Objective To explore the effect of sorafenib on HeLa cell proliferation by inducing cell apoptosis and autophagy and its impact on drug resistance.Methods The drug-resistant cell strains were constructed through in-termittent induction method,with concentrations of 0,2.5,5.0,7.5,10.0,15.0,20.0 μmol/L.HeLa cells were incubated with increasing concentrations of sorafenib with each concentration for 1 week.The drug-resistant cell strains with stable passages were collected.MTT assay was used to detect the effect of sorafenib on cell prolifer-ation.Cell cycle distribution was analyzed by flow cytometry.The change in the expression of drug-resistant and ap-optotic genes in the parents and drug-resistant cell strains under different drug concentrations was examined by semi-quantitative PCR.The changes of apoptotic related marker proteins LC3-Ⅰ and LC3-Ⅱ were detected by Westernblot.Results Stable drug-resistant strains were successfully obtained;Drug-treated cells were more blocked in the G1 phase.In drug-resistant cells,the expression of apoptosis suppressor gene Bcl-2 was significantly decreased and the apoptotic gene Bax as well as the drug-resistant genes were all significantly increased(P＜0.05).The LC3-Ⅱ/LC3-Ⅰ ratio of drug-resistant cells was significantly higher than that of parent cells(P＜0.05).Conclusions Sorafenib may block the cell cycle,suppress malignant cell proliferation and promote autophage.On one hand,autophagy participates in the development of cell drug resistance and promotes cell survival.On the other hand,drug-induced autophagy may activate some of apoptotic signaling pathway in drug-resistant cells and promote the reversal of cell drug resistance.

Objective:To observe the curative effects and complications of open reduction and fixation with cannulated screws and an augmented plate for Pauwels type Ⅲ femoral neck fractures.Methods:A retrospective study was conducted to analyze the data of 8 patients with fresh Pauwels Ⅲ femoral neck fracture who had been treated from January 2015 to October 2018 at Department of Trauma and Orthopaedics, Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine. There were 7 males and 1 female with an age of (47.7±14.0) years. The Pauwels angle ranged from 50° to 70° in 6 cases and was >70° in 2 cases. As the original closed reduction was not ideal in all the patients, open reduction via the modified Smith-Petersen approach and fixation with cannulated screws and an augmented plate were performed. Fracture healing, Harris hip score, and complications were followed up at 1 month, 6 months, 1 year, and 3 years postoperatively.Results:At 1 month after operation: 8 patients were followed up, their Harris hip score was (38.4±3.6) points, and there were 7 cases of femoral neck shortening and 1 case of incision fat liquefaction. At 6 months after operation: 7 patients were followed up, their Harris hip score was (70.6±2.8) points, and 1 patient healed anatomically, 4 patients healed with shortening, and 2 patients healed with delay and shortening. Femoral neck shortening, withdrawal of cannulated screws, and screw loosening within the augmented plate were all increased compared with 1 month after operation. At 1 year after operation: 7 patients were followed up, their Harris hip score was (85.5±4.4) points, there were no significant changes in fracture healing or complications compared with 6 months after operation. At 3 years after operation: the patient lost to prior follow-up died of heart disease 34 months after operation, 1 patient had to undergo total hip arthroplasty due to fracture nonunion and cutout of cannulated screws at 16 months after operation, and the other 6 patients had a Harris hip score of (93.6±2.5) points. Of the 6 patients, femoral neck fracture healed in 5 (shortening healing in 4, including 1 case complicated with femoral head necrosis, and anatomical healing in 1) but did not in one.Conclusions:In the treatment of Pauwels type Ⅲ femoral neck fractures, open reduction and fixation with cannulated screws and an augmented plate does not lead to ideal curative effects. The main complication is shortening of the femoral neck. The auxiliary role of augmented plate fixation is not obvious.

Objective:To explore the application and effect of mixed teaching based on Blackboard network teaching platform in basic chemistry teaching.Methods:The study included in 240 undergraduate students majoring in clinical medicine of Batch 2018 as the research subjects, and they were divided into the experimental group and the control group, with 120 students in each group. The control group was taught by the traditional teaching mode, and the experimental group was taught by mixed teaching method based on the Blackboard network teaching platform. A unified test was conducted for both groups of students. At the end of the course, a questionnaire survey was conducted among the students in the experimental group. SPSS 13.0 was used to process the data and independent sample t-test was performed. Results:The overall scores of the experimental group [(76.45 ± 2.62) points] were higher than those of the control group [(65.38 ± 3.09) points], with statistical significance ( t = 19.472, P < 0.001). The experimental group's satisfaction with the mixed teaching method was more than 75%. Conclusion:The mixed teaching method based on Blackboard network teaching platform is helpful to improve the quality and effect of basic chemistry teaching, and improve students' autonomous learning ability.

