Objective:The study investigated the full-time Clinical Research Coordinators (CRCs) working in hospitals on their current working situation and explored affecting factors to provide suggestions for a professional and systemic clinical research workforce establishment in municipal medical institutions.Methods:A questionnaire survey was designed for CRCs in municipal hospitals in Shanghai, descriptive and one-way cross-tabulation analysis were conducted, using t-test for continuous numerical variables, rank-sum test for count variables and chi-square test for categorical variables.Results:Totaling 177 CRCs in 9 municipal hospitals in Shanghai answered the questionnaire. The average age of the respondents was 28.56±7.299 years old. Their professional background was mainly nursing and pharmacy (139/177, 87.53%), and bachelor degree (114/177, 64.41%). Averagely worked 2.50±1.632 years, the average number of research projects undertaken by CRC was 3.45±2.179, and the average number of cumulative projects involved was 8.72±9.341. The CRCs employed by hospitals mainly undertook Investigator-Initiated clinical Trial/Research projects (IITs) (26/36, 72.22%), while the CRCs employed by SMO companies mainly undertook Industry-Sponsored Clinical Trial (IST) projects (96/141, 68.09%). 85.88% (152/117) of CRCs held GCP certificates valid within three years, and the proportion of CRCs employed by hospitals held GCP certificates was lower than that of SMO companies ( P<0.05). Among the CRCs employed by hospitals, 23 (63.89%) said they had no position or were not clear about their position; The CRCs in SMO companies were mainly primary and intermediate (χ 2=84.119, P<0.05). The average number of research projects undertaken by CRC was 3.45±2.179, and the average number of cumulative projects involved was 8.72±9.341. Conclusions:With the development of clinical research, the full-time specialized CRCs in medical institutions mainly have 2 sources: from SMO/CRO companies or self-employment by medical institutions. In general, there are still problems in the CRC talent team as unclear entry standards, insufficient, lack career positioning planning, large mobility, imperfect training system, and imperfect promotion mechanism. It is suggested to unify occupational access standards and set specialty in colleges or universities. Strengthen post-service education and training system, establish multi-party collaborative training mechanism, standardize the assessment and evaluation, improve the job title promotion system, to promote the rapid development of CRC team.

Objective:The study investigated the full-time Clinical Research Coordinators (CRCs) working in hospitals on their current working situation and explored affecting factors to provide suggestions for a professional and systemic clinical research workforce establishment in municipal medical institutions.Methods:A questionnaire survey was designed for CRCs in municipal hospitals in Shanghai, descriptive and one-way cross-tabulation analysis were conducted, using t-test for continuous numerical variables, rank-sum test for count variables and chi-square test for categorical variables.Results:Totaling 177 CRCs in 9 municipal hospitals in Shanghai answered the questionnaire. The average age of the respondents was 28.56±7.299 years old. Their professional background was mainly nursing and pharmacy (139/177, 87.53%), and bachelor degree (114/177, 64.41%). Averagely worked 2.50±1.632 years, the average number of research projects undertaken by CRC was 3.45±2.179, and the average number of cumulative projects involved was 8.72±9.341. The CRCs employed by hospitals mainly undertook Investigator-Initiated clinical Trial/Research projects (IITs) (26/36, 72.22%), while the CRCs employed by SMO companies mainly undertook Industry-Sponsored Clinical Trial (IST) projects (96/141, 68.09%). 85.88% (152/117) of CRCs held GCP certificates valid within three years, and the proportion of CRCs employed by hospitals held GCP certificates was lower than that of SMO companies ( P<0.05). Among the CRCs employed by hospitals, 23 (63.89%) said they had no position or were not clear about their position; The CRCs in SMO companies were mainly primary and intermediate (χ 2=84.119, P<0.05). The average number of research projects undertaken by CRC was 3.45±2.179, and the average number of cumulative projects involved was 8.72±9.341. Conclusions:With the development of clinical research, the full-time specialized CRCs in medical institutions mainly have 2 sources: from SMO/CRO companies or self-employment by medical institutions. In general, there are still problems in the CRC talent team as unclear entry standards, insufficient, lack career positioning planning, large mobility, imperfect training system, and imperfect promotion mechanism. It is suggested to unify occupational access standards and set specialty in colleges or universities. Strengthen post-service education and training system, establish multi-party collaborative training mechanism, standardize the assessment and evaluation, improve the job title promotion system, to promote the rapid development of CRC team.

