1.Palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis: A new target for anti-myocardial fibrosis.
Xuewen YANG ; Yanwei ZHANG ; Xiaoping LENG ; Yanying WANG ; Manyu GONG ; Dongping LIU ; Haodong LI ; Zhiyuan DU ; Zhuo WANG ; Lina XUAN ; Ting ZHANG ; Han SUN ; Xiyang ZHANG ; Jie LIU ; Tong LIU ; Tiantian GONG ; Zhengyang LI ; Shengqi LIANG ; Lihua SUN ; Lei JIAO ; Baofeng YANG ; Ying ZHANG
Acta Pharmaceutica Sinica B 2025;15(9):4789-4806
Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.
2.Endovascular recanalization for symptomatic non-acute internal carotid artery occlusion:analysis of its short-term efficacy
Junlei CUI ; Xinyu XIE ; Dayong DU ; Yanwei HOU ; Wenlong ZHANG ; Bo LI ; Hongwu ZHANG ; Heliang ZHANG ; Zaiyu GUO
Journal of Interventional Radiology 2025;34(10):1105-1109
Objective To discuss the short-term efficacy of endovascular recanalization for symptomatic non-acute internal carotid artery occlusion.Methods A total of 90 patients with symptomatic non-acute internal carotid artery occlusion,who were admitted to the Department of Neurology of Tianjin Municipal Teda Hospital of China from August 2017 to December 2021,were selected as the research objects.The patients were divided into study group(n=45)and control group(n=45).Percutaneous endovascular recanalization of internal carotid artery occlusion was performed for the patients of the study group,and standardized antiplatelet aggregation and anti-lipid therapy(including oral aspirin,clopidogrel bisulphate and atorvastatin)was adopted for the patients of the control group.The symptom recurrence rate at one year after treatment in both groups was analyzed.Results Of the 45 patients in the control group,4 were lost in touch,and 41 completed the one-year follow-up.Of the 45 patients in the study group,2 patients had failure of surgery,one patient had lost contact visit,and 42 completed the one-year follow-up.Postoperative intracranial hemorrhage occurred in 2 patients.After one year of follow-up,in the control group 26 patients(63.41%)developed recurrence of symptoms,presenting as transient ischemic attack(TIA,n=13,31.7%)and cerebral infarction(n=13,31.7%),and in the study group 8 patients(4.76%)developed recurrence of symptoms,presenting as TIA(n=6,14.3%)and cerebral infarction(n=2,4.8%);the incidence of cerebral infarction in the study group was strikingly lower than that in the control group,and the difference between the two groups was statistically significant(P<0.05).In the patients with grade Ⅲ compensation,the recurrence rate of symptoms was remarkably decreased after endovascular recanalization of internal carotid artery occlusion,and the difference between the two groups was statistically significant(P<0.05).However,in the patients with grade Ⅰ or grade Ⅱ compensation,although the recurrence rate of symptoms was decreased after endovascular recanalization of internal carotid artery occlusion,the difference between the two groups was not statistically significant(P>0.05).Conclusion For the treatment of patients with symptomatic non-acute internal carotid artery occlusion,percutaneous endovascular recanalization of internal carotid artery occlusion is clinically safe,it can significantly decrease the recurrence rate of symptoms.
