1.Tanyu Tongzhi Youhua Prescription Regulates cGAS/STING Signaling Pathway to Inhibit Inflammation and Ameliorate No-reflow Phenomenon in Myocardial Ischemia/Reperfusion Injury
Sijia WU ; Yingying LI ; Haonan WU ; Xiang LI ; Lingfeng ZHOU ; Huamin ZHANG ; Danli TANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):99-107
ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription(TYTZP) against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley (SD) rats were randomly divided into sham group, model group, ticagrelor group (32.4 mg·kg-1), RU320521 (RU.521cGAS inhibitors) group (5 mL·kg-1), groups of TYTZP with low dose (3.6 g·kg-1), medium dose (7.2 g·kg-1), and high dose (14.4 g·kg-1), with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin (HE) staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA (dsDNA) levels were detected by using PicoGreen. The protein expression of cGAS, STING, and nuclear factor-κB (NF-κB) p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ (cTNⅠ), cardiac troponin T (cTNT), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the sham group, the model group showed a significantly increased myocardial no-reflow area (P<0.01). Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P<0.01) were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged (P<0.01), and the levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), cTNⅠ, cTNT, and dsDNA were significantly elevated (P<0.01). Western blot results showed that the myocardial protein expressions of cGAS, STING, and NF-κB p65 were upregulated (P<0.01). ELISA results showed that the inflammatory factors in the serum such as IL-6, IL-1β, and TNF-α were increased (P<0.01). Compared with the model group, the group of the TYTZP significantly reduced the levels of myocardial enzyme, troponins, and dsDNA (P<0.01, P<0.05), improved cardiac function and myocardial microcirculation, alleviated histopathological morphology and inflammatory infiltration, inhibited activation of the cGAS/STING pathway, reduced the expression of NF-κB p65 (P<0.01, P<0.05), and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury, and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.
2.Tanyu Tongzhi Youhua Prescription Regulates cGAS/STING Signaling Pathway to Inhibit Inflammation and Ameliorate No-reflow Phenomenon in Myocardial Ischemia/Reperfusion Injury
Sijia WU ; Yingying LI ; Haonan WU ; Xiang LI ; Lingfeng ZHOU ; Huamin ZHANG ; Danli TANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):99-107
ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription(TYTZP) against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley (SD) rats were randomly divided into sham group, model group, ticagrelor group (32.4 mg·kg-1), RU320521 (RU.521cGAS inhibitors) group (5 mL·kg-1), groups of TYTZP with low dose (3.6 g·kg-1), medium dose (7.2 g·kg-1), and high dose (14.4 g·kg-1), with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin (HE) staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA (dsDNA) levels were detected by using PicoGreen. The protein expression of cGAS, STING, and nuclear factor-κB (NF-κB) p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ (cTNⅠ), cardiac troponin T (cTNT), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the sham group, the model group showed a significantly increased myocardial no-reflow area (P<0.01). Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P<0.01) were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged (P<0.01), and the levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), cTNⅠ, cTNT, and dsDNA were significantly elevated (P<0.01). Western blot results showed that the myocardial protein expressions of cGAS, STING, and NF-κB p65 were upregulated (P<0.01). ELISA results showed that the inflammatory factors in the serum such as IL-6, IL-1β, and TNF-α were increased (P<0.01). Compared with the model group, the group of the TYTZP significantly reduced the levels of myocardial enzyme, troponins, and dsDNA (P<0.01, P<0.05), improved cardiac function and myocardial microcirculation, alleviated histopathological morphology and inflammatory infiltration, inhibited activation of the cGAS/STING pathway, reduced the expression of NF-κB p65 (P<0.01, P<0.05), and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury, and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.
3.Research progress on the role of macrophages in atherosclerosis
Wenxiu MA ; Li BAI ; Wen MA ; Tingting QI ; Haonan ZHANG ; Xuan WANG ; Xin ZHANG
Acta Universitatis Medicinalis Anhui 2026;61(4):770-775
Atherosclerosis (AS) is a chronic and inflammatory vascular disease. Macrophages are common immune cells and play an important role in the development of AS. In recent years, research has found that the formation of AS plaques is closely related to pathological and physiological processes such as macrophage polarization, energy metabolism, and lipid phagocytosis. This review aims to summarize the mechanism of macrophages in the development of AS, and to explore potential therapeutic methods for delaying AS by regulating macrophages, providing new ideas for the treatment and research of AS.
