[This corrects the article DOI: 10.1016/j.ijcrp.2026.200671.].

Background: The hemoglobin glycation index (HGI) is defined as the difference between the observed and predicted values of glycosylated hemoglobin (HbA1c), which is closely associated with a variety of poor prognoses. However, the relationship between HGI and short-term mortality risk in patients with a first diagnosis of acute myocardial infarction (AMI) remains unclear. This study aims to provide a better understanding of the relationship between HGI and mortality risk in patients with a first diagnosis of AMI. Methods: We conducted a cohort study using data from 1,961 patients with a first diagnosis of AMI from the Medical Information Mart for Intensive Care IV (MIMIC-IV; version 2.2) database. Patients were divided into four groups based on HGI quartiles. A Cox proportional hazards model and a two-segmented Cox proportional hazards model were used to elucidate the non-linear relationship between HGI in patients with a first diagnosis of AMI and mortality. Results: Of the surveyed population, 175 patients (8.92%) died within 90 days, and 210 patients (10.71%) died within 180 days. A low HGI was significantly associated with 90-day mortality [HR, 1.99; 95% CI (1.22, 3.08); P < 0.001] and 180-day mortality [HR, 1.74; 95% CI (1.18, 2.43); P < 0.001] in patients with a first diagnosis of AMI in the completely adjusted Cox proportional risk model, showing a non-linear correlation with an inflection point at 0.16 and 0.44. In the subgroup analysis, patients with prediabetes mellitus (pre-DM) and lower HGI levels had increased 90-day [HR, 8.30; 95% CI (2.91, 23.68)] and 180-day mortality risks [HR, 6.84; 95% CI (2.86, 16.34)]. Conclusion: There is a significant correlation between HGI and all-cause mortality in patients diagnosed with AMI, especially those with lower HGI. HGI can serve as a potential indicator for evaluating the 90 and 180-day death risk of such patients.

Background:The consumption of sugar-sweetened beverages (SSBs) has been linked to numerous health complications, including chronic kidney disease due to type 2 diabetes mellitus (CKD-T2DM). However, the global burden of CKD-T2DM attributable to high SSB consumption among elderly populations remains poorly characterized. Methods:Using data from the Global Burden of Disease Study 2021, we examined age-standardized mortality rates (ASMR) and disability-adjusted life year rates (ASDR) of CKD-T2DM attributable to high SSB consumption among individuals aged 60 years and older across 204 countries and territories from 1990 to 2021. We employed joinpoint regression analysis to assess temporal trends and conducted decomposition analysis to quantify the contributions of population growth, aging, and epidemiological changes to the observed burden. Results:Globally, the ASMR of CKD-T2DM attributable to high SSB consumption among elderly increased from 0.21 (95% UI: 0.10-0.38) per 100,000 in 1990 to 0.37 (95% UI: 0.18-0.62) per 100,000 in 2021, with an average annual percent change (AAPC) of 1.89% (95% CI: 1.47-2.31). The ASDR similarly increased from 4.5 (95% UI: 2.12-7.66) to 7.24 (95% UI: 3.49-11.69) per 100,000. We observed pronounced socioeconomic and geographical disparities, with high socio-demographic index (SDI) regions experiencing the highest burden and fastest increase. Notably, decomposition analysis revealed that population growth was the primary driver of increased burden globally, while epidemiological changes played a more dominant role in high SDI regions. Conclusion:Our findings highlight a substantial and increasing burden of CKD-T2DM attributable to high SSB consumption among elderly populations globally, with distinct patterns across socioeconomic development levels. These results underscore the importance of targeted interventions to reduce SSB consumption, particularly in regions experiencing rapid increases in disease burden, as part of comprehensive strategies to address the growing challenge of diet-related kidney disease in aging populations.

