AIM:To investigate the protective ef-fect of midazolam(MID)on cardiac function and angiogenesis in myocardial infarction(MI)rats and its effect on c-Jun N-terminal kinase-signal trans-ducer and activator of transcription 3(JNK/STAT3)pathway.METHODS:MI rat model was established by left anterior descending coronary artery ligation method.A total of 68 rats were modeled.After ex-cluding the rats that died(n=3,mortality rate≈4.4％)or failed modeling(n=5),the 60 MI rats in-cluded in this experiment were randomly divided in-to the model group(Model group),MID low,medi-um and high dose group(1 mg/kg MID-L group,3 mg/kg MID-M group,6 mg/kg MID-H group),MID high dose+JNK activator Anisomycin group(6 mg/kg MID-H+Anisomycin group),12 rats in each group.Another 12 rats undergoing sham surgery were selected as the control group.All rats were echocardiographic and evaluated for cardiac func-tion.The myocardial tissue pathological morpholo-gy and the myocardial fibrosis degree were ob-served by hematoxylin-eosin(HE)staining and Mas-son staining.The serum myocardial injury markers[creatine kinase isoenzyme(CK-MB)and brain na-triuretic peptide(BNP)]and inflammatory factors[tumor necrosis fa ctor-α(TNF-α),interleukin-1β(IL-1β)and C-reactive protein(CRP)],myocardial tis-sue oxidative stress indicators[malondialdehyde(MDA),superoxide dismutase(SOD)and reduced glutathione(GSH)]levels were detected by enzyme-linked immunosorbent assay(ELISA).The vascular endothelial growth factor(VEGF),vascular endothe-lial growth factor receptor 2(VEGFR2),p-JNK,JNK,p-STAT3 and STAT3 proteins expression levels were detected by Protein blot method(Western blot).RE-SULTS:Compared with Control group,the myocar-dial tissue damage degree in Model group was more severe,the myocardial interstitial fibrosis de-gree was greatly deepened,the collagen volume fraction was significantly increased,the left ventric-ular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),CK-MB,BNP,CRP,TNF-α,IL-1β and MDA levels were significantly in-creased,the left ventricular ejection fraction(LVEF),left ventricular short axis shortening rate(LVFS),GSH and SOD levels were significantly de-creased,and the VEGF,VEGFR2 proteins expression levels were significantly decreased,the p-JNK/JNK and p-STAT3/STAT3 were significantly increased(P＜0.05).Compared with Model group,with the MID dose increase,the myocardial tissue damage de-gree in MID-L,MID-M and MID-H groups was signif-icantly reduced,the myocardial interstitial fibrosis degree was reduced,the collagen volume fraction was decreased,the LVESD,LVEDD,CK-MB,BNP,CRP,TNF-α,IL-1β and MDA levels were significantly decreased,the LVEF,LVFS,GSH and SOD levels were significantly increased,and the VEGF,VEGF2R protein expression levels were significantly in-creased,p-JNK/JNK and p-STAT3/STAT3 were signifi-cantly decreased(P＜0.05).Compared with MID-H group,the myocardial tissue damage degree in MID-H+Anisomycin group was more severe,the myocardial interstitial fibrosis degree was greatly deepened,the collagen volume fraction was signifi-cantly increased,the cardiac function was weak-ened,the oxidative stress and inflammation were aggravated,LVESD,LVEDD,CK-MB,BNP,CRP,TNF-α,IL-1β and MDA levels were increased,the LVEF,LVFS,GSH,SOD,VEGF and VEGFR2 proteins expres-sion levels were significantly decreased,p-JNK/JNK and p-STAT3/STAT3 were significantly increased(P＜0.05).CONCLUSION:MID may improve myocardial tissue damage in MI rats by regulating JNK/STAT3 pathway,reduce oxidative stress and inflammatory response,promote angiogenesis,so as to play a role in cardiac protection.

