BACKGROUND:Ischemia/reperfusion injury can cause the necrosis of cardiomyocyte,and it can also induce cell apoptosis.However,cell apoptosis may be the main death type of cardiomyocyte at the early stage of infarction,and it may be one of causes for expanding myocardial infarction area.OBJECTIVE:The goal of this study was to observe the anti-apoptotic effect of adenosine (ADO) preconditioning on cardiomyocytes during the ischemia/reperfusion,and to investigate the role of apoptosis-related gene protein Bcl-2 and Bax.DESIGN:A randomized controlled animal experiment.SETTING:First College of Clinical Medical Science,China Three Gorges University&Department of Cardiology,Yichang Central People's Hospital.MATERIALS:Thirty-six healthy male rabbits of clean grade,weighing 2.5 to 3.0 kg,were provided by Laboratory Animal Department,Tongji Medical College,Huazhong University of Science and Technology.The protocol was carried out in accordance with animal ethics guidelines for the use and care of animals.All rabbits were divided into 3 groups according to random number table.There were 12 animals in either control,ADO or ADO+DPCPX (an adenosine A1 receptor antagonist).METHODS:This experiment was carried out in the Central Laboratory,China Three Gorges University between October 2005 and October 2006.Ex vivo rabbit myocardial ischemia/reperfusion models were prepared.After being anesthetized,the rabbits were performed anticoagulation with heparin and carried out Langendorff retroperfusion.In the control group,the hearts of animals subjected to 40 minutes of ischemia and 60 minutes of reperfusion.Six of them were used for determining myocardial infarct size after reperfusion,another six for cardiomyocyte apoptosis,gene expression and ultrastructural analysis of myocardium.In the ADO group:The ADO hearts were continuously infused with 10 μmol/L of adenosine 30 minutes before ischemia,and operated according to the requirement of control group.In the DPCPX roup:the isolated hearts of animals were infused for 15 minutes with 10 mmol/L of DPCPX 45 minutes before ischemia.and operated in accordance with ADO group.MAIN OUTCOME MEASURES:①The heart rate and blood pressure of animals in 3 groups were measured during ischemia/reperfusion process.②The infarct size was determined by triphenyltetrazolium chloride(TTC) staining.③The apoptotic index of cardiomyocytes was detected by histological TUNEL staining and DNA ladder on agarose gel electrophoresis.④Apoptosis-related protein Bcl-2 and Bax expressions were detected by in situ immunohistochemical staining.RESULTS:Thirty-six rabbits were enrolled in the final analysis.①Comparison of heart rate and blood pressure:During the process of ischemia/reperfusion,both heart rate and blood pressure were persistently decreased significantly (P＜0.01).There were no significant differences in two indexes between any two groups (P＞0.05).②Comparison of myocardial infarct size:There were no significant differences in myocardial infarct size among the control group,ADO group and DPCPX group (P＞0.05).The myocardial infarct size of rabbits in the ADO group was significantly smaller than that in the control group.It suggested that ADO preconditioning could contract the myocardial infarct size of rabbits.The myocardial infarct size of rabbits in the ADO+DPCPX group was significantly larger than that in the ADO group,but significantly smaller than that in the control group (P＜0.01).It suggested that DPCPX could partially inhibit the protective effect of ADO.③Comparison of apoptosis of cardiomyocytes: Apoptotic cells were not found in the non-ischemic myocardial tissue,but found in the infarct tissue and infarct edge ischemic tissue.Apoptotic cells in the control group and ADO+DPCPX group were significantly more than those in the ADO group.Apoptotic index in the control group and ADO+DPCPX group was significantly higher than that in the control group,respectively (P＜0.01).④Comparison of apoptosis-related protein expression:The absorbance of Bax in the ADO group was significantly lower than that in the control group(P＜0.01).The absorbance of Bax in the ADO+DPCPX group was significantly lower than that in the control group,but significantly higher than that in the ADO group (P＜0.01).The value of Bcl-2/Bax in the control group was significantly lower than that in the ADO group (P＜0.01).The value of Bcl-2/Bax in the ADO+DPCPX group was significantly higher than that in the control group,but significantly higher than that in the ADO group(P＜0.01).CONCLUSION:Exogenous ADO inhiblts reperfusion-induced apoptosis of cardiomyocytes,which is partially mediated by DPCPX:Down-regulation of apoptosis-related Bax protein plays an important role in the anti-apoptotic effect of exogenous ADO.

