Serum cystatin C,monocyte/high-density lipoprotein-C ratio,and uric acid for the diagnosis of coronary heart disease and heart failure

BACKGROUND Coronary heart disease(CHD)and heart failure(HF)are the major causes of morbidity and mortality worldwide.Early and accurate diagnoses of CHD and HF are essential for optimal management and prognosis.However,conventional diagnostic methods such as electrocardiography,echocardiography,and cardiac biomarkers have certain limitations,such as low sensitivity,specificity,availability,and cost-effectiveness.Therefore,there is a need for simple,noninvasive,and reliable biomarkers to diagnose CHD and HF.AIM To investigate serum cystatin C(Cys-C),monocyte/high-density lipoprotein cholesterol ratio(MHR),and uric acid(UA)diagnostic values for CHD and HF.METHODS We enrolled 80 patients with suspected CHD or HF who were admitted to our hospital between July 2022 and July 2023.The patients were divided into CHD(n=20),HF(n=20),CHD+HF(n=20),and control groups(n=20).The serum levels of Cys-C,MHR,and UA were measured using immunonephelometry and an enzymatic method,respectively,and the diagnostic values for CHD and HF were evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Serum levels of Cys-C,MHR,and UA were significantly higher in the CHD,HF,and CHD+HF groups than those in the control group.The serum levels of Cys-C,MHR,and UA were significantly higher in the CHD+HF group than those in the CHD or HF group.The ROC curve analysis showed that serum Cys-C,MHR,and UA had good diagnostic performance for CHD and HF,with areas under the curve ranging from 0.78 to 0.93.The optimal cutoff values of serum Cys-C,MHR,and UA for diagnosing CHD,HF,and CHD+HF were 1.2 mg/L,0.9×10^(9),and 389μmol/L;1.4 mg/L,1.0×10^(9),and 449μmol/L;and 1.6 mg/L,1.1×10^(9),and 508μmol/L,respectively.CONCLUSION Serum Cys-C,MHR,and UA are useful biomarkers for diagnosing CHD and HF,and CHD+HF.These can provide information for decision-making and risk stratification in patients with CHD and HF.

Effect of dapagliflozin on uric acid in patients with chronic heart failure and hyperuricemia

BACKGROUND Patients with chronic heart failure(CHF)frequently develop hyperuricemia,an elevated serum uric acid level,associated with adverse outcomes.Dapagliflozin,a sodium-glucose cotransporter-2 inhibitor,demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction(HFrEF),irrespective of diabetes.However,dapagliflozin’s effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear.AIM To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia.METHODS We conducted a randomized,double-blind,placebo-controlled trial in 200 patients with CHF and hyperuricemia,with HFrEF and serum uric acid levels≥7 mg/dL(≥416μmol/L).The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months.The primary endpoint was the change in serum uric acid level from baseline to 24 months.Secondary endpoints included changes in left ventricular ejection fraction(LVEF),Nterminal pro-B-type natriuretic peptide(NT-proBNP),and quality of life(QoL)scores,as well as the incidence of cardiovascular death and hospitalization for heart failure.RESULTS At 24 months,dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL(71μmol/L)compared with placebo(95%CI:-1.5 to-0.9;P<0.001).Dapagliflozin also significantly improved LVEF by 3.5%(95%CI:2.1-4.9;P<0.001),NT-proBNP by 25%(95%CI:18-32;P<0.001),and QoL scores by 10 points(95%CI:7-13;P<0.001)and reduced the risk of cardiovascular death and hospitalization for heart failure by 35%(95%CI:15–50;P=0.002)compared with the placebo.Adverse events were similar between the two groups,except for a higher rate of genital infections in the dapagliflozin group(10%vs 2%,P=0.01).CONCLUSION Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia.Therefore,dapagliflozin may be a useful therapeutic option for this high-risk population.

