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Objective:To evaluate the effect of rat cardiac fibroblasts (RCF) on the expression of connexin43 (Cx43) in H9c2 cells during hypothermic hypoxia/reoxygenation.Methods:H9c2 cells cultured in vitro were divided into 4 groups ( n=12 each) using the random number table method: control group (group C), hypothermic hypoxia/reoxygenation group (group HHR), RCF co-culture group (group Co) and RCF co-culture plus hypothermic hypoxia/reoxygenation group (group Co+ HHR). Group C was incubated at 37℃ in 5% CO 2 + 95% air for 5 h. Group HHR was incubated at 4 ℃ in 5% CO 2 + 95% N 2 for 1 h and then at 37 ℃ in 5% CO 2 + 95% air for 4 h. In group Co and group Co+ HHR, H9c2 cells 0.3×10 5 cells/well were inoculated in the lower chamber and RCF 0.6×10 5 cells/well in the the upper chamber of a transwell ? culture dish.Group Co was incubated at 37 ℃ in 5% CO 2 + 95% air for 5 h. Group Co+ HHR was incubated at 4℃ in 95% N 2 + 5% CO 2 for 1 h, and then incubated at 37 ℃ in 5% CO 2 + 95% air for 4 h. The mortality rate of H9c2 cells was measured by trypan blue staining, the expression of Cx43 and extracellular signal-regulated protein kinases 1/2 (ERK1/2) by immunofluorescence, and the expression of Cx43, phosphorylated Cx43, ERK1/2 and phosphorylated ERK1/2 by Western blot. Results:Compared with group C, the mortality rate of H9c2 cells was significantly increased, the expression and phosphorylation of Cx43 were decreased, and the expression and phosphorylation of ERK1/2 were increased in group HHR ( P<0.05), and no significant change was found in the mortality rate of H9c2 cells or expression and phosphorylation of Cx43 and ERK1/2 in group Co ( P>0.05). Compared with group Co, the mortality rate of H9c2 cells was significantly increased, and the expression and phosphorylation of Cx43 and ERK1/2 were decreased in group Co+ HHR ( P<0.05). Compared with group HHR, the mortality rate of H9c2 cells was significantly increased, and the expression and phosphorylation of Cx43 and ERK1/2 were decreased in group Co+ HHR ( P<0.05). Conclusions:RCFs can decrease the expression and activity of Cx43 in H9c2 cells during hypothermic hypoxia/reoxygenation, and the mechanism may be related to the down-regulation of ERK1/2 expression and inhibition of ERK1/2 activity.
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Objective:To analyze the overall situation and existing problems of the scientific and technological innovation capacity of hospitals in Shandong Province, propose strategies for the construction of first-class medical disciplines in hospitals, promote the transformation of medical science and technology achievements into clinical application, and provide a reference basis for building a highland of health scientific and technological innovation.Methods:Science and Technology Evaluation Metrics (STEM) data of hospitals in Shandong Province in 2020 were obtained by network research method, and the scientific and technological innovation capacity and sustainability of hospitals and disciplines were analyzed by statistical description method, assignment method, and NetDraw visualization tool.Results:The number of national top 100 hospitals and disciplines in Shandong Province ranks seventh and sixth in China, respectively. Only three hospitals in Shandong Province are among the national top 50, covering 80.6% of provincial top-ranked disciplines, while 41.6% of the national top 100 disciplines in Shandong Province are ranked after the top 50 in their respective discipline lists. The hospital scientific and technological innovation capacity of Shandong Province is at the middle-upper level with few and uneven distributions of first-class hospitals and disciplines, leading to a relatively weak overall science and technology impact.Conclusions:Given the current situation in Shandong Province, it is suggested that hospitals should take STEM as a guide to strengthen the construction of scientific research environments, vigorously develop clinical research, continuous strengthen discipline construction, and emphasize scientific innovative talent training and research integrity education, providing a science and technology strategic support for the acceleration of the medical scientific and technologic innovation and the promotion of high-level innovative province construction.