4.Metabolomics Insights into Lidan Huatan Huoxue Decoction Improving Cognitive Impairment in Obese Rats
Yang ZHANG ; Jialu LYU ; Tiegang XIAO ; Haonan SHANG ; Yueshuang ZHAO ; Xiangyu DU ; Jun XU ; Bing WANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(10):2851-2863
Objective To explore the mechanism of Lidan Huatan Huoxue Decoction improving cognitive impairment caused by obesity based on metabolomics.Methods Twenty-four 6-week-old male SD rats were randomly divided into a normal group fed with regular diet(Con,n=6)and a modeling group fed with high-fat and high-sugar diet(n=18).Rats with a body mass that is 20%higher than the standard body mass of their age-matched peers fed with ordinary diet were considered to have a successful obese model established.The presence of cognitive impairment was assessed by Morris water maze and Barnes maze tests.After the obese-induced cognitive impairment(OICI)model was established,the modeling rats were randomly divided into a model group(Model,n=6),a donepezil group(Donepezil,n=6),and a Lidan Huatan Huoxue Decoction group(LHH,n=6).Drugs were administered to the donepezil and LHH groups by gastric intubation.The donepezil group was administered with a dose of 0.45 mg·(kg·d)-1,while the LHH group was administered with a dose of 25 g·(kg·d)-1.The normal and model groups were given the same volume of normal saline by gastric intubation for 8 weeks.Before the rats were sacrificed,water maze and Barnes maze experiments were conducted to assess cognitive function.After sacrifice,specimens were collected for biochemical and histological examination of liver tissue and brain tissue.Non-targeted metabolomic analysis using liquid chromatography-mass spectrometry(LC-MS)was performed on feces,serum,and brain tissue to analyze changes in differential metabolites in rats.Results Compared with the model group,the intervention of Donepezil and LHH effectively improved the learning and memory ability of OICI rats(P<0.05 or P<0.01),inhibited the overactivation of hippocampal microglia,and increased the number of hippocampal synaptic proteins.LHH improved metabolic-related indicators in OICI rats(P<0.05 or P<0.01).Metabolomic analysis showed significant differences in metabolites in feces,serum,and brain tissue between the model group and the normal group.The main affected pathways in fecal metabolites included steroid biosynthesis,caffeine metabolism,lysosome,vitamin B6 metabolism,phenylalanine,tyrosine,and tryptophan biosynthesis.The main affected pathways in serum metabolites included central carbon metabolism in cancer,pentose phosphate pathway,mineral absorption,protein digestion and absorption,and aminoacyl-tRNA biosynthesis.The main affected pathways in brain tissue metabolites included glycerophospholipid metabolism,β-alanine metabolism,propionic acid metabolism,niacin and nicotinamide metabolism,and caffeine metabolism.After LHH intervention,fecal metabolites showed the most significant changes,mainly involving vitamin B6 metabolism,vitamin digestion and absorption,histidine metabolism,fructose and mannose metabolism,and steroid biosynthesis.Conclusion LHH can improve cognitive impairment in obese rats mainly by regulating fecal metabolites.The main pathways involved include vitamin B6 metabolism,vitamin digestion and absorption,histidine metabolism,fructose and mannose metabolism,and steroid biosynthesis.Among them,vitamin B6 metabolism and vitamin digestion and absorption may be the most important pathways.