INTRODUCTION:The aim of this study was to provide a comprehensive assessment of temporal trends in migraine prevalence among women of childbearing age (WCBA) at global, regional, and national levels from 1992 to 2021, with particular emphasis on examining the associations between prevalence patterns and age, period, and birth cohort effects across different sociodemographic index (SDI) regions. METHODS:We conducted a secondary analysis of data from the Global Burden of Disease Study 2021. Migraine prevalence estimates and 95% uncertainty intervals (UIs) for WCBA were extracted. An age-period-cohort model was employed to estimate the net drift (primary outcomes), local drift, and age/period/cohort relative risks (secondary outcomes). RESULTS:The global number of WCBA with migraine reached 493,937,856.01 (95% UI: 420,683,360.54-577,874,600.76) in 2021. The highest burden was found in India (95.7 million) and China (68.1 million), together accounting for substantial proportion of global prevalence. The global net drift showed a minimal change of 0.01% (95% CI: 0.00-0.02) per year, with variations across sociodemographic index (SDI) regions ranging from -0.03% per year (95% CI: -0.04 to -0.02) in low-middle-SDI regions to 0.16% (95% CI: 0.15-0.17) in middle-SDI regions. Local drift analysis reveals that migraine prevalence increases across young age groups (15-19 years) in high-SDI regions, while lower-SDI regions generally display stable rates. Globally, increases in migraine prevalence among young adults within WCBA are notably persistent. Across SDI regions, age effects follow similar patterns, with risk rising with age and peaking in the mid-reproductive years (ages 30-39). Over time, period risks and unfavorable trends across successive birth cohorts have intensified, particularly in high-, high-middle-, and middle-SDI regions. CONCLUSION:Although global migraine prevalence among WCBA remains stable, an unfavorable upward trend in younger age groups (15-19 years) in high-, high-middle-, and middle-SDI regions, alongside worsening period/cohort risks, highlights current gaps in prevention and management. Improved strategies are expected to reduce risks for younger birth cohorts and all age groups over time.

Previous studies have shown a positive association between sedentary behavior (SB) and metabolic syndrome (MetS), but no studies have assessed the mediating effect of depressive symptoms in this process. Participants from the 2007–2018 National Health and Nutrition Examination Survey (NHANES) were included. Multiple logistic regression analyses and restricted cubic splines (RCSs) were adopted to assess the correlations among SB duration, depressed mood and MetS. A mediation effect model was constructed to analyze whether there was a mediating effect of depressed mood on the relationship between SB duration and MetS. This study included 15,944 adults (7,268 patients with MetS in total). We identified high SB duration as an independent risk factor for MetS in a regression model adjusted for relevant confounders (odds ratio (OR) = 1.29, 95

Aim Epidemiological research on hypertensive heart disease (HHD) in women of childbearing age (WCBA) remains scarce. Our objective is to describe the current prevalence of HHD in WCBA at global, regional, and national levels and to analyze its temporal trends from 1990 to 2019. Methods WCBA was defined as women aged 15–49 years. Estimates and 95% Uncertainty Intervals (UI) of HHD prevalence numbers for seven age groups (15–19, 20–24, 25–29, 30–34, 35–39, 40–44, 45–49 years) were extracted from the 2019 Global Burden of Disease Study (GBD). The age-standardized prevalence rate (ASPR) of HHD in WCBA was estimated using the direct age-standardization method. Joinpoint regression analysis was used to calculate the Annual Percentage Change (APC) and Average APC (AAPC) along with their 95% Confidence Intervals (CI), analyzing the temporal trends from 1990 to 2019. Results In 1990 and 2019, the global ASPR of HHD in WCBA was 23.20 (95% UI: 12.72 to 38.43) and 23.67 (95% UI: 13.02 to 38.73), respectively, with high Socio-Demographic Index (SDI) regions generally exhibiting higher ASPRs than other regions. From 1990 to 2019, there was a significant global increase in HHD WCBA (AAPC = 0.08%, 95% CI:0.03 to 0.12; P < 0.001), with notable increases in high-middle SDI region (AAPC = 0.78%, 95%CI: 0.69 to 0.88; P < 0.001), middle SDI region (AAPC = 0.32%, 95%CI: 0.27 to 0.37; P < 0.001), low-middle SDI region (AAPC = 0.50%, 95%CI: 0.44 to 0.56; P < 0.001), and low SDI region (AAPC = 0.36%, 95%CI: 0.34 to 0.37; P < 0.001). However, HHD in high SDI regions significantly decreased (AAPC = -0.52%, 95% CI: -0.74 to -0.31; P < 0.001). The most significant changes occurred in different periods. The ASPR trends of HHD in WCBA varied greatly among 204 countries and territories. Conclusions Between 1990 and 2019, there was strong heterogeneity in the ASPR of HHD in WCBA globally and in its temporal trends (1990–2019). The ASPR decreased in high SDI regions but continuously increased in low SDI regions. These findings highlight the stark global disparities in HHD among WCBA, with significant implications for the equitable allocation of medical resources and the formulation of relevant health policies.

