PCI-32765,an oral selective and irreversible inhibitor of Bruton tyrosine kinase (BTK),inhibits survival,activation,proliferation and migration of malignant B cells by blocking B cell receptor signaling pathway.PCI-32765 not only acts on malignant B cell,but also prevents resistance to chemical drugs.Therefore,PCI-32765 has broad prospects in the treatment of B cell malignancies.

Objective To screen proteins binding with interferon?(IFN?)from human hepatic cDNA libraty by yeast-two hybrid technique.Methods The IFN?gene was amplified by polymerase chain reaction(PCR)and constructed into pGBKT7 vector as the bait plasmid in yeast-two hybrid system3,pGBKT7-IFN?was then transfected into yeast AH109.The transfected yeast were mated with yeast Y187 containing liver cDNA library plasmid in 2?YPDA medium.Diploid yeast was plated on synthetic dropout nutrient medium(SD/-Trp Leu-His-Ade)and synthetic dropout nutrient medium(SD/-Trp-Leu-His-Ade)containing X-?-gal for selecting.After plasmid extracting and en- zyme cutting analysis,the blue colonies were performed sequence analysis,the results were analyzed by bioinformatics.Results IFN?gene was successfully cloned and expressed in yeast cells.Thirty- four positive colonies were obtained using yeast-two hybrid technique.After sequence analysis,eight clones were found may have a binding effect with IFN protein.Conclusions IFN?genes was success- ful cloned and eight proteins that could bind with IFN?protein were also screened.

Objective To investigate the prevention and treatment effects of Compound Kushen Injection on acute radiation esophagitis. Methods Eighty-two eligible patients with esophageal cancer were randomly divided into the treatment group (41 cases) and the control group (41 cases). All the patients received radiotherapy. Throughout the course of radiotherapy, patients in the treatment group received Compound Kushen Injection, and patients in the control group received Kangfuxin Liquid. Occurrence time and level of radiation esophagitis, and dosage of painkillers were observed. Results Different degrees of acute esophageal toxicity were observed in the two groups. The occurrence rate of high level (degree III and degree IV) acute radiation esophagitis was 7.3%(3/41) in the treatment group, and 31.7%(13/41) in the control group. There was significant difference between the two groups (P<0.05). The dosage of the analgesic drug (Fentanyl Transdermal System) in the treatment group was far less than the controlled group (P<0.001). Conclusion Compound Kushen Injection could decrease the incidence rate of acute radiation esophagitis, and reduce the high-level esophagitis and the dosage of the analgesic drug, which can help the completion of radiation.

Immunotherapy is revolutionizing the treatment of non-small cell lung cancer (NSCLC).Programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) monoclonal antibodies have recently led to significant and durable improvements in the clinical outcome of NSCLC,and the anti-PD-1 antibody has been approved to use in first-line and second-line treatment of NSCLC.However,there are still many problems to be solved.The role of PD-L1 as a predictive biomarker remains unclear.Combination treatment models are being explored.This review summarizes the clinical efficacy,drug adverse reaction,combined treatment,and potential immune biomarkers of anti-PD-1/PD-L1 antibody research progress in the treatment of NSCLC.

Objective To investigate the correlation between serum proprotein convertase subtilisin/kexin 9 (PCSK9) level and the severity of angiographic coronary artery disease (CAD) in elderly patients with acute myocardial infarction (AMI) complicated with type 2 diabetes mellitus (T2DM). Methods The patients over the same period were divided into three groups:the elderly patients with AMI and T2DM (observation group, n=46), the elderly non diabetic patients with AMI (positive control group, n=34) and patients with chronic stable coronary heart disease (negative control group, n=33). The serum PCSK9 level was detected by enzyme-linked immunosorbent (ELISA) in three groups. The correlation between serum PCSK9 level and low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), total cholesterol (TC), glycosylated hemoglobin (HbA1c), high sensitive C reactive protein (Hs-CRP) and Gensini score were analyzed. Results The levels of PCSK9, HbA1c, Hs-CRP and Gensini score showed a gradually increased tendency in negative control group, positive control group and observation group. Multiple comparison differences between groups were statistically significant (P<0.05). The serum PCSK9 level was positively correlated with Hs-CRP and Gensini score in observation group (P<0.05), and showed no correlation with HbA1c, TG, TC, LDL-C and HDL-C (P>0.05). Conclusion The serum level of PCSK9 is positive correlated with the severity of CAD, which can be used to determine the severity of coronary artery lesions in elderly patients with AMI complicated with T2DM.