Objective:Hypoxia is a common pathological phenomenon,usually caused by insufficient oxygen supply or inability to use oxygen effectively.Hydroxylated and methoxylated flavonoids have significant anti-hypoxia activity.This study aims to explore the synthesis,antioxidant and anti-hypoxia activities of 6-hydroxygenistein(6-OHG)and its methoxylated derivatives. Methods:The 6-OHG and its methoxylated derivatives,including 4',6,7-trimethoxy-5-hydroxyisoflavone(compound 3),4',5,6,7-tetramethoxyisoflavone(compound 4),4',6-imethoxy-5,7-dihydroxyisoflavone(compound 6),and 4'-methoxy-5,6,7-trihydroxyisoflavone(compound 7),were synthesized by methylation,bromination,methoxylation,and demethylation using biochanin A as raw material.The structure of these products were characterized by 1hydrogen-nuclear magnetic resonance spectroscopy(1H-NMR)and mass spectrometry(MS).The purity of these compounds was detected by high pressure chromatography(HPLC).The antioxidant activity in vitro was investigated by 1,1-diphenyl-2-picrylhydrazyl radical(DPPH)free radical scavenging assay.PC12 cells were divided into a normal group,a hypoxia model group,rutin(1×10-9-1×10-5 mol/L)groups,and target compounds(1×10-9-1×10-5 mol/L)groups under normal and hypoxic conditions.Cell viability was detected by cell counting kit-8(CCK-8)assay,the target compounds with excellent anti-hypoxia activity and the drug concentration at the maximum anti-hypoxia activity were screened.PC12 cells were treated with the optimal concentration of the target compound or rutin with excellent anti-hypoxia activity,and the cell morphology was observed under light microscope.The apoptotic rate was determined by flow cytometry,and the expressions of hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)were detected by Western blotting. Results:The structure of 6-OHG and its 4 methylated derivatives were correct,and the purity was all more than 97%.When the concentration was 4 mmol/L,the DPPH free radical removal rates of chemical compounds 7 and 6-OHG were 81.16%and 86.94%,respectively,which were higher than those of rutin,the positive control.The removal rates of chemical compounds 3,4,and 6 were all lower than 20%.Compared with the normal group,the cell viability of the hypoxia model group was significantly decreased(P<0.01).Compared with the hypoxia model group,compounds 3,4,and 6 had no significant effect on cell viability under hypoxic conditions.At all experimental concentrations,the cell viability of the 6-OHG group was significantly higher than that of the hypoxia model group(all P<0.05).The cell viability of compound 7 group at 1×10-7 and 1×10-6 mol/L was significantly higher than that of the hypoxia model group(both P<0.05).The anti-hypoxia activity of 6-OHG and compound 7 was excellent,and the optimal drug concentration was 1×10-6 and 1×10-7 mol/L.After PC12 cells was treated with 6-OHG(1×10-6 mol/L)and compound 7(1×10-7 mol/L),the cell damage was reduced,the apoptotic rate was significantly decreased(P<0.01),and the protein expression levels of HIF-1α and VEGF were significantly decreased in comparison with the hypoxia model group(both P<0.01). Conclusion:The optimized synthesis route can increase the yield of 6-OHG and obtain 4 derivatives by methylation and selective demethylation.6-OHG and compound 7 have excellent antioxidant and anti-hypoxia activities,which are related to the structure of the A-ring ortho-triphenol hydroxyl group in the molecule.

Flavonoids have been reported to possess significant pharmacological activities,such as antioxidant, anti-inflammatory and anticancer effects. However, the low solubility and low bioavailability limits their clinical application. Nanocrystal technology can solve the delivery problems of flavonoids by reducing particle size, increasing the solubility of insoluble drugs and improving their bioavailability. This article summaries nanosuspension preparation methods and the stabilizers for flavonoid nanocrystals, and reviews the drug delivery routes including oral, Injection and transdermal of flavonoid nanocrystals, to provide information for further research on nanocrystal delivery system of flavonoids.
Flavonoids/pharmacology* ; Pharmaceutical Preparations/chemistry* ; Biological Availability ; Nanoparticles/chemistry* ; Anti-Inflammatory Agents ; Particle Size