Objectives: To study the changes of blood levels of soluble semaphorin 4D (sSema4D) and matrix metalloproteinases-14 (MMP-14);to explore the correlation between sSema4D and ventricular remodeling in patients of dilated cardiomyopathy with chronic heart failure.
Methods: Our research included in 2 groups:Dilated cardiomyopathy group, n=86 patients and Control group, n=32 healthy subjects. Blood levels of sSema4D, MMP14, Pro-BNP and hs-CRP were examined by ELISA. Left atrial diameter (LAD), right ventricular diameter (RVD), ejection fraction (EF), left ventricular end diastolic diameter (LVEDD), left ventricular fractional shortening (LVFS) were measured by echocardiography. Correlation analysis between blood levels of sSema4D, MMP-14 and the parameters for left ventricular remodeling was conducted.
Results: Blood levels of sSema4D and MMP14 were different between 2 groups, P<0.005. In Dilated cardiomyopathy group, sSema4D level was positively related to MMP-14 and LVEDD (r=0.462, P=0.001 and r=0.643, P<0.001) respectively.
Conclusion: Serum level of sSema4D might be related to ventricular remodeling in patients with dilated cardiomyopathy which could be used as risk factor for predicting the prognosis of heart failure in relevant patients.

Objective To understand antimicrobial resistance and therapeutic efficacy of imipenem/cilastatin and meropenem for treatment of multidrug-resistant Pseudomonas aeruginosa (MDRPA)from patients with mechanical ventilation.Methods From January 2010 to December 2015,78 patients with mechanical ventilation and isolated MDRPA from sputum cultures were selected and divided into imipenem/cilastatin (n=44)and meropenem(n=34) treatment groups,basic condition,time of emergence of drug resistance,and therapeutic efficacy of antimicrobial agents between two groups were compared.Results The basic data of two groups were comparable,before treat-ment by imipenem/cilastatin and meropenem,resistance rates of Pseudomonas aeruginosa (P .aeruginosa )to quinolones,ceftazidime,piperacillin,and amikacin were not significantly different (all P >0.05).After patients received antimicrobial agents for 6 days,difference in antimicrobial resistance between imipenem /cilastatin and meropenem treatment groups were not significantly different (22.73% vs 8.82%,P >0.05).On the 8th,10th,and 12th day of treatment,resistance rates of imipenem treatment group were 40.91%,77.27%,and 97.73%, respectively,which were all higher than meropenem treatment group (17.65%,32.35%,44.12%,respectively,all P <0.05).After the treatment with different antimicrobial agents,the average time for the emergence of resistance in imipenem/cilastatin and meropenem treatment group were 9.0 days and 13.5 days respectively.Therapeutic efficacy between two groups was not significantly different (64.71% vs 74.19%,P =0.41).Conclusion Compared with meropenem,imipenem/cilastatin shows higher risk for the emergence of drug resistance during therapy of P . aeruginosa infection in patients with mechanical ventilation,there is no significant difference in therapeutic efficacy between two groups of patients after 7 days of treatment.

Objective: To evaluate the risk factors for contrast-induced nephropathy (CIN) in patients of acute coronary syndrome (ACS) with normal or slightly impaired renal function after percutaneous coronary intervention (PCI).
Methods: A total of 254 consecutive ACS patients with normal or slightly impaired renal function received PCI in the Second Artillery General Hospital from 2013-06 to 2015-06 were retrospectively studied. All patients had eGRF≥60 ml (min?1.73 m2) and they were divided into 2 groups:CIN group, the patients with serum creatinine increased by 0.5mg/dl (44.2μmol/L) or elevated to 25%higher than the baseline, n=23;Non-CIN group, n=231. The basic condition with laboratory tests, operative indexes were recorded and eGRF value were calculated in all patients.
Results: There were 9%(23/254) patients suffered from CIN after PCI. Multivariate regression analysis indicated that emergent PCI (OR=0.370, 95%CI 0.060-2.297), increased plasma level of NT-proBNP (OR=4.209, 95%CI 1.202-14.742) and without pre-operative aspirin administration (OR=7.950, 95%CI 1.108-57.034) were the clinical risk factors for post-operative CIN occurrence.
Conclusion: Emergent PCI, higher plasma level of NT-proBNP and no pre-operative aspirin administration were the risk factors for CIN occurrence in ACS patients with normal or slightly impaired renal function after PCI.

