Objective To compare the pre-existing mutations in reverse transcription region of HBV in patients with different HBV infection stages.Methods Totally 474 patients with chronic HBV infections,including 205 with chronic hepatitis B (CHB),153 with liver cirrhosis and 116 with hepatocellular carcinoma (HCC),were enrolled from the People' s Hospital of Shangyu and the First Affiliated Hospital of Zhejiang University during January 2011 and June 2013.All patients had not received nucleos (t)ide analogues treatment.HBV RT region mutations and genotypes were determined by PCR followed by sequencing.SPSS14.0 was used for statistical analysis.Results There were 387 (81.6％) patients with HBV genotype B,in which 156 were with CHB,124 were with liver cirrhosis,and 107 were with HCC.Nucleos(t)ide analogues-related mutations were observed in all the above 387 patients.rtS106C mutation was more popular in CHB and liver cirrhosis (14.1％ and 14.5％) patients than that in patients with HCC (4.7％) (x2 =6.126,6.207,P ＜0.05); And the positive rates of rtD134E/G/N/S mutations were also higher in CHB and cirrhotic patients (21.8％ and 20.2％) than that in HCC patients (10.3％,x2 =5.933,4.263,P ＜ 0.05).rtD134E/G/N/S and rtS106C mutations were correlated with HBeAg (P ＜0.01) and gender (P ＜ 0.05),but not with HBV virus load and age (P ＞ 0.05).The mutation frequencies in A-B interdomain were higher in CHB and cirrhotic patients (5.3％ and 5.6％) than that in HCC patients (3.5％,x2 =9.018,11.018,P ＜ 0.01).Conclusions Nucleos (t) ide analogues-related mutations exist in various HBV infection stages.rtSl06C and rtD134E/G/N/S mutations may be involved in necro-inflammation,and A-B interdomain mutations may be correlated with necro-inflammation,immune response and fibrosis in chronic liver diseases.

Objective To investigate the clinical characteristics of multisystem impairment of Sj(o)gren's syndrome (SS) to make quick and accurate diagnose and treatment to decrease the rate of misdiagnosis and mistreatment.Methods A case of thrombotic thrombocytopenic purpura with SS was reported and the related literatures were reviewed.The clinical manifestations,laboratory examinations,diagnostic criteria and therapy of thrombotic thrombocytopenic purpura with SS were analyzed.Results Purpura haemorrhagica,hemolytic anemia,central nervous systemic symptoms,kidney impairment and fever were the representative clinical manifestations of thrombotic thrombocytopenic purpura with SS.Plasmapheresis was the most effective therapy with the background treatment with glucocorticosteroid and immunosuppressive agents.Conclusion Thrombotic thrombocytopenic purpura with SS presents a complicated clinical manifestations,so misdiagnosis and mistreatment is very frequent.More attention should be paid to this specific situation because the disease is rare and has high mortality rate.

Objective To analyze the therapeutic effect of intracoronary versus intravenous bolus tirofiban on myocardial perfusion and major cardiovascular events (MACE) in elderly patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and explore the optimal route of tirofiban application. Methods From July 2009 to July 2010, 120 NSTE-ACS patients undergoing percutaneous coronary intervention (PCI ) were consecutively enrolled in this study. They were randomly divided into two groups: intracoronary (60 cases) versus intravenous (60 cases) bolus tirofiban. Thrombolysis in myocardial infarction (TIMI) flow, TIMI myocardial perfusion grade (TMPG) and MACE 30 days after PCI were observed. Results The incidence of TIMI flow and TMPG 3 grade in intracoronary group were higher than in intravenous group [53(88.3%) vs. 38(63.3%); 53(88.3%) vs. 40(66.7%), respectively, both P＜0.05]. However, MACE incidence and bleeding complications during hospital 30 days after PCI had no significant difference between the two groups [1 (1.7%) vs. 0; 3(5.0%) vs. 5(8.3%)], which were not statistically significant (P＞0.05). Conclusions Intracoronary bolus tirofiban before PCI more effectively increases coronary blood flow and myocardium blush than intravenous route in elderly NSTE-ACS patients.