OBJECTIVE To explore the protective effect and possible mechanism of baicalein on hypoxia-induced cortical neuron injury in rats. METHODS The cortical neurons of rats （RN-C cells） were studied and cultured under hypoxic conditions （5%CO2， 94% N2， 1%O2） for 24 hours； the effects of different concentrations of baicalein （0.01， 0.1， 1， 10， 100 μmol/L） on the survival rate of hypoxic RN-C cells were investigated； the effects of baicalein （0.1 μmol/L） on the activities of lactate dehydrogenase （LDH） and superoxide dismutase （SOD）， the content of malondialdehyde （MDA）， migration rate， apoptotic rate， cell cycle and the expressions of cleaved caspase-3， B-cell lymphoma-2 （Bcl-2） and Bcl-2 X protein （Bax） were all detected. RESULTS Compared with control group， the survival rate of cells in the hypoxia group was significantly reduced （P＜0.01）； 0.01， 0.1 and 1 μmol/L baicalein could reverse survival rate of hypoxia-induced cortical neurons （P＜0.05 or P＜0.01）. Scratch experiments showed that baicalein significantly increased the migration rate of hypoxic RN-C cells （P＜0.01）. Compared with control group， the activity of LDH in the supernatant and the content of MDA in the cells， apoptotic rate and the proportion of cells in G1 phase， were significantly increased in the hypoxia group， while SOD activity and the proportion of cells in G2+S phase was decreased significantly （P＜0.01）. The protein expressions of cleaved caspase-3 were increased significantly， while the ratio of Bcl-2/Bax in cells was significantly reduced （P＜0.05 or P＜0.01）. Compared with hypoxia group， the above indexes were all reversed significantly in baicalein group （P＜0.01）. CONCLUSIONS Baicalein can promote the proliferation and migration of cortical neurons， improve hypoxia-induced cell apoptosis and cell cycle distribution， decrease the activity of LDH in supernatant and the level of cellular lipid peroxidation， and improve antioxidant levels. Its mechanism may be related to regulating the caspase- 3/Bax/Bcl-2 pathway.

Objective To study the possible mechanism of 7-hydroxyethyl chrysin (7-HEC) on high altitude cerebral edema (HACE). Methods A rat model of high altitude cerebral edema was established. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in rat brain tissues were measured. The expression levels of apoptosis, cell cycle and autophagy related proteins were detected by Western blotting to explore the protective effect of 7-HEC on high altitude cerebral edema and its mechanism. Results Compared with the control group, the content of MDA in the brain tissue of the hypoxia model group was significantly up-regulated; the activity of SOD was significantly down-regulated, the relative expression of CyclinD1, CyclinE1, CDK6 and CDK2, apoptotic proteins Bcl-2, PARP, and autophagy protein LC3-B were down-regulated; and the relative expression of apoptotic protein Bax and autophagy protein P62 were up-regulated; the difference was statistically significant (P<0.05); Compared with the hypoxia model group, the content of MDA was down-regulated and the activity of SOD was significantly up-regulated in the 7-HEC administration group. The relative expression of CyclinD1, CyclinE1, CDK6, CDK2, apoptotic proteins Bcl-2, PARP, autophagy protein LC3-B was up-regulated and the relative expression of apoptotic proteins Bax and the relative expression of autophagy protein P62 was down-regulated in the 7-HEC administration group. The difference was statistically significant (P<0.05). Conclusion 7-HEC has a certain protective effect on high altitude cerebral edema, and its mechanism may be related to the regulation of cell cycle, autophagy, apoptosis and oxidative stress pathways.

Objective To study the protective effect and mechanism of Saussurea involucrata flavone capsule on the myocardial tissue of mice in simulated plateau hypoxia environment. Methods 64 Balb/c mice were randomly divided into normal control group, hypoxia model group, positive control group and Xuelian flavonoid capsule group. Myocardial tissue was observed microscopically and ultra-structurally, and the changes of hypoxia-related indexes were detected. The changes in the transcription levels of hypoxia-related genes were detected by RT-PCR, and the changes in the protein expressions of hypoxia-related genes were detected by Western blotting to study the mechanism of action of Xuelian flavone capsules. Results Saussurea involucrata flavone capsule had significantly alleviated the pathological damage to the myocardium of mice caused by simulated altitude hypoxia, increased the activity of T-AOC in myocardial tissue, reduced the accumulation of LD, and also reduced the expression levels of HIF-1α and VEGF mRNA in myocardial tissue, increased the SOD, CAT mRNA and protein expression levels. Conclusion Saussurea involucrata flavone capsule have good anti-altitude hypoxia effect, which could protect myocardial tissue structure and function, regulate energy metabolism, and improve antioxidant capacity. The mechanism might be related to improving the antioxidant capacity, regulating energy metabolism, and affecting the protein expression of HIF-1α, VEGF, SOD and CAT mRNA in high altitude hypoxic mice.

