Objective: To investigate the protective effect of neurotrophic factor(MANF) derived from midbrain astrocytes on myocardial injury induced by sepsis by activating SIRT1/AMPK signaling pathway. Methods: 48 mice were randomly divided into 4 groups: control group, recombinant mouse MANF(rmMANF) group, cecal ligation and puncture(CLP) group and CLP+rmMANF group, with 12 mice in each group.The survival rate, sepsis score, anal temperature, blood biochemical indexes, pathological indexes of myocardial injury and the expression of endoplasmic reticulum stress(ERS) related proteins were detected 8 h after CLP.H9C2 cells were divided into control group(Con),LPS group, LPS+rmMANF group, LPS+rmMANF+EX527 group and LPS+rmMANF+Cpd C group.The cells were collected after 24 h treatment with LPS,and the expression of ERS protein and apoptosis in cells were analyzed. Results: Compared with CLP group, the sepsis score and serum Lactate dehydrogenase(LDH),creatine kinase(CK),aspartateaminotransferase(AST) and blood urea nitrogen(BUN) levels in CLP+rmMANF group decreased significantly(P<0.01),and the anal temperature and serum albumin(ALB) levels increased significantly(P<0.05).Compared with CLP group, the expression of MANF in CLP+rmMANF group increased significantly(P<0.01),and the expression of glucose-regulated protein 78(GRP78),C/EBP homologous protein(CHOP) and the percentage of TUNEL positive cells decreased significantly(P<0.05).In vitro, LPS stimulation down-regulated the expression of SIRT1 and AMPK in H9C2 cells, while rmMANF further increased the expression level of SIRT1 and AMPK.Compared with LPS+rmMANF group, the expression of GRP78 and CHOP protein and the apoptosis rate of H9C2 cells in LPS+rmMANF+EX527 group and LPS+rmMANF+Cpd C group increased significantly(P<0.05). Conclusion rmMANF inhibits ERS related to sepsis-induced myocardial injury by activating SIRT1/AMPK signaling pathway, thereby protecting myocardial injury.

Fusobacterium nucleatum (F. nucleatum) is an early pathogenic colonizer in periodontitis, but the host response to infection with this pathogen remains unclear. In this study, we built an F. nucleatum infectious model with human periodontal ligament stem cells (PDLSCs) and showed that F. nucleatum could inhibit proliferation, and facilitate apoptosis, ferroptosis, and inflammatory cytokine production in a dose-dependent manner. The F. nucleatum adhesin FadA acted as a proinflammatory virulence factor and increased the expression of interleukin(IL)-1β, IL-6 and IL-8. Further study showed that FadA could bind with PEBP1 to activate the Raf1-MAPK and IKK-NF-κB signaling pathways. Time-course RNA-sequencing analyses showed the cascade of gene activation process in PDLSCs with increasing durations of F. nucleatum infection. NFκB1 and NFκB2 upregulated after 3 h of F. nucleatum-infection, and the inflammatory-related genes in the NF-κB signaling pathway were serially elevated with time. Using computational drug repositioning analysis, we predicted and validated that two potential drugs (piperlongumine and fisetin) could attenuate the negative effects of F. nucleatum-infection. Collectively, this study unveils the potential pathogenic mechanisms of F. nucleatum and the host inflammatory response at the early stage of F. nucleatum infection.
Humans ; Fusobacterium nucleatum/metabolism* ; NF-kappa B/metabolism* ; Periodontal Ligament/metabolism* ; Signal Transduction ; Fusobacterium Infections/pathology* ; Stem Cells/metabolism*