Objective:To investigate the effect of circular RNA (circRNA)_005987 on contrast-associated acute kidney injury (CA-AKI) and its mechanism, and provide new ideas for the prevention and treatment of CA-AKI.Methods:CA-AKI rat models and HK-2 cell injury models were established using iopromide, and CA-AKI-related circRNA_005987 was screened based on circRNA expression chip and real-time quantitative PCR (RT-qPCR). Knockdown and overexpression of circRNA_005987 were performed in HK-2 cell model, respectively. Cell counting kit-8 (CCK-8) and Edu staining assays were used to evaluate cell proliferation. Western blotting was used to detect the protein expression of autophagy-related protein microtubule-associated protein 1 light chain 3B (LC3B), P62, beclin-1 and autophagy-related gene 14 (ATG14). Immunofluorescence staining was used to detect protein expression of LC3B. Electron microscope was used to observe the autophagosome formation. Autophagy activator rapamycin and autophagy inhibitor 3-methyladenine were used for in vitro rescue experiments to observe the changes of the above indicators. Mechanistically, bioinformatics analysis was applied to analyze the binding site among circRNA_005987, miR-129-5p and ATG14, and dual luciferase reporter assay was used to verify their interactions. CircRNA_005987 was knocked down and overexpressed in HK-2 cell model, and RT-qPCR was used to detect the expression of miR-129-5p. HK-2 cells were treated with miR-129-5p inhibitor and mimic, Western blotting was used to detect the protein expression of ATG14, and CCK8 and Edu staining assays were used to evaluate cell proliferation. Results:CircRNA_005987 expression was up-regulated in vitro and vivo CA-AKI models (both P<0.05). Overexpression of circRNA_005987 inhibited cell proliferation and promoted cell autophagy, while knockdown of circRNA_005987 had opposite effects (all P<0.05). In vitro rescue experiments confirmed that circRNA_005987 inhibited cell proliferation by activating autophagy ( P<0.05). The dual luciferase reporter assay suggested that there was an interaction between circRNA_005987, miR-129-5p and ATG14. Knockdown of circRNA_005987 increased miR-129-5p expression, while overexpression of circRNA_005987 inhibited miR-129-5p expression (both P<0.05). Knockdown of miR-129-5p inhibited cell proliferation, while overexpression of miR-129-5p reversed the effect (both P<0.05). Conclusion:CircRNA_005987 promotes CA-AKI through activating autophagy via sponging miR-129-5p, suggesting that circRNA_005987 plays an important role in the pathological process of CA-AKI.

AIM:To investigate the protective ef-fect of midazolam(MID)on cardiac function and angiogenesis in myocardial infarction(MI)rats and its effect on c-Jun N-terminal kinase-signal trans-ducer and activator of transcription 3(JNK/STAT3)pathway.METHODS:MI rat model was established by left anterior descending coronary artery ligation method.A total of 68 rats were modeled.After ex-cluding the rats that died(n=3,mortality rate≈4.4％)or failed modeling(n=5),the 60 MI rats in-cluded in this experiment were randomly divided in-to the model group(Model group),MID low,medi-um and high dose group(1 mg/kg MID-L group,3 mg/kg MID-M group,6 mg/kg MID-H group),MID high dose+JNK activator Anisomycin group(6 mg/kg MID-H+Anisomycin group),12 rats in each group.Another 12 rats undergoing sham surgery were selected as the control group.All rats were echocardiographic and evaluated for cardiac func-tion.The myocardial tissue pathological morpholo-gy and the myocardial fibrosis degree were ob-served by hematoxylin-eosin(HE)staining and Mas-son staining.The serum myocardial injury markers[creatine kinase isoenzyme(CK-MB)and brain na-triuretic peptide(BNP)]and inflammatory factors[tumor necrosis fa ctor-α(TNF-α),interleukin-1β(IL-1β)and C-reactive protein(CRP)],myocardial tis-sue oxidative stress indicators[malondialdehyde(MDA),superoxide dismutase(SOD)and reduced glutathione(GSH)]levels were detected by enzyme-linked immunosorbent assay(ELISA).The vascular endothelial growth