Aim To explore the relationship between serum levels of proprotein convertase subtilisin/kexin type 9(PCSK9),macrophage migration inhibitory factor(MIF)and the severity of coronary artery lesions in patients with coro-nary heart disease(CHD).Methods A cross-sectional study was conducted involving 139 patients with CHD and 69 control subjects who underwent coronary angiography during the same period,all of whom were admitted to the People's Hospital of Xinjiang Uygur Autonomous Region from November 2023 to May 2024.Clinical data and coronary angiography results were collected,and the severity of coronary artery stenosis was quantitatively assessed using the Gensini score.Pa-tients with the Gensini scores＞0 were classified into three groups based on tertiles:the mild stenosis group(1～18 points,54 cases),the moderate stenosis group(19～36 points,54 cases),and the severe stenosis group(＞36 points,54 ca-ses).Serum levels of PCSK9 and MIF were measured by ELISA kit.Results Serum levels of PCSK9 and MIF were significantly higher in the CHD group than those in the control group(P＜0.05).Multivariable Logistic regression analy-sis revealed that high levels of serum PCSK9 and MIF were independent risk factors for CHD.Spearman correlation analy-sis showed that serum PCSK9 and MIF levels were positively correlated with Gensini score(rs=0.619 6 and r,=0.411 4,both P＜0.001).Further subgroup analysis showed that serum total cholesterol and low density lipoprotein cholesterol lev-els were significantly increased in patients with high-level PCSK9,while patients with high-level MIF had higher inflamma-tory coefficients such as systemic inflammatory response index(SIRI)and systemic immune-inflammation index(SII)(all P＜0.05).Conclusion Serum levels of PCSK9 and MIF are positively correlated with the severity of coronary artery stenosis.High levels of serum PCSK9 and MIF are independent risk factors for CHD.

Objectives:This study aims to evaluate the causal relationship between plasma proteins and myocardial infarction(MI)using two-sample bidirectional Mendelian randomization(MR)analysis,identify key biomarkers,and validate their expression.Methods:The study utilized publicly available genome-wide association study(GWAS)data of 4 907 plasma proteins as the exposure factor,with single nucleotide polymorphisms(SNPs)as instrumental variables,and four MI datasets as outcomes.Two-sample MR analysis was performed using the inverse variance weighted(IVW)method,complemented by simple model,weighted model,weighted median estimator(WME),and MR-Egger regression methods to assess the causal relationship between exposure factors and outcomes.Venn diagrams and word clouds were used to screen proteins associated with MI as candidate biomarkers.Reverse MR analysis was conducted to evaluate reverse causality.Sensitivity analysis was performed to assess the robustness of the results.Immunohistochemistry(IHC)was used to validate the expression of proteasome activator subunit 1(PSME1)and vacuolar protein sorting 29(VPS29)in the aorta of mice,and enzyme-linked immunosorbent assay(ELISA)was used to verify the expression of PSME1 and VPS29 in plasma from patients with acute myocardial infarction(AMI).Results:The two-sample MR analysis indicated that PSME1 was significantly negatively associated with myocardial infarction in all four datasets,with OR(95%CI)of 0.684(0.557-0.839),0.990(0.987-0.993),0.579(0.448-0.748),and 0.993(0.990-0.996),respectively,with all P<0.001.Similarly,VPS29 also showed a significant negative association with MI in all four datasets,with OR(95%CI)of 0.902(0.862-0.945),0.998(0.997-0.999),0.866(0.808-0.929),and 0.998(0.997-0.999),respectively,with all P<0.001.Reverse MR analysis did not detect reverse causality,and sensitivity analysis confirmed the robustness of the results.IHC results showed significantly reduced expression of PSME1 and VPS29 in the aortas of AMI mice with an atherosclerotic background compared to control mice(both P<0.05).ELISA results indicated significantly lower plasma levels of PSME1 and VPS29 in AMI patients compared to healthy controls(both P<0.05).Conclusions:Higher levels of PSME1 and VPS29 are negatively associated with the risk of MI,suggesting that PSME1 and VPS29 may serve as protective biomarkers for cardiovascular diseases.