Analysis of Blood Lipids, Blood Glucose, Blood Uric Acid, and Blood Routine Test Results in Retired Employees of a Unit in the Civil Aviation System

Objective:To investigate and analyze the annual physical examination results of retired employees from a unit in the civil aviation system,focusing on blood lipids,blood glucose,blood uric acid,and blood routine results.The study aims to provide relevant references for formulating reasonable disease management measures for preventing and controlling hyperlipidemia,hyperuricemia,and other conditions in retired employees.Methods:The examination results of 231 participants were collected and analyzed.The participants were divided into four groups based on age:middle-aged group,young-old group,middle-old group,and old-old group.The blood test results were compared across these groups,and an assessment of atherosclerotic cardiovascular disease(ASCVD)risk levels was completed in conjunction with medical history.Blood test results were also compared by gender.Results:There were no significant statistical differences in blood test results when grouped by age.However,the prevalence of hyperuricemia was higher in males than in females,while the prevalence of hypercholesterolemia was higher in females than in males.The LDL-C target achievement rate was lower in the moderate-and-high-risk group as well as the very high-risk group as defined by ASCVD risk levels.Conclusion:Management of hyperuricemia and hyperlipidemia in retired employees(elderly patients)should be strengthened to reduce the risk of ASCVD events and alleviate the potential medical burden associated with disease progression.

Association between Serum Uric Acid to HDL-Cholesterol Ratio and Nonalcoholic Fatty Liver Disease Risk among Chinese Adults

Objective The aim of this case-control study was to explore the association between serum uric acid to high density lipoprotein cholesterol ratio(UHR) and the risk of nonalcoholic fatty liver disease(NAFLD) in Chinese adults.Methods A total of 636 patients with NAFLD and 754 controls were enrolled from the Affiliated Hospital of Qingdao University, China, between January and December 2016. All patients completed a comprehensive questionnaire survey and underwent abdominal ultrasound examination and a blood test. NAFLD was diagnosed using ultrasonography after other etiologies were excluded. Logistic regression and restricted cubic spline model were conducted to evaluate the relationship of UHR with NAFLD risk.Results The multivariable adjusted odds ratio(95% confidence interval, CI) for NAFLD in the highest versus lowest quartile of UHR was 3.888(2.324–6.504). In analyses stratified by sex and age, we observed significant and positive associations between UHR and the risk of NAFLD in each subgroup. In analyses stratified by body mass index(BMI), a significant and positive association was found only in individuals with a BMI of ≥ 24 kg/m2. Our dose-response analysis indicated a linear positive correlation between UHR and the risk of NAFLD.Conclusion UHR is positively associated with the risk of NAFLD and may serve as an innovative and noninvasive marker for identifying individuals at risk of NAFLD.

Association between Serum Uric Acid and the Early Marker of Kidney Function Decline among Chinese Middle-Aged and Older Population:Evidence from the China Health and Retirement Longitudinal Study

Objective To evaluate the association between serum uric acid(SUA)and kidney function decline.Methods Data was obtained from the China Health and Retirement Longitudinal Study on the Chinese middle-aged and older population for analysis.The kidney function decline was defined as an annual estimated glomerular filtration rate(e GFR)decrease by>3 mL/min per 1.73 m^(2).Multivariable logistic regression was applied to determine the association between SUA and kidney function decline.The shape of the association was investigated by restricted cubic splines.Results A total of 7,346 participants were included,of which 1,004 individuals(13.67%)developed kidney function decline during the follow-up of 4 years.A significant dose-response relation was recorded between SUA and the kidney function decline(OR 1.14,95%CI 1.03-1.27),as the risk of kidney function decline increased by 14%per 1 mg/d L increase in SUA.In the subgroup analyses,such a relation was only recorded among women(OR 1.22,95%CI 1.03-1.45),those aged<60 years(OR 1.22,95%CI 1.05-1.42),and those without hypertension and without diabetes(OR 1.22,95%CI 1.06-1.41).Although the dose-response relation was not observed in men,the high level of SUA was related to kidney function decline(OR 1.83,95%CI 1.05-3.17).The restricted cubic spline analysis indicated that SUA>5 mg/dL was associated with a significantly higher risk of kidney function decline.Conclusion The SUA level was associated with kidney function decline.An elevation of SUA should therefore be addressed to prevent possible kidney impairment and dysfunction.

