Objective To evaluate the role of phosphatidylinositol 3-kinase/protein-serine-threonine kinases (PI3K/Akt) signaling pathway and autophagy in reduction of adriamycin-induced myocardial injury by sevoflurane in the rats.Methods Thirty-six healthy male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 6 groups (n =6 each) using a random number table:control group (group C),adriamycin-induced myocardial injury group (group Dox),sevoflurane group (group Sev),LY294002 inhibitor group (group LY),solvent control group (group dimethyl sulfoxide [DMSO]),and 3-MA inhibitor group (group 3-MA).Adriamycin 4 mg/kg was injected intraperitoneally once a week for 3 weeks in all the groups except group C.The rats were mechanically ventilated for 2 h in C and Dox groups.The rats inhaled 2.4％ sevoflurane for 2 h in group Sev.In group LY,0.3 mg/kg LY294002 was injected via the tail vein at 10 min before anesthesia,and the rats inhaled 2.4％ sevoflurane for 2 h.In group DMSO,the equal volume of DMSO was injected,and the rats inhaled 2.4％ sevoflurane for 2 h.After the blood samples were collected from the heart,the rats were sacrificed,and myocardial specimens were obtained for determination of cardiac troponin Ⅰ (cTnI) concentrations in serum (by enzyme-linked immunosorbent assay),expression of total Akt (t-Akt),phosphorylated Akt (p-Akt),mammalian target of rapamycin (mTOR),phosphorylated mTOR (p-mTOR) and autophagy marker microtubule-associated protein light chain 3 Ⅱ (LC3 Ⅱ) (by Western blot),and cell apoptosis (by TUNEL).Apoptosis index (AI) was calculated.Results Compared with group C,the expression of p-Akt and p-mTOR was significantly down-regulated,and the expression of LC3 Ⅱ,AI,and serum cTnI concentration were significantly increased in the other five groups (P＜ 0.05).Compared with group Dox,the expression of p-Akt and p-mTOR was significantly up-regulated,and the expression of LC3 Ⅱ,AI,and serum cTnI concentration were significantly decreased in group Sev (P＜0.05).Compared with group Sev,the expression of p-Akt and p-mTOR was significantly down-regulated,and the expression of LC3 Ⅱ,AI,and serum cTnI concentration were significantly increased in group LY,and the expression of LC3 Ⅱ was significantly down-regulated,and serum cTnI concentrations were significantly decreased in group 3-MA (P＜0.05).Conclusion Sevoflurane can activate PI3K/Akt signaling pathway and inhibit autophagy,thus reducing adriamycin-induced myocardial injury in rats.

Objective To discuss the significance of the application of real-time quantitative PCR(RQ PCR)for diagnosis and guidance therapy of cytomegalovirus(CMV)infection after allo- hematopoietic stem cell transplantation(allo-HSCT).Methods Thirty-three patients were undergo- ing allo-HSCT.After hematopoietic reconstitution,patients'peripheral blood samples were detected for CMV DNA by RQ-PCR periodically.Anti-viral therapy was begun,attenuated and stopped ac- cording to the results of CMV DNA detection.The effects of anti-viral therapy and patients' clinical results were observed.Results CMV DNA was detected in blood samples from 13 of 33 patients. There were 21 episodes in these patients.Only 1 episode wasn't controlled hecause the patient gave up the therapy.CMV DNA copies were disappeared soon or decreased and then disappeared during anti-viral therapy in the others'.Patients which had symptoms and/or dysfunction of organs were cured too.Each course of anti-viral therapy was shorter than ordinary course.Conclusions CMV in- fection can he diagnosed as early as possible by RQ PCR.To begin,attenuate and stop anti-viral ther- apy according to the results of RQ-PCR is safe.The course is shortened and the side effects of anti vi- ral drugs were attenuated.

