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OBJECTIVES@#Hyperhomocysteinaemia (Hcy) is an independent risk factor for cardiovascular and cerebrovascular diseases. MicroRNA (miR)-18a-5p is closely related to cardiovascular diseases. This study aims to investigate the effects of miR-18a-5p on homocysteine (Hcy)-induced myocardial cells injury.@*METHODS@#H9c2 cells were transfected with miR-18a-5p mimic/miR-18a-5p mimic negative control (NC) or combined with Hcy for intervention, and untreated cells were set as a control group. The transfection efficiency was verified by real-time RT-PCR, and cell counting kit-8 (CCK-8) assay was used to determine cell viability. Flow cytometry was used to detect apoptosis and reactive oxygen species (ROS) levels. Western blotting was performed to measure the protein levels of microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, Beclin1, p62, Bax, Bcl-2, and Notch2. Dual luciferase reporter assay was used to detect the interaction of miR-18a-5p with Notch2.@*RESULTS@#Compared with the control, treatment with Hcy or transfection with miR-18a-5p mimic alone, or combined treatment with Hcy and miR-18a-5p mimic/miR-18a-5p mimic NC significantly reduced the H9c2 cell viability, promoted apoptosis and ROS production, up-regulated the expressions of Bax and Beclin, down-regulated the expressions of Bcl-2, p62, and Notch2, and increased the ratio of LC3-II/LC3-I (all P<0.05). Compared with the combined intervention of miR-18a-5p mimic NC and Hcy group, the above indexes were more significantly changed in the combined intervention of miR-18a-5p mimic and Hcy group, and the difference between the 2 groups was statistically significant (all P<0.05). There is a targeted binding between Notch2 and miR-18a-5p.@*CONCLUSIONS@#MiR-18a-5p could induce autophagy and apoptosis via increasing ROS production in cardiomyocytes, and aggravate Hcy-induced myocardial injury. Notch2 is a target of miR-18a-5p.
Subject(s)
Rats , Animals , Apoptosis/genetics , Autophagy/genetics , bcl-2-Associated X Protein , MicroRNAs/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Reactive Oxygen Species , Myocytes, Cardiac/drug effects , Homocysteine/adverse effects , HyperhomocysteinemiaABSTRACT
Objective:To explore the pathogenesis of primary hemophagocytic syndrome with UNC13D and MYO5A gene mutations.Methods:A case of adult hemophagocytic syndrome with gene mutation of UNC13D and MYO5A admitted to The 940th Hospital of the Joint Logistic Support Force of the PLA on January 28, 2022 was retrospectively analyzed in terms of laboratory examination, gene atlas of its close relatives and prognosis, and related literature was reviewed.Results:The patient was finally diagnosed with primary hemophagocytic syndrome, and chemotherapy was performed twice with hemophagocytic lymphohistiocytosis(HLH)-2004 regimen. The HLA matching of his cytoplasm was semi-compatible. Considering that his cytoplasm carried blood-macrophage related genes, it was not suitable to be selected as a donor, and there were no other suitable relatives. He was transferred to another hospital for allogeneic hematopoietic stem cell transplantation, but failed to receive allogeneic hematopoietic stem cell transplantation during telephone follow-up, and died.Conclusion:The gene mutation of primary hemophagocytic syndrome is the gold standard for the diagnosis of primary HLH. There may be dual gene inheritance pattern in primary HLH, and the combination of immune disorder caused by viral infection and genetic factors may lead to the pathogenesis of primary HLH.
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Objective:Analyze the ethical issues encountered or potential in the use of ChatGPT and explore its ethical norms and requirements.Methods:Based on the ethical perspective of medical scientific research, this paper analyzed the disputes existing in ChatGPT from the perspectives of morality, fairness, responsibility and supervision, and explored the reasons for the disputes from both subjective and objective aspects.Results:ChatGPT has ethical issues, fairness issues, accountability issues, and regulatory issues.Conclusions:Ethical issues in ChatGPT should be regulated from the perspectives of people-oriented, limiting monopoly, strengthening responsibility and insisting on development, to reduce potential risks and negative effects.
