrolled in 31 hospitals.Patients were randomly assigned to receive intravenous staphylokinase or alteplase in a ratio of 1∶1.Vascular recanalization was evaluated by clinical indicators 30 minutes,60 minutes and 120 minutes after the initiation of thrombolysis.Coronary angiography was performed 90 to 120 minutes after the initiation of thrombolysis.The proportion of infarct-related artery(IRA)with thrombolysis in myocardial infarction(TIMI)grade Ⅱ and Ⅲ,corrected TIMI frame count(CTFC)and TIMI myocardial perfusion grade(TMPG)were analyzed Major adverse cardiac events(MACE,including all-cause death,rehospitalization,reinfarction,urgent target vessel revascularization)and bleeding events were followed up at 30 days(±2 days)after thrombolysis.Results After excluding 7 subjects who did not use thrombolytic drugs,244 subjects were finally eligibled from 31 hospitals(117 in trial group and 127 in control group),and 232 subjects completed the follow-up(111 in trial group and 121 in control group).The vascular recanalization rate evaluated by clinical indicators at 120 minutes after thrombolysis was 85.6% in trial group and 83.5% in control group(P=0.657).The difference between the two groups was 2.11(95%CI-7.19-11.41).Given that the lower confidence limit of the 95%CI was greater than-12%,the non-inferiority of the vascular recanalization rate was established based on clinical judgment.Coronary angiography showed that the total patency rate of IRA(TIMIⅡ-Ⅲ)was 77.5% in trial group and 77.7% in control group(P=0.970).The difference between the two groups was-0.21(95%CI-10.95-10.54),with the lower bound of the 95%CI exceeding-12%.Therefore,the non-inferiority of the TIMI blood flow grade was confirmed,indicating that the total patency rate of IRA in the trial group was not inferior to that in the control group.The CTFC was(32.7±17.6)frames in trial group and(37.6±16.6)frames in control group,with no statistically significant difference between the two groups(P=0.054).The difference between the two groups was-4.9(95%CI-10.0-0.1).As the lower limit of the 95%CI exceeded-12%,the noninferiority of CTFC was successfully demonstrated.The proportions of TMPG 0-Ⅲ were 20.7%,6.3%,2.7%and 69.4%in trial group,and 22.3%,4.1%,6.6% and 66.9% in control group,respectively.There was no significant difference in TIMI myocardial perfusion grade between the two groups(P=0.086).The incidence of MACE was 7.7% in trial group and 7.1% in control group within 30 days after the initiation of thrombolysis,and there was no significant difference between the two groups(P=0.857).Further analysis showed that there was no significant difference in cardiovascular mortality(3.4% vs.4.7%,P=0.751).All 244 subjects were included in the safety analysis set.There was no significant difference in the total incidence of bleeding events between the two groups(22.2% vs.15.0%,P=0.144).There was no significant difference in the incidence of major bleeding(1.7% vs.0.8%,P=0.609).Conclusions Recombinant staphylokinase is simple to use and has a rapid onset of action.The efficacy and safety of recombinant staphylokinase are not inferior to alteplase in the treatment of acute STEMI.
10.Astragaloside Ⅳ inhibits LPS-induced RAW 264.7 macrophage polarization and regulates their migration via cGAS/STING/NF-κB pathway
Chang-chao YANG ; Guo-ting LI ; Lin LIU ; Zi-xian ZHAO ; Wei-kang LI ; Qing-xin SUN ; Yu-ying ZHAO ; Jing-shan ZHAO
Chinese Pharmacological Bulletin 2025;41(7):1290-1297
Aim To explore the effect of astragalosideⅣ(AS-Ⅳ)on lipopolysaccharide(LPS)-induced po-larization and migration of RAW 264.7 macrophages and the underlying mechanism.Methods 1 mg·L-1 LPS was used to construct cell migration model.Scratch assay was utilized to determine cell migration rate.Immunofluorescence staining was utilized to de-tect the expression and location of F4/80,iNOS and Arg-1.CCK-8 assay was used to determine the viabili-ty of RAW 264.7 cells.Griess assay was used to measure NO content.Molecular docking was used to analyze the interaction between AS-Ⅳ and the core tar-gets such as cGAS and STING protein.Western blot was employed to detect the expression of iNOS,Arg-1,cGAS,STING,NF-κB p65 and p-NF-κB p65 protein.Results AS-Ⅳ significantly inhibited the migration and M1 polarization of RAW 264.7 cells induced by LPS.Moreover,AS-Ⅳ could interact with cGAS and STING protein,especially cGAS.Further Western blot assay showed that AS-Ⅳ significantly downregulated the expression of iNOS,cGAS,STING and p-NF-κB p65 protein.Conclusions AS-Ⅳ could promote mac-rophage M1 to M2 polarization,thereby inhibited mac-rophage migration through restraining the cGAS/STING/NF-κB signaling pathway,which provides a new therapeutic target for AS-Ⅳ to improve the early inflammatory response of AS.


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