Objective To screen specific mutations on extracellular regions of membrane proteins ( extracellular membrane protein mutations ) in tumor cells and provide the reference information for target searching in cancer precision medicine .Methods Somatic mutations on extracellular regions of membrane proteins of 7042 tumor samples were collected to screen all specific extracellular membrane protein mutations, and the overall distribution of these mutations were obtained by statistical analysis.Genes, gene site and cancer types occured high frequency of extracellular membrane protein mutations were identified.Results 97193 specific extracellular membrane protein mutations were obtained from 4938362 somatic mutations in 7042 tumor samples (30 cancer types), the statistical analysis showed that 4347 genes and 65532 sites were involved in these specific mutations.The study further analyzed five genes (MUC16、LRP1B、CSMD3、RYR2、USH2A), one site (17:37868208) and six cancer types (including colorectal cancer, melanoma, uterine cancer, brain lower grade glioma, lung adenocarcinoma and stomach adenocarcinoma) which occured high frequency of extracellular membrane protein mutations.Conclusion An information library of specific mutations on extracellular regions of membrane proteins was established and the distribution of these specific mutations was obtained which can provide reference information for target detection in targeted cancer therapy and immunological therapy.

Objective:To systematically review the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs)on two common respiratory system adverse events (RSAE:nasopharyngitis and upper re-spiratory tract infection)among type 2 diabetes (T2DM).Methods:Medline,Embase,Clinical trials and Cochrane library were searched from inception through May 201 5 to identify randomized clinical trials (RCTs)assessed safety of GLP-1 RAs versus placebo or other anti-diabetic drugs in T2DM.Network meta-analysis within a Bayesian framework was performed to calculate odds ratios for the incidence of RSAE.Results:In the study,50 RCTs were included,including 1 3 treatments:7 GLP-1 RAs (exenati-de,exenatide-long-release-agent,liraglutide,lixisenatide,taspoglutide,albiglutide and dulaglutide), placebo and 5 traditional anti-diabetic drugs(insulin,metformin,sulfonylureas,sitagliptin and thiazo-lidinediones ketones).Compared with insulin,taspoglutide significantly decreased the incidence of naso-pharyngitis (OR =0.67,95%CI:0.46 -0.96).Significant lowering effects on upper respiratory tract infection were found when taspoglutide versus placebo (OR =0.57,95%CI:0.34 -0.99)and insulin (OR =0.39,95%CI:0.23 -0.73).The result from the network meta-analysis based on Bayesian theo-ry could be used to rank all the treatments included,which showed that taspoglutide ranked last with mi-nimum risk on nasopharyngitis and upper respiratory tract infection.Conclusion:Taspoglutide was associ-ated with significantly lowering effect on RSAE.

Objective:To systematically evaluate the incidence of liver injury in multi-drug resistant tu-berculosis ( MDR-TB ) patients with the treatment of second-line anti-TB drugs.Methods: Medline (January 1, 1966 to March 1, 2014), Embase (January 1, 1974 to March 1, 2014) and the Cochrane library (January 1, 1993 to March 1, 2014) with four Chinese databases including VIP ( January 1, 1989 to March 1, 2014), CBMDisc (January 1, 1978 to March 1, 2014), CNKI (January 1, 1994 to March 1, 2014)and Wanfang (January 1, 1998 to March 1, 2014), were systematically searched with the keywords including “Tuberculosis”,“multidrug-resistant”,“MDR-TB”,“side effect”,“adverse”,“safety” and “tolerability” for the follow-up studies of MDR-TB patients with liver injury during the treatment of second-line anti-TB drugs.The relevant information was extracted and the data were analyzed using the random-effects model .Subgroup and sensitivity analyses were performed based on the diagnostic criteria, study population , study design , history of anti-TB treatment and treatment length .Results: A total of 26 articles with 3 875 MDR-TB patients were included , of which 373 patients developed liver in-jury, and the weighed combined incidence of liver injury was 7.7%(95%CI:5.5%-10.8%).There was some heterogeneity among the studies .Subgroup analyses showed that the incidence of liver injury was higher in groups with treatment length≥18 months and non-Asian populations , but there was no sig-nificant difference between the groups (P>0.05).Among the 26 articles, only nine of them reported the diagnostic criteria of liver injury , while the criteria were not uniform .Conclusion:The incidence of liver injury during the treatment of second-line anti-TB drug in MDR-TB patients was high , and the diag-nostic criteria were not uniform .We should pay attention to the prevention and treatment of liver injury , and develop standard diagnostic criteria for it .