BackgroundOur objective is to describe the current prevalence and death of ischemic heart disease (IHD) in women of childbearing age (WCBA) at the global, regional, and national levels and to analyze its temporal trends from 1990 to 2019.MethodsWCBA was defined as women aged 15–49 years. Estimates and 95% Uncertainty Intervals (UI) of IHD prevalence and death numbers for seven age groups were extracted from the 2019 Global Burden of Disease Study. The age-standardized prevalence and death rate (ASPR and ASDR) of IHD in WCBA was estimated using the direct age-standardization method. Joinpoint regression analysis was used to calculate average annual percent change (AAPC) to represent the temporal trends from 1990 to 2019.ResultsBetween 1990 and 2019, the global ASPR of IHD experienced a 3.21% increase, culminating in 367.21 (95% UI, 295.74–430.16) cases per 100,000 individuals. Conversely, the ASDR decreased to 11.11 (95% UI, 10.10–12.30) per 100,000 individuals. In 2019, among the five sociodemographic index (SDI) regions, the highest ASPR was observed in the high-middle SDI region, whereas the highest ASDR was found in the low-middle SDI region. Regionally, the Caribbean reported the highest ASPR (563.11 per 100,000 individuals; 95% UI, 493.13–643.03), and Oceania reported the highest ASDR (20.20 per 100,000 individuals; 95% UI, 13.01–31.03). At the national level, Trinidad and Tobago exhibited the highest ASPR (730.15 per 100,000 individuals; 95% UI, 633.96–840.13), and the Solomon Islands had the highest ASDR (77.77 per 100,000 individuals; 95% UI, 47.80–121.19). Importantly, over the past three decades, the global ASPR has seen a significant increase [AAPC = 0.11%, 95% Confidence Interval (CI): 0.09–0.13; P < 0.001], while the ASDR has demonstrated a significant decreasing trend (AAPC = −0.86%, 95% CI: −1.11 to −0.61; P < 0.001). Air pollution, tobacco use, high systolic blood pressure, elevated body mass index, dietary risks, and high LDL cholesterol have been identified as the leading six risk factors for IHD-related deaths among WCBA in 2019.ConclusionsDespite the significant decline in the global ASDR for IHD among WCBA over the last thirty years, the ASPR continues to escalate. We need to remain vigilant about the increased burden of IHD in WCBA. It calls for aggressive prevention strategies, rigorous control of risk factors, and the enhancement of healthcare coverage to mitigate the disease burden of IHD among WCBA in forthcoming years.

