BACKGROUND: One of important mechanisms underlying myocardial fibrosis is that transforming growth factor β1(TGF-β1) stimulates the proliferation and differentiation of cardiac fibroblasts via Smads signaling pathway.Previous studies have confirmed that tanshinone ⅡA can effectively inhibit myocardial fibrosis.But whether blockage of TGF-β1/Smads signaling pathway is involved in this process remains unclear. OBJECTIVE: To investigate the effects of tanshinone ⅡA on TGF-β1 signal transduction in rat cardiac fibroblasts. METHODS: Neonatal rat cardiac fibroblasts were harvested by trypsin digestion and differential attachment and treated with 5 μg/L TGF-βI and different concentrations of tanshinone Ⅱ A(106,10-5 and 10-4 mol/L).At 6,12,and 24 hours after TGF-β1 application,fibronectin expression was detected by reverse transcription-polymerase chain reaction and Western blot analysis.At 15,30,60,and 120 minutes after TGF-β1 application,Smads protein expression was determined by Western blot analysis. RESULTS AND CONCLUSION: Fibronectin mRNA and protein expression began to increase at 6 hours after TGF-β1 application and was 1.3 and 1.8 times higher than initial level,respectively(P < 0.01),at 24 hours after TGF-β1 application.Phosphorylated Smad2/3 protein expression began to increase at 15 minutes after TGF-β1 application,peaked at 1 hour,decreased at 2 hours,but it was still 3.9 times higher than initial level(P < 0.01).Tanshinone ⅡA(10-5 and 10-4 mol/L)pretreatment downregulated fibronectin and phosphorylated Smad2/3 expression(P < 0.05 or P < 0.01)in a dose-dependent manner.These findings demonstrate that TGF-β1 induced fibronectin protein and mRNA expression and Smad2/3 protein expression in a time-dependent manner.Tanshinone ⅡA against myocardial fibrosis was likely related to its inhibition of TGF-β1-induced Smad2/3 phosphorylation and blockage of TGF-β1/Smads signaling pathways within cardiac fibroblasts.

Objective: This study was aimed to explore antitumor responses induced by recombinant vaccinia viruses expressing a point mutant p53 (rVV-p53FL) and enhancive effects of recombinant vaccinia viruses expressing costimulatory molecule B7 (rVV-B7). Methods: A 135 Cys to Tyr point mutant p53 protein was used as the model of tumor associated antigen. rVV-of3FL and rVV-B7 were used as vaccines to test their induction of CTLs and antitumor immunity. Results: Immunization BABL/c mice with rVV-p53FL could elicited specific CD8+ CTLs that could effecively lyse P815-mp53 cells, a transfectant of the murine P815 mastocytoma containing the mutant p53 gene. Treatment with rVV-p53FL could survive a part of mice challenged with 1 ? 106 P815-mp53. Treatment with rVV-p53FL could significantly prolong survival of tumor-bearing force. Admixture at 1: 1 ratio of rVV-p53FL and rVV-B7 could enhance therapeutic antitumor effects of rVV-p53FL. ~Conclusion: Mutant P53 over-expressed in tumor cells can render cells targets for specific CTLs generated by immunization with mutant p53 protein based vaccine. Costimulatory molecule H7 can enhance tumor-associated antigen inducing antitumor responses.

Objective To assess the efficiency and safety of alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis (GIOP).Methods The electronic databases of PubMed,EMBASE,Cochrane Library,Web of Science,Chinese BioMedical Literature Database (CBM) and Wanfang Data were searched for all randomized controlled trials (RCT) of alendronate vs.placebo.Two reviewers independently selected trials for inclusion,assessed trial quality using Jadad's scale and extracted the data.RevMan 5.1 software was used for data synthesis and Meta-analysis.Results Seven studies with 1111 patients were included.Compared with placebo,alendronate significantly increased bone mineral density (BMD) at the lumbar spine[MD ＝3.35,95％CI (2.67-4.02),P =0.000] and the femoral neck[MD =1.90,95％ CI (0.89-2.92),P =0.000] after 12 months of therapy.After 24 months of therapy,alendronate significantly increascd BMD at the lumbar spine [MD =3.91,95％ CI (2.37-5.45),P =0.000],but not at the femoral neck [MD =1.91,95％ CI (-1.15-5.02),P =0.22].Compared with placebo,no significant reduction was found by the use of alendronate in the incidence of vertebral fractures [RR =1.00,95％ CI (0.49-2.07),P =0.99] or nonvertebral fractures[RR ＝ 1.02,95％ CI (0.49-2.14),P =0.95].No difference was shown with the adverse event between the two groups[RR =0.97,95％ CI (0.90-1.05),P =0.47].Conclusions Alendronate is effective for the prevention and treatment of glucocorticoid-induced bone loss at the lumbar spine and the femoral neck with relatively good safety profile.Yet,there is no significant difference between the two groups in reducing the incidence of vertebral fractures and non-vertebral fractures.Large-scale RCT designed to observe whether different lengths of alendronate therapy will influence the efficiency should be conducted in the future and to further explore whether it can reduce the incidence of fractures.

