Objective To investigate the effect of miR-486-5P on ferroptosis in H9c2 cardiomyocytes after hypoxia/reoxygenation(H/R),and to analyze its mechanism.Methods Using H9c2 cardiomyocytes as the research object,a H/R injury model was established using cobalt chloride(CoCl2)and fresh culture medium.The cells were divided into control group,H/R group,H/R+miR-486-5P mimic NC group,H/R+miR-486-5P mimic group,H/R+miR-486-5P inhibitor NC group and H/R+miR-486-5P inhibitor group.The relative expression level of miR-486-5P was detected by quantitative reverse transcription-polymerase chain reaction(qRT-PCR).The cell viability was detected by CCK-8 method.The activities or levels of lactate dehydrogen-ase(LDH),glutathione(GSH),Fe2+and malondialdehyde(MDA)were detected by colorimetric method.The levels of reactive oxygen species(ROS)and mitochondrial membrane potential(MMP)were detected by DCFH-DA fluorescent probe and JC-1 assay,respectively.Western blot was used to detect the levels of AkT/mTOR signaling pathway proteins and ferroptosis related protein solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4)and acyl-coa synthetase long chain family member 4(ACSL4).Results Compared with the control group,the level of miR-486-5P and cell viability in the H/R group de-creased significantly(P＜0.05),while LDH activity,MDA,Fe2+level,ROS level and ACSL4 protein level in-creased significantly(P＜0.05).The GSH,MMP,SLC7A11 and GPX4 levels and p-Akt/Akt and p-mTOR/mTOR ratios were significantly decreased(P＜0.05).After H/R treatment,compared with the H/R+miR-486-5P mimic NC group,the cell viability of the H/R+miR-486-5P mimic group was significantly increased(P＜0.05).The LDH activity,MDA,Fe2+level,ROS level and ACSL4 protein level were significantly de-creased(P＜0.05),while GSH,MMP,SLC7A11 and GPX4 levels and p-Akt/Akt and p-mTOR/mTOR ratios were significantly increased(P＜0.05).Compared with the H/R+miR-486-5P inhibitor NC group,the trend of the above indicators in the H/R+miR-486-5P inhibitor group was opposite.Conclusion miR-486-5P allevi-ates hypoxia/reoxygenation-induced ferroptosis in H9c2 cells by regulating Akt/mTOR signaling pathway,and thus alleviates hypoxia/reoxygenation induced cardiomyocyte injury.

Introduction::The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel biomarker for metabolic syndrome (MetS), has been validated in the general population as being significantly correlated with cardiovascular disease (CVD) risk. However, its capabilities to predict CVD in people living with human immunodeficiency virus (HIV; PLWH) remain underexplored.Methods::We conducted a retrospective cohort study of 16,081 PLWH who initiated antiretroviral therapy (ART) at the Third People’s Hospital of Shenzhen (China) from 2005 to 2022. The baseline TG/HDL-C ratio was calculated as TG (mmol/L) divided by HDL-C (mmol/L). We employed a multivariate Cox proportional hazards model to assess the association between the TG/HDL-C ratio and CVD occurrence, using Kaplan-Meier curves and log-rank tests to compare survival distributions. The increase in prediction risk upon the addition of the biomarker to the conventional risk model was examined through the assessment of changes in net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Nonlinear relationships were investigated using a restricted cubic spline plot, complemented by a two-piecewise Cox proportional hazards model to analyze threshold effects.Results::At the median follow-up of 70 months, 213 PLWH developed CVD. Kaplan-Meier curves demonstrated a significant association between the increased risk of CVD and a higher TG/HDL-C ratio (log-rank P <0.001). The multivariate-adjusted Cox proportional hazards regression model indicated that the CVD hazard ratios (HR) (95% confidence intervals [95% CIs]) for Q2, Q3, and Q4 versus Q1 of the TG/HDL-C ratio were 2.07 (1.24, 3.45), 2.17 (1.32, 3.57), and 2.20 (1.35, 3.58), respectively ( P <0.05). The consideration of the TG/HDL-C ratio in the model, which included all significant factors for CVD incidence, improved the predictive risk, as indicated by the reclassification metrics (NRI 16.43%, 95% CI 3.35%-29.52%, P = 0.014). The restriction cubic spline plot demonstrated an upward trend between the TG/HDL-C ratio and the CVD occurrence ( P for nonlinear association = 0.027, P for overall significance = 0.009), with the threshold at 1.013. Significantly positive correlations between the TG/HDL-C ratio and CVD were observed below the TG/HDL-C ratio threshold with HR 5.88 (95% CI 1.58-21.88, P = 0.008), but not above the threshold with HR 1.01 (95% CI 0.88-1.15, P = 0.880). Conclusion::Our study confirms the effectiveness of the TG/HDL-C ratio as a predictor of CVD risk in PLWH, which demonstrates a significant nonlinear association. These findings indicate the potential of the TG/HDL-C ratio in facilitating early prevention and treatment strategies for CVD among PLWH.

