Traditional four examinations of traditional Chinese medicine （TCM） are based on the symptoms and signs of patients， which are the advantages of TCM but also have shortcomings. Chronic kidney disease has the characteristics of insidiousness， long-term， deficiency and variability during its onset， which are difficult to be intervened in time based on only symptoms， therefore it is necessary to extend the application of the four examinations in the diagnosis and treatment process of chronic kidney disease. Based on the background of the continuous development of TCM syndrome differentiation techniques， this article proposed the extension and application strategies of the traditional four examinations in chronic kidney disease， including the incorporation of microscopic syndrome differentiation to identify the causes of kidney disease and prevent symptom deterioration； the utilization of accurate examination information enhanced by artificial intelligence for controlling development of existing disease； the integration of disease differentiation and syndrome differentiation to summarize clinical rules towards using constant to measure variation； and the establishment of a kidney disease database for the storage of four examinations information to prevent recurrence after recovery. The four above extension and application strategies can be used to achieve the long-term management and treatment effects of timely and early diagnosis， dynamic observation of the condition， accurate application of intervention， and strengthened prognosis assessment in the diagnosis and treatment of chronic kidney disease， and expand the advantages of TCM in the prevention and treatment of chronic kidney disease.

Aim To systematically analyze the risk factors for comorbid ischemic cardiovascular and cerebrovas-cular diseases using principal component analysis.It seeks to identify key risk factors influencing comorbidity and to con-struct a predictive model to serve as a screening tool for the prevention and management of comorbidities.Methods This retrospective study included patients diagnosed with coronary artery disease from December 1,2009 to June 30,2020,at the First Affiliated Hospital of Xinjiang Medical University,using data from the hospital's integrated coronary heart dis-ease prevention platform.Patients were divided into two groups:those with both cardiovascular and cerebrovascular disea-ses and those with only coronary artery disease based on inclusion and exclusion criteria.Clinical indicators during hospi-tal admission were collected.The sample was randomly divided into a modeling set and a validation set in a 7∶3 ratio.In the modeling set,principal component analysis was used to explore the distribution differences in risk factors between the comorbid group and the single-disease group.By analyzing factor load contributions,the most significant variables were i-dentified.Logistic regression was then used to construct a predictive model,and a nomogram was generated.The model's predictive ability and robustness were evaluated in the validation set.Results A total of 11 808 participants were included,with 2 781(23.6%)in the comorbid group and 9 027(76.4%)in the coronary heart disease-only group.Compared with the single-disease group,the comorbid group had a higher average age,a greater proportion of females,and higher systolic blood pressure levels at admission(P<0.001).Additionally,thelevelsof hemoglobin,platelet distri-bution width,low density lipoprotein,and blood sodium were significantly higher in the comorbid group(P<0.05).A total of 8 265 participants were randomly assigned to the modeling set.Principal component analysis identified seven key factors with factor load contributions greater than 5:sodium level,systolic blood pressure,diastolic blood pressure,age,hemoglobin concentration,platelet distribution width,and total bilirubin level.Using these factors,a nomogram was con-structed via Logistic regression.The nomogram's area under the receiver operating characteristic curve for predicting co-morbid ischemic cardiovascular and cerebrovascular diseases was 0.630(95%CI:0.600～0.768,P<0.001).A total of 3 543 participants were randomly assigned to the validation set.In the validation set,the receiver operating characteristic curve was 0.628.Conclusion Elevated sodium level,higher systolic and diastolic blood pressure at admission,older age,increased hemoglobin concentration,higher platelet distribution width,and lower total bilirubin level are risk factors for comorbid ischemic cardiovascular and cerebrovascular diseases.The nomogram constructed has clinical value for screening patients with such comorbidities.

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.