Aims The Stress Hyperglycemia Ratio (SHR) potently predicts adverse outcomes in patients with cardiovascular and cerebrovascular diseases. However, the relationship between SHR and short-term mortality risk in patients with a first diagnosis of acute myocardial infarction (AMI) remains contentious. This study sought to understand better the relationship between SHR and short-term mortality risk in patients with a first diagnosis of AMI.Methods We conducted a cohort study using data from 1961 patients with a first diagnosis of AMI from the MIMIC-IV (version 2.2) database. Patients were divided into three groups based on SHR tertiles. The Cox proportional hazards model and a two-segmented Cox proportional hazards model were used to elucidate the nonlinear relationship between SHR in patients with a first diagnosis of AMI and mortality.Results Of the surveyed population, 175 patients (8.92%) died within 90 days, and 210 patients (10.71%) died within 180 days. After multivariate adjustments, elevated SHR levels were significantly and non-linearly associated with a higher risk of 90-day and 180-day mortality in patients with a first diagnosis of AMI, showing a J-shaped correlation with an inflection point at 0.9. Compared to participants with SHR levels below the inflection point, those with higher SHR levels had a fivefold increased risk of 90-day mortality (hazard ratio [HR] 5.74; 95% confidence interval [CI] 3.19, 10.33) and a fourfold increased risk of 180-day mortality (HR 4.56; 95% CI 2.62, 7.95). In the subgroup analysis, patients with pre-diabetes mellitus (pre-DM) and higher SHR levels had increased 90-day (HR 6.90; 95% CI 1.98, 24.02) and 180-day mortality risks (HR 5.30; 95% CI 1.96, 14.27).Conclusion In patients with a first diagnosis of AMI, there is a J-shaped correlation between SHR and 90-day and 180-day mortality, with an adverse prognostic inflection point of SHR at 0.9.

Although in vitro experiments have demonstrated the potential of flavonoid compounds in regulating blood pressure, there is still a lack of evidence from large population studies. We conducted a cross-sectional study using the National Health and Nutrition Examination Survey to investigate the relationship between flavonoid intake levels (natural log transformation) and hypertension events. A total of 15 752 participants aged over 20 years were included, and a weighted multivariable logistic regression analysis was performed to explore the relationship between total flavonoids, five sub types intake, and hypertension events. Smooth curve fitting was used to explore potential nonlinear relationships. Higher total flavonoids intake was associated with a lower risk of hypertension than the lowest group. The adjusted odds ratios (95% CIs) were 0.79 (0.70-0.88) for total flavonoids intake. Elevated total flavonoids intake levels were significantly and linearly associated with a lower risk of hypertension. For each unit increase in the total flavonoids intake level, the adjusted ORs for risk of hypertension decrease by 5% (OR 0.95; 95% CI, 0.92-0.98). In addition, in restricted cubic spline regression, we found that flavan-3-ols, anthocyanidins, and flavonols intake were linearly and negatively related to prevalence of hypertension. Flavones intake showed nonlinear associations with prevalence of hypertension with inflection points of -1.90. Within a certain range, a negative correlation exists between flavonoids intake and hypertension events. This finding provides insights into dietary modifications in the prevention of hypertension.

Background: We investigated the relationship between remnant cholesterol and carotid intraplaque neovascularization (IPN) assessed by contrast -enhanced ultrasonography (CEUS) in patients with ischemic stroke. Methods: This was a single -center study. Remnant cholesterol is calculated as total cholesterol minus low -density lipoprotein cholesterol (LDL-C) minus high -density lipoprotein cholesterol (HDL-C). All patients underwent CEUS. IPN is graded according to the presence and location of microbubbles within each plaque. Results: The cohort included 110 patients with ischemic stroke. Patients with an IPN grading of 2 had higher triglyceride (TG), nonHDL-C, and remnant cholesterol concentrations than those with an IPN grading of < 2 (TG: 1.45 +/- 0.69 vs. 0.96 +/- 0.24 mmol/L, P < 0.001; non-HDL-C: 2.63 +/- 0.85 vs. 2.31 +/- 0.64 mmol/L, P = 0.037; remnant cholesterol: 0.57 +/- 0.23 vs. 0.44 +/- 0.07 mmol/L, P < 0.001). The multivariate -adjusted odds ratio (95% confidence interval) for remnant cholesterol was 27.728 (2.714 - 283.253) for an IPN grading of 2 in the subset of patients with an optimal LDL-C concentration. Conclusions: The remnant cholesterol concentration is significantly associated with carotid IPN on CEUS in patients with ischemic stroke with an optimal LDL-C concentration. Remnant cholesterol may be an important indicator of risk stratification in patients with ischemic stroke.