Objective To investigate the protective effect of insulin-like growth factor-1(IGF-1)precondi-tioning on hypoxic injury in H9c2 rat cardiomyocytes and its mechanism.Methods H9c2 cells were randomly divided into four groups,control group,hypoxia group(CoCl2 group),hypoxia+IGF-1 pretreatment group(CoCl2+IGF-1 group),hypoxia+IGF-1 pretreatment+phosphatidylinositol 3 kinase(PI3K)/protein kinase B(Akt)pathway specific inhibitor LY294002 group(CoCl2+IGF-1+LY294002 group).CCK8 assay was used to detect the survival rate of H9c2 cells,and Tunel assay was used to detect the apoptosis of H9c2 cells,DCFH-DA probe method was used to detect the reactive oxygen species(ROS)level of H9c2 cells in each group.The activities of superoxide dismutase(SOD)and lactate dehydrogenase(LDH)in culture supernatant were detected by kit.The levels of glutathione peroxidase(GSH-Px)and malondialdehyde(MDA)in culture supernatant were detected by enzyme-linked immunosorbent assay(ELISA).Western blot was used to detect the expression of pro-apoptotic protein B cell lymphoma 2 associated X protein(Bax),Caspase-3,anti-apoptot-ic protein Bcl-2,pathway proteins Akt and phosphorylated Akt(p-Akt)in H9c2 cells.Results IGF-1 could increase cell viability(P＜0.05),reduced cell apoptosis rate(P＜0.05),reduced ROS level(P＜0.05),re-duced MDA production(P＜0.05),reduced LDH activity(P＜0.05),and increased SOD and GSH-Px activi-ties(P＜0.05).It also promoted the expression of p-Akt(P＜0.05),reduced the expression of pro-apoptotic proteins Bax and Caspase-3(P＜0.05),and increased the expression of anti-apoptotic protein Bcl-2(P＜0.05).After the addition of PI3K pathway specific inhibitor LY294002,the protective effect of IGF-1 on hy-poxic H9c2 cells disappeared.Conclusion IGF-1 protects cardiomyocytes from hypoxia injury by inhibiting oxidative stress and apoptosis of cardiomyocytes through activating PI3K/Akt pathway and improving the survival rate of cardiomyocytes.

Objective:This study aimed to explore whether there are abnormalities in the kynurenine pathway in patients with depression and suicidal ideation, and their dynamic relationship with clinical symptoms.Methods:According to the DSM-5 diagnostic criteria, a total of 68 patients with depression were prospectively enrolled, including 28 males and 40 females, aged( M ( Q1, Q3)) 22.0 (17.3, 47.8) years, who were the inpatients in the Division of Mood Disorders of Shanghai Mental Health Center from July 2019 to July 2022. The depressed patients were divided into groups with ( n=41) or without suicidal ideation ( n=27) based on whether they chose "weak" or "moderate to strong" suicidal ideation in questions 4 and 5 of the Beck Scale for Suicide Ideation (BSI). And 72 gender-matched healthy controls were also enrolled, including 29 males and 43 females, aged 25.5 (24.0, 36.8) years. Hamilton Depression Rating Scale-24 (HAMD 24), Hamilton Anxiety Rating Scale (HAMA), and BSI were used to evaluate the depression symptoms, anxiety symptoms, and suicidal ideation of depressed patients. All the participants received fasting venous blood collection to measure the levels of kynurenine metabolites in plasma. Among them, depressed patients with suicidal ideation were followed up, and the assessment s of depression symptoms, anxiety symptoms, and suicidal ideation, as well as kynurenine metabolites measurements, were repeated at the end of the 2nd and 4th weeks. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry was used to measure the levels of kynurenine metabolites in plasma. The hematological indicators were log-transformed, Z-score standardized, and false discovery rate correction was used for multiple comparisons of different metabolites. The relationship between baseline kynurenine metabolites and scale scores was analyzed. The relationship between kynurenine metabolites and scale scores during the follow-up process was analyzed by a linear mixed-effects model. Results:The peripheral picolinic acid (0.39±0.87 vs -0.23±1.09, t=3.89), 3-hydroxykynurenine/kynurenine (3-HK/KYN) (0.38±0.85 vs -0.09±1.01, t=2.98) and 3-HK (0.31±0.81 vs 0.14±1.04, t=2.78) of patients with depression were lower than those of healthy controls (both P<0.05). No statistically significant difference was found between patients with depression with or without suicidal ideation in kynurenine metabolites. In patients with depression and suicidal ideation, baseline HAMD 24 and HAMA scores were positively correlated with plasma 3-HK (HAMD 24: r=0.38; HAMA: r=0.39) and 3-HK/KYN (HAMD 24: r=0.34; HAMA: r=0.37) levels (all P<0.05). After adjusting for age and gender factors, a linear mixed-effects model was established for the follow-up scale scores, and kynurenine metabolite levels of this group of patients, and the results showed that the positive effect of HAMA score on 3-HK/KYN during follow-up was statistically significant ( B=0.04, t=2.46, P<0.05). Conclusion:There are abnormalities in the kynurenine pathway of tryptophan metabolism in patients with depression. 3-HK and 3-HK/KYN are related to the severity of depression and anxiety in patients with depression and suicidal ideation, among which 3-HK/KYN, representing the activity of kynurenine-3-monooxygenase, is dynamically associated with anxiety level.