Objectives:This study aims to evaluate the causal relationship between plasma proteins and myocardial infarction(MI)using two-sample bidirectional Mendelian randomization(MR)analysis,identify key biomarkers,and validate their expression.Methods:The study utilized publicly available genome-wide association study(GWAS)data of 4 907 plasma proteins as the exposure factor,with single nucleotide polymorphisms(SNPs)as instrumental variables,and four MI datasets as outcomes.Two-sample MR analysis was performed using the inverse variance weighted(IVW)method,complemented by simple model,weighted model,weighted median estimator(WME),and MR-Egger regression methods to assess the causal relationship between exposure factors and outcomes.Venn diagrams and word clouds were used to screen proteins associated with MI as candidate biomarkers.Reverse MR analysis was conducted to evaluate reverse causality.Sensitivity analysis was performed to assess the robustness of the results.Immunohistochemistry(IHC)was used to validate the expression of proteasome activator subunit 1(PSME1)and vacuolar protein sorting 29(VPS29)in the aorta of mice,and enzyme-linked immunosorbent assay(ELISA)was used to verify the expression of PSME1 and VPS29 in plasma from patients with acute myocardial infarction(AMI).Results:The two-sample MR analysis indicated that PSME1 was significantly negatively associated with myocardial infarction in all four datasets,with OR(95%CI)of 0.684(0.557-0.839),0.990(0.987-0.993),0.579(0.448-0.748),and 0.993(0.990-0.996),respectively,with all P<0.001.Similarly,VPS29 also showed a significant negative association with MI in all four datasets,with OR(95%CI)of 0.902(0.862-0.945),0.998(0.997-0.999),0.866(0.808-0.929),and 0.998(0.997-0.999),respectively,with all P<0.001.Reverse MR analysis did not detect reverse causality,and sensitivity analysis confirmed the robustness of the results.IHC results showed significantly reduced expression of PSME1 and VPS29 in the aortas of AMI mice with an atherosclerotic background compared to control mice(both P<0.05).ELISA results indicated significantly lower plasma levels of PSME1 and VPS29 in AMI patients compared to healthy controls(both P<0.05).Conclusions:Higher levels of PSME1 and VPS29 are negatively associated with the risk of MI,suggesting that PSME1 and VPS29 may serve as protective biomarkers for cardiovascular diseases.

Aim To explore the relationship between serum levels of proprotein convertase subtilisin/kexin type 9(PCSK9),macrophage migration inhibitory factor(MIF)and the severity of coronary artery lesions in patients with coro-nary heart disease(CHD).Methods A cross-sectional study was conducted involving 139 patients with CHD and 69 control subjects who underwent coronary angiography during the same period,all of whom were admitted to the People's Hospital of Xinjiang Uygur Autonomous Region from November 2023 to May 2024.Clinical data and coronary angiography results were collected,and the severity of coronary artery stenosis was quantitatively assessed using the Gensini score.Pa-tients with the Gensini scores＞0 were classified into three groups based on tertiles:the mild stenosis group(1～18 points,54 cases),the moderate stenosis group(19～36 points,54 cases),and the severe stenosis group(＞36 points,54 ca-ses).Serum levels of PCSK9 and MIF were measured by ELISA kit.Results Serum levels of PCSK9 and MIF were significantly higher in the CHD group than those in the control group(P＜0.05).Multivariable Logistic regression analy-sis revealed that high levels of serum PCSK9 and MIF were independent risk factors for CHD.Spearman correlation analy-sis showed that serum PCSK9 and MIF levels were positively correlated with Gensini score(rs=0.619 6 and r,=0.411 4,both P＜0.001).Further subgroup analysis showed that serum total cholesterol and low density lipoprotein cholesterol lev-els were significantly increased in patients with high-level PCSK9,while patients with high-level MIF had higher inflamma-tory coefficients such as systemic inflammatory response index(SIRI)and systemic immune-inflammation index(SII)(all P＜0.05).Conclusion Serum levels of PCSK9 and MIF are positively correlated with the severity of coronary artery stenosis.High levels of serum PCSK9 and MIF are independent risk factors for CHD.

Objectives:A two-sample,multivariable,bidirectional Mendelian randomization (MR) analysis was conducted to explore the causal relationships between serum micronutrients (including vitamin A,vitamin B6,vitamin B9,vitamin B12,vitamin C,vitamin D,vitamin E,copper,iron,selenium,zinc,calcium,magnesium,and potassium) and coronary atherosclerosis (CA).Methods:Publicly available data from genome-wide association studies in European populations were analyzed,14 serum micronutrients were used as exposure factors and single nucleotide polymorphisms (SNPs) were used as instrumental variables,outcome was defined as CA.A two-sample MR analysis was performed using inverse variance weighted (IVW) method,MR-Egger regression,weighted median estimator (WME),simple model,and weighted model to assess the relationship between each micronutrient and CA.Multivariable MR analysis was used to evaluate the independent impacts of single exposure factors on CA,reverse MR was applied to assess the potential for reverse causality.Sensitivity analysis was conducted using Cochran's Q test,MR-Egger regression,MR-PRESSO,and leave-one-out analysis to evaluate the robustness of the results.Results:The univariable two-sample MR study evidenced the significant associations between serum levels of vitamin A (IVW:OR=0.019,95％CI:0.001-0.451,P=0.014),vitamin B12 (IVW:OR=1.221,95％CI:1.015-1.469,P=0.034),copper (IVW:OR=1.023,95％CI:1.003-1.044,P=0.026),and potassium (IVW:OR=0.837,95％CI:0.714-0.980,P=0.027) with the risk of CA.After adjustment using multivariable MR analysis,independent causal effects on CA were observed for serum levels of vitamin A (IVW:OR=0.016,95％CI:0.001-0.214,P=0.002) and copper (IVW:OR=1.029,95％CI:1.002-1.056,P=0.036).Reverse MR analysis observed a reverse causal relationship between CA risk and serum vitamin A level,though the effect was minimal (IVW:OR=0.999),while no reverse causality was found between CA risk and serum copper level.There was no evidence to support a causal relationship between the remaining serum micronutrients and CA.These findings were robust through extensive sensitivity analyses.Conclusions:The levels of serum vitamin A and copper may relate to the susceptibility of CA in the studied population.

Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

Thrombocytopenia is one of the common complications of cirrhotic patients, which can induce an increasing bleeding risk and closely correlate with bleeding following invasive procedures. Consequently, how to respond to thrombocytopenia is crucial for improving the prognosis of patients with cirrhosis. This article reviews the main mechanisms of cirrhosis concurrent with thrombocytopenia, as well as the corresponding clinical management strategies.

Objective:To analyze the effect of traditional Chinese medicine fasting therapy on atherogenic index of plasma and metabolic indices in patients with metabolic syndrome.Methods:A case-control study was conducted on 90 patients with metabolic syndrome who were treated at Wenzhou Traditional Chinese Medicine Hospital between June 2021 and June 2023. The patients were divided into two groups with 45 patients in each group using a random number table method. The control group was given a normal diet, while the observation group underwent traditional Chinese medicine fasting therapy. Blood lipid indexes, atherogenic index of plasma, Homeostasis Model Assessment of Insulin Resistance index, anthropometric indices, and oxidative stress response were compared between the two groups.Results:After treatment, the levels of low-density lipoprotein cholesterol, total cholesterol, and triglyceride in the observation group were (2.11 ± 0.26) mmol/L, (4.31 ± 0.26) mmol/L, and (1.39 ± 0.26) mmol/L, respectively. They were significantly lower than those in the control group [(2.95 ± 0.34) mmol/L, (5.24 ± 0.33) mmol/L, (2.68 ± 0.41) mmol/L, t = 13.16, 14.85, 17.82, all P < 0.05]. After treatment, the level of high-density lipoprotein cholesterol was significantly higher in the observation group than in the control group [(1.18 ± 0.09) mmol/L vs. (1.03 ± 0.04) mmol/L, t = 10.21, P < 0.001]. After treatment, atherogenic index of plasma and Homeostasis Model Assessment of Insulin Resistance index in the observation group were (0.10 ± 0.04) and (5.12 ± 0.42), respectively in the observation group. They were significantly lower than those in the control group [(0.28 ± 0.10), (5.80 ± 0.67), t = 11.21, 5.76, both P < 0.001]. After treatment, waist circumference, hip circumference, and visceral adiposity index in the observation group were (91.05 ± 4.26) cm, (98.16 ± 5.06) cm, and (3.94 ± 0.52), respectively. They were significantly lower than those in the control group [(95.55 ± 9.87) cm, (102.64 ± 9.84) cm, (5.66 ± 1.04), t = 2.80, 2.71, 9.92, all P < 0.05). After treatment, the level of superoxide dismutase in the observation group was significantly higher than that in the control group [(101.52 ± 13.52) U/mL vs. (80.01 ± 6.82) U/mL, t = 9.52, P < 0.001]. After treatment, the level of malondialdehyde in the observation group was significantly lower than that in the control group [(4.41±0.35) nmol/L vs. (6.26 ± 0.61) nmol/L, t = 17.64, P < 0.001). Conclusion:Traditional Chinese medicine fasting therapy can effectively reduce the atherogenic index of plasma, blood lipid level, waist circumference, hip circumference, and visceral adiposity index in patients with metabolic syndrome. It also reduces oxidative stress reactions and is highly effective.

AIM:Clopidogrel and aspirin are com-monly used drugs for the secondary prevention of cerebrovascular disease.Due to drug resistance,their preventive effect is often affected.This article explores the clinical value of clopidogrel and aspirin pharmacogenetic genetic testing in the secondary prevention of ischemic stroke.METHODS:220 pa-tients with mild ischemic stroke or TIA admitted to our hospital from 2021.7 to 2022.9 were included and randomly divided into individualized treatment group and clopidogrel conventional treatment group(control group).The patients were followed up for one year to observe stroke recurrence and hemorrhagic events.RESULTS:(1)Compared with the control group,the recurrence rate of ischemic stroke in the individualized treatment group after 1-year follow-up was slightly lower(5.82％vs.7.92％,P＞0.05),the risk of cerebral hemorrhage was simi-lar,but the risk of other occurrences was increased(6.79％vs.0.99％,P＜0.05).(2)COX regression analy-sis showed that ESRS(HR 2.576,95％CI 1.226-5.413,P=0.013)and history of hypertension(HR 5.517,95％CI 1.624-18.737,P=0.006)were associated with recurrence of ischemic stroke,independent of anti-thrombotic regimen(HR 0.918,95％CI 0.291-2.894,P=0.883).CONCLUSION:Aspirin GPIBA,PTGS1,and ITGB3 gene polymorphisms have limited signifi-cance in guiding antiplatelet medication.Selecting aspirin maintenance therapy for clopidogrel CYP2C19*2*3 allele carriers cannot significantly re-duce the risk of recurrence of minor ischemic stroke and may increase other bleeding risks.COX regression analysis shows that ESRS and history of hypertension are independent risk factors for stroke recurrence.

Humans ; Glycated Hemoglobin ; Diabetes Mellitus, Type 1 ; Blood Glucose ; Diabetes Mellitus, Type 2