Background: Road injuries among the working-age population significantly impact overall health and employment prospects, leading to declines in social and economic productivity and increased poverty rates. However, research on this demographic remains limited. Methods: The working-age population is defined as individuals aged 15-64 years. Data from the Global Burden of Disease Study 2021 were analyzed for ten age groups within this range, including total road injuries and five specific subtypes: pedestrian, cyclist, motorcyclist, motor vehicle, and other road injuries. Joinpoint regression analysis was employed to determine the average annual percentage changes (AAPCs) from 1990 to 2021. Findings: Overall, in 2021, the age-standardized incidence rates (ASIR), age-standardized death rates (ASMR), and the age-standardized disability-adjusted life years rates (ASDR) for road injuries in the global working-age population were 788.27 (95% UI: 598.8-1020.24), 17.37 (16.16-18.68), and 1015.13 (941.99-1091.97), respectively. From 1990 to 2021, these indicators showed a declining trend, with AAPCs of -1.19, -1.09, and -1.22, respectively. North Africa and the Middle East bore the heaviest burden, while Central Europe, Eastern Europe, and Central Asia saw the fastest declines in ASMR and ASDR. Pedestrian and motor vehicle road injuries accounted for the highest proportion of road injuries in the global working-age population, followed by motorcyclist and cyclist road injuries. Notably, over the 32-year period, the ASMR of motorcyclist road injuries in the global working-age population showed a significant upward trend (AAPC = 0.29). The ASIR (AAPC = 2.57), ASMR (1.67), and ASDR (1.67) of motorcyclist road injuries in Latin America and the Caribbean grew the fastest. Furthermore, the decline rates of various road injuries were faster in countries and regions with higher SDI, with the burden more concentrated in underdeveloped countries. Interpretation: Despite the overall decline in road injuries among the global working-age population from 1990 to 2021, deaths from motor vehicle road injuries increased, with a heavier burden in low- and middle-income countries and regional differences in various types of road injuries. These findings underscore the urgent need for governments to develop flexible health policies to alleviate the burden of road injuries among the working-age population worldwide. Funding: No funding. Declaration of Interest: The authors declare no competing interests. Ethical Approval: Ethical approval and consent to participate were not necessary for this study. This study follows the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).

Purpose The aim of our study was to compare the efficacy and safety of uterine artery embolization (UAE) for symptomatic uterine fibroids with surgery. Methods Both a randomized, controlled trial and meta-analysis of existing studies were performed. Results Patients were randomly assigned in a 1:1 ratio to undergo either UAE or surgery with 63 patients undergoing UAE and 64 undergoing surgery. A meta-analysis of existing studies was also performed.There were significant improvements in UAE groups in most components of quality of life assessment at 6 months. Besides, the UAE group had a shorter hospital stay ( P < 0.01) and a shorter recovery time ( P < 0.01) compared with the surgical group. During the follow-up, there were no difference in complications incidence (58 vs. 65%, P > 0.05), but the UAE group had less major complications (0 vs. 6%, P < 0.05). Meta-analysis of existing studies including those from the current study, further suggested that UAE group had a shorter hospital stay, a shorter recovery time and less major complications than the surgical group. Conclusions Compared with surgery, UAE has a shorter hospital stay, a shorter recovery time, and less major complications. More studies in the future need to done to evaluate its long-term effects and impact on fertility.