Objective:To explore the early and medium-long term outcomes of steatosis donor liver transplantation(LT)for an optimal clinical application.Methods:From January 2015 to December 2020, this retrospective cohort study was conducted jointly at Shulan (Hangzhou) Hospital, First Affiliated Hospital of Zhejiang University and First Hospital of Jilin University. The relevant clinicopathological and follow-up data were collected from 1535 LT recipients. For comparison, propensity score was utilized for case-control matching of steatosis and non-steatosis donor livers. According to presence or absence of liver steatosis, the recipients were divided into two groups of steatosis donor liver (n=243) and non-steatosis donor liver (n=1292). And 1∶1 propensity score matching was made for two groups. Then early and medium-long term outcomes of two groups were examined. Counts were described as absolute numbers. Kaplan-Meier method was employed for calculating survival time and plotting survival curve and Log-rank test for survival analysis. COX regression model was utilized for univariate and multivariate analyses. Based on basic metabolic disease pre-LT, steatosis donor liver recipients were divided into three subgroups: BMI ≥25 kg/m 2 with hypertension or diabetes (n=21), BMI<25 kg/m 2 and no hypertension or diabetes (n=130) and other recipients (n=92). A comparative study was performed for determining the prognosis of subgroups according to the different characteristics of recipient and donor liver. Results:No significant inter-group difference existed in 2-year survival post-LT ( P=0.174). However, significant inter-group difference in survival existed after 2 years post-LT ( P=0.004). And 3/5-year survival rate of steatosis donor liver was 66.4% and 44.2% respectively. Both were significantly lower than those of non-steatosis donor liver. Multivariate Cox regression analysis indicated that steatosis donor liver and male recipients were independent risk factors for prognosis >2 years survival post-LT( P=0.008, P=0.004). Subgroup analysis of steatosis liver donors showed that the prognosis of patients with BMI ≥25 kg/m 2 with hypertension or diabetes was significantly worse than other subgroups (BMI <25 kg/m 2 with no hypertension or diabetes and other recipients) <2 years survival post-LT ( P=0.029, P=0.043). Conclusions:Steatosis donor liver does not affect early survival of recipients, yet reduces medium-long term survival rate of recipients notably. In steatosis donor liver recipients, early survival rate declines markedly in recipients with preoperative BMI ≥25 kg/m 2 with hypertension or diabetes as compared with BMI <25 kg/m 2 with no hypertension or diabetes group.

Objective: To evaluate the effects L-apigenin A on Alzheimer＇s disease(AD), and analyze the correlation between MMSE and ADAS-cog scores. Methods: From January 2009 to December 2014, 34 patients with AD were selected in Qinhuangdao Military Industry Hospital.They were treated with celery seed extract L-apigenin.The MMSE scores and ADAS-cog scores were evaluated before treatment and 18, 36 and 72 d after treatment.The correlation between MMSE scores and ADAS-cog scores was analyzed. Results: There were statistically significant differences in the MMSE scores between 72d after treatment[(22.59±1.13)points]and before treatment[(20.53±1.42)points], 18d after treatment[(20.44±1.24)points]and 36d after treatment[(20.97±1.17)points](t=6.619, 7.473, 5.807, all P<0.05). There were statistically significant differences in ADAS-Cog scores between 72d after treatment[(17.09±1.53)points]and before treatment[(20.47±2.85)points], 18d after treatment[(20.18±2.34)points]and 36d after treatment[(20.18±2.49)points](t=6.093, 6.445, 6.165, all P<0.05). The MMSE score and ADAS-Cog score had negative correlation by Pearson analysis (r=-0.259, P=0.000). Conclusion L-apigenin A can significantly improve the cognitive function of patients with AD.There is significant negative correlation between the MMSE scores and ADAS-cog scores.

Objective To explore the value of cardiovascular magnetic resonance feature tracking (CMR-FT) in quantita tive evaluation of myocardium deformation in patients with hypertrophic cardiomyopathy (HCM).Methods Sixteen HCM patients (HCM group) and 18 healthy volunteers (control group) were enrolled and measured with CMR-FT.The differences of left ventricular (LV) end diastolic volume (LVEDV),LV end systolic volume (LVESV),LV ejection fraction (LVEF),left ventricular mass (LVMASS) and LV global radial strain (RS),LV global circumferential strain (CS) were compared between the two groups.The correlations between segmental wall thickness and segmental RS and CS were studied.And the correlation among global RS,CS and LVEDV,LVESV,LVEF,LVMASS were analyzed.Results LVMASS in HCM group was higher than that in control group ([133.74±79.13]g vs [76.87±14.15]g,P=0.01).No sig nificant differences of LVEDV,LVESV,LVEF were found between HCM group and control group (all P＞0.05).Global RS and CS were significantly lower in HCM group than those in control group (RS:[27.05 ± 13.35]％ vs [40.62 ± 4.92] ％,P＜0.01;CS:[-8.68± 5.56] ％ vs [-20.73 ± 1.56] ％,P＜0.01).No significant correlations was observed between segmental wall thickness and segmental RS (r=-0.41,P＜0.01),CS (r=0.28,P＜0.01),respectively.In HCM group,no significant correlations was observed between global RS (r=-0.36,-0.41,0.22,-0.36),CS (r=0.34,0.10,0.22,0.42) and LVEDV,LVESV,LVEF,LVMASS,respectively (all P＞0.05).Conclusion CMR-FT is conducive to quantitative evaluate myocardial deformation in HCM patients.