Objective To discuss the levels of evidence provided by different study designs.Methods Websites of N Engl J Med, JAMA, Lancet, and BMJ were accessed to identify research articles (systematic review and meta-analysis included) published in 2009. A standardized data collection form was established using Epidata 3. 1 software to extract the "title", "country of lead author", "clinical problem" (such as treatment, diagnosis, etc. ) and "study design" of eligible studies. Descriptive statistics was conducted with SPSS 13.0. Results Over all, 844 studies were included, among which 35.7% were RCT,9. 4% systematic review and Meta-analysis, and 54. 9% other types of studies. Regarding clinical problems,34. 2%, 19. 7%, 13.7%, 6. 0% and 5. 1% of the included researches addressed the issues of treatment,etiology/risk factors, prevention, disease frequency and prognosis, respectively. The study designs that were most frequently adopted to explore these problems were RCT (70.6%), cohort study (44. 6% ), RCT (68. 1% ), cross-sectional study ( 56. 9% ), and cohort study ( 93.0% ), respectively. Conclusions High-level evidence does not come exclusively from RCT and systematic review, as each type of study may have its unique value in health related research. The clinical problem of interest, the previous work that has been done to approach the same issue, as well as other factors should be taken into account when deciding whether the selected study design is appropriate.

Objective To investigate the characteristics of inanune status change in sepsis and severe sepsis patients by quantitative analysing the serum concertrations of pro-and anti-inflammatory cytokines. Method Serum of 38 sepsis patients, 32 severe sepsis patients were collected and 15 health individuals were as controls.ELJSA method was used to quantify the serum levels of inflammatory cytokines. The severity of patient's condition was assessed according to the APACHE Ⅱ system, Retolts The serum concentrations of inflammatory cytokines were different among sepsis and severe sepsis patients. In the serum of sepsis patients the pro-inflammatory eytokine were dominant. But in the serum of severe sepsis patients the anti-inflammatory cytokine were dominant.The serum levels of TNF-α, IL-6, IL-1, IL-10 were obviously different among control, sepsis and severe sepsis groups ( P<0.05). The serum levels of IL-1 and IL-10 were significantly correlated with APACHE II scores. The multiple linear regression eqution was APACHE Ⅱ=- 9.393 + (IL-10 x 0.550) + (IL-1 x 0.305) (F =26.198,P<0.001) Conclusions The serum levels of pro-and anti-inflammatory cytokines were significantly different among patients with different stages of sepsis, and the immune status were different. The activation of inflatrmmtory reaction were constant in sepsis patients, while the expression of anti-inflammatory cytokines increased in severe sepsis patients.

Objective To explore the value of applying flipped classroom in human parasitology. Methods Totally 430 students of 5-year program were divided into experimental group and control group. The experimental class received human parasitology teaching through flipped classroom teaching mode, while the control class received traditional teaching. The effect of teaching was evaluated by questionnaire and examination. The data were analyzed through t-test. Result Meanwhile, statistical difference was found in aver age score of total between experiment group and control group [(68.2 ±8.6) vs. (66.6 ±11.0), P=0.032]. There was also statistical difference in average score of comprehensive analysis [(16.4±3.2) vs. (16.1 ±3.9), P=0.038]. Questionnaire survey of satisfaction showed that 191 students of experimental class (90.95%) felt new teaching mode could improve autonomous learning ability, 199 students (94.76%) in-creased interest in learning;185 students (88.10%) had more interactive with teachers, 178 students (84.76%) enhanced cooperation between st udents, 186 students (88.57%) approved of small group discussion learning and 165 students (78.57%) had no extra burden. Conclusion Flipped classroom teaching mode can improve students' autonomous learning ability and cultivate their abilities of independent thinking, cooperation, criti-cism, innovation, analyzing and solving problems. Thus this new teaching mode is worthy of reference and popularization.

