Malaria, a parasitic disease caused by infection with the species of Plasmodium and transmitted by Anopheles mosquito bites, is one of the major public health challenges that seriously threaten human health. Malaria parasites present diverse immune escape strategies to escape from the recognition and clearance of the host immune system, which poses a great challenge to the malaria control programme. This review presents the advances in the mechanisms underlying the immune escape of Plasmodium, including antigenic variation, epigenetic regulation, antagonism against IgM antibody, activation of the cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling, suppression of splenic immune functions, and molecular camouflage, so as to provide insights into development of malaria vaccines and antimalarial agents and formulation of the malaria control strategy.

As a new strategy for the application of sacubitril/valsartan (LCZ696) in patients with CKD, much evidence showed that it improved the prognosis of patients with CKD. This review summarizes the efficacy and safety of sacubitril/valsartan in physiology, pathology, pharmacology and clinical application by searching Wanfang, CNKI, PubMed and other databases for related articles on the application of sacubitril/valsartan in CKD patients. Although LBQ657, the active product of sacubitril, has a high drug accumulation in patients with moderate, severe renal injury, and ESRD, it is not cleared in hemodialysis, and has very little eliminated in peritoneal dialysis, which does not affect its safety. Compared with angiotensin converting enzyme inhibitor and angiotensin receptor blocker drugs, LCZ696 could increase the blood pressure control rate, improve cardiac function, slow down the decline of glomerular filtration rate, and significantly improve cardiovascular outcomes without more adverse events. Sacubitril/valsartan can be used in all levels of CKD patients complicated with hypertension and/or heart failure, with reliable safety and tolerance.

Objective:To explore the method of selecting the supporting institutions of the national clinical medical research center by using the third-party evaluation data.Methods:Select disease fields/clinical specialties as research objects based on the criteria of having at least 5 national clinical research centers established in the field of major diseases and at least 3 established in the field of non major diseases. Collected data on the ranking of scientific and technological evaluation metrics in Chinese hospitals from the official website of the Institute of Medical Information, Chinese Academy of Medical Sciences, and collected standardized research value ranking data on the reputation ranking of Chinese hospitals and specialties from the official website of Fudan University. Based on the correspondence between the disease field/clinical specialty and the disciplines and specialties in the two major rankings, the top 5 and top 10 hospitals in the corresponding disease fields/clinical specialties in the two ranking lists were selected respectively, and the comprehensive scores of the included hospitals were calculated using the grade scoring method and ranked accordingly. Then, determine the number of hospitals to be selected based on the criteria of fully covering the recognized national clinical medical research centers supporting institutions.Results:The study focused on six disease fields/clinical specialties, including chronic kidney disease, obstetrics and gynecology, digestive system diseases, oral diseases, hematological diseases, and eye, ear, nose, and throat diseases. In the hospital ranking list formed by the top 5 hospitals included in the two rankings, a maximum of 11 hospitals needed to be included to fully cover the recognized supporting institutions, while in the hospital ranking list formed by the top 10 hospitals included in the rankings, a maximum of 6 hospitals needed to be included to achieve full coverage. Therefore, the optimal selection method was to include the top 10 hospitals in the two rankings and calculate their comprehensive scores, and select the top 6 hospitals based on their comprehensive scores.Conclusions:The selection method based on the third-party evaluation data is scientific and reliable, and can provide reference for the evaluation work of the management department of the national clinical medical research center.