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Objective:To investigate the effect of diabetes mellitus on pulmonary uptake of sevoflurane.Methods:Twenty patients with type 2 diabetes mellitus, aged 40-64 yr, with body mass index of 18.5-22.9 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, undergoing elective surgery with general anesthesia, served as diabetes group (group D). Twenty non-diabetic patients matched by age, gender and surgery were selected as control group (group C). After anesthesia induction and tracheal intubation, sevoflurane was inhaled at a concentration of 2% (oxygen flow 2 L/min). The inhaled concentration (Fi) and exhaled concentration (Fa) at 1, 3, 5, 10, 15, 20 and 30 min of inhalation of sevoflurane were recorded, and the Fa/Fi ratio was calculated.The time required for the Fa/Fi ratio to reach 0.7 was recorded. Results:Compared with group C, the Fa/Fi ratio was significantly increased at each time point, and the time required for the Fa/Fi ratio to reach 0.7 was shortened in group D ( P<0.05). Conclusion:Diabetes mellitus can reduce pulmonary uptake of sevoflurane in the patients.
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Objective:To determine the changes in the expression of myocardial miRNA and the target genes in the rats with hypothermic ischemia-reperfusion (I/R) arrhythmia.Methods:Clean-grade healthy male Sprague-Dawley rats, aged 2-3 months, weighing 300-400 g, were anesthetized, the chest was opened, and the heart was taken to establish an isolated heart perfusion model.Six successfully perfused isolated hearts were divided into 2 groups ( n=3 each) using a random number table method: control group (group C) and heart I/R group (IR group). The model of hypothermic global I/R injury was established by interrupting perfusion for 60-min followed by 30-min reperfusion in chloral hydrate-anesthetized rats.The arrhythmia score was recorded during reperfusion.High-throughput sequencing was used to identify the differentially expressed miRNAs in two groups.The RNAhybrid and miRanda databases were used to predict the target genes of mRNA regulated by the differentially expressed miRNAs, and the enrichment for target genes was performed by Gene Ontology and KEGG databases, and the miRNAs closely related to arrhythmia and with higher expression were selected to carry out the real-time polymerase chain reaction detection. Results:The results of high-throughput sequencing showed that there were 7 differentially expressed miRNAs (novel-miR-17, novel-miR-19, novel-miR-30, novel-miR-43, rno-miR-122-5p, novel-miR-16 and rno-miR-429) in group IR as compared with group C. There were 4 miRNAs that were closely related to arrhythmia and had higher expression: the expression of novel-miR-17, novel-miR-30 and rno-miR-122-5p was significantly up-regulated, and the expression of rno-miR-429 was down-regulated in group IR when compared with group C ( P<0.05). The miRNA-mRNA correlation analysis revealed that GJA1 gene was the target of novel-miR-17. Conclusion:Myocardial novel-miR-17 is involved in the occurrence of hypothermic I/R arrhythmia probably by acting on GJA1 gene in rats.
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Objective:To evaluate the effect of electroacupuncture (EA) on electrophysiological characteristics of ventricular myocardium during myocardial ischemia-reperfusion (I/R) in rats.Methods:Twenty-four clean-grade healthy adult male Sprague-Dawley rats, weighing 280-320 g, were divided into 3 groups ( n=8 each) using a random number table method: sham operation group (group SH), I/R group and group EA.The model of myocardial I/R injury was established by ligating the left anterior descending branch of coronary artery for 30 min followed by 30-min reperfusion in anesthetized rats.Bilateral Neiguan acupoints in forelimbs were stimulated for 30 min during the period of reperfusion in group EA.Heart rate (HR), monophasic action potential amplitude (MAPA), maximum depolarization rate (V max), and monophasic action potential duration at 90% repolarization (MAPD 90) were recorded.The development of arrhythmias and arrhythmias score were recorded during reperfusion. Results:Compared with group SH, HR was significantly decreased, MAPA and V max were decreased, MAPD 90 was prolonged, and the incidence of ventricular premature beat, ventricular tachycardia and ventricular fibrillation and arrhythmias score were increased at T 1, 2 in I/R and EA groups ( P<0.05). Compared with group I/R, HR was significantly increased, MAPA and V max were increased, MAPD 90 was shortened, and the incidence of ventricular tachycardia and ventricular fibrillation and arrhythmias score were decreased at T 2 in EA group ( P<0.05). Conclusion:EA can accelerate myocardial depolarization and shorten repolarization, thus decreasing the occurrence of reperfusion arrhythmia in rats.
