Evolocumab is a lipid-lowering agent used to reduce low-density lipoprotein cholesterol levels and decrease the all-cause mortality rate of cardiovascular diseases.There are few ocular adverse reactions when the drug is used clinically.This article reports a case of primary angle-closure glaucoma.After three sessions of lipid-lowering treatment with the proprotein convertase subtilisin type 9(PCSK9)inhibitor Evolocumab,the patient developed swelling and pain in the left eye and blurred vision.Ophthalmic examination revealed a significant increase in intraocular pressure in the left eye,suggesting an acute attack of angle-closure glaucoma.After treatment,the intraocular pressure dropped to the normal level.This article discusses this case and reviews relevant literature,suggesting that when using PCSK9 inhibitors in clinical practice,the ocular conditions of patients should be closely monitored,especially for those with risk factors for glaucoma.

Objective·To identify relevant biomarkers for patients with coronavirus disease 2019-associated kidney injury(COVID-19-associated KI)and explore the mechanisms underlying the involvement of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)proteins in infection-related KI by affecting the interactions between renal cells and macrophages.Methods·A retrospective analysis was conducted on the clinical characteristics of COVID-19 patients with KI treated in Shanghai Ninth,People's,hospital from December 2022 to February 2023.Serum levels of inflammatory factors and chemokines were measured by using enzyme-linked immunosorbent assay(ELISA).In vitro,human macrophage cell line THP-1 cells were stimulated with recombinant S1 subunit protein derived from SARS-CoV-2 spike protein.The cells and culture supernatants were collected to detect the levels of inflammatory factors and chemokines by using quantitative real-time PCR(qRT-PCR)and ELISA.Conditioned medium was prepared from the cell culture supernatants of S1-stimulated THP-1 cells and used to stimulate human renal epithelial cells(HK-2)in vitro to assess cytokine secretion.Antibody blocking experiments were performed to analyze the effects of the conditioned medium on the production of cytokines in HK-2 cells.Results·Among 39 patients with COVID-19,8(20.50%)had creatinine levels above the reference interval,which indicated the occurrence of KI.The levels of peripheral tumor necrosis factor-α(TNF-α)in the COVID-19 patient with KI group[(18.33±8.20)pg/mL]were significantly higher than those in the non-KI group[(11.88±6.50)pg/mL](P=0.015).In vitro assay has shown that S1-spike protein stimulation promoted the level of gene transcription and production of TNF-α,interleukin-1β(IL-1β)and chemokine C-X-C motif ligand 10(CXCL10)in THP-1 macrophage cells(P＜0.001).Furthermore,the conditioned medium from S1-stimulated THP-1 cells promoted the secretion of TNF-α,IL-1β and CXCL10 by HK-2 cells(P=0.005).When anti-TNF-α antibody(Infliximab)was used to block TNF-α in the culture supernatants from S1-stimulated THP-1 cells,the secretion level of TNF-α by HK-2 cells decreased dramatically(P＜0.001).Conclusion·TNF-α levels increase significantly in COVID-19 patients with KI,implying the significance of TNF-α in the occurrence of COVID-19-associated KI.In vitro experiments confirm that the S1 protein induces TNF-α secretion from THP-1 cells,leading to increased inflammatory responses in renal cells,which may contribute to the development of COVID-19-associated KI.Therefore,targeting TNF-α may become an alternative strategy to reduce the occurrence of COVID-19-associated KI.

Obesity is a common chronic disease associated with an increased risk of multiple comorbidities and premature mortality. Tirzepatide, a glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide 1 (GLP-1) receptor agonist, has demonstrated significant efficacy in multiple studies in reducing body weight and fat mass, improving body composition and metabolic parameters, lowering the risk of obesity-related complications and improving health and quality of life. This review summarizes the underlying mechanisms of tirzepatide and recent advances in its clinical research, providing a reference for clinical practice.

Recent large cardiovascular outcomes trials(CVOT) in patients with type 2 diabetes mellitus have demonstrated that several glucose-lowering agents provide cardiovascular benefits, advancing treatment concepts while also posing new ethical and clinical challenges for the design and conduct of future trials if traditional placebo-controlled designs are continued. In this context, conducting active-controlled CVOTs with optimized design strategies should be considered as a future research trend. This article reviews the design and clinical implications of CVOTs for glucose-lowering agents and explores potential directions for improvement, aiming to provide insights into optimized design strategies for future trials.

Obesity has become a chronic non-communicable disease that seriously endangers human health,with nearly half of adults in China suffering from overweight or obesity.Body mass index as the most commonly used measure of obesity in clinical practice,can be used to screen for obesity but cannot define diseases or guide clinical decision-making,and has certain limitations.This article introduces a new obesity staging system:the Edmonton Obesity Staging System,and reviews its applications in bariatric surgeryand other fields,in order to provide effective means for accurate diagnosis and treatment of obese patients.

Evolocumab is a lipid-lowering agent used to reduce low-density lipoprotein cholesterol levels and decrease the all-cause mortality rate of cardiovascular diseases.There are few ocular adverse reactions when the drug is used clinically.This article reports a case of primary angle-closure glaucoma.After three sessions of lipid-lowering treatment with the proprotein convertase subtilisin type 9(PCSK9)inhibitor Evolocumab,the patient developed swelling and pain in the left eye and blurred vision.Ophthalmic examination revealed a significant increase in intraocular pressure in the left eye,suggesting an acute attack of angle-closure glaucoma.After treatment,the intraocular pressure dropped to the normal level.This article discusses this case and reviews relevant literature,suggesting that when using PCSK9 inhibitors in clinical practice,the ocular conditions of patients should be closely monitored,especially for those with risk factors for glaucoma.