Aim To systematically analyze the risk factors for comorbid ischemic cardiovascular and cerebrovas-cular diseases using principal component analysis.It seeks to identify key risk factors influencing comorbidity and to con-struct a predictive model to serve as a screening tool for the prevention and management of comorbidities.Methods This retrospective study included patients diagnosed with coronary artery disease from December 1,2009 to June 30,2020,at the First Affiliated Hospital of Xinjiang Medical University,using data from the hospital's integrated coronary heart dis-ease prevention platform.Patients were divided into two groups:those with both cardiovascular and cerebrovascular disea-ses and those with only coronary artery disease based on inclusion and exclusion criteria.Clinical indicators during hospi-tal admission were collected.The sample was randomly divided into a modeling set and a validation set in a 7∶3 ratio.In the modeling set,principal component analysis was used to explore the distribution differences in risk factors between the comorbid group and the single-disease group.By analyzing factor load contributions,the most significant variables were i-dentified.Logistic regression was then used to construct a predictive model,and a nomogram was generated.The model's predictive ability and robustness were evaluated in the validation set.Results A total of 11 808 participants were included,with 2 781(23.6%)in the comorbid group and 9 027(76.4%)in the coronary heart disease-only group.Compared with the single-disease group,the comorbid group had a higher average age,a greater proportion of females,and higher systolic blood pressure levels at admission(P<0.001).Additionally,thelevelsof hemoglobin,platelet distri-bution width,low density lipoprotein,and blood sodium were significantly higher in the comorbid group(P<0.05).A total of 8 265 participants were randomly assigned to the modeling set.Principal component analysis identified seven key factors with factor load contributions greater than 5:sodium level,systolic blood pressure,diastolic blood pressure,age,hemoglobin concentration,platelet distribution width,and total bilirubin level.Using these factors,a nomogram was con-structed via Logistic regression.The nomogram's area under the receiver operating characteristic curve for predicting co-morbid ischemic cardiovascular and cerebrovascular diseases was 0.630(95%CI:0.600～0.768,P<0.001).A total of 3 543 participants were randomly assigned to the validation set.In the validation set,the receiver operating characteristic curve was 0.628.Conclusion Elevated sodium level,higher systolic and diastolic blood pressure at admission,older age,increased hemoglobin concentration,higher platelet distribution width,and lower total bilirubin level are risk factors for comorbid ischemic cardiovascular and cerebrovascular diseases.The nomogram constructed has clinical value for screening patients with such comorbidities.

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:To investigate the expression and clinical implication of long non-coding RNA(lncRNA)metastasis associated lung adenocarcinoma transcript 1(MALAT1)in peripheral blood of patients with acute coronary syndrome(ACS). Methods:A total of 159 patients diagnosed with ACS who were admitted to the heart center of the First Affiliated Hospital of Xinjiang Medical University from January 2015 to December 2018 were selected as the ACS group,and 148 participants without coronary heart disease confirmed by physical examination and enhanced coronary CT examination in the physical examination center of our hospital during the same period were selected as the control group.Peripheral blood mononuclear cells of patients in two groups were extracted,and the expression level of MALAT1 was detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR),and the correlation between the expression level of MALAT1 and ACS and the diagnostic and prognostic value of MALATI expression level for ACS were analyzed. Results:The expression level of MALAT1 in peripheral blood was significantly higher in the ACS group than in the control group(P<0.05).Multivariate logistic regression analysis showed that the expression level of MALAT1 in peripheral blood was independently correlated with ACS(OR=1.193,95%CI:1.037-1.372,P=0.014).ROC curve showed that the expression level of MALAT1 in peripheral blood was of certain diagnostic value for ACS(AUC=0.664,95%CI:0.600-0.720).Kaplan-Meier survival analysis showed that ACS patients with high expression level of MALAT1 in peripheral blood(≥0.816)had higher cumulative incidence of major adverse cardiovascular events than those with low expression level of MALAT1 in peripheral blood(<0.816)during(558±223)days follow-up(39.05%vs.30.61%,P<0.05). Conclusions:The expression level of MALAT1 in peripheral blood of patients with ACS is significantly increased,and the expression level of MALAT1 in peripheral blood has potential clinical value for the diagnosis and prognosis of patients with ACS.

