TRIM35 mediates protection against influenza infection by activating TRAF3 and degrading viral PB2

Tripartite motif (TRIM) family proteins are important effectors of innate immunity against viral infections. Here we identified TRIM35 as a regulator of TRAF3 activation. Deficiency in or inhibition of TRIM35 suppressed the production of type I interferon (IFN) in response to viral infection. Trim35-deficient mice were more susceptible to influenza A virus (IAV) infection than were wild-type mice. TRIM35 promoted the RIG-I-mediated signaling by catalyzing Lys63-linked polyubiquitination of TRAF3 and the subsequent formation of a signaling complex with VISA and TBK1. IAV PB2 polymerase countered the innate antiviral immune response by impeding the Lys63-linked polyubiquitination and activation of TRAF3. TRIM35 mediated Lys48-linked polyubiquitination and proteasomal degradation of IAV PB2, thereby antagonizing its suppression of TRAF3 activation. Our in vitro and in vivo findings thus reveal novel roles of TRIM35, through catalyzing Lys63- or Lys48-linked polyubiquitination, in RIG-I antiviral immunity and mechanism of defense against IAV infection.

Current situation analysis of ethical review and implementation of animal welfare about animal experiments in hospitals / 中华医学科研管理杂志

Objective This paper analyzes the situation and problems of animal experiments in hospitals,which including the ethical review,regulatory compliance of animal welfare and animal experimental use,proposing possible measurements for reference.Methods We retrospectively searched Wanfang database,used specific search terms and classification methods to analyze the current situation and problems of ethical review in conducting animal experiment in hospitals.Results In all papers,71 mentioned that the experiment got ethical review approval,accounting for 9.2％;411 mentioned about content of animal welfare,accounting for 53.3％;and 75 referred to the laws and regulations of animal experiments,taking up 9.7％.70 (9.6％) papers focused on both feeding conditions and euthanasia.However,339 (46.4％) papers did not mention any of them.In reference to the approval of animal welfarecommittee,there was a significant difference between funded papers and non-funded papers.In animal welfare,there was no significant difference between papers with funds or not.In the laws and regulations of animal experiment,there were significant differences between state-funded papers and non-state-funded papers.Conclusions So far,when carrying out animal experiments in hospitals,little attention has been paid to the ethical review,so was to the regulatory compliance of animal welfare and animal experimental use.Researchers should constantly strengthen their awareness of animal protection,make sure compliance with the welfare principles of experimental animals,animal protection laws and regulations,and further standardize animal research.

Exploration of the ethical review mechanism of serious adverse events in hospital clinical trials / 中华医学科研管理杂志

Objective To continuingly update the ethical review mechanism of Serious Adverse Events (SAE) in hospital clinical trials .Methods The definition of serious adverse events and the status quo of SAE review was analyzed ,considering the standard operating procedures of SAE review in our hospital ,as well as related measurements for improvement .Results At present ,there still exists some disadvantages in the report and ethical review of SAE ,which the ethical review committee should pay more attention .Conclusions It is important that the ethics committee review of SAE happened in clinical trial effec-tively and efficiently ,which helps to maximize the protection of the subject's health and rights .

Current situation analysis and countermeasures of informed consent and ethical review about clinical trial involving human subject in hospitals / 中华医学科研管理杂志

Objective To explore the current situation of informed consent and ethical review of clinical trial involving human subject in hospitals,and provide related countermeasures.Methods This study searches the website (http://med.wanfangdata.com.cn/Paper),selects "hospital" as the search term,and uses "all fields" as the search criteria.Collected papers were about clinical trial involving human subject that published during Jan.2018 to Feb.2018 in internal medicine,surgery,obstetrics and gynecology,pediatrics.The current situation of informed consent and ethical review of these papers were analyzed from various aspects,including the hospital grades,medical institutions types,clinical research methods,study types,fund projects,periodical category.Results (1) Among 1964 papers,only 538 (27.4％) papers obtained informed consent of subjects and the ethical review approval.(2) There are no significant differences between different hospital grades,and different medical institutions about informed consent and ethical review.(3) Experimental studies focus more on informed consent and ethical review than observational studies.(4) Drug clinical trials focuses more on informed consent and ethical review than non-drug related clinical study.(5) Fund projects focus more on informed consent and ethical review than non-fund pro jects.(6) Papers published in core periodical focus more on informed consent and ethical review than papers published in other periodical.Conclusions Currently,conducting clinical trial involving human subject still does not pay enough attention to the informed consent of subjects and ethical review,more countermeasures are needed to change the current situation and to standardize human clinical trials.

Analysis of patent application and authorization in a hospital and countermeasures / 中华医学科研管理杂志

Objective To share the experience of the patent application,authorization,and transfer in a hospital in last five years,this study aims to improve the patent application and authorization in hospitals.Methods Using data from China Patent Infonet and State Intellectual Property Office of People's Republic of China,we searched the patent application and authorization during Jan.2012 to Dec.2016,and included those that patentee was our hospital or the employee of our hospital.Results The number of patent applications was 215,including 151 service intention-creation applications,and 64 non-service intention-creation applications.Patent application and authorization in our hospital have been increasing year by year,covering internal medicine,surgery,obstetrics and gynecology,pediatrics and so forth.Conclusions We accumulated some experience in patent application,authorization and transfer which provide reference for further,more comprehensive and integrated,patent management system.

The development and improvement of ethical review of multi-center clinical trial / 中华医学科研管理杂志

Objective Improve the ethical review models of multi-center clinical trial.Methods Analyze the ethical review models of multi-center clinical trial in China,and summarize advantages and disadvantages of the different methods.Then,clarify the development of ethical review methods of multi-center clinical trial in our hospital.Results Four methods were used to review the multi center clinical trial in China,including independent ethical review,central institutional ethical review,central review made by committee cooperation,collaborative review.Each method has its advantages and disadvantages.Collaborative review about multi-center clinical trial is adopted now in our hospital.Conclusions Using collaborative review model of multi-center clinical trial,the ethical review could achieve timely and uniformly.