3.Balloon stent kissing technique versus jailed wire technique in treating coronary bifurcation lesions in the elderly patients:comparison of curative efficacy
Yanwei WANG ; Yali FENG ; Litao DU ; Yutong HU
Journal of Interventional Radiology 2025;34(11):1241-1245
Objective To compare the curative efficacy of balloon stent kissing technique and jailed wire technique in treating coronary bifurcation lesions(CBL)in the elderly patients.Methods A total of 104 elderly patients with CBL,who received interventional surgery from January 2023 to December 2023 in the First Hospital of Hebei University and Hebei Provincial Hospital of Traditional Chinese Medicine were enrolled in this study.The patients were divided into balloon stent group(n=51,using balloon stent kissing technique)and jailed wire group(n=53,using jailed wire technique).The postoperative changes in diseased vessels,myocardial and endothelial function injuries were compared between the two groups,and the incidence of postoperative major adverse cardiovascular event(MACE)was calculated.Results Half a year after surgery,in both groups the minimum internal diameters of the arterial main branch and lateral branches were larger than their preoperative values(P<0.05),and the stenosis ratio of the lesion segment was smaller than the preoperative value(P<0.05).In balloon stent group,the minimum internal diameter of lateral branches was larger than that in jailed wire group(P<0.05),and the stenosis ratio of the lesion segment was smaller than that in jailed wire group(P<0.05).Seven days after surgery,in both groups the levels of serum BNP,hs-cTnI,CK-MB,ET-1 and vWF were lower than their preoperative values,while the level of serum NO was higher than its preoperative value.The changes in the above indicators in balloon stent group were more obvious than in jailed wire group.No statistically significant difference in the incidence of MACE existed between the two groups(x2=1.605,P=0.205).Conclusion In treating elderly patients with CBL,both balloon stent kissing technique and jailed wire technique can improve the stenosis degree of the arterial main branch and lateral branches,but balloon stent kissing technique is superior to jailed wire technique in improving postoperative short-term myocardial function and endothelial function.
4.Impact of δ-catenin expression level on resting-state brain function in breast cancer patients
Mingtuan XUE ; Wei DU ; Jiajun CAO ; Yuhan JIANG ; Duan SONG ; Junyi ZHANG ; Yanwei MIAO
Chinese Journal of Medical Imaging Technology 2024;40(5):724-729
Objective To explore the impact of δ-catenin expression level on resting-state brain function in breast cancer patients.Methods Totally 104 female breast cancer patients were prospectively enrolled and divided into δ-catenin high expression group(DH group,n=51)and δ-catenin low expression group(DL group,n=53)according to δ-catenin expression level,while 36 female healthy volunteers were selected as controls(control group).Neuropsychological tests were performed,and resting-state functional MRI(rs-fMRI)were acquired,then parameters of brain function,including amplitude of low frequency fluctuation(ALFF),fractional ALFF(fALFF),regional homogeneity(ReHo)and functional connectivity strength(FCS)of brain regions with differences among groups were obtained.Spearman correlation analysis was used to evaluate the correlations of function parameters of brain regions with general data and neuropsychological test scores.Results Significant differences of fALFF,ReHo and FCS values were found among 3 groups(familywise error rate[FWE]correction,all P<0.05).fALFF value of left inferior temporal gyrus in DH and DL groups were both higher than that in control group(FWE correction,both P<0.05),ReHo value of right inferior temporal gyrus in DH group,as well as of right middle temporal gyrus,right inferior temporal gyrus and right fusiform gyrus in DL group were all lower than that in control group(FWE correction,all P<0.05),FSC value of left lenticular nucleus,left putamen,left fusiform gyrus,left calcarine fissure surrounding cortex and left inferior temporal gyrus in DH group were all higher than that in DL group(FWE correction,all P<0.05),FSC value of left lenticular nucleus,left putamen,left fusiform gyrus and left calcarine fissure surrounding cortex in DH group were all higher than that in control group(FWE correction,all P<0.05),while FSC value of left lingual gyrus,left lenticular nucleus and left putamen were both higher than that in control group(FWE correction,both P<0.05).In brain regions with different fMRI indexes between DH group and DL group,FSC values were lowly positively correlated with CogPCA results(r=0.313,P<0.05).In brain regions with different fMRI indexes between DH group and control group,fALFF value were lowly positively correlated with trail making test A(TMT A)and trail making test B(TMT B)(r=0.301,0.310,both P<0.05),ReHo values were lowly negatively correlated with TMT B(r=-0.307,P<0.05),FCS values were weakly/lowly positively correlated with TMT A and TMT B(r=0.282,0.309,both P<0.05)and lowly negatively correlated with results of digital symbol substitution test(DSST)(r=-0.363,P<0.05).In brain regions with different fMRI indexes between DL group and control group,fALFF values were weakly/lowly negatively correlated with results of mini mental state examination(MMSE),Montreal cognitive assessment(MoCA),auditory verbal learning test(AVLT)short-term memory and DSST(r=-0.399,-0.362,-0.344,-0.288,all P<0.05).Conclusion The expression level of δ-catenin had certain impact on brain function of breast cancer patients,resulted in asymmetry changes of brain network in bilateral hemispheres,as well as memory loss through affecting left inferior temporal gyrus,left lenticular nucleus,left putamen and left fusiform gyrus.