factor(VEGF),vascular endothe-lial growth factor receptor 2(VEGFR2),p-JNK,JNK,p-STAT3 and STAT3 proteins expression levels were detected by Protein blot method(Western blot).RE-SULTS:Compared with Control group,the myocar-dial tissue damage degree in Model group was more severe,the myocardial interstitial fibrosis de-gree was greatly deepened,the collagen volume fraction was significantly increased,the left ventric-ular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),CK-MB,BNP,CRP,TNF-α,IL-1β and MDA levels were significantly in-creased,the left ventricular ejection fraction(LVEF),left ventricular short axis shortening rate(LVFS),GSH and SOD levels were significantly de-creased,and the VEGF,VEGFR2 proteins expression levels were significantly decreased,the p-JNK/JNK and p-STAT3/STAT3 were significantly increased(P＜0.05).Compared with Model group,with the MID dose increase,the myocardial tissue damage de-gree in MID-L,MID-M and MID-H groups was signif-icantly reduced,the myocardial interstitial fibrosis degree was reduced,the collagen volume fraction was decreased,the LVESD,LVEDD,CK-MB,BNP,CRP,TNF-α,IL-1β and MDA levels were significantly decreased,the LVEF,LVFS,GSH and SOD levels were significantly increased,and the VEGF,VEGF2R protein expression levels were significantly in-creased,p-JNK/JNK and p-STAT3/STAT3 were signifi-cantly decreased(P＜0.05).Compared with MID-H group,the myocardial tissue damage degree in MID-H+Anisomycin group was more severe,the myocardial interstitial fibrosis degree was greatly deepened,the collagen volume fraction was signifi-cantly increased,the cardiac function was weak-ened,the oxidative stress and inflammation were aggravated,LVESD,LVEDD,CK-MB,BNP,CRP,TNF-α,IL-1β and MDA levels were increased,the LVEF,LVFS,GSH,SOD,VEGF and VEGFR2 proteins expres-sion levels were significantly decreased,p-JNK/JNK and p-STAT3/STAT3 were significantly increased(P＜0.05).CONCLUSION:MID may improve myocardial tissue damage in MI rats by regulating JNK/STAT3 pathway,reduce oxidative stress and inflammatory response,promote angiogenesis,so as to play a role in cardiac protection.

Despite that sleep disturbance and poor neurocognitive performance are common complaints among coronavirus disease 2019 (COVID-19) survivors, few studies have focused on the effect of post-COVID-19 sleep disturbance (PCSD) on cognitive function. This study aimed to identify the impact of PCSD on neurocognitive function and explore the associated risk factors for the worsening of this condition. This cross-sectional study was conducted via the web-based assessment in Chinese mainland. Neurocognitive function was evaluated by the modified online Integrated Cognitive Assessment (ICA) and the Number Ordering Test (NOT). Propensity score matching (PSM) was utilized to match the confounding factors between individuals with and without PCSD. Univariate analyses were performed to evaluate the effect of PCSD on neurocognitive function. The risk factors associated with worsened neurocognitive performance in PCSD individuals were explored using binary logistic regression. A total of 8692 individuals with COVID-19 diagnosis were selected for this study. Nearly half (48.80%) of the COVID-19 survivors reported sleep disturbance. After matching by PSM, a total of 3977 pairs (7954 individuals in total) were obtained. Univariate analyses revealed that PCSD was related to worse ICA and NOT performance (P<0.05). Underlying disease, upper respiratory infection, loss of smell or taste, severe pneumonia, and self-reported cognitive complaints were associated with worsened neurocognitive performance among PCSD individuals (P<0.05). Furthermore, aging, ethnicity (minority), and lower education level were found to be independent risk factors for worsened neurocognitive performance in PCSD individuals (P<0.05). PCSD was related to impaired neurocognitive performance. Therefore, appropriate prevention and intervention measures should be taken to minimize or prevent PCSD and eliminate its potential adverse effect on neurocognitive function.