Objective To evaluate the value of rs61330082 and rs4730153 polymorphisms of Visfatin locus for the diagnosis of type 2 diabetes mellitus(T2DM)in a high-risk population.Methods SNPscanTM high-throughput single nucleotide polymorphism typing technique was used to genotype Visfatin gene loci rs61330082 and rs4730153 in 346 T2DM patients(T2DM group)and 1426 normal controls(NC group).Logistic regression analysis was used to analyze T2DM risk factors.ROC curves were used to analyze the optimal cut-off values of Visfatin gene rs61330082 and rs4730153 for the diagnosis of T2DM.Results The proportion of women,age,obesity,smoking,hypertension,FPG,HbA1c and TG were higher in T2DM group than those in NC group(P<0.01)and HDL-C was lower than in NC group(P<0.01).The frequency of G allele and GG genotype was higher in T2DM group compared with NC group(P<0.05).Logistic regression analysis showed that age,female,obesity,hypertension,TG,and GG genotype at rs4730153 locus were risk factors for T2DM,HDL-C was a protective factor for T2DM.The area under the ROC curve of GG genotype at Visfatin rs4730153 mutation for diagnosis of T2DM was 0.668 and the optimal cut-off point for predicting T2DM was 20.04%,with sensitivity 60.1%and specificity 66.1%,respectively.Conclusion The GG genotype of Visfatin gene rs4730153 locus is associated with the risk of T2DM and can beused as a candidate gene for predicting phenotype of T2DM.

Objectives:To investigate the effect of inhibition of long non-coding RNA(lnc RNA)in human metastasis associated lung adenocarcinoma transcript 1(MALAT1)on glycolipitoxicity-induced human umbilical vein endothelial cell dysfunction. Methods:Human umbilical vein endothelial cells were treated with glucose and palmitic acid in vitro to establish the glycolipitoxic endothelial cell models.Following groups were examined:control group,high-glucose and high-fat group,high-glucose and high-fat + non-targeting RAN control group,high-glucose and high-lipid+MALAT1 siRNA group,and high-glucose and high-lipid+MAPK1 siRNA group.RT-qPCR was used to detect the mRNA expression of MALAT1 and MAPK1.Western blot was used to detect the expression levels of autophagy,mitochondrial fusion division,apoptosis,and pathway-related proteins.Immunofluorescence confocal localization was used to detect the fluorescence colocalization of autophagy and lysosome-related proteins.The number of autophagolysosomes in endothelial cells was observed by transmission electron microscopy.Mitochondrial probe staining was used to detect mitochondrial morphology,immunofluorescence was used to detect intracellular reactive oxygen species(ROS)production,flow cytometry was used to detect the apoptosis of cells in each group,cell proliferation and scratch assays were used to detect the proliferation and migration ability of cells in different groups at different time points.The angiogenesis was quantified by counting the number of new blood vessels in each group. Results:Compared with the control group,the expression of lncRNA MALAT1 mRNA and the expression of phosphorylated mito-activated protein kinase 1(p-MAPK1)were upregulated(both P＜0.05)and the expression of phosphorylated mammalian target protein(p-mTOR)was downregulated in the high-glucose and high-fat group and the high-sugar and high-fat control group(all P＜0.01).Compared with the high-glucose and high-fat non-targeting RNA control group,the expressions of microtubule-associated protein 1A/1B-light chain 3(LC3)and p62 were downregulated(P＜0.01,P＜0.05),LC3 and lysosome-associated membrane protein 2(LAMP2)protein co-localized positive fluorescence particles were increased(both P＜0.01),number of lysosomes were decreased,the expression of ROS was decreased(P＜0.01),the expression level of mitochondrial fusion protein optic nerve atrophin 1(OPA1)was increased(P＜0.05),the expressions of cleaved caspase-3 and BCL-2-related X protein(BAX)were decreased and BCL-2 was increased(all P＜0.05),cell proliferation,migration,and tube-forming ability were increased(all P＜0.01),and the expression of p-MAPK1 was decreased(P＜0.05)and p-mTOR expression was increased(both P＜0.05)in the high-glucose and high-lipid+si-MALAT1 group.Compared with the high-glucose and high-fat non-targeting RNA control group,the expression of p-MAPK1 in endothelial cells was decreased and the expression of p-mTOR was increased in the high-glucose and high-lipid+si-MAPK1 group(both P＜0.01). Conclusions:Inhibition of lncRNA MALAT1 expression can reduce the level of mitophagy in glycolipidotoxic environments,reduce apoptosis of endothelial cells and improve endothelial cell function,which may be related to the regulation of MAPK1/mTOR signaling pathway.