Obesity is a common chronic disease associated with an increased risk of multiple comorbidities and premature mortality. Tirzepatide, a glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide 1 (GLP-1) receptor agonist, has demonstrated significant efficacy in multiple studies in reducing body weight and fat mass, improving body composition and metabolic parameters, lowering the risk of obesity-related complications and improving health and quality of life. This review summarizes the underlying mechanisms of tirzepatide and recent advances in its clinical research, providing a reference for clinical practice.

Recent large cardiovascular outcomes trials(CVOT) in patients with type 2 diabetes mellitus have demonstrated that several glucose-lowering agents provide cardiovascular benefits, advancing treatment concepts while also posing new ethical and clinical challenges for the design and conduct of future trials if traditional placebo-controlled designs are continued. In this context, conducting active-controlled CVOTs with optimized design strategies should be considered as a future research trend. This article reviews the design and clinical implications of CVOTs for glucose-lowering agents and explores potential directions for improvement, aiming to provide insights into optimized design strategies for future trials.

Objective:To explore the association of blood and urinary cadmium levels with lipid profile levels and dyslipidemia in Chinese adults aged 18 to 79 years.Methods:Based on the China National Human Biomonitoring (CNHBM) program, a cross-sectional survey was conducted from 2017 to 2018 using a multi-stage stratified random sampling method, including a total of 10 713 adults aged 18 to 79 years. Data was obtained through questionnaires, physical examinations, biological sample collection, and laboratory testing. Multiple linear mixed effect model (MLMM) and generalized linear mixed effect model (GLMM) were used to analyze the association of blood and creatinine-corrected urinary cadmium levels with lipid profile levels as well as dyslipidemia among adults.Results:The age of 10 713 participants was (47.23±0.24) years, with 5 372 males accounting for 61.3% of the national population. The weighted mean±standard error (SE) of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was (5.21±0.03), (1.86±0.03), (2.96±0.03), and (1.43±0.01) mmol/L, respectively. The prevalence rate of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, low HDL-C, and high LDL-C was 16.0%, 21.6%, 6.6%, 13.5%, and 10.0%, respectively. MLMM showed that, after adjusting for relevant confounders, log-transformed blood cadmium levels were positively associated with increased levels of TC, TG and LDL-C ( P<0.05). When blood cadmium levels were categorized into quartiles, compared to the lowest exposure group ( Q1), participants in the highest blood cadmium exposure group ( Q4) had increases of 0.19 (95% CI: 0.06, 0.32) mmol/L in TC and 0.25 (95% CI: 0.08, 0.43) mmol/L in TG. GLMM indicated that, after adjusting for confounders, higher blood cadmium exposure levels were associated with increased risks of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, and high LDL-C ( P<0.05). Further analysis by quartiles showed that, compared to the blood cadmium Q1 exposure group, the OR value (95% CI) for the Q4 group was 1.53 (1.12, 2.08) for hypercholesterolemia, 1.54 (1.09, 2.17) for hypertriglyceridemia, 2.24 (1.47, 3.40) for mixed hyperlipidemia, and 1.49 (1.07, 2.09) for high LDL-C. Conclusion:The cadmium internal exposure levels are associated with blood lipid profile levels as well as the incidence of dyslipidemia in Chinese adults aged 18 to 79.

Objective To investigate the corr-elation between MRI burden and inflammatory factors and depression in elderly patients with cerebral small vessel disease(CSVD).Methods The clinical data of 150 patients with CSVD confirmed by brain MRI(CSVD group)and 40 patients with normal brain MRI(control group)were collected.The Hamilton depression rating scale 17-item(HAMD-17)was used to evaluate the degree of depression of the patients.The differences in CSVD burden,inflammatory markers and risk factors between the depressed group and the non-depressed group were compared,and the predictive value of the three and their combined predictions on depression were analyzed.The difference and correlation of HAMD-17 item scale scores between control group and CSVD group were compared.Results There were statistically significant differences in women,stress level,and high-sensitivity C-reactive protein(hs-CRP)level between the depressed group and the non-depressed group(all P＜0.05).Logistic regression analysis showed that CSVD burden degree,female,and hs-CRP were independent risk factors for depression(all P＜0.05).The ROC curve showed that the cut-off value of CSVD burden for depression was moderate,the sensitivity was 73％,the specificity was 47％,and the area under the curve(AUC)was 0.648(95％CI:0.558-0.738,P=0.002);the cut-off value of hs-CRP for depression was 3.73 mg/L,the sensitivity was 60％,the specificity was 73％,and the AUC area was 0.657(95％CI:0.566-0.748,P=0.001);the sensitivity of gender to depression was 68％,the specificity was 52％,and the AUC area was 0.597(95％CI:0.505-0.690,P=0.045).The combined sensitivity and specificity of the three were 70％and 73％,and the AUC area was 0.738(95％CI:0.656-0.820,P＜0.001).Compared with that in the control group,the HAMD-17 score of patients in the mild,moderate and severe burden groups were significantly increased(H=21.854,P＜0.001).Spearman correlation analysis showed that CSVD burden was positively correlated with HAMD-17 score(r=0.330,P＜0.001).Conclusions CSVD burden,female and elevated hs-CRP are independent risk factors for depression in elderly patients with CSVD.The degree of CSVD burden is positively correlated with depression score,and the accuracy of the combined prediction model is high,which has certain predictive value for senile depression.