Objective To evaluate the clinical effectiveness and the safety of the traditional chinese medicine named YanTing Medincinal Broth on retention enema treatment of chronic pelvic inflammatory disease.Methods The research method of random,multicentre and parallel contrast were used.There are 92 cases divided into retention enema group and suppository contrast group at random,there are 47 cases in retention enema group and 45 cases in contrast group.Respectively use retention enema method with YanTing Medincinal Broth and the other method with KangFu inflammation eliminated suppository to treat the chronic pelvic inflammatory disease.The course of the treatment are all 10 days.Traditional chinese medicine syndrome and clinical physical signs are observed before and after the treatment in every group,the contrast curative effect are observed at the same time.Results Traditional chinese medicine syndrome and clinical physical signs are all improved than before treatment(P

Objective To investigate the effect of IGF-1R inhibitor AG1024 on the esophageal cancer xenografts and the underlying mechanisms.Methods The mouse model was established by injecting EC9706 cells subcutaneous in nude mice.When the tumors were 100 mm3 in size,the mice were divided into 4 groups randomly withcontrol group with no treatment; irradiation group with 8 Gy 6 MV Xrays at 1 and 8 d each time; AG1024-treatment group with 30 μg/(kg-d) AG1024 injected intraperitoneally (ip) 5 times a week for two weeks ; combination group:receiving both 30 μg/(kg· d)-1 AG1024 ip and irradiation of 8 Gy X-rays.The diameters of the tumors were measured every 3 days.The mice were sacrificed and the weights of tumors were measured at 15 d after treatment.Tumor inhibition rate was calculated.The cell cycle was examined by flow cytometry.The expression of cell cycle protein D1 (CyclinDl) of the tumors were detected by immunohistochemical staining.Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay was used to detect the cell apoptosis in the tumor tissue.Results The tumor weight in the irradiation group,AG1024-treatment group and combination group were significantly decreased compared with the control group,and the inhibition rate were 39.16％,18.73％,57.04％,respectively (F =13.566,P ＜ 0.05).After treatment with AG1024 and irradiation,tumor tissue cells were significantly accumulatedin the G0/G1 and G2/M phases and decreased in S phase compared to the irradiation group (t =-6.654,-16.738,12.871,P ＜ 0.05).The CyclinD1 expression of the combination group was significantly decreased compared with the control group.In the combination group,the apoptotic cells were detected by TUNEL assay.Conclusions IGF-1R inhibitor AG1024 could change the cell cycle and induce cell apoptosis,which might result in the enhancement of radiosensitivity on the esophageal cancer xenografts.

The incidence rate of biliary tract cancer is increasing year by year. Systemic therapy is the most important treatment for patients with advanced or unresectable biliary tract cancer. Gemcitabine combined with cisplatin is still the standard first-line chemotherapy, while gemcitabine combined with TS-1 and gemcitabine combined with nab-paclitaxel are also the first-line treatment options. Studies have confirmed that immunotherapy as a back-line treatment has a significant advantage in survival, and the disease control rate of nivolumab is 61% and the median overall survival is more than 1 year. In addition, targeted drugs targeting FGFR2, IDH1/2, HER-2 and other major driving genes of biliary tract cancer also show good antitumor activity, and become research hotspots in the treatment of advanced biliary tract cancer. Summarizing the research progress of systematic chemotherapy, immunotherapy and molecular targeted therapy for advanced biliary tract cancer can provide help for clinical practice.

objective To study the reationship beween drug-resistance gene mutation and drug-resistance level in M. tuberculosis. Methods 108 M. tuberculosis clinical isolated strains from sputum specimens were analyzed by PCR-SSCP and traditional drug susceptibility tests. Results the gene mutation rate of SM, RFP, INH and EMBresistance climical isolated strains was 78.5%, 68.2%, 70.5% and 48.6% respectively, and the mutation rate of SM, RFP, INH and EMB high concentration resistance isolated strains was 86.5% , 89% , 84% and 48.6% respectively, but 28.5 % , 16.6% and 7.1% was the mutation rate of low concentration resistance strains. Conclusion The gene mutation was in relation with drug resistance level of M. tube rculosis. The gene mutation rate was hiher in high concentration resistance isolated strains than in low concentration resistane isolated strains.

Dimethyl sulfide (DMS) has been historically recognized as a metabolite of the marine microorganism or a disgusting component for the smell of halitosis patients. In our recent study, DMS has been identified as a cytoprotectant that protects against oxidative-stress induced cell death and aging. We found that at near- physiological concentrations, DMS reduced reactive oxygen species (ROS) in cultured PC12 cells and alleviated oxidative stress. The radical-scavenging capacity of DMS at near-physiological concentration was equivalent to endogenous methionine(Met)-centered antioxidant defense. Methionine sulfoxidereductase A (MsrA), the key antioxidant enzyme in Met-centered defense, bound to DMS and promoted its antioxidant capacity via facilitating the reaction of DMS with ROS through a sulfonium intermediate at residues Cys72, Tyr103, Glu115, followed by the release of dimethyl sulfoxide (DMSO). MTT assay and trypan blue test indicated that supplement of DMS exhibited cytopro?tection against 6-hydroxydopamine and MPP + induced cell apoptosis. Furthermore, MsrA knockdown abolished the cytoprotective effect of DMS at near- physiological concentrations. The present study reveals new insight into the potential therapeutic value of DMS in Parkinson disease.