Objective To explore the molecular mechanism of prolonged atrial repolarization in rats with reperfusion atrial arrhythmia.Methods Sixteen Langendorff isolated heart perfusion models made by male SD rats were randomly divided into control group(group C,n = 8)and hypothermic ischemia-reperfusion group(group IR,n = 8).According to the occurrence of atrial arrhythmia after reperfusion,group IR was further subdivided into reperfusion non-atrial arrhythmia subgroup(group N-RAA)and reperfusion atrial arrhythmia subgroup(group R-AA).Group C was perfused with 37℃K-H solution for 120 min.In group IR,the isolated heart was perfused with 37℃K-H solution for 30 min and stopped,and the isolated heart was perfused with 4℃Thomas solution(20 mL/kg)for 60 mins.When the heart stopped for 30 mins,the isolated heart was perfused with a half dose of 4℃Thomas solution(10℃).During cardioplegia,the isolated heart was protected by low temperature Thomas solution(4℃),and then reperfused for 30 mins with 37℃K-H solution.The monophasic action potential(MAP)of the right atrium was recorded at balanced perfusion for 30 mins(T0),balanced perfusion for 105 mins in group C/reperfusion for 15 mins in group IR(T1)and balanced perfusion for 120 mins in group C/reperfusion for 30 min in group IR(T2);The duration of 50%and 90%repolarization of monophasic action potential(MAPD50 and MAPD90)was measured.After electrophysiological monitoring,the expression of Kir2.1 and CaMKⅡ in right atrium was detected by Western blot.Results Compared with T0,MAPD50 and MAPD90 at T1 and T2 were significantly prolonged in group R-AA(P<0.05),and MAPD90 at T1 and T2 in group R-NAA and group R-AA were significantly longer than those in group C(P<0.05).Compared with group R-NAA,MAPD50 and MAPD90 in group R-AA were significantly prolonged at T1 and T2(P<0.05).The results of Western blot showed that the expression of Kir2.1 in group R-NAA and group R-AA was significantly lower than that in group C(P<0.05),and that in group R-AA was significantly lower than that in group R-NAA(P<0.05).The expression of CaMKⅡ in group R-NAA and group R-AA was significantly higher than that in group C(P<0.05),and the expression of CaMKⅡ in group R-AA was significantly higher than that in group R-NAA.Conclusion The prolonged duration of atrial repolarization in rats with hypothermic ischemia-reperfusion atrial arrhythmia may be related to the down-regulation of Kir2.1 expression and the up-regulation of CaMKⅡ expression.

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.

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.

Objective:To provide references for cardiovascular health management of military pilots by investigating the risk of ischemic cardiovascular diseases (ICVD) in military pilots.Methods:The physical examination data of military pilots in Air Force Healthcare Center for Special Services Hangzhou were retrospectively analyzed. The military pilots were divided into 2 groups by age (22-34 years, 35-56 years), and they were divided into 5 groups by flying hours (≤500 h, 500-≤1 000 h, 1 000-≤2 000 h, 2 000-≤3 000 h, >3 000 h). The 10-year ICVD incidence risk of pilots was evaluated according to the 10-year ICVD incidence risk assessment table of Chinese people. The distribution and influencing factors of absolute risk and relative risk of ICVD incidence in military pilots were analyzed, and the risk factors between different age groups were compared.Results:①A total of 337 military pilots were included, 194 in the 22-34 years group and 143 in the 35-56 years group. ②Absolute risk detection: there were 336 very low-risk military pilots and a low-risk military pilot. Relative risk detection: 87 (25.82%) military pilots were relatively high risk including 41 (21.13%) cases in 22-34 years group, 46 (32.17%) cases in 35-56 years group, the difference between 2 groups was statistically significant ( χ2=5.23, P=0.022); there were 250 (74.18%) relatively low-risk military pilots. ③Among the pilots aged 22-34 years, there was significant difference in relative high-risk ratio between flying hours ( χ2=17.00, P<0.001). The relative high-risk ratio of the pilots with flying hours 500-≤1 000 h was higher than that of pilots with flying hours ≤500 h, and the difference was statistically significant ( P<0.05); the proportion of pilots with elevated triglyceride and low density lipoprotein cholesterol indexes was higher than that of those with normal indicators (all P<0.05). The relative high-risk ratio of pilots with hypertension in 35-56 years group was higher than that of those with normal blood pressure ( χ2=23.70, P<0.001); the proportion of pilots with elevated triglyceride indicators was higher than that of high-risk groups ( P<0.05). ④The smoking rate, BMI and total cholesterol abnormality rate were higher in the 35-56 years group than in the 22-34 years group, and the differences were statistically significant ( χ2=9.71, 29.72, 19.17, P=0.002, <0.001,<0.001). ⑤The aggregation analysis of the risk factors of smoking, BMI, total cholesterol, systolic blood pressure and diabetes showed that the number of risk factor aggregates ≥2 species accounted for 51.04%, and the aggregation of risk factors in different age groups was statistically significant ( Z=6.38, P<0.001). Conclusions:The relative risk of ICVD in pilots is high, and the aggregation of risk factors is serious. Simply improving a single index is hardly to meet the demand of risk reduction. It needs a variety of joint interventions to improve the lifestyle and reduce the abnormal rate of total cholesterol, overweight rate, systolic blood pressure level and smoking rate. It is suggested that ICVD incidence risk prediction score should be routinely used in the risk assessment of chronic diseases in aviation medicine.