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Objective:To evaluate the relationship between decreased atrial myoelectric conduction and gap junction protein 40 (Cx40) and Cx43 in rats with reperfusion atrial arrhythmia.Methods:Sixteen Langendorff-isolated heart perfusion models were randomly divided into control group (group C) and ischemia-reperfusion group (group IR), with 8 rats in each group.According to whether the atrial arrhythmia occurred after reperfusion, group IR was further divided into reperfusion non-atrial arrhythmia subgroup (group R-NAA) and reperfusion atrial arrhythmia subgroup (group R-AA). Group C was balanced perfusion with K-H solution (37 ℃) for 120 min.In group IR, hearts were perfused with K-H solution (37 ℃) for 30 min, perfusion was then stopped, Thomas solution (4 ℃, 20 ml/kg) was injected to induce cardiac arrest for 60 min, the surrounding of the heart was protected with 4 ℃Thomas solution, and hearts were perfused with Thomas solution (4 ℃, 10 ml/kg) again after 30 min of cardiac arrest and then with K-H solution 37 ℃ for 30 min.At 120 min of equilibration or 30 min of reperfusion, the effective refractory period (ERP) and conduction velocity (CV) of the right atrium were measured, the expression of Cx40 and Cx43 in the right atrial myocardium was detected by Western blot, and ratio of Cx40 to Cx40+ Cx43 and the ratio of Cx43 to Cx40+ Cx43 were calculated.Results:The incidence of reperfusion atrial arrhythmia was 38% in group IR.Compared with group C, ERP was significantly prolonged, CV was decreased, the expression of Cx40 and Cx43 was down-regulated, the ratio of Cx40 to Cx40+ Cx43 was increased, and the ratio of Cx43 to Cx40+ Cx43 was decreased in R-NAA and R-AA groups ( P<0.05). Compared with group R-NAA, ERP was significantly prolonged, CV was decreased, the expression of Cx40 and Cx43 was down-regulated, the ratio of Cx40 to Cx40+ Cx43 was increased, and the ratio of Cx43 to Cx40+ Cx43 was decreased in group R-AA ( P<0.05). Conclusion:The decreased atrial myoelectric conduction may be related to the down-regulation of Cx40 and Cx43 expression in rats with reperfusion atrial arrhythmia.
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Objective:To observe the changes in the expression of microRNAs in ventricular myocardium in a rat model of hypothermic ischemia-reperfusion (I/R).Methods:Healthy clean-grade male Sprague-Dawley rats, aged 2-3 months, weighing 300-400 g, were anesthetized with intraperitoneal chloral hydrate.Their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95%O 2-5%CO 2.Sixteen Langendorff-perfused hearts were prepared and divided into 2 groups ( n=8 each) by a random number table method: control group (group C) and hypothermic I/R group (group I/R). The hearts were made globally ischemic for 60 min followed by 30-min hypothermic (4 ℃) reperfusion to establish the model of hypothermic I/R injury.The type and duration of arrhythmia and time of recovery of spontaneous heartbeats were recorded during reperfusion.The rats in group I/R were further divided into low-risk group (I/R-L group) and high-risk group (I/R-H group). The left ventricular myocardium was collected after the end of perfusion for high throughput sequencing to screen the differentially expressed microRNAs, and the reliability of the sequencing results was verified by quantitative real-time polymerase chain reaction.Gene Ontology and KEGG databases were used to analyze the biological regulatory pathways of differentially expressed target genes. Results:Compared with group C, there were 437 up-regulated microRNAs and 242 down-regulated microRNAs in group I/R-L and 419 up-regulated microRNAs and 260 down-regulated microRNAs in group I/R-H.Compared with group I/R-L, 392 microRNAs were up-regulated, and 287 microRNAs were down-regulated in group I/R-H.There were 84 microRNAs with absolute value of fold change ≥2 and significantly differential expression ( P<0.01) among the three groups.Subsequently, 4 microRNAs were randomly selected for validation using quantitative real-time polymerase chain reaction, confirming that the sequencing results were reliable.These differentially expressed target genes were involved in 11 biological processes and 6 KEGG pathways which were related to reperfusion arrhythmia.Potassium ion transmembrane transport and the adrenergic receptor signaling pathway in cardiomyocytes were enriched by the largest number of target genes. Conclusion:The expression of microRNAs in ventricular myocardium changes significantly after heart hypothermic I/R.These differentially expressed microRNAs regulate potassium ion transmembrane transport probably and mainly through the adrenergic receptor signaling pathway in the cardiomyocytes and thus are involved in the occurrence and development of hypothermic I/R arrhythmias.