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Objective:To investigate any effect of repeated transcranial magnetic stimulation (rTMS) on the expression of P2X7 receptor (P2X7R) and glial fibrillary acid protein (GFAP) in the prefrontal cortex and hippocampus of mice modeling depression.Methods:Thirty C57BL/6 mice were divided into a control group ( n=10) and a depression group ( n=20). The mice of the control group were raised in group (five mice per cage), while those of the depression group were kept alone for six weeks to induce depression. Among them, 16 were successfully modeled and randomly divided into a model group ( n=8) and an rTMS group ( n=8). The rTMS group received five sessions per week of 10Hz rTMS for 4 weeks. Any changes in depression-like behavior were observed and the expression of P2X7R and GFAP in the prefrontal cortex and hippocampus was measured. Results:Compared to the control group, a significant decrease was observed in the sucrose consumption rate in the sucrose preference test, in the distance moved in the open field test and in the expression of GFAP protein. But there was a significant increase in the immobile time in the tail suspension test and in the expression of P2X7R protein in the prefrontal cortex and hippocampus in the model group. At the conclusion of the experiment the differences in the sucrose consumption rate, the distance moved, GFAP protein expression, immobile time and P2X7R protein expression between the rTMS and the model group were all statistically significant.Conclusion:rTMS can reduce depression-like behavior, at least in mice. That may be related to inhibiting P2X7R expression and promoting GFAP expression in the prefrontal cortex and hippocampus.
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Mesenchymal stem cells (MSCs) are pluripotent stem cells with self-renewing differentiation, immunoactivity and anti-inflammatory potentials.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the most effective treatment for hematologic malignancies.However, the presence of graft-versus-host disease (GVHD) after transplantation has hindered the development of allo-HSCT.MSC-derived exosomes (MSC-exo) derived from mesenchymal stem cells have been confirmed to have broad therapeutic prospects in allo-HSCT and GVHD.This review focused upon immunomodulatory effects of MSC, biological activities of MSC-exo and research advances of MSC-exo on managing GVHD, aiming to provide new therapeutic rationales for GVHD in the future.
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Objective:To build an investigator-initiated clinical research process management indicator system based on the theory of Hazard Analysis and Critical Control Point(HACCP).Methods:A plan was developed according to HACCP principles, and 23 experts were invited to form an expert advisory group. Literature research, panel discussion, and Delphi method were used to collect clinical research process management indicators, and the weight of each indicator was calculated via Analytic Hierarchy Process(AHP).Results:Two rounds of expert consultation were carried out with a high positive coefficient and a high expert authority level, and finally formed 3 primary indicators and 14 secondary indicators. The primary indicators were project establishment, project process management, and project implementation assessment, with weights of 0.142 8, 0.714 4, and 0.142 8, respectively.Conclusions:This study established a clinical research process management system based on HACCP theory from 3 dimensions: project establishment, project process management, and project implementation assessment, carried out precise management of clinical research according to the weights of secondary indicators, focusing on the content of indicators with great weight, and provided an important reference for the management of investigator-initiated clinical research.
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OBJECTIVE：To stu dy the improvement effects o f Trillium tschonos kii total sapo nins（TTM）on adjuvant-induced arthritis model rats and its mechanism. METHODS ：SD rats were randomly divided into model group （n＝44）and blank group （n＝6）. Model group was given Complete Freund ’s adjuvant to induce the adjuvant-induced arthritis model ；blank group was given constant volume of normal saline with same method. Model group were divided into model group ，Tripterygium wilfordii polyglycoside tablets group （40 mg/kg），TTM low-dose ，medium-dose and high-dose groups （50，100，200 mg/kg），with 6 rats in each group. Administration groups were given relevant medicine intragastrically ；blank group and model group were given normal saline intragastrically ，once a day ，for consecutive 9 days. After last intragastric administration ，the body weight and foot swelling degree （bilateral）were detected ，and arthritis score was performed. The contents of tumor necrosis fator α（TNF-α）， interleukin 1β（IL-1β）and IL- 6 were detected ；the pathomorphological changes of rat ankle were observed ；protein expression of NOD-like receptor protein 3 （NLRP3），apoptosis associated spot-like protein （ASC），caspase-1 were detected ；the protein expression of NLRP 3 in synovial tissue of ankle joint were also determined. RESULTS ：Compared with blank group ，foot swelling degree，serum contents of TNF-α，IL-1β and IL-6，the protein expression of NLRP 3，ASC and caspase- 1 in knee tissue as well as the protein expression of NLRP 3 in synovial tissue of ankle joint were increased significantly in model group （P＜0.05 or P＜ 0.01），while the body weight was decreased significantly （P＜0.05）. The obvious proliferation of synovial cells ，the congestion and inflammatory cell infiltration of synovial tissue were all observed. Compared with model group ，most of the above indexes were all reversed significantly in TTM groups （P＜0.05 or P＜0.01）；the pathological changes such as synovial cell proliferation ， congestion of synovial tissue and chondrocyte destruction were all relieved ，and inflammatory cell infiltration was alleviated.CONCLUSIONS：TTM can improve rheumatoid arthritis of rats， the mechanism of which may be associated with 用。E-mail：yulingling@ctgu.edu.cn inhibiting the activity of NLRP 3/caspase-1 signaling pathway and decreasing the expression of inflammatory factors TNF-α，IL-1β，IL-6.