Objective:This study aimed to explore whether there are abnormalities in the kynurenine pathway in patients with depression and suicidal ideation, and their dynamic relationship with clinical symptoms.Methods:According to the DSM-5 diagnostic criteria, a total of 68 patients with depression were prospectively enrolled, including 28 males and 40 females, aged( M ( Q1, Q3)) 22.0 (17.3, 47.8) years, who were the inpatients in the Division of Mood Disorders of Shanghai Mental Health Center from July 2019 to July 2022. The depressed patients were divided into groups with ( n=41) or without suicidal ideation ( n=27) based on whether they chose "weak" or "moderate to strong" suicidal ideation in questions 4 and 5 of the Beck Scale for Suicide Ideation (BSI). And 72 gender-matched healthy controls were also enrolled, including 29 males and 43 females, aged 25.5 (24.0, 36.8) years. Hamilton Depression Rating Scale-24 (HAMD 24), Hamilton Anxiety Rating Scale (HAMA), and BSI were used to evaluate the depression symptoms, anxiety symptoms, and suicidal ideation of depressed patients. All the participants received fasting venous blood collection to measure the levels of kynurenine metabolites in plasma. Among them, depressed patients with suicidal ideation were followed up, and the assessment s of depression symptoms, anxiety symptoms, and suicidal ideation, as well as kynurenine metabolites measurements, were repeated at the end of the 2nd and 4th weeks. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry was used to measure the levels of kynurenine metabolites in plasma. The hematological indicators were log-transformed, Z-score standardized, and false discovery rate correction was used for multiple comparisons of different metabolites. The relationship between baseline kynurenine metabolites and scale scores was analyzed. The relationship between kynurenine metabolites and scale scores during the follow-up process was analyzed by a linear mixed-effects model. Results:The peripheral picolinic acid (0.39±0.87 vs -0.23±1.09, t=3.89), 3-hydroxykynurenine/kynurenine (3-HK/KYN) (0.38±0.85 vs -0.09±1.01, t=2.98) and 3-HK (0.31±0.81 vs 0.14±1.04, t=2.78) of patients with depression were lower than those of healthy controls (both P<0.05). No statistically significant difference was found between patients with depression with or without suicidal ideation in kynurenine metabolites. In patients with depression and suicidal ideation, baseline HAMD 24 and HAMA scores were positively correlated with plasma 3-HK (HAMD 24: r=0.38; HAMA: r=0.39) and 3-HK/KYN (HAMD 24: r=0.34; HAMA: r=0.37) levels (all P<0.05). After adjusting for age and gender factors, a linear mixed-effects model was established for the follow-up scale scores, and kynurenine metabolite levels of this group of patients, and the results showed that the positive effect of HAMA score on 3-HK/KYN during follow-up was statistically significant ( B=0.04, t=2.46, P<0.05). Conclusion:There are abnormalities in the kynurenine pathway of tryptophan metabolism in patients with depression. 3-HK and 3-HK/KYN are related to the severity of depression and anxiety in patients with depression and suicidal ideation, among which 3-HK/KYN, representing the activity of kynurenine-3-monooxygenase, is dynamically associated with anxiety level.