Objective: To analyze the basic thyroid hormone level on long term prognosis and peri-operative recovery in patients after heart transplantation (HT) at the terminal stage of heart failure (HF).
Methods: A total of 270 consecutive patients who received HT at the terminal stage of HF in our hospital from 2009-09 to 2014-07 were retrospectively studied. According to serum levels of thyroid stimulating hormone (TSH), the patients were divided into 3 groups: TSH < 0.55 mIU/L group, TSH (0.55-2.5) mIU/L group and TSH > 2.5 mIU/L group. The peri-operative recovery condition and long term prognosis were observed and compared among 3 groups.
Result: The average age of patients was at (44.58 ± 13.30) years including 228 (84.4%) male and 42 (15.6%) female. The average post-operative follow-up period was (31.88 ± 17.48) months with 100% follow-up rate. There were 41.8% of patients with hypothyroidism, and 46 (17.0%) patients with low T3 syndrome, 56 (20.7%) with subclinical hypothyroidism and 11 (4.1%) with clinical hypothyroidism. The ratio of low level thyroid hormone in HT patients was much higher than general population. For peri-operative recovery, the ICU stay time and mechanical ventilation time were similar among 3 groups,P>0.05, while TSH (0.55-2.50) mIU/L group had the shortest times and TSH > 2.50 mIU/L group had longest times. For long term prognosis, no matter uni-/multi- aviate regression analysis or Kaplan-Meier surviving curve all suggested that TSH > 2.50 mIU/L was the independent risk factor inlfuencing the prognosis of HT patients at the terminal stage of HF. Upon TSH increasing, the patients would have worse prognosis accordingly.
Conclusion: Serum level of TSH > 2.50 mIU/L was the independent risk factor in HT patients at the terminal stage of HF.

Objective To compare the 2-year efficacy of de novo combination therapy with lamivudine (LAM) and adefovir dipivoxil (ADV) to that of entecavir (ETV) monotherapy in treatment of patients with hepatitis B virus ( HBV )-related decompensated cirrhosis.Methods A total of 120 naive patients with HBV-related decompensated cirrhosis admitted to Shangyu People's Hospital and the First Affiliated Hospital of Zhejiang University from January 2007 to April 2008 were enrolled,in which 60 were treated with LAM and ADV combination therapy,and other 60 patients were treated with ETV monotherapy.Tests for liver and kidney function,alpha-fetoprotein,HBV serum markers,HBV DNA load,prothrombin time (PT),and ultrasonography or CT scan of liver were performed every 1-3 months.Repeated measure ANOVA and x2test were used to compare the efficacy,side effects and accumulated survival rates at 12 and 24 month in two groups.Results Forty-five patients in each group were followed-up for 24 months.There was no significant difference in HBV DNA negative rates and ALT normalization rates at month 12 (x2 =2.12 and 2.88,P ＞0.05 ) and month 24 between two groups (x2 =3.21 and 3.24,P ＞ 0.05); while HBeAg seroconversion rate in LAM + ADV group at month 24 was significantly higher than that in ETV group (43.5％ vs.36.4％,x2 =4.09,P＜0.05).Viral breakthrough occurred in 2 cases (4.4％) by month 12 and 3 cases (6.7％) by month 24 in LAM + ADV group,and no viral mutation was observed; while in ETV group,viral breakthrough occurred in 1 case ( 2.2％ ) by month 12 and 2 cases (4.4％) by month 24,and viral mutation was observed in 1 case (2.2％) by month 24.At the end of month 24,increase of AIb (F=18.9 and 17.3,P＜0.05),decrease of TBil and ALT (F=16.5,17.1 and 23.7,24.8,P ＜0.05 ),shortening of PT ( F =22.7 and 24.5,P ＜ 0.05 ),and the improvements of CTP and MELD scores (F=18.5,17.8 and 24.2,23.8,P＜0.05) were observed in both groups.The accumulative rates of mortality or liver transplantation were 16.7％ ( 10/60 ) and 18.3％ ( 11/60 ) in LAM + ADV and ETV groups,respectively.No blood creatinine increased above the normal upper limit was observed in both groups.Conclusion Both LAM + ADV combination therapy and ETV monotherapy can effectively inhibit HBV replication,improve liver function,decrease mortality and viral resistance,but the 24-month HBeAg seroconversion rate in combination therapy group is higher than that in monotherapy group.