Study on the effect of lowering uric acid and effect on the kidney of Poriae cutis in hyperuricemia mice

Objective:To explore the pharmacodynamic and renal protective effects of Poriae cutis extract on hyperuricemia(HUA)mice.Methods:The active components from the Poriae cutis were extracted with Alcohol solvent and aqueous solvent,HUA mice were established by hypoxanthine with potassium oxonate.Totally70 male Kunming mice were randomly divided into normal,model(500 mg/kg hypoxanthine+250 mg/kg potassium oxonate),Poriae cutis ethanol(PCE)and water extract(PCW)with high and low dose(388 mg/kg and 97mg/kg),benzbromarone(BEN)groups(7.5 mg/kg),all mice were administered with corresponding medication for 16 d.After the last administration,collected the 24 h urine volume,the urine uric acid(UUA)and urine creatinine(UCr)were determined.The morphological changes of the left kidney were viewed and the pathological changes in right kidneys were observed by hematoxylin-eosin(HE)staining.The serum contents of uric acid(SUA),creatinine(SCr)and urea nitrogen(BUN)were measured.Uric acid excretion index include fractional uric acid excretion(FEUA)and uric acid clearance rate(CUr)were calculated.The contents of OAT1,URAT1,GLUT9,TNF-αand IL-6 in the kidney were detected by ELISA.Results:PCE and PCW could increase UUA,UCr,FEUA,CUr and OAT1(P<0.05,P<0.01),reduce SUA,SCr,BUN,URAT1,GLUT9,TNF-αand IL-6(P<0.05,P<0.01).The pathological and morphological changes of kidneys in HUA mice were improved and the effect is better than BEN.Conclusion:Poriae cutis extractscould lower uric acid and possessed a protective effect on the kidney of mice with HUA,which was achieved by promoting uric acid excretion,regulating the expression of uric acid transporters and reducing the level of inflammatory factors.

Clinical significance of serum oxidative stress and serum uric acid levels before surgery for hepatitis B-related liver cancer

BACKGROUND The incidence and mortality of liver cancer are among the highest of all malignant tumors in China.The high recurrence rate after conventional hepatectomy is worrying.There is a lack of effective prognostic indicators for liver cancer.AIM To explore the clinical significance of preoperative serum oxidative stress and serum uric acid(UA)levels in hepatitis B-related liver cancer.METHODS The medical records of 110 hepatitis B-related liver cancer patients who under-went hepatectomy in Gansu Provincial Hospital were retrospectively analyzed.Recurrence in patients within 3 years after surgery was determined.The logistic regression model and Pearson or Spearman correlation were used to analyze the correlation between oxidative stress level and UA,and the recurrence of hepatitis B-related liver cancer.RESULTS Compared with the non-recurrence group,the levels of superoxide dismutase(SOD)and glutathione(GSH)in the recurrence group were lower and the levels of malondialdehyde(MDA)and UA were higher(all P<0.05).UA,SOD,MDA,and GSH were risk factors for postoperative recurrence in hepatitis B-related liver cancer patients(P<0.05).UA was positively correlated with MDA(r=0.395,P<0.001)and negatively correlated with GSH(r=-0.204,P=0.032).The area under the receiver operating characteristic curve(AUC)of SOD,MDA,GSH,and UA in predicting the prognosis was 0.276,0.910,0.199,and 0.784,respectively(all P<0.001).CONCLUSION The preoperative serum SOD,GSH,MDA,and UA levels had significant predictive effects on postoperative recurrence of hepatitis B-related liver cancer.