5.Real world research on prognosis and associated risk factors of postoperative radiotherapy in breast cancer patients undergoing postmastectomy breast reconstruction
Haonan HAN ; Hailing HOU ; Baozhong ZHANG ; Jing WANG ; Yuanjie CAO ; Jinqiang YOU ; Zhongjie CHEN ; Jie CHEN ; Bailin ZHANG ; Li ZHU ; Xiangpan LI ; Ping WANG ; Liming XU
Chinese Journal of Radiation Oncology 2025;34(5):453-460
Objective:To evaluate the impact of postoperative radiotherapy (RT) and associated risk factors on the prognosis of patients undergoing postmastectomy breast reconstruction (PMBR) for breast cancer.Methods:A retrospective analysis was conducted on 1593 breast cancer patients who underwent PMBR at Tianjin Medical University Cancer Institute & Hospital between January 2010 and October 2023. Patients were divided into an RT group ( n = 351) and a non-RT group ( n =1242) based on whether postoperative radiotherapy was administered. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was the incidence of revision surgery. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used for pairing. Continuous variables were compared between the two groups using the independent samples t-tests, while categorical variables were compared using chi-square tests, and survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards model was used to analyze survival influencing factors, and include propensity factors with P<0.2 in univariate analysis into multivariate analysis. Results:In the RT group, there were 3 deaths (0.9%) and 21 cases of disease progression (6.0%); in the non-RT group, 7 patients died (0.56%) and 40 experienced disease progression (3.22%). The median OS was 20.1 months (range: 0.1-164.9), and the median PFS was 19.5 months (range: 0.1-160.9). Pregnancy-associated breast cancer and higher N stage were identified as significant risk factors for OS, while neoadjuvant therapy, absence of adjuvant chemotherapy or endocrine therapy, and higher T stage were significant risk factors affecting patients' PFS. Radiotherapy significantly reduced the survival risk for PMBR patients with pregnancy-associated breast cancer or those receiving neoadjuvant therapy ( P=0.019, 0.027). Compared with other reconstruction methods, implant-based reconstruction was associated with a lower incidence of postmastectomy revision surgery(10.5% vs. 17.0%, P<0.001). Even after radiotherapy, the revision surgery incidence for implant-based reconstruction remained lower than that of other methods (12.2% vs. 14.2%, P=0.591). Compared with other reconstruction types, expander-based reconstruction was associated with an increased incidence of revision surgery (31.9% vs. 10.9%, P<0.001). Conclusions:Postmastectomy radiotherapy can reduce survival risk in PMBR patients with pregnancy-associated breast cancer or who received neoadjuvant therapy, showing positive effects on OS and PFS in high-risk patients. Pregnancy, higher T/N stage, and specific treatment strategies are critical factors influencing the prognosis of PMBR patients. Implant-based reconstruction is associated with a lower incidence of revision surgery, which remains low even after RT, whereas expander-based reconstruction may increase the long-term risk of revision surgery.
6.Tumor budding and its correlation with clinicopathological features and prognosis in penile squamous cell carcinoma
Wen HAN ; Qian ZHANG ; Xiang YONG ; Yi ZHANG ; Chun WANG ; Haonan LIU ; Xiaotong GUO
Chinese Journal of Clinical and Experimental Pathology 2025;41(5):608-613
Purpose To investigate the correlation between tumor budding in penile squamous cell carcinoma(SCC)and its clinicopathological features.Methods Clinical data and pathological slides from 69 cases of penile SCC were collected.Tumor budding was examined microscopically,and statistical analyses were performed to assess the relationship between tumor budding and various clinicopathological features.Results Among the 69 cases of pe-nile SCC,41 cases exhibited low-grade tumor budding and 28 cases displayed high-grade tumor budding.Tumor bud-ding was significantly correlated with tumor size,urethral invasion,invasion of the urethral corpus spongiosum,inva-sion of the penile corpus cavernosum,tumor necrosis,nerve invasion,vascular tumor thrombus,and pathological T stage(all P<0.05).In contrast,no significant association was found between tumor budding and HPV-related versus non-HPV-related penile SCC(P>0.05).Log-rank survival analysis indicated that patients with high-grade tumor bud-ding had a significantly lower survival rate compared to those with low-grade tumor budding(P<0.05).Conclusion Tumor budding is a distinct pathological feature of penile SCC,and high-grade tumor budding is associated with a more aggressive biological behavior.