Objective: To explore the correlation between antithrombotic strategy and its prognostic value in coronary artery disease (CAD) patients combining with atrial ifbrillation (AF) after percutaneous coronary intervention (PCI).
Methods: A total of 570 CAD patients with AF received PCI in our hospital from 2012-01 to 2013-12 were retrospectively analyzed by CHADS2 and HAS-BLED Score system. According to CHADS2 < 2 and CHADS2 ≥ 2 or with/without warfarin medication, the patients were divided into 2 groups:①CHADS2 < 2 (Low risk of stroke) group,n=339 including 309 patients without warfarin and 30 with warfarin medication;②CHADS2 ≥ 2 (High risk of stroke) group,n=231 including 200 patients without warfarin and 31 with warfarin medication. All patients were followed-up for 15 months to compare the different anti-platelet/ anti-coagulation strategies for the occurrence rate of MACCE, ischemic and bleeding events.
Results: Compared with Low risk of stroke group, the patients in High risk of stroke group had the worse prognosis and higher rate of MACCE occurrence,P<0.001, HR=2.677, 95% CI (1.535-4.635), more ischemic events,P=0.013, HR=2.080, 95% CI (1.167-3.709). Multi-factor Cox surving analysis indicated that compared with low risk patients without warfarin medication, the high risk patients without warfarin had the higher rate of MACCE occurrence,P=0.001, HR=2.985, 95% CI (1.532-5.816), more ischemic events,P=0.026, HR=2.068, 95% CI (1.090-3.925). Whereas, the occurrence rates of MACCE and ischemic events in high risk, low risk patients with warfarin and low risk patients without warfarin were similar, all P>0.05. The major bleeding events in patients with warfarin were a little higher than those without warfarin,P>0.05. The minor bleeding events were increased in both Low risk stroke group asP<0.001, OR=4.458, 95% CI (1.934-10.277) and High risk stroke group asP=0.002, OR=4.155, 95% CI (1.717-10.055).
Conclusion: Warfarin medication may obviously decrease the occurrence rates of MACCE and ischemic events in high risk of stroke patients, while in low risk patients, warfarin could not further decrease the occurrence of MACCE and ischemic events. Warfarin could increase the risk for minor bleeding in both low risk and high risk of stroke in CAD patients combining with AF after PCI.

At present, the treatment of advanced tumors has entered the immune era, and immune checkpoint inhibitors have shown good efficacy in prostate cancer. Cellular immunotherapy such as CAR-T therapy (chimeric antigen receptor T-cell immunotherapy) has shown excellent results in hematological and digestive system malignancies, but its efficacy in urinary system tumors is not yet clear. This review will explain the current status and application prospects of CAR-T in the treatment of prostate cancer, including target selection, predicament, and function enhancement strategies of CAR molecules in prostate cancer, aiming to open up new perspectives for cellular immunotherapy of prostate cancer and ideas.