5.Tirofiban therapy in acute cerebral infarction with broadened therapeutic time window
Dayong DU ; Lianhua ZHAO ; Bo LI ; Qian CHEN ; Wei ZHAO ; Yanwei HOU ; Heliang ZHANG ; Zaiyu GUO
Chinese Journal of Neuromedicine 2020;19(5):470-476
Objective:To investigate the safety and efficacy of tirofiban therapy in acute cerebral infarction patients having broadened therapeutic time window.Methods:Eighty-four acute cerebral infarction patients having broadened therapeutic time window (the onset time was within 4.5-8 h), admitted to our hospital from January 2016 to May 2018, were chosen in our study. Forty-two patients (treatment group), with the informed consent of himself or his family, received emergent cerebral angiography and treated with tirofiban (the load of tirofiban was pumped via the microductal artery, and the maintenance load was continuously pumped intravenously for 48 h) right after the angiography; the other 42 patients (control group) received emergent cerebral angiography and treated with intensive antiplatelet aggregation therapy right after the angiography; intensive lipid-lowering therapy was given in both groups. The efficacy, safety and follow-up rehabilitation were compared between the two groups. According to the locations of acute cerebral infarction, patients in the treatment group were divided into anterior circulation infarction subgroup ( n=24) and posterior circulation infarction subgroup ( n=18); the efficacy and follow-up rehabilitation were compared between the two subgroups. Results:Patients from the treatment group had significantly lower National Institutes of Health Stroke Scale (NIHSS) scores 48 h, 7 d, and 10 d after treatment, and significantly higher NIHSS score difference values before and after treatment than those from control group ( P<0.05); the proportion of patents having good prognosis (modified Rankin scale [mRS] scores≤2) in the treatment group 3 months after treatment (78.57%) was significantly higher than that in the control group (52.38%), and the Barthel index in the treatment group 3 months after treatment (94.76±11.67) was significantly higher than that in the control group (85.00±15.17, P<0.05). Patients from the posterior circulation infarction subgroup had significantly lower NIHSS scores 48 h, 7 d, and 10 d after treatment, and significantly higher NIHSS score difference values before and after treatment than those from anterior circulation infarction subgroup ( P<0.05); the proportion of patents having good prognosis in the posterior circulation infarction subgroup 3 months after treatment (94.44%) was significantly higher than that in the anterior circulation infarction subgroup (66.67%, P< 0.05). There were no statistically significant differences in platelet count and coagulation tests between the treatment group and control group, and between the posterior circulation infarction subgroup and anterior circulation infarction subgroup ( P>0.05). Conclusion:Tirofiban could improve the prognoses of patients with acute cerebral infarction in broadened therapeutic time window, enjoying high effectiveness and safety, which are more obvious in the posterior circulation infarction.