Clinical Significance of Serum Uric Acid Combined with Cystatin C Detection in Patients with Different Levels of Hypertension with High Risk Degree and Above

Objective: To explore the clinical significance of serum uric acid combined with cystatin C detection in high risk degree of hypertension of different grades. Methods: The patients who were treated in the Department of Cardiovascular Medicine of our hospital from January to December 2022 were selected as the study subjects, and the high risk and extremely high risk groups of grade I, II and III hypertension were selected for comparative analysis to explore their clinical significance. Results: There was a statistically significant difference in the number of patients with extremely high risk of grade II hypertension between men and women (P 0.05), which showed that there was no specificity in the concentration detection of serum uric acid and cystatin C in different grades of hypertension;there was no significant difference in serum uric acid concentration between grade II and grade III of hypertension with high risk grade and cystatin C concentration between grade I and grade III of hypertension with high risk grade (P > 0.05), but there was significant difference in the concentration detection of serum uric acid and cystatin C between the other groups (P < 0.05), which indicates that the detection of serum uric acid and cystatin C has important clinical significance in the high risk degree of hypertension. Conclusion: In the comparison of the detection of blood uric acid and cystatin C in different levels of hypertension with extremely high risk, the difference of cystatin C in grade I and grade III was not statistically significant, and the rest were statistically significant;therefore, the detection of serum uric acid and cystatin C can provide reliable laboratory data for clinical diagnosis and treatment of the extremely high risk degree of different levels of hypertension.

Preparation of New Uric Acid Sensors Based on Iodide Selective Electrode

An electrode for uric acid has been prepared by using an iodide selective electrode with the uricase enzyme. The iodide selective electrode used was prepared from 10% TDMAI and PVC according to our previous study. The enzyme was immobilized on the iodide electrode by holding it at pH 7 phosphate buffer for 20 min at room temperature. The H2O2 formed from the reaction of uric acid was determined from the decrease of iodide concentration that was present in the reaction cell. The potential change was linear in the 2 × 10-5 to 2 × 10-4 M uric acid concentration (3 - 34 mg uric acid/100ml blood) range. Uric acid contents of some blood samples were determined with the new electrode and consistency was obtained with a colorimetric method. The effects of pH, iodide concentration, the amount of enzyme immobilized and the operating temperature were studied. No interference of ascorbic acid, glucose and urea was observed.

Linking uric acid metabolism to diabetic complications

Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase(XDH/XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid(UA) generation inhibitor in the 1950 s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target forvascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted.

Serum Uric Acid is Associated with the Predicted Risk of Prevalent Cardiovascular Disease in a Community-dwelling Population without Diabetes

Objective To examine the association between serum uric acid levels and cardiovascular disease risk among individuals without diabetes.Methods We investigated the association between serum uric acid levels and the risk of prevalent cardiometabolic diseases, 10-year Framingham risk for coronary heart disease, and 10-year risk for atherosclerotic cardiovascular diseases （ASCVD） among 8,252 participants aged 〉 40 years without diabetes from Jiading district, Shanghai, China.Results Body mass index, waist circumference, blood glucose, glycated hemoglobin, blood pressure, and serum lipids increased progressively across the sex-specific quartiles of uric acid （all P trend 〈 0.05）. Compared with individuals in the lowest quartile, those in the higher quartiles had a significantly higher prevalence of obesity, hypertension, and dyslipidemia （all P trend 〈 0.05）. A fully adjusted logistic regression analysis revealed that individuals in the highest quartile had an increased risk of predicted cardiovascular disease compared with those in the lowest quartile of uric acid. The multivariate adjusted odds ratios （ORs） [95% confidence intervals （C/s）] for the highest quartiles for high Framingham risk were 3.00 （2.00-4.50） in men and 2.95 （1.08-8.43） in women. The multivariate adjusted ORs （95% C/s） for the highest quartile for high ASCVD risk were 1.93 [1.17-3.17） in men and 4.53 （2.57-7.98） in women.Conclusion Serum uric acid level is associated with an increased risk of prevalent obesity, hypertension, dystipidemia, 10-year Framingham risk for coronary heart disease, and lO-year risk for ASCVD among Chinese adults without diabetes.