Objective:To construct a value evaluation framework for high-value medical consumables,providing a guidance for medical insurance access and hospital access management scenarios in China.Methods:It conducted literature review,qualitative in-terviews and quantitative surveys.A total of 12 experts were invited for qualitative interviews,while 100 experts from four fields of health technology assessment,medical insurance,hospital management,and clinical practice participated in the quantitative survey.Through those process,it generated the composition of the value framework and the scoring of each item.Differences in ratings be-tween different scenarios and experts were analyzed through chi-square tests.The recommendation level for each item was graded.Re-sults:A comprehensive value evaluation framework for high-value medical consumables was established,which included 6 core dimen-sions,comprised 16 items for secondary dimensions and 50 items for tertiary dimensions.It showed significant differences between the medical insurance access and hospital access scenarios,as well as among different fields of experts in the same scenario.furthermore,grading the items in two scenarios.The medical insurance access scenario had 8 highly recommended items,and the hospital access scenario had 24 highly recommended items.Conclusion:Value evaluation should encourage multi-dimensional assessments and inter-disciplinary participation,continually improving the management of high-value medical consumables in medical insurance and hospital access.

Objective:To systematically review the severe risk in common chronic diseases and coronavirus disease 2019 (COVID-19) cases.Methods:PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, China Biology Medicine disc, medRxiv, SSRN and ChinaXiv were searched for clinical and epidemiological studies that reported chronic diseases in patients with COVID-19. Only studies of severe COVID-19 in comparison with non-severe controls were included. The prevalence rates of chronic diseases including chronic obstructive pulmonary disease (COPD), diabetes mellitus, hypertension, malignant tumor, cardiovascular diseases, cerebrovascular disease, chronic kidney disease, and chronic liver disease were estimated. Pooled odds ratio ( OR) with 95% confidence interval ( CI) between patients with severe COVID-19 and non-severe groups were calculated. R 3.6.3 software was used for meta-analysis. Results:The search yielded 2 455 articles. A total of 19 eligible comparative studies with 4 792 patients were included in a quantitative analysis. Meta-analysis showed that there was a proportion of 55.0% (95% CI 40.0%-80.0%) male among patients with COVID-19, and the overall pooled prevalence of any chronic diseases in COVID-19 cases was 30.4% (95% CI 24.0%-37.0%). The most prevalent comorbidity was hypertension (16.9%(95% CI 14.0%-20.0%)), followed by diabetes mellitus (8.3%(95% CI 8.0%-9.0%)). The proportion of male patients with severe COVID-19 was higher than that of male patients with non-severe COVID-19 (64.4% vs 52.8%, OR=1.49, 95% CI 1.08-2.05, Z=4.63, P<0.01). The prevalence rates of COPD, cerebrovascular disease, diabetes mellitus, chronic kidney disease, hypertension, cardiovascular diseases and malignant tumor in severe COVID-19 patients were higher than those of non-severe patients ( OR=5.77, 95% CI 3.80-8.74; OR=4.47, 95% CI 2.71-7.38; OR=3.55, 95% CI 2.86-4.40; OR=3.05, 95% CI=1.76-5.28; OR=2.82, 95% CI=1.96-3.97; OR=2.39, 95% CI=1.77-3.23; OR=2.15, 95% CI 1.27-3.66, respectively, Z=8.37, 6.01, 11.60, 4.20, 5.46, 5.71, 3.12, all P<0.01). There was no significant difference in the prevalence of chronic liver disease between severe and non-severe patients ( OR=1.35, 95% CI 0.84-2.17, P=0.11). Conclusion:COVID-19 patients with chronic diseases have higher risk of developing severe disease, and the ORs from high to low are COPD, cerebrovascular disease, diabetes mellitus, chronic kidney disease, hypertension, cardiovascular diseases and malignant tumor.

Objective:To analyze the intensity and epidemiological characteristics of hepatitis B virus (HBV) reactivation among inactive HBsAg carriers (IHC) of rural areas in Ji'nan.Methods:In 2018 and 2020, follow-up investigations were conducted on IHC identified in the population physical examination in Zhangqiu district of Ji'nan. The results of the two follow-up visits were compared to analyze the incidence and distribution characteristics of HBV reactivation in IHC at the community level.Results:A total of 424 IHC completed two follow-up visits, and 47 cases of HBV reactivation were found, the cumulative reactivation rate was 11.08%, and the incidence density was 5.46/100 person-years. Multivariate analysis showed that gender, age, smoking, drinking , family history of liver disease and chronic diseases were not associated with HBV reactivation ( P>0.05), and baseline HBV DNA load was associated with reactivation ( P<0.05), in the HBV DNA level ≥1 000 IU/ml group, the reactivation rate could reach 18.92%. After reactivation, the mean level of ALT increased from baseline and the abnormal rate increased, liver function tended to be abnormal in reactivated patients. 4 (8.51%) reactivators had hepatitis, and 1 (2.13%) had jaundice hepatitis. Conclusions:The incidence of HBV reactivation was higher among IHC in rural communities in Ji'nan. Most of the reactivators were asymptomatic or mildly reactivated. Follow-up of inactive HBsAg patients should be strengthened and changes in ALT and HBV DNA levels should be closely monitored.