Objective To evaluate the clinical efficacy and safety of retroperitoneal laparoscopic pyelolithotomy in the treatment of intrarenal pelvic staghorn calculus or multiple renal calculi. Methods Fifteen patients(9 males and 6 females)with average age of 40 years old were treated. The diameters of the calculi were from 1.5 cm to 3.7 cm. Three trocars were used in this procedure as rou-tine. The renal sinus was exposed by separating the pelvis from outside to inside until reaching the in-fundibulum of the renal calyx. Then the renal calyx was cut open and the calculus was taken out. Double J stent was placed in the ureter and the incision of pelvis was closed by 3-0 absorbable suture. The drainage tube was pulled out 3-4 d post-operatively according to the drainage quantity. Double J stent was then pulled out 2 weeks after surgery. Results All the 15 procedures were successfully completed. The average operation time was 170 min and the average post-operative hospital stay was 7 d. During the 3-15 months' follow-up, 2 patients had calculus remnants with the size of 0. 2-0.5cm in diameter. Conclusions Retroperitoneal laparoscopic pyelolithotomy provides a minimally inva-sive treatment option in patients with intrarenal pelvic staghorn calculus or multiple renal calculi. It has the advantages of good exposure, little bleeding, small incision and fast recovery.

Objective To investigate the association of rs1412125 at high-mobility group box 1 (HMGB1) gene with atrial fibrillation (AF) in Chinese Han population. Methods 396 patients with AF and 726 control subjects were recruited to this study. A case-control association analysis was applied to assess the as-sociation between rs1412125 in HMGB1 and AF. Results There were no significant differences in rs1412125 and the frequency of genotype distribution between the study group and the control group (allelic association:object P value was 1.05E-06, adjust P value was 0.176; genotypic association: additive P value was 0.146, dominant P value was 0.162, and recessive P value was 0.998). The interactions analysis showed that rs1412125 allele C increased the risk of AF in male subjects with rheumatic heart disease (adjust P value was 2.07E-04, rectify OR = 8.20, and 95%CI: 2.70-25.0). Conclusions There is no independent genetic association between rs1412125 at HMGB1 and atrial fibrillation. However , the interactions between rs1412125 and both gender and rheumatic heart disease might increase the risk of atrial fibrillation.

Objective To evaluate the clinical safety, efficacy and long-term outcome of transcatheter occlusion for ruptured aortic sinus of valsalva aneurysm (RASA) into the right atrium.Methods Between January 2006 and April 2013, fifteen patients [11 males and 4 females,aged from 21 to 48 years with an mean age of (35.50±8.79) years] with RASA ruptured into the right atrium were enrolled in this study.Domestic made patent ductus arteriosus (applied in six patients) or small waist double-disk ventricular septal defect (applied in nine patients) occluders were used for transcatheter closure.All the patients were followed up for any change in cardiac rhythm,and residual shunt,occluders morphology and possible valve regurgitation by echocardiography.Results All RASA were confirmed by aortography,including eleven cases with rupture of right coronary sinus of valsalva and four cases with rupture of the noncoronary sinus of valsalva shunting into the right atrium.NYHA function class was(2.56±0.63)before the occlusion.Cardiac catheterization showed mean pulmonary arterial pressure and Qp/Qs ratio were (25.38±8.21)mmHg (1 mmHg=0.133 kPa) and 1.34-2.81(1.93±0.39), respectively.Aortic angiography showed that the RSA was 4-10(6.42±1.92)mm at its narrowest end.There was no serious complication during the operation and all the patients had successful transcatheter closure without residual shunt.After transcatheter RASA occlusion, mean pulmonary artery pressure decreased to (16.1±5.3) mmHg (P<0.05).The diameter of right atrium,right ventricle, left atrium and pulmonary artery diameter and left ventricular end-diastolic dimension all showed significant decrease (P<0.01).All patients were followed up for 35-132(78.6±28.57)months.All patients presented with a NYHA function class Ⅰ to Ⅱ cardiac function in their last follow up which was significantly improved compare to pre-occlusion level (P<0.01).There were no infective endocarditis,device displacement and embolism,serious aortic regurgitation,myocardial ischemia,serious arrhythmia or death in any of the patients during follow up.Conclusions Transcatheter closure of Valsalva aneurysm ruptured into right atrium with the domestic made patient ductus arteriosus and small-waist ventricular septal defect occluder is safe and effective with a good long term prognosis.

Objective To evaluate the mid-to long-term survival benefits of preoperative sandwich-like neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC).Methods A total of 45 LARC patients who underwent neoadjuvant sandwich CRT in the form of XELOX regimen prior to,concurrently with,and following volumetric modulated arc radiotherapy (VMAT) in 2012 were enrolled in this study.VMAT was given at a gross tumor volume dose of 50 Gy in 25 fractions,and a clinical target volume dose of 45-46 Gy in 25 fractions.Total mesorectal excision was performed 6 to 8 weeks after completion of VMAT.The overall survival (OS) and disease-free survival (DFS) were determined by the Kaplan-Meier method,and survival comparison and univariate prognostic analysis were performed using the log-rank test.Results The median follow-up time was 46.7 months.There was no local recurrence detected among the patients.The 3-year distant metastasis (DM) rate was 18%,and the 3-year OS and DFS were 96% and 84%,respectively.Univariate analysis indicated that perineural invasion,N1-N2 pathology (pathological stage Ⅲ),and Ca-199>35 U/ml before treatment were risk factors for DM (P=0.000,0.000,and 0.013,respectively).Conclusions The significant short-term efficacy of preoperative sandwich-like neoadjuvant CRT can be extended to a positive mid-term survival in LARC patients.However,further phase Ⅲ clinical studies will be needed to confirm this finding.