Objective To study the clinical characteristics in the patients with different types of acute coronary syndrome(ACS) undergoing percutaneous coronary intervention (PCI) and the factors affecting the PCI treatment.Methods A total of 377 inpatients with ACS undergoing PCI in this hospital from January 2014 to March 2015 were selected,including 172 cases of ST-elevation acute coronary syndrome (ST-ACS) group and 205 cases of non-ST-elevation ACS (NST-ACS group).The baseline data and detection indexes were collected,the GRACE score on admission was calculated,the database was established,regular follow-up was performed,and the prognosis was analyzed.Results The smoking history,emergency PCI,coronary angi-ography TIMI grade ≤ 1,H MGB1,GRACE score,heart rate on admission,white blood cell(WBC) count,neutrophil ratio,lymphocyte ratio,monocytes ratio,absolute neutrophil count,high density lipoprotein,apolipoprotein b,number of lesion vessels and left ventricular ejection fraction had statistical differences between the ST-ACS group and NST-ACS group (P ＜ 0.05);the correlation analysis showed that HMGB1 and GRACE score were significantly correlated (r=0.836,P＜0.01).The 2-year follow-up results showed that the previous myocardialinfarction and PCI history,Killip grade(Ⅱ-Ⅳ),coronary angiography TIMI grade≤ 1,HMGB1,GRACE score,mean platelet volume,age and number of lesion vessels had differences between the end point event occurrence group and end point event non-occurrence group (P＜0.05).The Logistic regression analysis showed that HMGB1,GRACE score,age,previous PCI histoty,Killip grade (Ⅱ-IV) were the independent risk factors for cardiovascular events (P ＜ 0.05).The Cox survival analysis showed that HMGB1,previous PCI history,Killip grade (Ⅱ-Ⅳ) were the independent risk factors for cardiovascular events (P＜0.05).The ROC survival curve showed that the accuracy of HMGB1 was good,the areas under the curve was 0.844 (95％CI:0.803-0.885,P＜0.05),the critical value predicting the end point events was 480.44 ng/mL.Conclusion HMGB1 has difference between the ST-ACS group and NST-ACS group,and has a good correlation with GRACE score.

AIM: To compare the protective effects of tongxinluo, a Chinese medicine, and carvedilol and valsartan on myocardium microvascular endothelial function and integrity after late reperfusion of acute myocardial infarction (AMI) in rabbits. METHODS: Forty-eight rabbits were randomly assigned to the following groups: (1) sham operated rabbits; (2) ischemia-reperfusion (I-R) controls; (3) tongxinluo (1.0 g?kg~ -1?d~ -1); (4) carvedilol (5 mg?kg~ -1?d~ -1); (5) valsartan (10 mg?kg~ -1?d~ -1) and (6) ticlopidine + aspirine (30 and 20 mg?kg~ -1?d~ -1, respectively) groups. After 3 d of drug treatment, the left coronary artery in the rabbit was ligated for 2 h and loosed subsequently for another 2 h. The serum levels of nitric oxide (NO_2~-/NO_3~-) and endothelin (ET) at baseline before AMI, 2 h after both AMI and reperfusion were examined. Also, the number of circulating endothelial cells (CEC), MI size and percentage myocardium focal bleeding incidence were determined 2 h after reperfusion. RESULTS: (1) The baseline level of NO_2~-/NO_3~- was significantly higher in tongxinluo group than that in other groups (all P

Trace amines(TAs)are metabolically related to catecholamine and associated with cancer and neuro-logical disorders.Comprehensive measurement of TAs is essential for understanding pathological pro-cesses and providing proper drug intervention.However,the trace amounts and chemical instability of TAs challenge quantification.Here,diisopropyl phosphite coupled with chip two-dimensional(2D)liquid chromatography tandem triple-quadrupole mass spectrometry(LC-QQQ/MS)was developed to simul-taneously determine TAs and associated metabolites.The results showed that the sensitivities of TAs increased up to 5520 times compared with those using nonderivatized LC-QQQ/MS.This sensitive method was utilized to investigate their alterations in hepatoma cells after treatment with sorafenib.The significantly altered TAs and associated metabolites suggested that phenylalanine and tyrosine metabolic pathways were related to sorafenib treatment in Hep3B cells.This sensitive method has great potential to elucidate the mechanism and diagnose diseases considering that an increasing number of physiological functions of TAs have been discovered in recent decades.