7.Physical activity and health for college students:cross-sectoral integration and development of health and educa-tion policies
Chinese Journal of Rehabilitation Theory and Practice 2025;31(8):869-875
Objective To systematically analyze the cross-sectoral health policy frameworks and strategic priorities of the World Health Organization(WHO),United Nations Educational,Scientific and Cultural Organization(UNESCO),Euro-pean Union(EU),and China in promoting college students'physical activity,adolescent health and mental health,to explore the ways integrating physical activity-related health policies with the polices of college students health and quality physical education.Methods Based on WHO's health promotion framework and with reference to the"Health in All Policies"(HiAP)ap-proach,a content analysis was conducted on health-related policies of WHO,UNESCO,EU and China.Results In the health sector,the international community established a policy system centered on health promotion and the governance concept of HiAP.WHO's Global Action Plan on Physical Activity 2018-2030 and related strate-gies on mental health identified physical activity as a core measure to promote both physical and mental health.The EU's recommendations on Health-Enhancing Physical Activity provided a scheme for translating global strat-egies into monitorable cross-sectoral regional actions.China's national strategies,such as Healthy China 2030 Planning Outline and Integration of Sports and Education demonstrated strong advantages in policy mobilization and resource allocation,with distinct focuses compared to international frameworks in terms of policy systematic-ity,participatory implementation and evaluation orientation.In the education sector,international policies empha-sized the integration of health promotion and education,evolving from ensuring Physical Education Hours to pro-moting Quality Physical Education and Physical Literacy.Through the frameworks like Kazan Action Plan and Health Promoting Universities represented by Okanagan Charter,campus sports was elevated to a level of serv-ing sustainable development and promoting overall well-being.China's National Fitness Program(2021-2025)and Basic Standards for Physical Education in Higher Education Institutions provided specific implementation plans for such integration.Conclusion For the cross-sectoral issue of college students physical activity and health,the international community has constructed an integrated policy framework based on health promotion,integrating policies on physical activity,adolescent health and mental health,to establish a more comprehensive,systematic and inclusive path.In higher education,the trend of integrating health and education policies is significant;physical activity is no longer re-garded as an isolated issue in physical education,but as a key cross-cutting strategy and policy to address non-communicable diseases,improve mental health,promote the holistic development of youth,and achieve the Sus-tainable Development Goals.China should,on the basis of Integration of Sports and Education,further expand HiAP-based cross-sectoral collaboration in accordance with health promotion principles;policy goals should not only focus on physical fitness standards,but also consider intrinsic interest,enjoyable experience and lifelong habit formation;and actively draw on the holistic systems perspective of Health Promoting Universities to build a supportive campus health promotion ecosystem that facilitates the comprehensive physical and mental develop-ment of every student.
8.The biological role of YTHDF2 and its application in tumors
Dengxinjie SHI ; Hongjin SHI ; Nan ZHANG ; Shi FU ; Qun WANG ; Haonan DONG ; Jiansong WANG ; Haidan LI ; Haifeng WANG
The Journal of Practical Medicine 2025;41(4):615-620
YTHDF2 is a key m6A RNA modification"reader"that plays a crucial role in cell biological processes and tumor development.This review deeply explores the biological role of YTHDF2 and the advances in its application in tumors.The YTHDF2 structures are divided into mRNA procsomes and YTH domains,which recognize and bind m6A modified RNA molecules.It plays a biological role by promoting mRNA degradation,regu-lating cell signaling pathways and metabolism,and can regulate macrophage function and maintain an immunosup-pressive state in the tumor microenvironment.YTHDF2 has the potential to serve as diagnostic markers,therapeu-tic targets and prognostic evaluation biomarkers in different tumors,but currently relevant studies are insufficient in sample size,molecular mechanism and clinical application.In the future,research can be conducted on compre-hensive clinical research,in-depth analysis of molecular mechanisms,and research and development of optimized treatment strategies.