Objective To evaluate the safety and comfort of postoperative patients with hepatocellular carcinoma after interventional therapy in the early stage and late stage, so as to determine the time to get out of bed after operation. Methods We searched PubMed, EMbase, Cochrane Library (2016 second), Web of Science, CBM, Wanfang Data and CNKI database, collect test/ambulation time of hepatocellular carcinoma after interventional therapy were searched from inception to September 10, 2016. Meta analysis was performed by 2 reviewers independently by screening literature, extracting data and evaluating the risk of bias in the study. RevMan 5.0 software was used to analyze the data. Results A total of 9 studies were included in the study, and 1164 patients were included. The Meta analysis results showed that:compared with 24 hours in bed after operation, 12 hours early ambulation method to reduce postoperative pain, postoperative [odds radio (OR)=0.07, 95% confidence interval (CI) 0.03-0.15, P <0.05] and dysuria (OR =0.18, 95% CI 0.10-0.33, P < 0.05), abdominal distension (OR =0.14, 95% CI 0.07-0.29, P<0.05), insomnia (OR=0.15, 95% CI 0.05-0.43, P<0.05). But in the local punctura, such as congestion (OR=0.99, 95%CI 0.45-2.18, P=0.98), hematoma (OR=0.90, 95% CI 0.38-2.13, P=0.80), the difference was not statistically significant. Conclusions The available evidence indicates that the early postoperative 12 hours after interventional therapy can effectively reduce the incidence of postoperative complications. To be included in the quantity and quality of the research, the conclusion still need to carry out more high-quality research to be verified.

ObJective To explore the value of acute physiology and chronic health evaluation Ⅲ(APACHE Ⅲ ) score and the concentration of serum cholinesterase (ChE) in predicting the condition and prognosis of patients with severe acute pancreatitis (SAP) within 24 hours afar hospitalization.Methods Sixty-two SAP patients were enrolled and APACHE Ⅲ score was assessed and the concentration of serum ChE was detected within 24 hours after hospitalization.The correlation between the concentration of serum ChE,APACHE Ⅲ score and the condition and prognosis was analyzed.Results There were 44 survivalcases and 18 dead cases.The APACHE Ⅲ score of the surval patients was significantly lower than that of the dead patients [(52.16 ± 13.76) scores vs.(97.10 ± 15.85) scores] (P＜0.01).The concentration of serum ChE of survival patients was significantly higher than that of the dead patients [ (3685 ± 466) U/L vs.(2109 ± 345) U/L] (P＜ 0.01 ).The higher APACHE Ⅲ score was,the lower the serum ChE concentration was,and the higher the mortality rate was.APACHE Ⅲ score and the concontration of serum ChE both had statistical significances compared with the prognosis in the Logistic regression analysis (P =0.0043,0.0075);APACHE Ⅲ score (95％ CI 1.0306-1.1507),the concentration of serum ChE (95％ CI0.9986-1.0125 ).ROC areas under curve (AUC) of APACHE Ⅲ score,serum ChE concentration with the prognosis were 0.936 and 0.882,respectively.There was no significant difference (P=0.0820).In combined prediction of APACHE Ⅲ score and serum ChE concentration,AUC was 0.952,and its predicting accuracy was higher than either APACHE Ⅲ score or serum ChE concentration (P=0.0016,0.0027).Conclusions APACHE Ⅲ score and the concentration of serum ChE both are significantly correlated with the condition and prognosis of SAP patients.Their combined detection can significantly improve the accuracy of prognosis judgement and provide some clinical guidances for treatment.