OBJECTIVE To evaluate the long-term toxicity of fully human anti-human tumor necrosis factor-α monoclonal antibody(anti-hTNF-α FHMA)for injection in cynomolgus monkeys. METHODS Forty cynomolgus monkeys were randomly divided into 5 groups (4 males and 4 females in each group):negative control group,adalimumab 10 mg·kg-1 group,anti-hTNF-αFHMA 2,10 and 50 mg·kg-1 groups. Cynomolgus monkeys in each group were injected sc once a week for 5 consecutive times, followed by 4 weeks of recovery. During the test,general clinical observation,body mass,body temperature,electrocardiogram(ECG),hematology,coagulation function,blood biochemistry,urine, ophthalmology,immune index,and pathological changes in organs and tissues were observed. At the same time,plasma drug concentrations were detected and the toxicokinetics parameters were analyzed. RESULTS No significant toxicological changes related to drugs were observed in general clinical observation,body mass,body temperature,ECG,ophthalmic examination,blood cell counts,coagu?lation function,blood biochemistry,urine analysis,lymphocyte subsets,cytokines,serum immuno?globulin,serum complement. Neutralizing anti-drug antibody(ADA)could be detected in adalimumab group and anti-hTNF-αFHMA groups. Anti-hTNF-αFHMA showed linear dynamic characteristics in cyno?molgus monkeys. At the same dose(10 mg·kg-1),anti-hTNF-αFHMA had similar immunogenicity and kinetics characteristics to adalimumab. CONCLUSION The level of anti-hTNF-α FHMA at which no adverse effect was observed was 50 mg · kg-1,which is equivalent to 75 times clinical dosage of quasi (0.67 mg·kg-1),which suggests that anti-hTNF-αFHMA be safe in clinical use.

OBJECTIVE: Discussion of expression and its significance of CD44 in SP cells of nasopnaryngeal carcinoma. METHOD: Flow cytometry was used to sort cultured CNE-2 cells of nasopharyngeal carcinoma for obtaining CD44-SP and CD44+SP cells. Biological differences of CNE-2, CNE-2 SP, CNE-2 NSP, CNE-2 CD44+SP and CNE-2 CD44-SP cells were statistically analyzed by experiments such as cell migration experiments, plate clone formation assay, cell cycle analysis and sensitivity tests to chemotherapeutics. RESULT: Two point 3 perent of SP cells were extracted from CNE-2 cells of nasopharyngeal carcinoma, among which 36.5% was CD44+SP cells. Abilities of proliferation, cell migration and plate clone of CD44+SP cells were significantly higher than other cells (P < 0.01), and its tolerance to chemotherapeutics was significantly higher too (P < 0.01). CONCLUSION The proportion of SP cells in nasopharyngeal carcinoma cells was small, but SP cells had strong activeness in the aspect of cell proliferation with a "seed" characteristic of tumor cells. As CD44+SP cells played an important role in proliferation and chemotherapy resistance of nasopharyngeal carcinoma, it indicated that CD44 can be one of the surface markers of SP cells of nasopharyngeal carcinoma.
Biomarkers, Tumor ; metabolism ; Carcinoma ; Cell Cycle ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Flow Cytometry ; Humans ; Hyaluronan Receptors ; metabolism ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; metabolism

This paper introduces the revised Cochrane bias risk assessment tool for individual randomized,cross-over trials (RoB2.0),comparing RoB2.0 of cross-over design with RoB2.0 of parallel design,and illustrating the application of RoB2.0 for cross-over trials in a published clinical trial.As a comprehensive tool specially designed for cross-over design,it provides more information on risk of bias in systematic reviews for the evidence synthesis.

In order to fulfill the new requirement of educational and teaching reform in the new era, the Teaching and Research Section of Parasitology in Guangxi Medical University have constructed online courses of Parasites Invasion— Human Parasitology on the platform of Xueyin Online, providing resources in professional learning and general education. In the construction concept, we recombine teaching content to give consideration to both scientificity and interest. In terms of the curriculum content, the curriculum includes micro lecture, PPT, in-lass quiz, case analysis and other diversified teaching resources. In the curriculum management, teachers interact with students in real time with the help of various functions of the platform to fully play the role of supervision. In the assessment, teachers pay attention to students' learning process and carry out comprehensive evaluation. Since the online course was put into operation, good teaching effects has been achieved.