Objective To explore the experience of diagnosis and surgical treatment of carotid body tumor.Methods A retrospective analysis between November 2008 and November 2015 was proceeded,the clinical data of surgical treatment for 81 patients with carotid body tumor was collected,to analyze data by SPSS19.0,and summarize the diagnosis of carotid body tumor,choice of operation methods and curative effect and complications prevention.Results Seventy-four cases underwent surgery treatment:tumors of 52 cases were simply stripped,tumors of 13 cases were resected combined with ligation of external carotid artery.Tumors of 7 cases were resected with internal and external carotid artery ligation,3 cases of whom underwent artificial blood vessel internal carotid artery end to end anastomosis.Postoperative death in 1 case of acute myocardial infarction,complicated with cerebral infarction in 2 cases,6 cases of injury of cranial nerve relieved after symptomatic treatment.No hemiplegia,aphasia and other serious complications.Tumor size and the surgery time correlation analysis:the correlation coefficient was 0.226,no significant correlation.Conclusions CTA is the most commonly used method of preoperative examination.Surgical resection is an effective method in treatment of carotid body tumor.Prevention injury of carotid artery cr internal carotid or common carotid artery and their reconstruction is the key to a successful operation.Sufficient preoperative assessment,select the appropriate operation method,intraoperative careful performance can ensure the cerebral perfusion,is the key to prevent and reduce the complications.

BACKGROUNDCoronary heart disease (CHD) is the most common type of heart disease and cause of heart attacks. This study investigated the epidemiological characteristics of CHD and its risk factors in Jiaozhou, Shandong province, to ultimately find a way of reducing the prevalence of cardiovascular disease, and to provide a theoretical basis for establishing a cardiovascular disease management path under the regional medical collaborative mechanism.

METHODSA questionnaire survey was performed including 1 952 people aged 35 years or older who were questioned by means of stratified, cluster, proportional sampling to investigate the prevalence of CHD and its risk factors. The data were inputted into SPSS11.0 statistical software for processing and analysis. We advised the local medical institutions to establish health files for the residents with CHD and risk factors. They were followed up regularly. Their risk factors and life-style were monitored, and advice was given as to proper medications. Green channels were established, and the patients were transmitted in a timely manner to superior hospitals for better treatment if the necessary treatments were not available in the local hospitals. The control of risk factors was observed after the follow-up for half a year.

RESULTSIn Jiaozhou, the rates of coronary artery disease, hypertension, diabetes, hyperlipidemia and overweight were 8.15%, 28.54%, 11.43%, 35.46%, and 18.70% respectively. The rates of hypertension, diabetes, hyperlipidemia and overweight were higher than the data published in "The report of Chinese cardiovascular disease 2012"; which are 24%, 9.7%, 18.6%, and 9.7%, respectively. The control of risk factors improved significantly after the guidance of the residents lifestyle and medication for six months.

CONCLUSIONSThe high prevalence of coronary artery disease in Jiaozhou is closely related to age, gender, diet structure, family history of cardiovascular disease, hypertension, diabetes, hyperlipidemia, overweight, and unhealthy lifestyle. Under the regional medical coordination mechanism, the collaborative management of cardiovascular disease can provide new management concepts for the areas short of medical resources, so as to reduce the prevalence of cardiovascular disease.