Objective To explore the clinical characteristics of patients with transjugular intrahepatic portosystemic shunt (TIPS) and literature review in patients with clinical features ,and provide clinical reference for carrying out the TIPS .Methods Totally 31 patients in our hospital from January 2009 to May 2014 who received TIPS treatment and strict follow‐up were retro‐spectively analyzed ,the preoperative basic situation ,laboratory index ,the incidence of postoperative bleeding again ,surgical compli‐cations ,the use of anticoagulant drugs and thrombosis ,dissolved ,etc .were statistical analyzed .Results In all patients with TIPS in the diagnosis of cirrhosis and portal hypertension ,hepatitis B ,hepatitis C cirrhosis and portal hypertension ,alcoholic liver cirrhosis and portal hypertension ,unknown cause of liver cirrhosis and portal hypertension ,Budd Chiari syndrome ,hepatitis B and hepatitis C cirrhosis and portal hypertension ,primary biliary cirrhosis and portal hypertension in proportion of 45 .16% ,16 .13% ,12 .90% , 12 .90% ,6 .45% ,3 .22% ,3 .22% respectively ;the incidence of postoperative bleeding again within six months was 9 .68% ;the Child‐Puhg score of preoperative and postoperative 1 week and 3 months ,6 months was (8 .35 ± 2 .52) ,(8 .32 ± 1 .76) ,(9 .29 ± 2 .55) ,(8 .10 ± 1 .85) respectively .Statistical results showed in postoperative 1 week and 3 months ,6 months ,there was no statisti‐cally significant difference compared with preoperative respectively (P>0 .05) ,postoperative 3 months liver function score of Child‐Puhg was higher than that of postoperative 1 week and 6 months (P<0 .05) operation;the rate of abdominal hemorrhage ,hepatic encephalopathy ,stent stenosis were 3 .22% ,22 .58% ,12 .90% ;the proportion of no postoperative taking anticoagulants ,taking as‐pirin ,clopidogrel ,and warfarin were 9 .68% ,38 .71% ,41 .94% ,9 .68% ,respectively ;the formation of portal vein thrombosis (inclu‐ding thrombosis increased) rate was 12 .90% ,thrombus dissolution rate was 100% .Conclusion In China ,liver cirrhosis and portal hypertension is the main source of TIPS and hepatitis B is a major cause of liver cirrhosis ;TIPS have no effect on liver function in Child‐Puhg score;hepatic encephalopathy ,stent restenosis is still the main postoperative complications of TIPS ;rules taking antico‐agulant drugs can dissolve thrombus of the portal vein and prevent thrombosis .

Objective To evaluate the clinical applications and surgical methods of combined laparoscopic common bile duct (CBD) exploration with choledochoscopy. Methods From 2006 to 2009,clinical data of 42 patients with choledocholithiasis undergoing laparoscopic common bile duct exploration were retrospectively analyzed. We applied a step-by-step electric coagulating incision technique on the CBD,the step-by-step suturing technique, and the step-by-step clamping technique with alligator forceps, and soft tube irrigating technique with suctioning by selecting the proper exploration route, improving the common bile duct incision technique and calculus removing techniques. Results Procedures were successful in all the cases. There was no conversions to open surgery, no postoperative bleeding and no operative mortality. The mean operating time was 120 minutes (ranging, 90 to 150 minutes) with minimal intraoperative blood loss ( ranging, 20 to 40 ml). Ductal stone clearance was successful in 41 out of 42 patients ( 93% ). The largest number of the common bile duct stones was 16. With the diameter of stones larger than 15 mm in 18 cases in which the biggest was 30 mm. Bile leak developed in 1 patient, retained stones found in 3 patients,including intrahepatic cholelithiasis in one case. As a result, 38 out of 42 patients underwent common bile duct exploration. 35 patients were placed on T-tubes. Four patients underwent cystic duct exploration in which 3 had primary suture of the cystic duct and 1 had drainage. There was no infection and stenosis of biliary tract in the 42 followed-up cases. Conclusions Laparoscopic common bile duct exploration with stone extraction can be performed with high efficiency, minimal morbidity and without mortality. Improving the way of operation and selecting suitable exploration can result in better clinical outcomes.

Summary: The effects of tanshinone Ⅱ A (TSN) on transforming growth factor β1 (TGFβ1) signal transduction in renal interstitial fibroblasts of rats were studied in order to investigate its mechanism in prevention of renal interstitial fibrosis. Rat renal fibroblasts of the line NRK/49F were cultured in vitro, stimulated with 5 ng/mL TGFβ1 and pretreated with 10-6, 10-5, 10-4 mol/L TSN respectively.The mRNA levels of fibronectin (FN) were examined by RT-PCR. The protein expression of FN and Smads was detected by Western blot. TGFβ1 induced the expression of FN mRNA and Smads in a time-dependent manner in a certain range. Compared with pre-stimulation, the FN mRNA and protein levels were increased by 1.1 times and 1.5 times respectively (P<0,01, P<0.01), and the protein expression of phosphorylated Smad2/3 (p-Smad2/3) increased by 7 times at the end of TGFβ1 stimulation (P<0.01). TSN pretreatment may down-regulate the FN and p-Smad2/3 expression in a dose-dependent manner. 10-6 mol/L TSN pretreatment had no effect on the FN and p-Smad2/3 expression (both P0.05). After pretreatment with 105 and 10-4 mol/L TSN, the FN mRNA levels were decreased by 28.1% and 43.8% respectively (P<0.05, P<0.01), the FN protein levels were decreased by 40% and 44% respectively (P<0.05, P<0.05), and the p-Smad2/3 protein expression were decreased by 40% and 65% respectively (P<0.05, P<0.01). The inhibitory effect of TSN on renal interstitial fibrosis may be related to its blocking effect on TGFβl-Smads signal pathway in renal interstitial fibroblasts.