Objective:To construct an index system for evaluating the development of research-oriented disciplines in medical institutions, and to provide a basis for guiding the superior disciplines towards international high-level disciplines.Methods:Through literature research and expert discussions, the basic framework of the research-oriented disciplines development evaluation system was established. The final version of the index system was determined using the Delphi method and expert interviews, and the weights of each index were established using the hierarchical analysis method.Results:After consultation, the framework of 5 first-class indexes, 16 second-class indexes, and 51 third-class indexes was finally constructed for the evaluation system of research-oriented discipline development, and the weights of indexes at different classes were calculated. The high-frequency terms " research mechanism construction" , " research team construction" and " representative research results" extracted from the expert interviews echoed the results of the weighting calculation.Conclusions:The evaluation system for research-oriented disciplines constructed in this study is relatively reasonable, scientific, reliable, and operable. The construction of the index system adapts to the characteristics of the development of research-oriented disciplines, with guiding significance for enhancing the development of research-oriented disciplines.

To investigate the active compounds from on the heart and brain of mice at simulated high altitude.Fifty healthy male adult BALB/c mice were randomly divided into normal control group, hypoxic model group, acetazolamide group, petroleum ether extract of (PESI) group and octacosan group with 10 mice in each group. Acetazolamide group, PESI group and octacosan group were treated with acetazolamide PESI (200 mg/kg) or octacosan by single tail vein injection, respectively. Except normal control group, the mice were exposed to a simulated high altitude of for in an animal decompression chamber. After the mice were sacrificed by cervical dislocation, the heart and brain were histologically observed by HE staining; superoxide dismutase (SOD) activity, total anti-oxidant capacity (T-AOC) and the content of malondialdehyde (MDA) in plasma, heart and brain tissues were detected by WST-1 method, ABTS method and TBA method, respectively; lactic acid and lactate dehydrogenase (LDH) activity in plasma, heart and brain tissues were detected by colorimetric method and microwell plate method, respectively; ATP content and ATPase activity in heart and brain tissues were detected by colorimetric method. PESI and octacosane significantly attenuated the pathological damages of heart and brain tissue at simulated high altitude; increased SOD activity, T-AOC and LDH activity, and decreased the contents of MDA and lactic acid in plasma, heart and brain tissues; increased the content of ATP in heart and brain tissues; increased the activities of Na-K ATPase, Mg ATPase, Ca ATPase and Ca-Mg ATPase in myocardial tissue; and increased the activities of Mg ATPase, Ca-Mg ATPase in brain tissue. PESI and octacosan exert anti-hypoxic activity by improving the antioxidant capacity, reducing the free radical levels, promoting the anaerobic fermentation, and alleviating the energy deficiency and metabolic disorders caused by hypoxia in mice.
Altitude ; Animals ; Brain/metabolism* ; Heart ; Male ; Malondialdehyde ; Mice ; Mice, Inbred BALB C ; Superoxide Dismutase/metabolism*

Objective:To investigate the knowledge level of hospice care and the related influencing factors among health providers in Shanghai.Methods:From November to December 2019,a questionnaire survey on the hospice care knowledge was conducted among 7 074 health providers from 223 registered hospice care clinics or institutions in 16 districts of Shanghai.Results:A total of 7 027 valid questionnaires were recovered, with an effective recovery rate of 99.3%. Among the 7 027 responders, there were 1 460 males (20.8%) and 5 567 females (79.2%) with an mean age of (36.9±9.3) years; 2 682 nurses (38.2%) and 2 442 doctors (34.8%); 5 065 (72.1%) from community health service centers; 2 982 (42.4%) involving in hospice care services and 4 039 (57.5%) willing to work in hospice care. The average score of hospice care knowledge was (8.9±2.6), and the average accuracy for questions was 59.0%. Health providers had the highest awareness rate for the composition of hospice care professional team (93.9%, 6 597/7 027) and the lowest awareness rate for the emotional commitment in hospice care service (16.6%, 1 165/7 027). Health providers with junior colleges degree ( B=-0.429), vocational college degree and below ( B=-0.544), nurses ( B=-0.652), working in suburban areas ( B=-0.278), social office ( B=-0.891), without witness of dying process of end-of-life patients ( B=-0.329), not involving in hospice care services ( B=-0.283), and not willing to participating in hospice care ( B=-0.820) had low knowledge scores ( P<0.05). Conclusions:The overall level of hospice care knowledge of health providers in Shanghai is generally at a medium level, and the training of hospice care knowledge should be strengthened for the better development of hospice care.