9.Multi-parameter synthetic sequences combined with microview diffusion weighted imaging in predicting the invasion of cavernous sinus by pituitary macroadenoma
Hedan LUO ; Yangyingqiu LIU ; Haonan ZHANG ; Na LIU ; Yukun ZHANG ; Chang YUAN ; Jiayi SUN ; Nan WANG ; Qingwei SONG ; Yanwei MIAO
Chinese Journal of Radiology 2025;59(1):70-76
Objective:To investigate the value of MULTI-parametric MR imaging with flexible design (MTP) combined with microview diffusion weighted imaging (DWI) in predicting pituitary tumor invasion of cavernous sinus.Methods:This was a cross-sectional study. The clinicopathological and imaging data of 59 patients with suspected pituitary tumor who were admitted to the First Affiliated Hospital of Dalian Medical University from December 2021 to August 2024 were prospectively analyzed. According to Knosp classification, patients with pituitary tumor were divided into non-invasive group (28 cases) and invasive group (31 cases). All patients underwent MTP and microview DWI sequence scanning, and the corresponding parameter values [T 1, R 2*, T 2* and apparent diffusion coefficient (ADC)] were measured on the MTP quantitative map and ADC map at the maximum diameter level of the pituitary tumor. Independent sample t test and Mann-Whitney U test were used to compare the clinical data, quantitative parameter values and proliferation index (Ki-67) between the non-invasive group and the invasive group. Quantitative parameter values with statistically significant differences were jointly included in logistic regression to construct the model. Receiver characteristic curve and area under the curve (AUC) were used to analyze single variables and logistic model in predicting the value invasion of pituitary tumor cavernous sinus invasion. Spearman correlation was used to analyze the correlation between the quantitative values and Ki-67 level. Results:There was no significant difference in age and gender between the non-invasive group and the invasive group ( P>0.05). T 1 and T 2* values in invasion group were higher than those in non-invasion group ( Z=4.42, P<0.001; Z=3.43, P<0.001), R 2* values and ADC values in the invasion group were lower than those in the non-invasion group, and the difference was statistically significant (t=4.07, P<0.001; Z=-3.07, P=0.002). The AUC values of T 1, R 2*, T 2*, ADC, logistic model 1(T 1+R 2*+ADC) and logistic model 2(T 1+T 2*+ADC) for predicting pituitary tumor cavernous sinus invasion were 0.835, 0.767, 0.760, 0.733, 0.926 and 0.925, respectively. Correlation analysis showed that the value of pituitary tumor T 1 was positively correlated with Ki-67 ( r=0.431, P=0.002). Conclusion:Quantitative parameters of MTP sequence and microview DWI sequence can quantitatively evaluate pituitary tumor invasion of cavernous sinus, and the combination of the two sequences can significantly improve the prediction efficiency.
10.Research on the comprehensive evaluation of the operation status of tertiary public hospitals based on extensible cloud model
Kangfei SHEN ; Ce ZHANG ; Haonan ZHOU ; Ruiwu ZHUANG ; Yuying FAN ; Zuowei ZHAO
Chinese Journal of Hospital Administration 2025;41(2):81-89
Objective:To explore an evaluation method for the operational status of tertiary public hospitals, identify strengths and weaknesses in hospital operations, and provide decision-making support for hospital managers.Methods:In 2023, an evaluation index system for the operation of tertiary public hospitals was constructed based on literature analysis and the Delphi method. The combined weights of the evaluation indexes were determined using the cooperative game theory method. An evaluation model for hospital operational status based on the extensible cloud model was established, with the determination of evaluation index thresholds and standards based on the operational data of a tertiary public hospital in Liaoning Province from 2020 to 2022. The operational status of the hospital was then comprehensively evaluated using the evaluation model based on the hospital′s operational data from 2023.Results:The constructed evaluation index system for the operation of tertiary public hospitals included five dimensions and 14 indicators: financial health, service efficiency, medical quality, satisfaction, and sustainable development. The indicators with higher weight values were net cash flow (0.135), average appointment rate for outpatient patients (0.088), and budget savings from government procurement (0.087). The overall operational status evaluation score of the sample hospital was 4.48, with an evaluation grade of level V. The scores for the dimensions of financial health, medical quality, and sustainable development were 4.99, 4.74, and 5.00, respectively, all reaching level V. The scores for service efficiency and satisfaction were 4.00 and 3.70, respectively, both at level Ⅳ.Conclusions:The evaluation index system and the determined weights constructed in this study were reasonable to a certain extent. The hospital operational status evaluation model based on the extensible cloud model can objectively reflect the operational status of the hospital, and the evaluation results can provide decision-making support for managers.

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