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Objective To investigate the electrophysiological characteristics of myocardium after hypothermic ischemia-reperfusion (I/R) in rats with different degrees of arrhythmia using an in vitro experiment.Methods Healthy clean-grade male Sprague-Dawley rats,aged 2-3 months,weighing 300-400 g,were used in this study.The rats were sacrificed after anesthesia,and their hearts were rapidly excised.Sixteen Langendorff-perfused hearts were prepared and divided into 2 groups (n=8 each) by a random number table method:control group (group C) and hypothermic I/R group (group I/R).The hearts were made globally ischemic for 60 min followed by 30-min hypothermic (4 ℃) reperfusion to establish the model of hypothermic I/R injury.The occurrence and duration of arrhythmia and time of recovery of spontaneous heartbeat were recorded during reperfusion.The rats in group I/R were further divided into low-risk group (I/R-L group,ventricular arrhythmia score≤3 points) and high-risk group (I/R-H group,ventricular arrhythmia score＞3 points) according to the arrhythmia score.Monophasic action potential amplitude (MAPA),monophasic action potential (MAP) duration at 50％ and 90％ repolarization (MAPDs0 and MAPD90) and maximum ascending velocity (Vmax) of phase 0 in the endocardium,myocardium and epicardium of the left ventricular anterior wall were recorded at 30 min of equilibration (T0) and 15 and 30 min of reperfusion (T1,2).The effective refractory period (ERP) and ventricular fibrillation threshold (VFT) of the left ventricle were measured by programmed electrical stimulation,and the ERP/MAPD90 ratio was calculated.Results Compared with the baseline at T0,MAPA in the three layers was significantly decreased,and MAPD50 and MAPD90 were prolonged at T1,2 in I/R-L and I/R-H groups,and V in the three layers was decreased at T1,2 in I/R-H group (P＜0.05).MAPD50 and MAPD90 in the three layers were significantly shorter at T2 than at T1 in I/R-L and I/R-H groups (P＜0.05).Compared with group C,MAPDs0,MAPDg0 and ERP in the three layers were significantly prolonged at T1,2,the ERP/MAPDg0 ratio was decreased,and VFT was increased in I/R-L and I/R-H groups (P ＜ 0.05).Compared with I/R-L group,the duration of arrhythmia and MAPD90 and ERP in the three layers were significantly prolonged at T2,the ERP/MAPDg0 ratio was decreased,and VFT was increased in group I/R-H (P＜0.05).Conclusion Myocardial depolarization is inhibited,repolarization duration is prolonged,and electrophysiological stability is decreased after hypothermic I/R in the rats with arrhythmia,and the prolongation of myocardial repolarization and decrease in electrophysiological stability are more obvious in the rats at high risk of arrhythmia.
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Objective To evaluate the electrophysiological changes of atrial myocardium in a rat model of hypothermic ischemia-reperfusion (I/R).Methods Sixteen isolated Sprague-Dawley rat hearts successfully perfused in the Langendorff apparatus were divided into control group (group C) and hypothermic I/R group (group IR) using a random number table method,with 8 heats in each group.Heats in group IR were further divided into reperfusion-non-atrial arrhythmia subgroup (group R-NAA) and reperfusion-atrial arrhythmia subgroup (group R-AA) depending on whether atrial arrhythmia occurred after reperfusion.In group C,the heart was perfused with K-H solution at 37 ℃ for 120 min.In group IR,the heart was perfused with K-H solution at 37 ℃ for 30 min and then perfusion was stopped,cardiac arrest was induced for 60 min through injecting Thomas solution (4 ℃,20 ml/kg),the area around the heart was protected with low temperature (4 ℃℃) Thomas solution,and hearts were resuscitated with 4 ℃ Thomas solution (10 ml/kg) at 30 min after cardiac arrest and with 37 ℃ K-H solution for 30 min staring from 60 min after cardiac arrest.At 30 min of equilibration (T0),105 min of equilibration/15 min of reperfusion (T1),and 120 min of equilibration/30 min of reperfusion (T2),right atrial monophasic action potentials,maximal velocity of phase zero,monophasic action potential amplitude (MAPA) and MAP duration at 50％ and 90％ of repolarization (MAPDs0and MAPDg0) were measured.Right-atrium conduction velocity and effective refractory period were recorded at T2,and the ratio of ERP to MAPD90 (ERP/MAPD90) was calculated.Atrial fibrillation was induced by programmed electrical stimulation,and the maximum pacing cycle length of inducing atrial fibrillation (AF-PCLm=) was recorded.Results Compared with C and R-NAA groups,the maximal velocity of phase zero was significantly decreased and MAPDg0 was increased at T1,the right-atrium conduction velocity and ERP/MAPDg0 ratio were decreased and MAPD90,effective refractory period and AF-PCLmax were increased at T2 in group R-AA (P＜ 0.05).Conclusion The decrease in depolarization velocity,prolongation of repolarization duration and decrease in conduction velocity,excitability and electrical stability may be the electrophysiological mechanism of reperfused atrial arrhythmia in rats.