6.Differential diagnosis between Rathke cleft cyst and cystic pituitary adenoma using MRI
Hui DU ; Zhijin LANG ; Shiyun TIAN ; Junyi DONG ; Li YANG ; Yanwei MIAO
Journal of Practical Radiology 2018;34(6):843-846
Objective To make correct diagnosis for Rathke cleft cyst(RCC)and cystic pituitary adenomas(CPA)through retrospective analysis of characteristics of MRI.Methods RCC (n=30)and CPA (n=30)confirmed by surgery and pathology were analyzed retrospectively.Following characteristics of lesions were observed:morphology,size,location,range,T1WI signal intensity and patterns of enhancement,presence of intracystic fluid level,septum,nodule,hypointense rim on T2WI and change of the pituitary stalk.The independent sample t-test and χ2 test were used respectively to analyze differences between two groups of continuous variables and categorical variables.Results Most of RCC were oval,less than 2 cm3,under the optic chiasm and within the bilateral cavernous sinus,various for signal intensity,without or with thin-walled contrast enhancement.Intracystic nodule accounted for 40% of cases and there were double cystic nodules in 1 case.Obvious contrast enhancement of intracystic nodule was found in 1 case.Pituitary stalk was in center.Most of CPA were snowman shaped,bigger than 2 cm3,off middle line location,with compression of the optic chiasm and sellar base,had thick-walled contrast enhancement,with intracystic fluid level and septum,had hypointense rim on T2WI.The pituitary stalk was shifted.Conclusion The MRI findings of RCC and CPA are significant differences in the shape,size,intracapsular structure,enhanced performance and changes of surrounding structure.
7.Effects of daily life on thyroid nodules of resident population in Beijing City
Bo LIU ; Jingbo ZHANG ; Shuo CHEN ; Yanghua LI ; Shuang LI ; Yanwei CHEN ; Dan DU ; Quanyi WANG ; Xinyu LI
Chinese Journal of Endemiology 2017;36(7):524-527
Objective To investigate the effect of daily behavior,life habits,mental status of the resident population in Beijing City on thyroid nodules.Methods A questionnaire survey was conducted using stratified sampling method to investigate the resident population in physical examination organization of Xicheng,Chaoyang,Mentougou and Shunyi districts,who lived in Beijing for more than 15 years,ages between 45-50 years old,and they did not know whether suffered from thyroid nodules.A 1:1 case-control study was used to analyze the relationships between thyroid nodules and mobile phone using time,exercise,sleep and mental stress in males and females.Logistic regression analysis was used to analyze relationships between various factors and thyroid nodule in single factor analysis,and if the influence factors in the single factor analysis had statistical significance they will be further analyzed in the multiple factors analysis.Results The total prevalence of thyroid nodules was 35.06% (331/944),males and females were 27.91% (144/516) and 43.69% (187/428),respectively.The prevalence of female was higher than that of male (x2 =25.60,P < 0.05).Logistic regression analysis showed that mental stress (males,females:OR =2.106,1.653,95%CI:1.158 ~ 3.831,1.042 ~ 2.622) and using the phone > 3 h (males,females:OR =12.863,5.315,95%CI:1.540 ~ 107.444,1.359 ~ 20.794) were risk factors for thyroid nodules in the male and female populations.Conclusion The occurrence of thyroid nodules maybe related to mental status and using the phone for a long time,but its mechanism needs to be further explored.