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Objective:Through the establishment of a tertiary hospital ethics review information system, the information management of ethics review is carried out, thereby improving the quality and efficiency of ethics review.Methods:Four steps that including status quo analysis and problem identifying, corrective action plan making, outcome monitoring, as well as experience analysis were conducted, according to which a full-chain ethical review information system was developed. This system has certain characteristics such as well-featured functions, reasonable structure and user friendly, which fulfilled the expectation of the information management of review work.Results:The updated ethics review information system provides much stronger support for ethics review management and also improves its efficiency.Conclusions:The information system makes the management of ethics review more efficient, standardized and well-organised.
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Objective:To introduce the experience of international Investigator- initiated Clinical Trials (IIT), provide suggestions for the construction of IIT management system in China. Methods:Applying the literature review research methodologies to analyze the document materials, five aspects including the funding source, technical support, personnel training, management mechanism and policy assurance were analyzed.Comparison was conducted to identify possible problems existed in Chinese IIT, and further explore possible lessons that we can learn in Chinese context.Results:Identified problems of Chinese IIT include insufficient funds, unsound scientific research design, imperfect data information system, lack of standard training for researchers, as well as the urgent need for more optimized whole-process management, quality control, and policy support.Conclusions:Suggested series of measurements that including expand the funding sources, improve the construction of scientific steering committee, improve the construction of data information platform at the national level, standardize the training of researchers, and update the operation mechanism and also the regulatory requirement are proposed to enhance the IIT research quality, as well as the IIT management.
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Objective:To evaluate the Scientific Research Efficiency in A Tertiary Hospital, and provide recommendations for further improvement based on evaluation results.Methods:We evaluated the scientific research efficiency of 35 disciplines in a Tertiary Hospital from 2015 to 2017 with Slack Based Measure based Data envelopment analysis(DEA).Results:The average efficiency value from 2015 to 2017 is 0.44-0.65.The efficiency of Scientific Research from high to low was: supportive department, surgery department, internal medicine.There are 13 disciplines (37.14%) which efficiency increases gradually and 7 discipline (20%) which efficiency decreases.9 disciplines are DEA valid (efficiency=1) for at least 2 years and 9 is DEA invalid (efficiency<1) in three years.The average slack variable of researchers is 18.6 while average slack variable of input scientific research fund is 23.38 million RMB.Conclusions:The average efficiency of the tertiary hospital shows a rising trend.However, the efficiency of disciplines varies largely.For DEA invalid disciplines, it is important to improve efficiency by increasing output and improving efficiency of scientific research funding.
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Objective:To analyze the current situation of human genetic resources management in a tertiary hospital, and propose improvement suggestions for the management of human genetic resources in tertiary hospitals.Methods:According to the review of laws and regulations of human genetic resources management in China, analyze the current situation, challenges and management suggestions of human genetic resources management in this particular tertiary hospital, and further management suggestions are proposed.Results:Main problems were identified in the tertiary hospital, including the knowledge of researchers needs to be improved, and due to lack of supervision and management on process of human genetic resources projects, the management of investigator initiated clinical trials needs to be further strengthened.Conclusions:The tertiary hospital needs to strengthen the researcher training on the management of human genetic resources, establish the whole-process supervision of human genetic resources project and pay more attention to the management of investigator initiated clinical trials.
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Objective:To evaluate the scientific research efficiency and its change in a tertiary hospital, provide recommendations for improvement based on evaluation findings.Methods:We evaluated the scientific research efficiency of 35 disciplines in a tertiary hospital from 2015 to 2017 with BCC model of Data Envelopment Analysis and Malmquist index.Results:The number of DEA valid disciplines was 10, 16, 10 respectively. The average efficiency value from 2015 to 2017 of internal medicine, surgery department and supportive department was 0.62, 0.71, 0.74. The Total Factor Productivity of 2017, compared with 2015, was 1.30, which was mainly attributed to increase of Pure Technical Efficiency. There were 23 disciplines which efficiency increased and 12 disciplines which efficiency decreased.Conclusions:The scientific research efficiency of the tertiary hospital showed a rising trend. The efficiency of disciplines varied largely. For disciplines of DEA invalid or with downward trend, it is important to improve efficiency by improving management, cultivating talents, improving technology and increasing scientific output, and so on.