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Objective@#To evaluate the electrophysiological changes of atrial myocardium in a rat model of hypothermic ischemia-reperfusion (I/R).@*Methods@#Sixteen isolated Sprague-Dawley rat hearts successfully perfused in the Langendorff apparatus were divided into control group (group C) and hypothermic I/R group (group IR) using a random number table method, with 8 heats in each group.Heats in group IR were further divided into reperfusion-non-atrial arrhythmia subgroup (group R-NAA) and reperfusion-atrial arrhythmia subgroup (group R-AA) depending on whether atrial arrhythmia occurred after reperfusion.In group C, the heart was perfused with K-H solution at 37 ℃ for 120 min.In group IR, the heart was perfused with K-H solution at 37 ℃ for 30 min and then perfusion was stopped, cardiac arrest was induced for 60 min through injecting Thomas solution (4 ℃, 20 ml/kg), the area around the heart was protected with low temperature (4 ℃) Thomas solution, and hearts were resuscitated with 4 ℃ Thomas solution (10 ml/kg) at 30 min after cardiac arrest and with 37 ℃ K-H solution for 30 min staring from 60 min after cardiac arrest.At 30 min of equilibration (T0), 105 min of equilibration/15 min of reperfusion (T1), and 120 min of equilibration/30 min of reperfusion (T2), right atrial monophasic action potentials, maximal velocity of phase zero, monophasic action potential amplitude (MAPA) and MAP duration at 50% and 90% of repolarization (MAPD50 and MAPD90) were measured.Right-atrium conduction velocity and effective refractory period were recorded at T2, and the ratio of ERP to MAPD90 (ERP/MAPD90) was calculated.Atrial fibrillation was induced by programmed electrical stimulation, and the maximum pacing cycle length of inducing atrial fibrillation (AF-PCLmax) was recorded.@*Results@#Compared with C and R-NAA groups, the maximal velocity of phase zero was significantly decreased and MAPD90 was increased at T1, the right-atrium conduction velocity and ERP/MAPD90 ratio were decreased and MAPD90, effective refractory period and AF-PCLmax were increased at T2 in group R-AA (P<0.05).@*Conclusion@#The decrease in depolarization velocity, prolongation of repolarization duration and decrease in conduction velocity, excitability and electrical stability may be the electrophysiological mechanism of reperfused atrial arrhythmia in rats.
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Objective To understand the overall situation of scientific and technological influence in hospitals of Shandoug Province,analyze the problems and put forward countermeasures for further development.Methods Related data of the influence of science and technology of hospitals in Shandong Province in 2017 were obtained by network investigation.Visualization map of hospital-subject co-occurrence matrix was drawn by using NetDraw visualization tool.Results The scientific and technological influence of hospitals in Shandong Province is in the middle level of the whole country,forming a certain number of superior disciplines and subject clusters,most of which show that the input of science and technology is higher than the output of science and technology and the influence of disciplines.Conclusions The overall level of scientific and technological influence of hospitals in Shandong Province is not high,and the contribution of academic influence and scientific and technological output is not high,there are still some gaps with the construction requirements of national clinical medical resarch platform.It is suggested that the establishment of research-based hospitals should be taken as an opportunity to comprehensively implement various measures to enhance the scientific and technological influence,such as the combination of disciplines,performance evaluation and talent integration.