8.Protective effect of Panaxadiol Saponins on acute alcohol myocardial inj ury in rabbits and mechanism
Xiaoqin WANG ; Yanwei DU ; Naiyan WEN ; Hongshuo CHU ; Na LI ; Bitao ZHU ; Yuming LU ; Lijing ZHAO
Journal of Jilin University(Medicine Edition) 2014;(3):471-475
Objective To observe the protective effect of Panaxadiol Saponins (PDS)on rabbit heart failure model induced by acute alcohol infusion, and to explore its action mechanism of protecting myocardium. Methods 1 5 healthy rabbits were randomly divided into control group, model group and PDS group, 5 rabbits in each group.The rabbits in control group were given 0.2 g·mL-1 saline by intravenous drip at constant speed,the rabbits in model group were given 20% ethanol with same method, and the rabbits in PDS group were given 0.025 g·kg-1 PDS by intravenous injection before intravenous drip of 20% ethanol.The hemodynamic changes were observed by ventricular intubation;the levels of serum lactate dehydrogenase (LDH),creatine kinase (CK), and creatine kinase isoenzyme (CKMB)were determined by colormetric method.The level of malondialdehyde (MDA)in myocardial tissue homogenate,the activities of superoxide dismutase (T-SOD),glutathione peroxidase (GSH-Px)and catalase (CAT)were also detected.Results Compared with control group,the left ventricular end-diastolic pressure (LVEDP)of the rabbits in model group was significantly decreased at 30 min(P<0.05);the serum LDH,CK and CKMB levels were increased(P<0.05),the MDA level in myocardial tissue homogenate was increased(P<0.05),and the T-SOD,GSH-Px and CAT activities were decreased (P<0.05).Compared with model group,the LVEDP of the rabbits in PDS group was increased,the serum LDH,CK,and CKMB levels were decreased(P<0.05),the MDA level was decreased(P<0.05),and the activities of T-SOD,GSH-Px and CAT were increased(P<0.05).Conclusion PDS has protective effect on heart failure induced by acute alcohol infusion,and its mechanism may be related to the improvement of cardiac peroxidation.
9.Practice and research of medical students' global health capacity development
Weiwei DU ; Yanwei LIU ; Lei ZHANG ; Qiudan SUN ; Hong LI
Chinese Journal of Medical Science Research Management 2014;27(3):310-314,319
Objective Examine and evaluate the influences and effects of Short-term Overseas Exchange Program (SOEP) on the medical students' global health capacity development.Methods This study collected data through interview and questionnaire of students participated in SOEP,and review of their exchange reports.The quantitative data was analyzed by using the SPSS 17.0 software.Results SOEP is a useful practice of global health capacity development of medicals students,the effects of which are shown in the following aspects:1.Learn and compare different medical education models; 2.Learn and compare different health care systems and models; 3.Cultivate students' global perspective; 4.Understand the different medical culture and medical humanistic philosophy; 5.Promote personal and career development.Conclusions SOEP has fundamental positive effects on the global health conception and capacities development of medical students.Therefore,SOEP should be promoted,and developed in a healthy,orderly and sustainable manner.
10.Research between blood-spleen barrier and hypersplenism
Qinglun GAO ; Yanwei XING ; Anlong ZHU ; Yi DU ; Daxun PIAO ; Hongchi JIANG
Chinese Journal of Hepatobiliary Surgery 2013;(3):183-185
Objective To study the morphological character of blood-spleen barrier in patients with hypersplenism,and to discuss the relevance and pathogenesis of hypersplenism.Methods The spleens of 33 patients with cirrhosis with portal hypertension were collected as the experimental group,and 20 patients with traumatic spleen as the matched group.Five pieces of tissues in each spleen were sampled.The samples were made into pathological sections,stained with H.E.and examined microscopically for the total number of germinal centers (GC).The data of patients before operation were collected which included:blood routine (count of RBC,WBC,PLT and HB) and splenic weight.The correlation of blood routine values and sum of GC was studied using relative linear analysis.Results In the experimental group:The blood routine values were remarkably lower,splenic weight (average 764.2 g) and the quantity of the germinal center (average 8817/case) were higher.There was a reverse relationship between the total quantity of germinal centers and the PLT.There was a close relationship between the quantity of germinal center and the extent of the hypersplenism,i.e.the lower the preoperative platelet number,the greater the total number of germinal center; the heavier the splenic weight,the greater the number of germinal center.Conclusions The total number of germinal center increased dramatically in patients with cirrhosis with portal hypertension.The change is accompanied by changes in morphology of the germinal centers and dysfunction in blood-spleen barrier.It is likely that hypersplenism develops on the basis of dysfunction of blood-spleen barrier.

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