BackgroundTo describe the burden and examine transnational inequities in overall cardiovascular disease (CVD) and ten specific CVDs across different levels of societal development.MethodsEstimates of disability-adjusted life-years (DALYs) for each disease and their 95% uncertainty intervals (UI) were extracted from the Global Burden of Diseases (GBD). Inequalities in the distribution of CVD burdens were quantified using two standard metrics recommended absolute and relative inequalities by the World Health Organization (WHO), including the Slope Index of Inequality (SII) and the relative concentration Index.ResultsBetween 1990 and 2019, for overall CVD, the Slope Index of Inequality changed from 3760.40 (95% CI: 3758.26 to 3756.53) in 1990 to 3400.38 (95% CI: 3398.64 to 3402.13) in 2019. For ischemic heart disease, it shifted from 2833.18 (95% CI: 2831.67 to 2834.69) in 1990 to 1560.28 (95% CI: 1559.07 to 1561.48) in 2019. Regarding hypertensive heart disease, the figures changed from-82.07 (95% CI: −82.56 to-81.59) in 1990 to 108.99 (95% CI: 108.57 to 109.40) in 2019. Regarding cardiomyopathy and myocarditis, the data evolved from 273.05 (95% CI: 272.62 to 273.47) in 1990 to 250.76 (95% CI: 250.42 to 251.09) in 2019. Concerning aortic aneurysm, the index transitioned from 104.91 (95% CI: 104.65 to 105.17) in 1990 to 91.14 (95% CI: 90.94 to 91.35) in 2019. Pertaining to endocarditis, the figures shifted from-4.50 (95% CI: −4.64 to-4.36) in 1990 to 16.00 (95% CI: 15.88 to 16.12) in 2019. As for rheumatic heart disease, the data transitioned from-345.95 (95% CI: −346.47 to-345.42) in 1990 to-204.34 (95% CI: −204.67 to-204.01) in 2019. Moreover, the relative concentration Index for overall CVD and each specific type also varied from 1990 to 2019.ConclusionThere’s significant heterogeneity in transnational health inequality for ten specific CVDs. Countries with higher levels of societal development may bear a relatively higher CVD burden except for rheumatic heart disease, with the extent of inequality changing over time.

Chronic liver disease is a serious threat to human health, and liver fibrosis is a key stage in the progress of chronic liver disease. Spleen is an important immune organ of human body, which can affect the progress of liver fibrosis by regulating liver immune cells. However, the mechanism of spleen regulating liver immune cells is unclear. Increasing evidence shows that immune cells can react to small metabolites other than cytokines and membrane proteins, such as GABA synthesized and secreted by B cells. Through splenectomy, we proved that splenectomy alleviated liver fibrosis in mice and reduced the number and proportion of liver B lymphocytes; After reinfusion of B cells, the number of B cells in liver increased and liver fibrosis aggravated. Combined with LC-MS analysis, the content of GABA in liver and serum of fibrosis mice increased significantly, and decreased significantly after splenectomy. Cell experiments showed that GABA could regulate the secretion of CCL2 and TGF- β by macrophages Raw264.7 making JS1 highly expressed α- SMA, thus promote fibrosis. Therefore, the spleen may affect the progress of liver fibrosis by influencing the production of GABA by B cells to regulate liver immunity.