Objective: To investigate the impact of levosimendan on mortality in patients with severe heart failure (HF) by Meta-analysis. Methods: We search the PubMed, EMBASE and Cochrane Central Registry of cardiovascular disease to identify all randomized impact of levosimendan vs other medications. The document retrieval was from the establishment of each database until 2014-07. The literatures were taken based on Jadad scale standard and the qualified control study was used without dose and time restrictions by Rev Man 5.2 soft ware, and a total of 37 articles with 4470 patients were finally enrolled for Meta-analysis. Results: Compared with controlling medications, levosimendan could decrease the mortality in patients with cardiac disease caused severe HF (RR: 0.85; 95% CI 0.75-0.97;P=0.02), and cardiac surgery caused severe HF (RR: 0.49; 95% CI 0.28-0.85;P=0.01). Compared with dobutamine, levosimendan could reduce the mortality in patients with severe HF (RR: 0.84; 95% CI 0.73-0.99;P=0.02) and severe ischemic HF (RR: 0.85; 95% CI 0.73-0.99;P=0.04). Conclusion: Levosimendan may reduce the mortality in patients with severe HF caused by cardiac disease, cardiac surgery and ischemic cardiac injury.

Chloroplast-based expression system is promising for the hyper-expression of plant-derived recombinant therapeutic proteins and vaccines. To verify the feasibility of obtaining high-level expression of the SARS subunit vaccine and to provide a suitable plant-derived vaccine production platform against the severe acute respiratory syndrome coronavirus (SARS-CoV), a 193-amino acid fragment of SARS CoV spike protein receptor-binding domain (RBD), fused with the peptide vector cholera toxin B subunit (CTB), was expressed in tobacco chloroplasts. Codon-optimized CTB-RBD sequence was integrated into the chloroplast genome and homoplasmy was obtained, as confirmed by PCR and Southern blot analysis. Western blot showed expression of the recombinant fusion protein mostly in soluble monomeric form. Quantification of the recombinant fusion protein CTB-RBD was conducted by ELISA analysis from the transplastomic leaves at different developmental stages, attachment positions and time points in a day and the different expression levels of the CTB-RBD were observed with the highest expression of 10.2% total soluble protein obtained from mature transplastomic leaves. Taken together, our results demonstrate the feasibility of highly expressing SARS subunit vaccine RBD, indicating its potential in subsequent development of a plant-derived recombinant subunit vaccine and reagents production for antibody detection in SARS serological tests.
Chloroplasts ; metabolism ; Cholera Toxin ; Protein Interaction Domains and Motifs ; Recombinant Fusion Proteins ; biosynthesis ; SARS Virus ; Spike Glycoprotein, Coronavirus ; biosynthesis ; Tobacco ; metabolism ; Vaccines, Subunit ; biosynthesis

Adult ; Female ; Humans ; Hyperlipoproteinemia Type II ; complications ; Ventricular Fibrillation ; complications

Objective: To investigate the effect of phosphocreatine (PCr) on angiotensin II (Ang II) induced proliferation and collagen synthesis of cardiac ifbroblasts in neonatal rats with its mechanism.
Methods: The cardiac ifbroblasts (CF) from neonatal rats were cultured in vitro and were divided into 4 groups.①Control group, the CF was cultured in non-serum DMEM,②Ang II group, the CF was cultured with Ang II at (1×10-6) mol/L,③PCr treated group, the CF was cultured with PCr at 10 mmol/L, and④Ang II+PCr group. The CF cell cycle percentage was detected by lfow cytometric assay, myocardial collagen content was observed by VG staining and protein expression of phosphorylated extracellular signal-regulated kinase (pERK1/2) was detected by immuneohistochemistry.
Results: ① Compared with Control group, the CF in Ang II group showed increased percentage of S phase and decreased percentage of G0/G1 and G2/M phases, increased collagen content and pERK1/2 protein expression, all P<0.01.② The CF cell cycle, collagen content and pERK1/2 protein expression were similar between Control group and PCr treated group, all P>0.05. ③ Compared with Control group, Ang II + PCr group had elevated pERK1/2 protein expression, P<0.01, while the CF cell cycle and collagen content were similar with Control group, P>0.05.④Compared with Ang II group, the CF in Ang II + PCr group had increased percentage of G0/G1 and G2/M phases, decreased percentage of S phase, decreased collagen content and pERK1/2 protein expression, all P<0.01.
Conclusion: PCr may partially inhibit Ang II induced CF proliferation and collagen synthesis which might be related to the inhibition of excessively activated ERK1/2. Therefore, PCr could improve Ang II induced myocardial ifbrosis in neonatal rats.