Serum uric acid as a prognostic marker in the setting of advanced vascular disease： a prospective study in the elderly

Background Many epidemiological studies analyze the relationship between hyperuricemia and cardiovascular outcomes. This observational prospective study investigates the association of serum uric acid （SUA） levels with adverse cardiovascular events and deaths in an elderly population affected by advanced atherosclerosis. Methods Two hundred and seventy six elderly patients affected by advanced atherosclerosis （217 males and 59 females; aged 71.2 ±7.8 years） were included. All patients were assessed for history of cardiovascular disease, cancer, obesity and traditional risk factors. Patients were followed for approximately 31 ±11 months. Major events were recorded during follow-up, defined as myocardial infarction, cerebral isehemia, myocardial and/or peripheral revascularization and death. Results Mean SUA level was 5.47 ±1.43 mg/dL; then we further divided the population in two groups, according to the median value （5.36 mg/dL）. During a median follow up of 31 months （5 to 49 months）, 66 cardiovascular events, 9 fatal cardiovascular events and 14 cancer-related deaths have occurred. The patients with increased SUA level presented a higher significant incidence of total cardiovascular events （HR： 1.867, P = 0.014, 95% CI： 1.134-3.074）, The same patients showed a significant increased risk of cancer-related death （HR： 4.335, P = 0.025, 95% CI： 1.204-15.606）. Conclusions Increased SUA levels are independently and significantly associated with risk of cardiovascular events and cancer related death in a population of mainly elderly patients affected by peripheral vasculopathy.

Science Letters:Evaluation of a kinetic uricase method for serum uric acid assay by predicting background absorbance of uricase reaction solution with an integrated method

A patented kinetic uricase method was evaluated for serum uric acid assay. Initial absorbance of the reaction mixture before uricase action （A0） was obtained by correcting the absorbance at 293 nm measured before the addition of uricase solution, and background absorbance （Ab） was predicted by an integrated method. Uric acid concentration in reaction solution was calculated from AA, the difference between A0 and Ab, using the absorptivity preset for uric acid. This kinetic uricase method exhibited CV〈4.3% and recovery of 100%. Lipids, bilirubin, hemoglobin, ascorbic acid, reduced glutathione and xanthine 〈0.32 mmol/L in serum had no significant effects. △A linearly responded to 1.2 to 37.5 μmol/L uric acid in reaction solution containing 15 μl serum. The slope of linear response was consistent with the absorptivity preset for uric acid while the intercept was consistent with that for serum alone. Uric acid concentrations in clinic sera by different uricase methods positively correlated to each other. By Bland-Altman analysis, this kinetic uricase method accorded with that by quantifying the total change of UV absorbance on the completion of uricase reaction. These results demonstrated that this kinetic uricase method is reliable for serum uric acid assay with enhanced resistance to both xanthine and other common errors, wider range of linear response and much lower cost.

Association Between Serum Uric Acid and Prevalence of Type 2 Diabetes Diagnosed using HbA1c Criteria Among Chinese Adults in Qingdao,China

Objective To determine whether elevated serum uric acid(UA)levels are associated with type 2 diabetes diagnosed using Hb A1 c levels among Chinese adults.Methods We conducted two population-based cross-sectional studies in Qingdao in China in 2006 and 2009.A total of 6894(39.4% men)subjects aged 35-74 years were included in the data analysis.Newly diagnosed diabetes was defined as Hb A1 c level of ≥6.5%,and prediabetes was classified as Hb A1 c level between 5.7% and 6.4% according to the International Diabetes Federation criteria.Multivariate logistic regression was employed to assess the association between UA and prevalence of type 2 diabetes defined using Glycated hemoglobin A1c(Hb A1 c levels.Results Subjects with prediabetes had higher UA levels than those with normal glucose tolerance,newly diagnosed diabetes,and known diabetes,with corresponding values of 325.1(82.5)μmol/L,310.9(84.2)μmol/L,291.3(81.7)μmol/L,305.2(83.6)μmol/L,respectively(P<0.001 for all comparisons).Binary logistic regression analysis showed that UA was a possible predictor for the prevalence of type 2 diabetes diagnosed using Hb A1 c levels,and the second quartile of UA levels had a higher odds ratio(OR:4.088;95% CI:2.900-5.765)for Hb A1 c than the other quartiles after adjusting for age,body mass index,sex,marital status,education,income,alcohol consumption,smoking,and cardiometabolic parameters.Conclusion Serum UA is significantly associated with type 2 diabetes diagnosed using Hb A1 c levels,independent of other cardiometabolic parameters.

