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.Analysis of the anticoagulant effect and influencing factors of warfarin in patients after left ventricular assist device implantation guided by gene test
Ying WANG ; Jin LI ; Sijia ZHAO ; Tao CHEN ; Chengbin TANG ; Jia LIU
China Pharmacy 2025;36(17):2160-2164
OBJECTIVE To evaluate the effectiveness and safety of warfarin anticoagulation therapy guided by gene test in patients undergoing left ventricular assist device (LVAD) implantation, and to analyze the influencing factors of warfarin anticoagulation efficacy. METHODS Patients who underwent LVAD implantation at the Heart and Vascular Center of Northern Jiangsu People’s Hospital from January 2023 to October 2024 and required warfarin anticoagulant therapy were selected as the study subjects. They were divided into genetic testing group (n=51) and empirical treatment group (n=17) based on whether they underwent CYP2C9 and VKORC1 gene test. The gene test group was given warfarin based on the predicted dose calculated by gene test, while the empirical treatment group was given warfarin by clinical doctors based on international normalized ratio (INR) experience, all patients were given warfarin once a day. Follow-up observation was conducted for 6 months to compare the effectiveness [time in therapeutic range(TTR), the time required to reach INR for the first time, the incidence of embolic events, the incidence of INR<1.5 events] and safety (the incidence of major and minor bleeding events,the incidence of INR>3.5 events) of warfarin treatment between two groups of patients. According to whether the patient’s TTR was ≥60%, they were divided into TTR≥60% group (n=20) and TTR<60% group (n=48). Univariate and multivariate binary Logistic regression analysis were used to determine the factors affecting the anticoagulant effect of warfarin in patients. RESULTS The TTR of patients in the gene test group was significantly higher than that in the empirical treatment group (P<0.05). The incidence of INR<1.5 events in the gene test group was significantly lower than in the empirical treatment group (P<0.05). The incidence of minor bleeding events and INR>3.5 events in the gene test group were lower than in the empirical treatment group, but the difference was not statistically significant (P>0.05). The results of multivariate binary Logistic regression analysis showed that gene test was an independent protective factor for warfarin anticoagulant therapy [odds ratio (OR)=10.842, 95% confidence interval (CI): 1.211-27.037, P=0.033], and the combination of statins was an independent risk factor for warfarin anticoagulant therapy [OR=0.196, 95%CI: 0.045-0.861, P=0.031]. CONCLUSIONS Under the guidance of gene test, warfarin anticoagulation therapy for LVAD patients after implantation can improve TTR, shorten the anticoagulation target time, and has good safety; meanwhile, it should be noted that the combination of statins may enhance the anticoagulant effect of warfarin, thereby increasing the risk of bleeding in patients.
4.Characteristics of injury cases among the elderly in Ningbo City from 2014 to 2023
SUN Qiang ; HUANG Ying ; LI Xiaoyong ; YANG Chenying ; WANG Sijia
Journal of Preventive Medicine 2025;37(8):822-826,831
Objective:
To analyze the characteristics of injury surveillance cases among the elderly in Ningbo City, Zhejiang Province from 2014 to 2023, so as to provide the basis for formulating targeted injury intervention measures.
Methods:
Injury surveillance cases aged ≥60 years were collected from seven injury sentinel hospitals in Ningbo City through the Zhejiang Provincial Chronic Disease Surveillance Information Management System from 2014 to 2023. Population distribution, temporal distribution, injury circumstances, and clinical characteristics were described.
Results:
A total of 67 259 injury surveillance cases among the elderly were reported in Ningbo City from 2014 to 2023, including 32 159 males (47.81%) and 35 100 females (52.19%). The median age was 68.00 (interquartile range, 14.00) years. The three months with a higher number of cases were December (6 271 cases, 9.32%), August (6 226 cases, 9.26%) and October (6 221 cases, 9.25%). The primary causes of injury were falls (25 276 cases, 37.58%), stabs (12 250 cases, 18.21%), and sprains (11 815 cases, 17.57%). The injury occurred mainly in homes (44 975 cases, 66.87%) and streets/urban areas (16 174 cases, 24.05%). The predominant activities at the time of injury were leisure activities (28 801 cases, 42.82%) and household chores (23 647 cases, 35.16%). The proportions of falls as the cause of injury and injuries occurring at home among females and people aged 80 years and above were relatively high. The predominant sites of injury were upper limbs (23 354 cases, 34.72%) and lower limbs (20 343 cases, 30.25%). The predominant nature of injury were soft tissue injuries (43 345 cases, 64.44%) and bone and joint injuries (22 042 cases, 32.77%). Injuries were primarily mild and moderate in severity, with 46 391 cases (68.97%) and 20 205 cases (30.04%), respectively. The proportion of bone and joint injuries, moderate in injuries among females and people aged 80 years and above was relatively high.