Objective To investigate the effect of liraglutide and metformin hydrochioride on overweight diabetic patients because of poor glycemic control.Methods Forty-four overweight patients with poor glycemic control were randomly divided to the control group,the liraglutide group and the metformin hydrochioride group.Patients in control group were given diet and exercise control,in liraglutide group and the metformin hydrochioride group were given subcutaneous injection liraglutide,metformin hydrochioride oral treatment respectively for 12 weeks.Body mass index(BMI),fasting blood glucose (FBG),2-hour postprandial blood glucose (2 hPBG) and glycosylated hemoglobin (HbA1c) were measured.Results Compared with pretreatment,FBG,2 hPBG and HbA1c of patients in liraglutide group and metformin hydrochioride group were lower after treatment,and there was significant difference between the two group and the control group after treatment(P ＜ 0.05).BMI of patients in liraglutide group was (24.61 ± 3.47) kg/m2,lower than of the control group((25.37 ± 4.70) kg/m2,P ＜ 0.05).2 hPBG of patients in the liraglutide group was (7.13 ± 3.85)mtmol/L,lower than that of the metformin hydrochioride group ((8.03 ± 4.33) mtmol/L,P ＜ 0.05).FBG level in metformin hydrochioride group ((6.31 ± 3.45) mmol/L) was lower than that of the liraglutide group ((6.98±2.97) mmol/L),but the difference was not statistically significant(P ＞ 0.05).Conclusion Liraglutide and metformin hydrochioride treatment can effectively reduce weight and blood sugar of the overweight diabetics.The effect of liraglutide to reduce postprandial blood glucose and weight of the patient is more significant than of metformin hydrochioride.

Actins ; metabolism ; Arm ; Diagnosis, Differential ; Fibrosarcoma ; metabolism ; pathology ; Hamartoma ; metabolism ; pathology ; surgery ; Humans ; Infant ; Lipoma ; metabolism ; pathology ; Male ; Myofibromatosis ; metabolism ; pathology ; S100 Proteins ; metabolism ; Vimentin ; metabolism

Objective To discuss the methods and evaluate the effects of initial muscle-enclosing protection of large segment of exposed Achilles tendon and second stage repair of Achilles tendon rupture complicated with cuta-neous defect.Methods Among patients treated between August 2005 to April 2014 in our hospital,there were 32 patients,who were diagnosed with Achilles tendon rupture complicated with cutaneous defect.Of the 32 patients, there are 21 male and 11 female.Their ages range from 23 to 69,with an average age of 46.2 ±3.5.In all the patients described above,there are soft tissue contusion injuries and cutaneous defects on their posterior lower legs near the ankles,with the area of skin defects ranging from 3cm ×4cm to 5 ×12cm,and the Achilles tendons were ruptured, extracted,dissociated and completely uncovered.All patients were initially treated with triceps surae muscle-enclosing method to put aside and protect the large segment of exposed Achilles tendon.Later,the ruptured Achilles tendons were repaired,together with the transfer of skin flap to repair skin defects,at the second stage.The therapeutic effects were evaluated during postoperative follow-up periods.Results The mean follow-up period was 18 months,ranged from 11 to 32 months.According to the therapeutic effect evaluation standard of Arner-Lindholm,there were Excellent results in 22 patients,Good in 7 cases and Poor in 3 cases,with a combined excellent/good rate of 90.62%.Conclusion Initial muscle-enclosing protection of large segment of exposed Achilles tendon and second stage repair of Achilles tendon rupture complicated with cutaneous defect is advantageous to the function of patients with rapid recovery.