Objective To investigate relationships between serum levels of anti?tyrosinase IgG antibody(TYR IgG)as well as anti?tyrosinase?related protein?1 IgG antibody(TRP?1 IgG)and vitiligo. Methods Enzyme linked immunosorbent assay(ELISA)was performed to detect serum levels of TYR IgG and TRP?1 IgG in 260 patients with vitiligo and 50 health controls. The threshold for defining a positive test result was set at 3 standard deviations above the mean serum level of TYR IgG or TRP?1 IgG in the healthy controls. Results The positive rate of TYR IgG and/or TRP?1 IgG in the vitiligo group was 57.31%(149/260). The positive rates of TYR IgG and TRP?1 IgG were both significantly higher in the vitiligo group than in the control group(TYR IgG:37.3%[97/260]vs. 0,χ2=25.441, P<0.01;TRP?1 IgG:33.5%[87/260]vs. 0,χ2=21.630, P<0.01). The positive rate of TYR IgG was not associated with that of TRP?1 IgG in the vitiligo group(r=-0.032, P>0.05). Among patients with vitiligo, the positive rate of TRP?1 IgG was significantly higher in females than in males(χ2=5.811, P<0.05), as well as in patients aged≤20 years than in those aged>20 years(χ2=6.498, P<0.05), while the positive rate of TYR IgG didn′t differ between females and males, or between patients aged ≤ 20 years and those aged > 20 years (both P >0.05). Conclusion Detection of TYR IgG and TRP?1 IgG may provide some evidence for the diagnosis and treatment of vitiligo.

Objective To reveal the role of serum ACE2/Ang (1-7)in the occurrence of atrial fibrillation (AF)and find new targets for the prevention and treatment of AF by analyzing the correlation between the serum concentration of ACE2/Ang (1-7 )in patients with rheumatic valvular heart disease and the occurrence of AF. Methods We collected the basic clinical information and peripheral venous blood of patients with rheumatic heart valve disease (totally 46 patients,including 24 with AF and 22 with SR).ELISA method was used to detect the serum concentration of ACE2,Ang (1-7)and AngⅡ in the serum samples.Then the differences and correlation between the two groups were analyzed.Results In the AF group ① the diameter of the left atrium was significantly greater than that in the SR group [(60.70±3.08 vs.48.15±2.16)mm,P<0.05];② the serum concentration of AngⅡ was significantly higher than that in the SR group [(45.88±2.87 vs.35.78±1.08)pg/mL, P<0.05],AngⅡ and left atrium diameter were positively correlated (Pearson test,P<0.05);③ the serum concentrations of ACE2 [(7.87±0.74 vs.11.65±0.57)U/L,P<0.05]and Ang (1-7)[(146.05±17.61 vs. 321.71±36.50)pg/mL,P<0.05]were significantly lower than those in the SR group,and negatively correlated with left atrium diameter (Pearson test,P<0.05);④ the serum concentration of Ang (1-7)was negatively correlated with AngⅡ concentration (Pearson test,P<0.05).Conclusion For patients with rheumatic valvular heart disease,ACE2/Ang (1-7 )may play a protective role in the occurrence of AF via antagonizing AngⅡ and inhibiting atrial remodeling.

Objective To analyze the treatment efficacy and safety of a modified GMALL protocol for adult acute lymphoblastic leukemia (ALL). Methods Data of 37 patients with newly diagnosed adult ALL treated with a modified GMALL protocol from January 2005 to December 2009 were retrospectively analyzed,and compared with that of 44 patients treated with an in-house conventional protocol at the same period.Results The complete remission (CR) rate was 89.2 %(33/37) treated with modified GMALL protocol. The cumulative overall survival (OS) rates at 1 year, 2 years, 3 years and 4 years were 77.5 %, 48.0 %, 40.0 %and 40.0 %, respectively. The main adverse events were grade 3 or grade 4 hematological toxicities and infections which were easily managed, and the treatment-related mortality rate was low. The OS of modified GMALL protocol was superior to that of the conventional protocol. Conclusion The modified GMALL protocol has a satisfying effect and the adverse events can be tolerated for adult ALL, so its clinical application can be encouraged.