Serum uric acid as an index of impaired renal function in congestive heart failure

Background Hyperuricemia is frequently present in patients with heart failure. Many pathological conditions, such as tissue ischemia, renal function impairment, cardiac function impairment, metabolic syndrome, and inflammatory status, may impact uric acid （UA） metabolism. This study was to assess their potential relations to UA metabolism in heart failure. Methods We retrospectively assessed clinical charac- teristics, echocardiological, renal, metabolic and inflammatory variables selected on the basis of previous evidence of their involvement in cardiovascular diseases and UA metabolism in a large cohort of randomly selected adults with congestive heart failure （n = 553）. By clustering of indices, those variables were explored using factor analysis. Results In factor analysis, serum uric acid （SUA） formed part of a principal cluster of renal functional variables which included serum creatinine （SCr） and blood urea nitrogen （BUN）. Univariate correlation coefficients between variables of patients with congestive heart failure showed that the strongest correlations for SUA were with BUN （r = 0.48, P 〈 0.001） and SCr （r = 0.47, P 〈 0.001）. Conclusions There was an inverse relationship between SUA levels and measures of renal function in patients with congestive heart failure. The strong correlation between SUA and SCr and BUN levels suggests that elevated SUA concentrations reflect an impairment of renal function in heart failure.

Confounders of uric acid level for assessing cardiovascular outcomes

We read the article entitled Serum uric＇ acid as a prognostic marker in the setting of advanced vascular disease： a prospective study in the elderly by Stolfo, et al. with great interest. The authors evaluated the association of serum uric acid （SUA） levels with adverse cardiovascular events and deaths in an elderly population affected by advanced atherosclerosis. They founded meaningful association between SUA levels and of cardiovascular events and cancer related death. We believe that these findings will lead for further studies on uric acid.

Associations between serum uric acid and hepatobiliary-pancreatic cancer:A cohort study

BACKGROUND Uric acid is the end product of purine metabolism.Previous studies have found that serum uric acid(SUA)levels are associated with the total cancer risk.However,due to the dual effect of uric acid on cancer,the relationship between the SUA levels and most specific-site cancer remains unclear.AIM To investigate the associations between the SUA levels and incidence of hepatobiliary-pancreatic cancer.METHODS In this prospective cohort study,444462 participants free of cancer from the UK Biobank were included.The SUA levels were measured at baseline,and the incidence of hepatobiliary-pancreatic cancer was determined by contacting the cancer registry.The hazard ratios(HRs)and 95%confidence intervals(CIs)between the SUA levels and hepatobiliary-pancreatic cancer were investigated using multiple adjusted Cox regression models adjusted for potential confounders.RESULTS In total,920 participants developed liver,gallbladder,biliary tract or pancreatic cancer during a median of 6.6 yrs of follow-up.We found that the HR of pancreatic cancer in the highest SUA group was 1.77(95%CI:1.29-2.42)compared with that in the lowest group.After stratifying by gender,we further found that SUA was associated with an increased risk of pancreatic cancer only among the females(highest quartile vs lowest quartile HR 2.04,95%CI:1.35-3.08).Among the males,the SUA levels were positively associated with the gallbladder cancer risk(highest quartile vs lowest quartile HR 3.09,95%CI:1.28-7.46),but a U-shaped association with the liver cancer risk was observed(P-nonlinear=0.03).CONCLUSION SUA is likely to have gender-specific effects on hepatobiliary-pancreatic cancer.High SUA levels are a risk factor for pancreatic cancer in females and gallbladder cancer in males.A U-shaped association with the liver cancer risk was identified.