Objective:To detect the inhibitory effects of CAL-101, a selective inhibitor of phosphoinostitide-3'-kinase delta (PI3Kδ), on Burkitt's lymphoma cell line Raji and diffused large B-cell lymphoma cell line SUDHL-10 and elucidate its relative mechanism. Methods:Raji and SUDHL-10 cells were treated with various concentrations of CAL-101. Methyl thiazolyl tetrazolium (MTT) assay was performed to determine the inhibitory effect of CAL-101 on lymphoma cells, and cell apoptosis was measured by Annexin V/PI and DAPI staining. Migration assays were performed with transwell to detect the migration of lymphoma cells derived from the stromal cell line HK. Western blot was used to detect the phosphorylation status of the ERK pathway. MTT and CalcuSyn software analyses were preformed to detect whether or not combining CAL-101 with bortezomib induces synergistic cytoxicity. Results:CAL-101 at con-centrations of 5, 10, 15, and 20μmol/L inhibited cell proliferation in a dose-dependent manner. The proliferation rates of the Raji cells treated with 5, 10, 15, and 20μmol/L for 48 h were 29.17%± 1.23%, 38.15%± 1.51%, 46.46%± 1.78%, and 55.8%± 2.01%, respec-tively, which were significantly higher (P<0.05) than that of the control group (1.15% ± 0.02%). Similar results were found in the SUDHL-10 cells after treatment with CAL-101 (P<0.05). CAL-101 also exerted an apoptotic effect on the lymphoma cells. The apop-totic rates of the Raji cells treated with CAL-101 for 21 h were 22.69%± 3.83%and 49.96%± 7.36%, respectively, which were signifi-cantly higher (P<0.05) than that of the control group (5.23%± 2.04%). Similar results were found in the SUDHL-10 cells (P<0.05). Treatment with 5 and 10 μmol/L CAL-101 dose-dependently inhibited the migration activity of lymphoma cells to stromal cells (P<0.05). Western blot analysis showed that the expression level of ERK phosphorylation protein was significantly downregulated in the cells treated with CAL-101. A synergistic effect between CAL-101 and bortezomib was verified. That is, these two drugs can signifi-cantly inhibit the proliferation of lymphoma cells with CI values less than 1. Conclusion:The PI3Kδ-specific inhibitor CAL-101 sup-pressed the proliferation of Raji and SUDHL-10 cells, induced apoptosis, and inhibited stromal cell-derived migration. This inhibitory effect may be induced by blocking the ERK pathway. Overall, our study indicated that CAL-101 is a novel and potential agent in the therapeutic strategy against aggressive B-cell lymphoma.

Objective To explore the role of GRK5 in sustained β adrenergic receptor (βAR)-stimulated increased levels of oxidative stress.Methods Male SD rats (180-200 g) were separated into 4 groups according to the random principal: control group (CTRL), control with NAC supplement group (CTRL+NAC), ISO treated group (ISO), and ISO treated with NAC supplement group (ISO+NAC), with 6 rats in each group.ISO group was treated by method of intraperitoneal injection for 3 mg/(kg· d).CTRL rats received same volume of physiological saline by same method, while NAC was treated by supplement in drinking water for 15 g/L per day.After 2 weeks of treatment, BP, heart mass index (HMI), histology changes, expression of NOX4 and GRK5 of myocardium was examined.Results HMI of ISO rats was significantly higher than that of the CTRL group [(3.99±0.10 vs 3.31±0.13) mg/g, P＜0.05], and the cardio-myocyte cross-sectional area of ISO group was also significantly increased compared with CTRL group [(11 117.00±387.57 vs 4572.23±176.39) μm, P＜O.05].ISO+NAC significantly reduced the ISO-induced increases of heart weight index (3.56±0.12 mg/g, vs ISO, P＜0.05) and myocyte cross-sectional area (6160.33±141.44 μm2, vs ISO,P＜0.05).The immunohistochemistry results showed that the expression of myocardial NOX4 of ISO group was significantly higher than that of CTRL group [(10.59±1.61 vs 4.35±1.65), P＜0.05], and NAC reduced the ISO induced NOX4 expression increase [(4.67±1.25 vs 10.59±1.61), P＜0.05].Western Blot and immunohistochemistry were used to detect the protein expression of myocardial GRK5.Both results showed that there were no significant differences between ISO and CTRL, ISO+NAC and ISO group (P＞0.05).RT-qPCR detected no significant differences of myocardial GRK5 mRNA expression between ISO and CTRL, ISO+NAC and ISO groups (P＞0.05).Arterial blood pressure showed no significant difference among the 4 groups of rats (P＞0.05).No significant differences were found between rats from CTRL+NAC and CTRL group.Conclusions In the mechanism of sustained βAR-stimulated cardiac hypertrophy, GRK5 may not participate the regulation of hypertrophy-induced factor, and this process needs to be proved in further study.