Purpose: Neutrophil infiltration is closely related with the progression of hepatocellular carcinoma (HCC). Previous results showed that splenectomy resulted in decreased neutrophils infiltration and tumor growth in liver. Here we aimed to explore the phenotype and function of splenic neutrophil during HCC progression. Methods: FACS analysis and Immunohistochemical staining were used to evaluate neutrophil infiltration. We investigated the phenotype and function of splenic neutrophils in hepatoma-bearing mice. Results: FACS analysis showed the infiltration level of neutrophil significantly increased, accompanied by increased proportion of CD101- neutrophil subsets in hepatoma bearing mice. Compared with control mice, neutrophils from the spleen and liver of tumor mice exhibited higher level of type I transmembrane glycoprotein CD101, chemokine receptor CXCR2, and PD-L1 expression. Functional analysis showed the phagocytic function was weakened but the level of ROS release was increased in splenic neutrophils from tumor-bearing mice than that of control mice. Co-injection of CD101+ splenic neutrophil subset from tumor mice with H22 cell line could promote tumor growth. Transcriptome sequencing analysis indicated that the expression of genes related in neutrophil activation, angiogenesis, extracellular matrix remodeling, tumor cell proliferation and immune suppression signaling pathway were higher in CD101+ neutrophil subset than CD101- neutrophil subset, suggesting that CD101+ neutrophil subsets may be involved in the progression of HCC through immune suppression. Conclusion: Our study suggested CD101+ splenic neutrophil subset in tumor-bearing mice significantly increased and could promote HCC tumor growth. This study implicated the critical role of the spleen via CD101+ neutrophil subset in the progression of HCC. Figure legend. Splenic CD101+ neutrophils increased and accumulated into the liver via overexpression of CXCR2, PD-L1 and thus participated in HCC progression.

Triple negative breast cancer (TNBC) is an invasive and metastatic phenotype of breast cancer with limited treatment options. Published studies have demonstrated an inhibitory effect of HIF-α inhibition by its inhibitor YC-1 (lificiguat) on growth and angiogenesis of TNBC. However, the underlying mechanism remains poorly understood. In the current paper, our results show that HIF-1α inhibitor significantly inhibited TNBC growth by increasing cellular apoptosis and decreasing MVD, independent of a cell-autonomous mechanism in both endothelial and tumor cells. Genetic screening and in vivo experiments showed that a large number of M2-polarized TAMs accumulated in the hypoxic peri-necrotic region (PNR), where placental growth factor (PlGF) and its ligand, vascular endothelial growth factor receptor-1 (VEGFR-1) were upregulated. Furthermore, YC-1 skewed the polarization of TAMs away from M2 to M1 phenotype, therefore inhibiting TNBC angiogenesis and growth. This effect was further abrogated by VEGFR-1 neutralization and TAM depletion following clodronate liposome injection. These findings provide preclinical evidence for an indirect mechanism underlying YC-1-induced suppression of TNBC growth and angiogenesis, thereby offering a treatment option for TNBC.

目的 观察血清凝集蛋白-1(ITLN-1)、血管生成素样蛋白4(ANGPTL4)在急性心肌梗死(AMI)患者血清中的表达水平,并探究二者与冠状动脉病变程度的相关性.方法 选取2019年6月—2021年7月安徽医科大学附属六安医院心血管内科收治AMI患者128例作为研究组,另外选取同期医院健康体检者120例作为健康对照组.根据冠状动脉病变Gensini评分将研究组患者分为轻度亚组35例(Gensini评分<18分),中度亚组43例(Gensini评分为18～40分),重度亚组50例(Gensini评分>40分).收集受试者临床资料,采用酶联免疫吸附法检测血清ITLN-1、ANGPTL4水平.Pearson法分析血清ITLN-1、ANGPTL4与Gensini评分的相关性.Logistic回归分析影响冠状动脉病变程度的因素.结果 研究组左心室射血分数(LVEF)低于健康对照组,高敏C反应蛋白(hs-CRP)、B型脑钠肽(BNP)、左心室舒张末期内径(LVEDD)均高于健康对照组(t/P=9.368/<0.001、2.810/0.005、8.229/<0.001、7.006/<0.001);研究组血清ITLN-1、ANGPTL4低于健康对照组(t/P=8.170/<0.001、7.986/<0.001),轻度亚组、中度亚组、重度亚组AMI患者血清ITLN-1、ANGPTL4水平依次降低(F=38.240、16.527,P均<0.001);经Pearson分析显示,血清ITLN-1、ANGPTL4与Gensini评分呈负相关(r=-0.397,-0.429,P<0.001);Logistic回归分析显示,ITLN-1低、ANGPTL4低、BNP高、LVEDD高、LVEF低是AMI患者冠状动脉病变程度的危险因素[OR(95％CI)=2.103(1.136～3.892)、2.114(1.170～3.821)、1.514(1.068～2.146)、2.514(1.340～4.716)、2.624(1.134～6.071)].结论 AMI患者血清中ITLN-1、ANGPTL4呈低表达,且与患者冠状动脉病变程度密切相关.