Conclusions
The main causes of injury surveillance cases among the elderly in Ningbo City from 2014 to 2023 were falls and stabs, and the injuries occurred mainly in homes and streets/urban areas. Female and elderly people have a higher risk of injury.
5.Changes in the intestinal microbiota structure of patients with colorectal adenoma
Meng SIJIA ; Li JIQIU ; Wang DAN ; Liu CHEN ; Li CHUNYAN ; Zhao JING ; Wang YU ; Du MEIZHI ; Wang YUAN ; Lu WENLI ; Zhu YUN ; Zhang KEMING
Chinese Journal of Clinical Oncology 2025;52(4):177-182
Objective:To investigate gut microbiota differences between individuals with and without colorectal adenoma(CRA)and to identify gut microbes associated with CRA.Methods:This cross-sectional study analyzed the gut microbiota of 100 patients with CRA and 68 individuals without CRA(aged 40-75 years)who underwent colonoscopies between March 2021 and March 2022 at Tianjin Nankai Hospital.Fecal samples were sequenced for the V3-V4 region of the bacterial 16S rRNA gene using the Illumina NovaSeq platform.Results:Compared to the non-CRA group,the CRA group exhibited reduced relative abundances of identified and unidentified Lachnospiraceae,with increased Faecalibacterium and Streptococcus.In the non-CRA group,the relative abundances of Coprococcus,unidentified Clostridiaceae,and Clostridium were higher.LEfSe analysis revealed significant enrichment of Gammaproteobacteria,Proteobacteria,Enterobacteriales,and Faecalibacterium in the CRA group,while the non-CRA group was enriched for Moraxellaceae,Acinetobacter,and Anaerostipes.Conclusions:These findings suggest a discernible disparity in the gut microbiota structure between CRA patients and individuals without adenoma.The enrichment of potential pathogenic taxa,such as Faecalibacterium and Streptococcus,in the CRA group suggests a possible association with adenoma development.
6.Effect of Lokomat robotic-assisted gait training on lower limb motor function in children with hemiplegia
Tiantian ZHOU ; Tong ZHANG ; Qi ZHANG ; Yanhua LIANG ; Yanqing ZHANG ; Qing YUE ; Sijia LI
Chinese Journal of Rehabilitation Theory and Practice 2025;31(6):711-720
Objective To explore the effect of Lokomat robotic-assisted gait training on lower limb motor function in children with hemiplegia.Methods From October,2023 to January,2025,a total of 52 children with hemiplegia admitted to Beijing Bo'ai Hospital were randomly divided into control group(n=26)and observation group(n=26).Both groups received conven-tional rehabilitation therapy,while the observation group additionally received Lokomat robotic-assisted gait training,for four weeks.Before and after intervention,the self-selected walking speed(SWS)and maximum walking speed(MWS)of 10-meter Walk Test,6-minute walking distance(6MWD),Physiological Cost Index(PCI),as well as gait line length asymmetry ratio,single support line asymmetry ratio,stance phase asymmetry ratio and step length ratio were compared.Results After intervention,SWS,MWS and 6MWD improved in both groups(|Z|>2.910,P<0.01),and were better in the the observation group than in the control group(|Z|>2.069,P<0.05);PCI significantly decreased in both groups(|Z|>4.458,P<0.001),and was lower in the observation group than in the control group(Z=-2.435,P<0.05);the gait line length asymmetry ratio,single support line asymmetry ratio and stance phase asymmetry ratio improved in both groups(Z=3.398,|t|>2.211,P<0.05),and were better in the observation group than in the control group(Z=2.802,|t|>2.107,P<0.05).Conclusion Lokomat robotic-assisted gait training can effectively improve walking speed and endurance in children with hemiplegia,reduce energy expenditure,enhance walking efficiency,and promote gait symmetry,thereby fa-cilitating symmetrical gait patterns.