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Objective To explore the management of science and technology plan by bringing in science and technology negative listmodel,through which to determine theblacklist,further enhancing the science and technology credit of the responsible personnel.Methods Literature review and comparative analysis were adopted to investigate the experiences of negative list model in the foreign investment management,according to which identify the negative list inscience and technology planmanagement.Results Taking medical science and technology plan as an example,this paper analyzed the scientific research misconduct in thenegative list,which occurred during the implementation process,proposed particular corrective management measurements.Conclusions Bring in thenegative list mode in the management of science and technology plan,adopt tailored management plan to particular responsible personnel who do not have a good credit would significantly help more regulated and organized research conduct.
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Four collective retractions events occurred in 2015,which involved mainly the Chinese authors in medical research field,with fraud in peer review process.Medical field is to be considered as the hardest hit of research integrity,clinicians also became the focal poing.The purpose,methods and needs of Sci-tech papers published from clinicians were analyzed,precautions of research integrity anomies from promotion,institutional accountability,third party scientific institutions regulatory,and Chinese scientific journals were proposed.
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Objective To establish staff performance evaluation system of academy of medical sciences.Methods The Delphi method was employed.Results The main indicators of staff performance evaluation were selected by two-round of the Delphi method,and the evaluation system was established.Evaluation indicators covered different types of jobs of science research,medical services,disease prevention,medical education,science and technology support.Conclusions After two-round of consultation,there were more consistencies among experts regarding to selection of evaluation indicators.It will be tested and justified by further theoretical and empirical research.
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Based on link control concepts, the life cycle of science and technology projects was divided into five stages,, such as project application, selection, implementation, output and assessment.All the science misconducts that might occur among these five stages were listed.Finally, different precautions were made to prevent different misconducts during different stage..
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Objective To promote the idea and practice of truthful conduct of research among fellow researchers by creating a research integrity training mode for Chinese postgraduates.Methods Based on the RCR (Responsible Conduct of Research) training module,a common research education initiative adopted by many American research institutes,and through literature review and social science study,this paper explored the idea of develop a research integrity training mode for Chinese postgraduates.Results A thorough explanation and analysis was given to the five major aspect of research integrity training mode,including theoretical basis,training objectives,operational procedure,neces sary conditions for application and training evaluation.Conclusion Research integrity training is one of the most important contents of graduate education,and a well designed training mode is the first and foremost step of developing a responsible and credible environment in academia of China.
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Depending on the performance,Type of management of medical scientific research managers is divided into four basic management types of positive push type,upload issued type,passive type,the individual barrier type.In addition,factors of management,management performance and the quality of recruits are resolved corresponding to the management type,and have proposed the corresponding practice and management recommendations from two angles of medical research managers and the upper decision makers.
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Appraisal of scientific and technological achievements is a kind of evaluation that have played an important role in the classification and promotion of research outcome.However,problem of non-normative practice has arisen out of the appraisal process.This is because it not only assesses the research outcome but also is closely related with the interests of the researchers.Introduction of third-party evaluation into the appraisal of scientific achievements is a new attempt that has been proved effective.Key steps in the appraisal includes the final evaluation of project,construction of the pool of experts,third-party monitor and double-blind review system,and most importantly,unbinding of personal interests with the appraisal.
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Based on public information on projects of medical and health technology development program in Shandong province,this article analyses the project approvals in Shandong medicine and health technology development program from 2005 to 2009.Characteristics in terms of project category,funding amount,host institution,subject distribution,etc.are presented,so as to provide reference for the relevant policy makers.
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The paper quantitatively evaluated the output of the scientific and technological Achievements of the 110 National Nine Five Key Technology Research and Development Programs in health field,with predefined the comprehensive evaluation scale of the output of the Sci-technical achievements .The results showed that:the comprehensive output score of the sci-technical achievements in the two major fields of the cardiopulmonary cerebrovascular disease and the basic and clinical of cancer are 12.9 points and 7.99 points,whereas the output score of the remaining 8 fields are all subaverage.At the same time,five achievements' comprehensive scores are all 0.The proposals are to operate the output evaluation of the output of sci-technical achievements,and publish the relevant out-put information of the approval projects,so as to establish and implement the system of accountability.