Humans ; COVID-19/epidemiology* ; Male ; Female ; Sleep Wake Disorders/epidemiology* ; Propensity Score ; Middle Aged ; Cross-Sectional Studies ; Adult ; SARS-CoV-2 ; Aged ; Risk Factors ; China/epidemiology* ; Cognition ; Cognitive Dysfunction/etiology* ; Neuropsychological Tests

Objective:To investigate the effect of circular RNA (circRNA)_005987 on contrast-associated acute kidney injury (CA-AKI) and its mechanism, and provide new ideas for the prevention and treatment of CA-AKI.Methods:CA-AKI rat models and HK-2 cell injury models were established using iopromide, and CA-AKI-related circRNA_005987 was screened based on circRNA expression chip and real-time quantitative PCR (RT-qPCR). Knockdown and overexpression of circRNA_005987 were performed in HK-2 cell model, respectively. Cell counting kit-8 (CCK-8) and Edu staining assays were used to evaluate cell proliferation. Western blotting was used to detect the protein expression of autophagy-related protein microtubule-associated protein 1 light chain 3B (LC3B), P62, beclin-1 and autophagy-related gene 14 (ATG14). Immunofluorescence staining was used to detect protein expression of LC3B. Electron microscope was used to observe the autophagosome formation. Autophagy activator rapamycin and autophagy inhibitor 3-methyladenine were used for in vitro rescue experiments to observe the changes of the above indicators. Mechanistically, bioinformatics analysis was applied to analyze the binding site among circRNA_005987, miR-129-5p and ATG14, and dual luciferase reporter assay was used to verify their interactions. CircRNA_005987 was knocked down and overexpressed in HK-2 cell model, and RT-qPCR was used to detect the expression of miR-129-5p. HK-2 cells were treated with miR-129-5p inhibitor and mimic, Western blotting was used to detect the protein expression of ATG14, and CCK8 and Edu staining assays were used to evaluate cell proliferation. Results:CircRNA_005987 expression was up-regulated in vitro and vivo CA-AKI models (both P<0.05). Overexpression of circRNA_005987 inhibited cell proliferation and promoted cell autophagy, while knockdown of circRNA_005987 had opposite effects (all P<0.05). In vitro rescue experiments confirmed that circRNA_005987 inhibited cell proliferation by activating autophagy ( P<0.05). The dual luciferase reporter assay suggested that there was an interaction between circRNA_005987, miR-129-5p and ATG14. Knockdown of circRNA_005987 increased miR-129-5p expression, while overexpression of circRNA_005987 inhibited miR-129-5p expression (both P<0.05). Knockdown of miR-129-5p inhibited cell proliferation, while overexpression of miR-129-5p reversed the effect (both P<0.05). Conclusion:CircRNA_005987 promotes CA-AKI through activating autophagy via sponging miR-129-5p, suggesting that circRNA_005987 plays an important role in the pathological process of CA-AKI.

To analyze correlation among serum homocysteine (Hcy) ,Cysteine C (CysC) levels and severi‐ ty of coronary artery disease .Methods : A total of 220 coronary heart disease (CHD) patients treated in our hospital from Sep 2015 to Dec 2017 were selected as CHD group .According to Gensini score ,CHD group were divided into mild stenosis group (n＝ 63 ) ,moderate stenosis group (n＝ 71 ) and severe stenosis group (n＝ 86 ).Another 200 healthy people were enrolled as healthy control group .Serum Hcy and CysC levels were measured and compared a‐mong all groups .Correlation among serum Hcy , CysC levels and severity of coronary artery disease were analyzed . Results : Compared with healthy control group ,there were significant rise in serum Hcy [ (8.29 ± 1.02) μmol／L vs. (16. 14 ± 3.01) μmol／L] and CysC [ (0. 65 ± 0.11) mg／L vs.(1. 21 ± 0.12) mg／L] levels in CHD group .P＝0. 001 all.Compared with mild stenosis group ,there were significant rise in serum Hcy [(9. 31 ± 1.12) μmol／L vs.(12. 13 ± 3.32) μmol／L vs.(14.61 ± 3.82) μmol／L] and CysC [ (1.05 ± 0.21) mg／L vs.(1. 51 ± 0. 52) mg／L vs.(3.42 ± 1.01) mg／L] levels in moderate stenosis group and severe stenosis group ,and those of severe stenosis group were significantly higher than those of moderate stenosis group , P＝0.001 all.Pearson correlation analysis indicated that serum Hcy ( r＝0.431 , P＝0.004) , CysC ( r＝0.640 , P＝0. 003) levels were significant positively correlated with Gensini score .Conclusion :Serum Hcy and CysC levels is closely correlated with severity of coronary artery disease . Its detect is help for therapeutic effect and prognosis assessment for CHD patients .