7.Effect of Ephedrine on OGD/R induced neuronal injury by regulating RIP1/RIP3/MLKL signaling pathway
Peng LI ; Aixin LI ; Sijia GUO
Chinese Journal of Immunology 2025;41(9):2161-2165,2171
Objective:To explore the effect of Ephedrine on oxygen glucose deprivation/reoxygenation(OGD/R)induced neu-ronal injury by regulating receptor interacting protein-1/receptor interacting protein-3/mixed lineage kinase domain-like protein(RIP1/RIP3/MLKL)signaling pathway.Methods:OGD/R model was constructed by hypoxia/reoxygenation;human cortical neuron HCN cells were separated into control group,model group(OGD/R group),Ephedrine group(800 μg/ml),Compound 6i group(RIP1 acti-vator Compound 6i,0.94 μmol/L),Ephedrine+Compound 6i group(800 μg/ml Ephedrine+0.94 μmol/L Compound 6i),Nec-1 group(RIP1 specific inhibitor Nec-1,5 μmol/L)and Ephedrine+Nec-1 group(800 μg/ml Ephedrine+5 μmol/L Nec-1);CCK-8 method was applied to detect HCN cell proliferation;DCFH-DA method was applied to detect ROS level in HCN cells;flow cytometry was ap-plied to detect HCN cell apoptosis;ELISA was applied to detect levels of TNF-α and IL-6;Western blot was applied to detect RIP1/RIP3/MLKL signaling pathway and apoptotic proteins expressions in HCN cells.Results:Compared with control group,ROS level,apop-tosis rate,p-MLKL,RIP3,Bax,IL-6,TNF-α and RIP1 expressions of HCN cells in OGD/R group were significantly increased,A450 value and Bcl-2 protein were significantly decreased(P<0.05);compared with OGD/R group,ROS level,apoptosis rate,p-MLKL,RIP3,Bax,IL-6,TNF-α and RIP1 expressions of HCN cells in Ephedrine group and Nec-1 group were significantly reduced,A450 val-ue and Bcl-2 protein were significantly increased,the trend of Compound 6i group was opposite(P<0.05);Compound 6i was able to weaken the effect of Ephedrine in improving OGD/R induced neuronal injury,Nec-1 was able to enhance the effect of Ephedrine in im-proving OGD/R induced neuronal injury.Conclusion:Ephedrine attenuates OGD/R induced neuronal injury by inhibiting RIP1/RIP3/MLKL signaling pathway.
8.Research progress in retinal structural alterations in patients with mental disorders
Sijia WANG ; Yanyan WEI ; Zhenying QIAN ; Qingwei LI ; Jijun WANG
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(2):247-252
Mental disorders frequently co-occur with other physical illnesses,becoming one of the leading causes of disability worldwide.Early diagnosis and intervention are crucial for the effective management of these disorders.Currently,biomarker studies on mental disorders predominantly concentrate on genes,blood indicators,and imaging features of the brain.There is a growing interest in objective phenotypic markers as a research focus.It is established that the retina is part of the central nervous system(CNS),which extends from the mesencephalon and develops concurrently with the brain during the embryonic period.Given the overlapping pathophysiological mechanisms between neurodegenerative diseases and mental disorders,studying the structural and functional changes in the inner layers of the retina has emerged as a new direction in mental health research.The advent of optical coherence tomography(OCT)has enabled microscopic imaging of retinal structures.OCT is capable of objectively quantifying the retinal sub-layers and offers the advantages of being non-invasive,non-contact,and high-resolution.The use of OCT to explore structural changes in the retina among individuals with schizophrenia,bipolar disorder,major depression and other psychiatric disorders has been well documented;however,there is a paucity of reviews on this topic.This review summarizes current research on retinal structural alterations in patients with mental disorders,and the results demonstrate reduced thickness in certain sub-layers of the retina structure in patients with several mental disorders,which supports that the retina structure has the potential to be a biomarker for mental disorders and offers a novel avenue for research in the diagnosis and treatment.