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Objective@#To explore the main layout and countermeasures of Scientific research projects during the public health emergency of COVID-19.@*Methods@#Literature investigation method is applied to collect information of scientific research and emergency research projects of COVID-19 funded since January 20th by different entities including national, provincial and municipal administrative departments, public health agencies, research institutes, universities and industries.@*Results@#Along with priorities identified for the emergency response and key research agendas, the national science and technology authorities at all levels and scientific research institutions have deployed a series of new science and technology projects, as well as a number of supporting policies and measures.@*Conclusions@#In the campaign of science and technology to deal with COVID-19, the leadership of Chinese government and their coordination with local agencies facilitated quick response in both R&D investment and supporting policies. Periodical achievement is recognized so far, and with the continuous development and in-depth research, the related scientific research results will be gathered into the core force of epidemic prevention. Moreover, it will improve China's capacity to deal with health emergencies and the level of medical health innovation, and better protect the health of the people.
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Objective:To build a comprehensive medical, teaching, and research discipline indicators system that is objective and easily accessible in data, and to develop a comprehensive evaluation method, at the same time provide references for discipline evaluation and orientation.Methods:Literature review was used in referring to the evaluation indicators of different ranking systems in China, Delphi method and Analytic Hierarchy Process(AHP) were applied to identify the indicators and their weight.Results:A comprehensive discipline evaluation indicator system, including 3 first-level indicators, 12 second-level indicators, and 41 third-level indicators, were constructed. The Cartesian coordinates allows for specifying the location of the medical, teaching, research level of certain discipline, and the distribution of relevant discipline groups in three-dimensional space.Conclusions:The indicators system for discipline evaluation in this study has the characteristics of refinedness, comprehensiveness, operability, and applicability, providing references for the future evaluation of disciplines.
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Objective:To explore the main layout and countermeasures of Scientific research projects during the public health emergency of COVID-19.Methods:Literature investigation method is applied to collect information of scientific research and emergency research projects of COVID-19 funded since January 20th by different entities including national, provincial and municipal administrative departments, public health agencies, research institutes, universities and industries.Results:Along with priorities identified for the emergency response and key research agendas, the national science and technology authorities at all levels and scientific research institutions have deployed a series of new science and technology projects, as well as a number of supporting policies and measures.Conclusions:In the campaign of science and technology to deal with COVID-19, the leadership of Chinese government and their coordination with local agencies facilitated quick response in both R&D investment and supporting policies. Periodical achievement is recognized so far, and with the continuous development and in-depth research, the related scientific research results will be gathered into the core force of epidemic prevention. Moreover, it will improve China's capacity to deal with health emergencies and the level of medical health innovation, and better protect the health of the people.
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Objective:Understand the status of clinical trials under primary response to major public health emergencies (COVID-19 epidemic) in tertiary hospital.Methods:The electronic questionnaire was used to collect information of clinical trials, including these have been approved by ethical committee, still in the recruiting process or in the following up of enrolled human subject. The questionnaire included basic information, measures adopted by the trials and experiences for dealing with the common problems associated conducting clinical trials during the pandemic.Results:A total of 198 questionnaires were returned, including 92 trials that have not yet recruited subjects and 106 trails that have recruited subjects. 59.15% of clinical trials that haven’t been initiated decide to postpone the starting date and 76.19% of clinical trials that haven’t recruited subjects decided to postpone subject recruitment. 36.87% of clinical trials made contingency plan or other similar documents. For those trials that have started to recruit subjects, 5.66% clinical trials prolonged follow-up time window, 61.32% of clinical trials followed up subjects and 51.89% of clinical trials provided instructions to subjects through remote technology, 51.89% of clinical trials allowed subjects to do lab tests in nearby hospitals. 38.68% clinical trials mailed drugs to subjects under guaranteed transportation conditions. For clinical trials that required subjects come to hospital to follow up, 92% of clinical trials will check whether subjects had been to high risk area and measure body temperature when follow-up. For clinical trials involving delayed follow-up, 46.97% of clinical trials would recorded and reported protocol deviation, 6.07% of clinical trials would not report or have not yet decided whether to report protocol deviation.Conclusions:Sponsors and hospitals conducting clinical trials abide by the basic principles of epidemic prevention and take corresponding measures according to local conducting, focusing on the protection of subjects. Most clinical trials comply with the Good Clinical Practice and ethical principles to ensure that clinical trial were carried out as effectively as possible.