As the main weapon of cellular immunity,CD4+ T cells play a vital role in controlling and eliminating infections,and are an important barrier for the body to resist infections.Respiratory tract infectious diseases caused by influenza virus infection have extremely high infectivity,morbidity and mortality.The infection mechanism is relatively complicated and has not been fully ex-plained.The exuberant immune response induced by the body after influenza virus infection is described as a"cytokine storm"which is related to pro-inflammatory cytokines and tissue damage,which may eventually lead to acute lung injury.Therefore,this article sum-marizes the current research progress,focusing on the mechanism of CD4+T cells in the cytokine storm induced by influenza virus in-fection and the impact of acute lung injury,providing relevant ideas and theoretical guidance for follow-up research,with a view to the disease caused by influenza virus bring new and effective methods of diagnosis and treatment.

Background: Insulin resistance (IR) is the key pathological basis of many metabolic disorders. Lack of asialoglycoprotein receptor 1 (ASGR1) decreased the serum lipid levels and reduced the risk of coronary artery disease. However, whether ASGR1 also participates in the regulatory network of insulin sensitivity and glucose metabolism remains unknown. Methods: The constructed ASGR1 knockout mice and ASGR1-/- HepG2 cell lines were used to establish the animal model of metabolic syndrome and the IR cell model by high-fat diet (HFD) or drug induction, respectively. Then we evaluated the glucose metabolism and insulin signaling in vivo and in vitro. Results: ASGR1 deficiency ameliorated systemic IR in mice fed with HFD, evidenced by improved insulin intolerance, serum insulin, and homeostasis model assessment of IR index, mainly contributed from increased insulin signaling in the liver, but not in muscle or adipose tissues. Meanwhile, the insulin signal transduction was significantly enhanced in ASGR1-/- HepG2 cells. By transcriptome analyses and comparison, those differentially expressed genes between ASGR1 null and wild type were enriched in the insulin signal pathway, particularly in phosphoinositide 3-kinase-AKT signaling. Notably, ASGR1 deficiency significantly reduced hepatic gluconeogenesis and glycogenolysis. Conclusion The ASGR1 deficiency was consequentially linked with improved hepatic insulin sensitivity under metabolic stress, hepatic IR was the core factor of systemic IR, and overcoming hepatic IR significantly relieved the systemic IR. It suggests that ASGR1 is a potential intervention target for improving systemic IR in metabolic disorders.

Objective To investigate the feasibility of non-operative management (NOM) by comparing the therapeutic effects between NOM and total mesorectal excision (TME) for rectal cancer patients with clinical complete response (cCR) after neo-adjuvant chemoradiotherapy.Methods A total of 135 patients with stage Ⅱ/Ⅲ rectal cancer who obtained cCR after neo-adjuvant chemoradiotherapy in Sun Yat-sen University Cancer Center from 2006 to 2016 were recruited and assigned into the NOM (n =43) and standard operative management (SOM) groups (n=92).The local recurrence rate,accumulative local control (LC) rate after salvage therapy,disease-free survival (DFS),overall survival (OS) and sphincter preservation rate were statistically compared between two groups.Kaplan-Meier analysis and log-rank test were utilized to calculate the LC,OS and DFS.Chi-square test was performed to calculate the sphincter preservation rate.Results The mean follow-up duration was 39 months (range:10-127 months).Of 135 patients,the local recurrence rate and distant metastasis rate were 3.7％ and 11.1％,and the 3-year DFS and OS were 90.5％ and 97.0％.In the NOM and SOM groups,the 3-year DFS were 87％ and 93％,and the 5-year DFS were 73％ and 87％(P=0.089).The 3-year OS were 98％ and 99％,and the 5-year OS were 98％ and 97％ (P=0.578).In the NOM group,the local recurrence rate was 12％ (n =5),80％ of patients received salvage treatment and the accumulative LC rate was calculated as 98％.In the SOM group,the local recurrence rate was 0,which was significantly lower than that in the NOM group (P=0.O10).In the NOM group,the sphincter preservation rate was 93％,significantly higher compared with 70％ in the SOM group (P=0.030).Conclusions It is feasible for rectal cancer patients with cCR to receive NOM following neo-adjuvant chemoradiotherapy.Partial locally recurrent patients can be healed by timely salvage therapy,thereby averting TME and relevant complications and enhancing the quality of life of rectal cancer patients.