Objective:To provide references for cardiovascular health management of military pilots by investigating the risk of ischemic cardiovascular diseases (ICVD) in military pilots.Methods:The physical examination data of military pilots in Air Force Healthcare Center for Special Services Hangzhou were retrospectively analyzed. The military pilots were divided into 2 groups by age (22-34 years, 35-56 years), and they were divided into 5 groups by flying hours (≤500 h, 500-≤1 000 h, 1 000-≤2 000 h, 2 000-≤3 000 h, >3 000 h). The 10-year ICVD incidence risk of pilots was evaluated according to the 10-year ICVD incidence risk assessment table of Chinese people. The distribution and influencing factors of absolute risk and relative risk of ICVD incidence in military pilots were analyzed, and the risk factors between different age groups were compared.Results:①A total of 337 military pilots were included, 194 in the 22-34 years group and 143 in the 35-56 years group. ②Absolute risk detection: there were 336 very low-risk military pilots and a low-risk military pilot. Relative risk detection: 87 (25.82%) military pilots were relatively high risk including 41 (21.13%) cases in 22-34 years group, 46 (32.17%) cases in 35-56 years group, the difference between 2 groups was statistically significant ( χ2=5.23, P=0.022); there were 250 (74.18%) relatively low-risk military pilots. ③Among the pilots aged 22-34 years, there was significant difference in relative high-risk ratio between flying hours ( χ2=17.00, P<0.001). The relative high-risk ratio of the pilots with flying hours 500-≤1 000 h was higher than that of pilots with flying hours ≤500 h, and the difference was statistically significant ( P<0.05); the proportion of pilots with elevated triglyceride and low density lipoprotein cholesterol indexes was higher than that of those with normal indicators (all P<0.05). The relative high-risk ratio of pilots with hypertension in 35-56 years group was higher than that of those with normal blood pressure ( χ2=23.70, P<0.001); the proportion of pilots with elevated triglyceride indicators was higher than that of high-risk groups ( P<0.05). ④The smoking rate, BMI and total cholesterol abnormality rate were higher in the 35-56 years group than in the 22-34 years group, and the differences were statistically significant ( χ2=9.71, 29.72, 19.17, P=0.002, <0.001,<0.001). ⑤The aggregation analysis of the risk factors of smoking, BMI, total cholesterol, systolic blood pressure and diabetes showed that the number of risk factor aggregates ≥2 species accounted for 51.04%, and the aggregation of risk factors in different age groups was statistically significant ( Z=6.38, P<0.001). Conclusions:The relative risk of ICVD in pilots is high, and the aggregation of risk factors is serious. Simply improving a single index is hardly to meet the demand of risk reduction. It needs a variety of joint interventions to improve the lifestyle and reduce the abnormal rate of total cholesterol, overweight rate, systolic blood pressure level and smoking rate. It is suggested that ICVD incidence risk prediction score should be routinely used in the risk assessment of chronic diseases in aviation medicine.

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.

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.