Abstract The prevalence of Essential Hypertension (EH) is increasing globally, and the effectiveness of pharmacological treatments remains far from ideal. Combining Mendelian Randomization (MR) to identify potential drug targets may be key to reducing the disease burden and developing potential treatments. We utilized the UK Biobank cohort (ncase = 54358, ncontrol = 408652) to extract summary statistics for EH and further validated in the FinnGen cohort (ncase = 92462, ncontrol = 265626). Cis-expression quantitative trait loci (cis-eQTL) from available druggable genes were retrieved and used as genetic instrumental variables. Two-sample MR analysis and colocalization analysis were conducted to examine whether identified genes and EH share variants, further consolidating MR results. Ten drug targets (FES, SLC22A4, PTK2B, BLK, ITPR1, NEGR1, GRK4, ADM, MAPK3, MAST3) showed significant MR results in two independent datasets, with no reverse causation observed. Colocalization analysis indicated that FES (PP.H4 = 0.99) and SLC22A4 (PP.H4 = 0.82) shared the same variants with EH, providing strong evidence. Additionally, FES showed significant associations with reduced risk of coronary artery disease, systolic blood pressure, and diastolic blood pressure, while SLC22A4 was significantly associated with increased diastolic blood pressure. Our results suggest that targeting FES and SLC22A4 might treat or cause EH, potentially revealing new pathophysiological pathways and treatment targets for EH.

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer (CRC). In this study, we identified reduced microvessel density (MVD) and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance. We focused on the effect of metformin on MVD, vascular maturity, and endothelial apoptosis of CRCs with a non-angiogenic phenotype, and further investigated its effect in overcoming chemoresistance. In situ transplanted cancer models were established to compare MVD, endothelial apoptosis and vascular maturity, and function in tumors from metformin- and vehicle-treated mice. An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis. Transcriptome sequencing was performed for genetic screening. Non-angiogenic CRC developed independently of angiogenesis and was characterized by vascular leakage, immaturity, reduced MVD, and non-hypoxia. This phenomenon had also been observed in human CRC. Furthermore, non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro. By suppressing endothelial apoptosis, metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity. Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling, which was abrogated by metformin administration. These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC. By suppressing endothelial apoptosis, metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.

目的 综合评价广西中医类医院服务能力,为促进广西中医药事业进一步发展提供循证依据.方法 选取广西中医类医院服务能力相关指标,分别运用熵权TOPSIS法与RSR法对2014-2020年广西中医类医院服务能力及2020年广西各地区中医类医院服务能力进行综合评价.结果 中医类医院门诊病人次均医药费用及住院病人人均医药费用从2016年开始出现较快增长;中医类医院病床使用率、总诊疗人次及出院人次在2020年出现较大幅度下降;基于TOPSIS法综合评价,2014-2020年广西中医类医院服务能力的Ci值依次为0.407、0.449、0.478、0.51、0.575、0.588、0.575.2019年排在第一,2014年排在最后;基于RSR法进行排序分档,2020年广西中医类医院服务能力被评定为"优"的地区为柳州、桂林、南宁,被评定为"差"的地区为防城港、北海,其余9个地区被评定为"中".结论 广西中医类医院医药费用上涨过快,且受新冠疫情影响各项服务指标出现大幅下降.应加强中医类医院医药费用控制,并提升抗运营风险能力与公共卫生应急能力;广西中医类医院服务能力总体呈上升趋势,但各地区间存在明显差异.应加强政府宏观调控,减小地区间中医类医院服务能力的差异.