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.

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.

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.

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.

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.

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.

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.

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.

To investigate the effects of Xinji' erkang (XJEK), a compound Chinese herbal medicine, on isoproterenol-induced ventricular remodeling in mice.

Objective To explore the relationship between MR enhancement signs with MVD and VEGF expression in early breast carcer or benign lesion,improve the correct diagnosis rate of breast mass.Methods The MR enhancement signs(early enhmcement rate,eurve type of enhancement)of 31 patients with breast cancer and 19 benign lesions were analyzed retrospectively.Results Mean early enhancement rate of 31 neoplasm(20 invasive duet csncer,6 invasive lobule cancer,2 mucous cancer,3 situ lobule caner)were(68.4±14.7)%,enhancement curve type of which manifested as 18 type Ⅰ curve,11 typeⅡcurve and 2 type Ⅲ curve.Mean early enhancement rate of 19 benign mass(11 fibre adenoma,6 cystic hyperplasia,1 angioma,lobular tumor,1 infecmd cyst)were(47.6 ±15.2)%,of which 2 were typeⅠcurve,10 type Ⅱ cnrve and 7 type Ⅲ curve.In early cancer focus,mean MVD and VEGF expression index were 48.2±5.6 and 1.8 ±0.3,while in benign mass they were 30.8 ±6.1,0.9 ±0.3 respectivdy.Condusion Early enhancement rate,MVD and VEGF expression index in malignant focus were higher than those in benign mass,type Ⅰ curves were predominate in malignant lesions,by which early breast cancer could be diagnosed in time.