9.Arthroscopic single-row fixation and knotless suture bridge fixation for rotator cuff injuries combined with osteoporosis
Haoliang ZHANG ; Sijia XIA ; Bingzhen ZHAN ; Shuo FENG ; Guochun ZHA ; Cheng LI
Chinese Journal of Tissue Engineering Research 2025;29(15):3188-3192
BACKGROUND:Arthroscopic single-row fixation with knotless suture bridge fixation techniques have been commonly used in the treatment of rotator cuff injuries,but the clinical efficacy in rotator cuff injuries combined with osteoporosis is unclear.OBJECTIVE:To investigate the clinical efficacy of arthroscopic single-row fixation versus knotless suture bridge fixation in the treatment of rotator cuff injuries combined with osteoporosis.METHODS:One hundred and twenty-two patients with rotator cuff injuries combined with osteoporosis who underwent arthroscopic treatment admitted to Affiliated Hospital of Xuzhou Medical University between January 2018 and August 2022 were retrospectively analyzed.They were divided into two groups according to the treatment plan.There were 63 patients with single-row fixation(single-row group)and 59 patients with knotless suture-bridge fixation(suture-bridge group).The visual analog scale scores for pain,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley score,and shoulder range of motion were compared between the two groups at the preoperative and 1 year postoperative periods.Rotator cuff re-tears were evaluated at 1 year postoperatively using the Sugaya staging criteria.The occurrence of complications was recorded in both groups.RESULTS AND CONCLUSION:(1)All patients received more than 1-year follow-up.No complications such as incision infection and nerve injury occurred in both groups after surgery.(2)Postoperative visual analog scale scores,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley scores,and shoulder range of motion were significantly improved 1 year postoperatively in both groups compared with the preoperative period(P<0.05).Visual analog scale scores,University of California Los Angeles Shoulder Score,American Shoulder and Elbow Surgeons Score,Constant-Murley scores,and shoulder range of motion were better in the suture-bridge group than in the single-row group 1 year postoperatively(P<0.05).(3)At 1 year postoperatively,the re-tear rate in the single-row group[22%(14/63)]was significantly higher than that in the suture-bridge group[7%(4/59)],and the difference between the two groups was statistically significant(x2=5.777,P=0.016).(4)It is indicated that arthroscopic single-row fixation and knotless suture bridge fixation for rotator cuff injuries combined with osteoporosis both yielded satisfactory clinical outcomes,but knotless suture bridge fixation was more clinically effective,with a lower rate of postoperative retear.
10.Impact of baicalein on airway inflammation in COPD rats by regulating TLR4/NF-κB pathway
Lin ZHANG ; Houping XU ; Daiqun LIU ; Sijia WANG ; Guangxia LI
Chinese Journal of Immunology 2025;41(4):903-907
Objective:To investigate impact of baicalein(BA)on airway inflammation in chronic obstructive pulmonary disease(COPD)rats by regulating TLR4/NF-κB pathway.Methods:Rats were randomly divided into model group(n=56)and sham operation group(n=10),COPD rat model was established by smoking and intratracheal instillation of LPS,successful modeling rats were randomly divided into COPD group,BA low dose(BA-L,100 mg/kg)group,BA high dose(BA-H,200 mg/kg)group,TLR4 activator LPS group(0.1 mg/kg)and BA-H+LPS group(0.1 mg/kg LPS+200 mg/kg BA).After 2 h,peak expiratory flow(PEF),forced expiratory volume in first second(FEV1),forced vital capacity(FVC)and other lung function indexes were measured;serum TNF-α,IL-6 and IL-8 levels were measured;bronchoalveolar lavage fluid(BALF)was collected to analyze number and classification of cells;lung tissues were isolated to analyze pathological changes and TLR4,p-NF-κB p65/NF-κB p65 expressions.Results:Com-pared with sham operation group,pathological damage in COPD group was serious,PEF,FEV1 and FVC were decreased significantly,serum IL-6,IL-8,TNF-α levels,leukocytes number,neutrophils and lymphocytes proportions,TLR4 and p-NF-κB p65/NF-κB p65 expressions were increased significantly(P<0.05);compared with COPD group,pathological damage in LPS group was further aggra-vated,PEF,FEV1 and FVC were reduced significantly,serum IL-6,IL-8,TNF-α levels,leukocytes number,neutrophils and lym-phocytes proportions,TLR4 and p-NF-κB p65/NF-κB p65 expressions were increased significantly(P<0.05),pathological damage in BA-L group and BA-H group gradually improved,PEF,FEV1 and FVC were increased significantly,serum IL-6,IL-8,TNF-α levels,leukocytes number,neutrophils and lymphocytes proportions,TLR4 and p-NF-κB p65/NF-κB p65 expressions were decreased significantly(P<0.05);LPS reversed protective effect of BA-H on COPD rats.Conclusion:BA can improve airway inflammation in COPD rats,which may be related to inhibition of TLR4/NF-κB pathway.


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