Single‑Atom Cobalt‑Based Electrochemical Biomimetic Uric Acid Sensor with Wide Linear Range and Ultralow Detection Limit

Uric acid(UA)detection is essential in diagnosis of arthritis,preeclampsia,renal disorder,and cardiovascular diseases,but it is very challenging to realize the required wide detection range and low detection limit.We present here a single-atom catalyst consisting of Co(Ⅱ)atoms coordinated by an average of 3.4 N atoms on an N-doped graphene matrix(A-Co-NG)to build an electrochemical biomimetic sensor for UA detection.The A-Co-NG sensor achieves a wide detection range over 0.4-41,950μM and an extremely low detection limit of 33.3±0.024 nM,which are much better than previously reported sensors based on various nanostructured materials.Besides,the A-Co-NG sensor also demonstrates its accurate serum diagnosis for UA for its practical application.Combination of experimental and theoretical calculation discovers that the catalytic process of the A-Co-NG toward UA starts from the oxidation of Co species to form a Co^3+-OH-UA*,followed by the generation of Co^3+-OH+^*UA_H,eventually leading to N-H bond dissociation for the formation of oxidized UA molecule and reduction of oxidized Co^3+to Co^2+for the regenerated A-Co-NG.This work provides a promising material to realize UA detection with wide detection range and low detection limit to meet the practical diagnosis requirements,and the proposed sensing mechanism sheds light on fundamental insights for guiding exploration of other biosensing processes.

Serum uric acid is a risk factor for large-artery atherosclerosis cerebral infarction

Using the Trial of Org 10172 in Acute Stroke Treatment （TOAST） classification for acute ischemic stroke, 371 patients with either acute large-artery atherosclerosis or small-artery oc-clusion cerebral infarction were recruited to investigate the potential impact of elevated serum uric acid on cerebrovascular disorders. The results showed that patients who have suffered from large-artery atherosclerosis, relative to small-artery occlusion patients, were characterized by elevated serum uric acid but reduced high-density lipoprotein cholesterol and triglyceride levels. Logistic regression showed that elevated uric acid and lower triglyceride levels were the main risk factors for patients with large-artery atherosclerosis. The findings of this study suggest that hyperuricemia may be a risk factor for stroke.

Uric acid enhances T cell immune responses to hepatitis B surface antigen-pulsed-dendritic cells in mice

AIM： To study the induction of T cellular immune responses in BALB/c mice immunized with uric acid and dendritic cells （DCs） pulsed with hepatitis B virus surface antigen （HBsAg）. METHODS： DCs were generated from bone-marrow cells of BABL/c mice, and then pulsed or unpulsed with HBsAg protein （HBsAg-pulsed-DCs or unpulsed-DCs） in vitro. BABL/c mice were immunized with HBsAg-pulsed- DCs （1 × 10^6） and uric acid, injected through the tail vein of each mouse. The mice in control groups were immunized with HBsAg-pulsed-DCs alone, unpulsed- DCs alone or 200 μg uric acid alone or PBS alone. The immunization was repeated 7 d later. Cytotoxic T lymphocytes （CTLs） in vivo were determined by the CFSE labeled spleen lysis assay. Spleen cells or spleen T cells were isolated, and re-stimulated in vitro with HBsAg for 120 h or 72 h. Production of IFN-γ, and IL-4 secreted by spleen cells were determined by ELISA method; proliferation of spleen T cells were detected by flow cytometry. RESULTS： The cytotoxicities of HBsAg-specific-CTLs, generated after immunization of HBsAg-pulsed-DCs and uric acid, were 68.63% ±11.32% and significantly stronger than that in the control groups （P 〈 0.01）. Compared with control groups, in mice treated with uric acid and HBsAg-pulsed-DCs, the spleen T cell proliferation to HBsAg re-stimulation was stronger （1.34 ± 0.093 vs 1.081±0.028, P 〈 0.01）, the level of IFN-t, secreted by splenocytes was higher （266.575 ± 51.323 vs 135.223 ±32.563, P 〈 0.01） , and IL-4 level wasower （22.385 ± 2.252 vs 40.598 ± 4.218, P 〈 0.01）. CONCLUSION： Uric acid can strongly enhance T cell immune responses induced by HBsAg-pulsed-DCs vaccine. Uric acid may serve as an effective adjuvant of DC vaccine against HBV infection.