Adult ; Aged ; China ; epidemiology ; Coronary Disease ; epidemiology ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Risk Factors

Objective:To observe and analyze the therapeutic effect and safety of tirofiban combined large dose statin in patients with acute myocardial infarction (AMI),and evaluate its influence on myocardial perfusion and cardiac function.Methods:A total of 97 consecutive AMI patients visited to our hospital from May 2011 to January 2013, who were beyond the emergency PCI time window (≥12h),their chest pain was remissive or not further aggravated were studied.All patients were pumped with tirofiban for 48h continuously;according to combined rosuvastatin dose,they were divided into large dose group (n = 52,20mg,once/d,until one month after infarction,then changed to routine dose of 10mg,once/d)and routine dose group (n=45,10mg,once/d).All patients received se-lective PCI after 7 ~ 10d conservative treatment.Myocardial perfusion level,left ventricular ejection fraction (LVEF)on one week after PCI and 30d after AMI,enzymology changes [creatine (CK),lactate dehydrogenase (LDH)]and major adverse cardiovascular events (MACE)during hospitalization were compared between two groups.Results:Compared with routine dose group,there were significant reductions in thrombus scores in infarct related artery (IRA)[(1.32±1.01)scores vs.(0.81±0.78)scores]and corrected TIMI frame [(32.4±4.73)vs. (26.8±2.34)]in large dose group (P =0.021,P <0.001);after selective PCI,TIMI flow of large dose group was significantly better than that of routine dose group (P =0.024).On one week after PCI,LVEF:(51.4±8.9)% of large dose group was significantly higher than that of routine dose group (47.7±8.7)%,P =0.021;there were no significant difference in levels of CK and LDH between two groups on 7d and 30d after PCI (P >0.05).There was no MACE in both groups during hospitalization and 30d after PCI.Conclusion:Tirofiban combined large dose statin is safe and effective in patients with acute myocardial infarction,it can reduce intra-coronary thrombus burden,im-prove myocardial tissue perfusion and cardiac function without increasing MACE.

Objective EpCam and Wnt/ β-catenin pathway in colon carcinoma and its clinic-pathological significance of the distribution,studying the relationship between EpCam and Wnt / β-catenin.Methods Retrospective analysis detected by immunohistochemistry 60 cases of colon cancer,20 cases of adjacent atypical hyperplasia,60 normal colon tissue EpCam and Wnt / β-catenin protein expression.Results (1)normal colon tissue,cancer tissue and cancer tissue showed positive expression EpCam clear upward trend,were 23.5％,62.3％,96.5％ ; with normal colonic mucosa to cancer transformation,β-catenin in the membrane expression of the positive rate decreased,while the cytoplasm is followed by increased expression rate in poorly differentiated carcinoma or even nuclear expression,EpCam strong positive expression of Wnt / β-catenin cytoplasmic-positive rate of histological type,depth of invasion,lymph node metastasis; (2)the EpCam with the Wnt / β-catenin expression showed a positive correlation (r =0.653,P ＜0.05) ;(3)high expression EpCam and Wnt / β-catenin in patients with colon significant increase in cancer recurrence rate and 5-year survival rate was significantly reduced.Conclusion EpCam and Wnt / β-catenin pathway in colon cancer positively is correlated,EpCam and Wnt / β-catenin is connected with high expression and tumor invasion,metastasis and prognosis.

Objective To investigate the expressions and clinical pathological significance of EpCAM and the β-catenin pathway in colon cancer,and the correlation between EpCAM andβ-catenin.Methods Immunohistochemistry was used to detecte the expressions of EpCAM and β-catenin proteins in colon cancer tissues and corresponding adjacent tissues of 70 cases of colon cancer patients,the clinical and pathological features of colon cancer and their relationship were retrospective analyzed.Results ①EpCAM and β-catenin protein expressions in colon cancer tissue was 52 cases (74.3％) and 55 (78.6％) positive respectively; EpCAM and β-catenin proteins in cancer adjacent tissues in 13 cases( 15.7％ ) and 9 cases ( 12.9％ ) were positive,the differences were statistically significant.②the EpCAM expression is positively correlated with the β-catenin expression ( r =0.616,P ＜ 0.01 ).③The expressions of EpCAM and β-catenin correlated with the tumor differentiation,invasion depth,lymph node metastasis and TNM staging related ( P ＜ 0.05).Conclusion EpCAM and β-catenin pathways in colon cancer positively correlate,and closely correlate with colon cancer.The expression level of EpCAM and β-catenin can be used as a reference for the colon disease course and healing.