Objective To investigate the effect of bone marrow mesenchymal stem cells (BMSCs) transplantation on expression of high mobility group box 1 protein (HMGB1) in rats with acute liver failure (ALF).Method SD rats were randomly divided into three groups:control group,ALF group and BMSCs transplantation group.Specimens were harvested in each group at 12 h,24 h and 72 h after ALF induction.Serum ALT and AST concentrations were determined,liver pathological changes were observed by HE staining,serum HMGB1 concentration detected by ELISA,and HMGB1 mRNA and protein in liver tissues examined by RT-PCR and immunohistochemistry respectively.Result The ALF models were successfully induced by D-GalN (900 rng/kg) and LPS (10 μg/kg) injection.Serum levels of ALT and AST in the ALF group were gradually increased with progression of the disease.As compared with the ALF group,significant improvement of liver function parameters and histological findings was observed in the transplantation group 72 h after transplantation (P＜0.01).The serum HMGB1 concentrations,the HMGB1 mRNA expression and the HMGB1 protein expression in liver tissue of control group were lowered at all time points,and they increased with time in the ALF group.After BMSCs transplantation,the serum HMGB1 concentrations,the HMGB1 mRNA and protein expression decreased with time.All the differences between ALF group and BMSCs transplantation group at 24 h and 72 h after transplantation were statistically significant (P＜0.01).At 24th h after transplantation,mortality rates of control group,ALF group,BMSC transplantation group were 0 (0/24),33.3％ (8/24) and 16.7％ (4/24) respectively with the difference being statistically significant (x2 =21.098,P＜ 0.01).Conclusion BMSCs transplantation can improve the liver function and pathological changes in rats with ALF,and decrease the expression of HMGB1.

Objective To systematically evaluate the efficacy of high-flow nasal cannulae oxygen (HFNC) in patients with respiratory failure.Methods Computerized PubMed, Embase, Web of Science, the Cochrane Library, CNKI, CBM, VIP, Wanfang Database up to March 31st, 2017, all published available randomized controlled trials (RCTs) or cohort studies about HFNC therapy for patients with respiratory failure were searched. The control group was treated with face mask oxygen therapy (FM) or non-invasive positive pressure ventilation (NIPPV), while the experimental group was treated with HFNC. The main outcomemeasurements included endotracheal intubation rate, patient comfort, and the secondary outcome was in-hospital mortality. The quality of the literature was completed by two professionally trained evidence-based medical students, and meta-analysis was performed on quality-compliant literature. Funnel plot was used to analyze the publication bias.Results A total of 17 articles were enrolled including 15 RCTs and 2 cohort studies. There were 3909 patients enrolled, 1907 patients in HFNC group, and 2002 in control group (1068 patients with FM, and 934 with NIPPV). Meta-analysis showed that HFNC had a significant advantage over FM in reducing the tracheal intubation rate of patients with respiratory failure [odds ratio (OR) = 0.51, 95% confidence interval (95%CI) = 0.29-0.89,P = 0.02], but there was no significant difference as compared with that of NIPPV (OR = 0.80, 95%CI = 0.54-1.17,P = 0.25). It was shown by pooled analysis of two subgroups that compared with FM/NIPPV, HFNC had a significant advantage in reducing tracheal intubation rate in patients with respiratory failure (pooledOR = 0.66, 95%CI = 0.47-0.94, P = 0.02). Compared with FM, patients with respiratory failure were more likely to receive HFNC for comfort [standardized mean difference (SMD) = -0.41, 95%CI = -0.56 to -0.26,P < 0.00001]. There was no significant difference in hospital mortality between HFNC and FM (OR = 0.82, 95%CI = 0.55-1.24,P = 0.35) or NIPPV (OR = 0.66, 95%CI = 0.37-1.17, P = 0.16). The results of pooled analysis of two subgroups were still unchanged (pooledOR = 0.75, 95%CI = 0.54-1.05, P = 0.09). It was shown by the funnel analysis that there was a bias in the study of tracheal intubation rate in the literature, while the bias of patient comfort and hospital mortality was low.Conclusions Compared with FM, HFNC could reduce the rate of tracheal intubation in patients with respiratory failure, but no difference was found as compared with NIPPV. Compared with FM, HFNC made patients more comfortable, and it was easier to be accepted and tolerated. However, there was no difference in hospital mortality among FM, NIPPV, and HFNC.