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Objective:The study aimed to determine researchers’ awareness on research integrity and scientific misconduct in the workplace in Tertiary Hospital.Methods:The electronic questionnaire was distributed to 278 researchers in 3 Tertiary Hospitals. Information collected included the demographic characteristics, the awareness of research integrity, attitude to scientific misconduct, occurrence of misconduct among colleagues and possible intentions of misconduct behaviors.Results:Questionnaires of 217 researchers were analyzed in this paper. Less than 20% of respondents were familiar with the definition of research integrity, fabrication, falsification, and so on. Regarding attitude towards scientific misconduct, less than 50% of respondents would like to stop the behavior, report to regulatory authorities if scientific misconduct was identified. Less than 50% of respondents agreed that all the authors should be punished if the paper was involved in scientific misconduct. 49.31% of researchers admitted that their colleagues had committed at least one of the nine listed forms of scientific misconduct. 37.33% of researchers admitted that their colleagues had admitted at least one of the FFP behaviors. Inappropriate authorship was the most common issue of scientific misconduct according to the study findings. Statistical analysis showed that the cognition of research integrity was negatively correlated with scientific misconduct intention.Conclusions:Researchers’ awareness on research integrity and scientific misconduct in workplace in Tertiary hospital was worrisome. A multi-faceted approach towards the issue will be required.
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Objective:To build a scientifically applicable scientific research evaluation system based on the Science and Technology Evaluation Metrics (STEM) of Chinese hospitals.Methods:Twenty-four experts were invited to form an expert advisory group, scientific research evaluation indicators were collected according to literature review, panel discussion and expert consultation. Use Delphi method to carry out two rounds of expert consultation, calculate the authority level and positive factor of experts, and use AHP to calculate the weight of each indicator.Results:The experts invited for consultation had a high positive coefficient and a high degree of expert authority, and finally, a scientific research evaluation index system including 3 first-level indicators, 10 second-level indicators and 24 third-level indicators was established.Conclusions:The research based on STEM has developed an evaluation system well combined quantity and quality from three dimensions, including scientific research input, scientific research output and scientific research influence. Taking into full consideration of the regulatory requirement of clinical trials and the research administration of research achievements transformation, this research established an evaluation system and management model applicable to the Tertiary class A general hospitals, provided reference value for the development of the hospital's scientific research.
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Objective:Understand the perceptions of research integrity and their attitudes to related integrity violations among newly recruited researchers in a tertiary hospital.Methods:The electronic questionnaire was distributed to a WeChat group of 123 newly recruited researchers in a tertiary hospital in 2018. The questionnaire included the demographic characteristics, the awareness of research integrity and attitude towards behaviors that violate research integrity.Results:The total number of respondents was 87 and 45.98% respondents received research integrity training. Less than 50% of respondents were familiar with the regulatory requirement of research integrity, the definition of research integrity, fabrication, falsification, plagiarism and other common problems violating research integrity. Regarding attitude towards scientific misconduct, most investigators (82.76%~90.8%) thought it incorrect. 64.37% of investigators would like to report to regulatory authorities if they found scientific misconduct. If the researchers strongly violated research integrity, 80.46%~81.61% of respondents voted for suspending his or her promotion, suspending his or her application for being a mentor and 58.62% of respondents voted for being banned for conducting any research forever. Receiving education of research integrity is an independent influence factor of awareness of fabrication, falsification and plagiarism (FFP).Conclusions:The proportion of newly recruited researchers receiving research integrity training in tertiary hospital is not big and most researchers don't know much about research integrity. Their attitudes to academic misconduct need to be further strengthened. Various measures are urgently needed to carry out to improve the integrity awareness and attitude of newly recruited researchers in tertiary hospitals.
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The cyanobacterial circadian clock has three relatively independent parts: the input path, the core oscillator, and the output path. The core oscillator is composed of three clock proteins: KaiA, KaiB, and KaiC. The interactions among these three proteins generate a rhythmic signal and convey the input signals to the output signals to maintain the accuracy and stability of the oscillation of downstream signals. Based on the cyanobacterial circadian clock and the structure, function, and interaction of the clock proteins of the core oscillator, combining the recent results from our laboratory, this review summarized the recent progresses of the molecular mechanism of KaiA in regulating KaiC's enzymatic activity, mediating phase reset of the oscillator, and competing with CikA for the binding site of KaiB.