Background Biomarkers-based prediction of long-term risk of acute coronary syndrome(ACS)is scarce.We aim to develop a risk score integrating clinical routine information(C)and plasma biomarkers(B)for predicting long-t...Background Biomarkers-based prediction of long-term risk of acute coronary syndrome(ACS)is scarce.We aim to develop a risk score integrating clinical routine information(C)and plasma biomarkers(B)for predicting long-term risk of ACS patients.Methods We included 2729 ACS patients from the OCEA(Observation of cardiovascular events in ACS patients).The earlier admitted 1910 patients were enrolled as development cohort;and the subsequently admitted 819 subjects were treated as valida-tion cohort.We investigated 10-year risk of cardiovascular(CV)death,myocardial infarction(MI)and all cause death in these pa-tients.Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was de-rived using main part of these variables.Results During 16,110 person-years of follow-up,there were 238 CV death/MI in the development cohort.The 7 most import-ant predictors including in the final model were NT-proBNP,D-dimer,GDF-15,peripheral artery disease(PAD),Fibrinogen,ST-segment elevated MI(STEMI),left ventricular ejection fraction(LVEF),termed as CB-ACS score.C-index of the score for predica-tion of cardiovascular events was 0.79(95%CI:0.76-0.82)in development cohort and 0.77(95%CI:0.76-0.78)in the validation co-hort(5832 person-years of follow-up),which outperformed GRACE 2.0 and ABC-ACS risk score.The CB-ACS score was also well calibrated in development and validation cohort(Greenwood-Nam-D’Agostino:P=0.70 and P=0.07,respectively).Conclusions CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS.This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.展开更多
Objective We aimed to investigate the patterns of fasting blood glucose(FBG)trajectories and analyze the relationship between various occupational hazard factors and FBG trajectories in male steelworkers.Methods The s...Objective We aimed to investigate the patterns of fasting blood glucose(FBG)trajectories and analyze the relationship between various occupational hazard factors and FBG trajectories in male steelworkers.Methods The study cohort included 3,728 workers who met the selection criteria for the Tanggang Occupational Cohort(TGOC)between 2017 and 2022.A group-based trajectory model was used to identify the FBG trajectories.Environmental risk scores(ERS)were constructed using regression coefficients from the occupational hazard model as weights.Univariate and multivariate logistic regression analyses were performed to explore the effects of occupational hazard factors using the ERS on FBG trajectories.Results FBG trajectories were categorized into three groups.An association was observed between high temperature,noise exposure,and FBG trajectory(P<0.05).Using the first quartile group of ERS1 as a reference,the fourth quartile group of ERS1 had an increased risk of medium and high FBG by 1.90and 2.21 times,respectively(odds ratio[OR]=1.90,95%confidence interval[CI]:1.17–3.10;OR=2.21,95%CI:1.09–4.45).Conclusion An association was observed between occupational hazards based on ERS and FBG trajectories.The risk of FBG trajectory levels increase with an increase in ERS.展开更多
Objective:Neuroblastoma is the most common extracranial solid tumor in children and has complex genetic underpinnings.Previous genome-wide association studies(GWASs)have identified many loci associated with neuroblast...Objective:Neuroblastoma is the most common extracranial solid tumor in children and has complex genetic underpinnings.Previous genome-wide association studies(GWASs)have identified many loci associated with neuroblastoma susceptibility;however,their application in risk prediction for Chinese children has not been systematically explored.This study seeks to enhance neuroblastoma risk prediction by validating these loci and evaluating their performance in polygenic risk models.Methods:We validated 35 GWAS-identified neuroblastoma susceptibility loci in a cohort of Chinese children,consisting of 402 neuroblastoma patients and 473 healthy controls.Genotyping these polymorphisms was conducted via the TaqMan method.Univariable and multivariable logistic regression analyses revealed the genetic loci significantly associated with neuroblastoma risk.We constructed polygenic risk models by combining these loci and assessed their predictive performance via area under the curve(AUC)analysis.We also established a polygenic risk scoring(PRS)model for risk prediction by adopting the PLINK method.Results:Fourteen loci,including ten protective polymorphisms from CASC15,BARD1,LMO1,HSD17B12,and HACE1,and four risk variants from BARD1,RSRC1,CPZ and MMP20 were significantly associated with neuroblastoma risk.Compared with single-gene model,the 8-gene model(AUC=0.72)and 13-gene model(AUC=0.73)demonstrated superior predictive performance.Additionally,a PRS incorporating six significant loci achieved an AUC of 0.66,effectively stratifying individuals into distinct risk categories regarding neuroblastoma susceptibility.A higher PRS was significantly associated with advanced International Neuroblastoma Staging System(INSS)stages,suggesting its potential for clinical risk stratification.Conclusions:Our findings validate multiple loci as neuroblastoma risk factors in Chinese children and demonstrate the utility of polygenic risk models,particularly the PRS,in improving risk prediction.These results suggest that integrating multiple genetic variants into a PRS can enhance neuroblastoma risk stratification and potentially improve early diagnosis by guiding targeted screening programs for high-risk children.展开更多
BACKGROUND The prevalence of coronary heart disease(CHD)is higher in patients with depression than in the general population.Recently,multiple novel biomarkers have been proposed to predict CHD risk,and these factors ...BACKGROUND The prevalence of coronary heart disease(CHD)is higher in patients with depression than in the general population.Recently,multiple novel biomarkers have been proposed to predict CHD risk,and these factors have been reported to be altered in patients with depression.AIM To explore whether these new biomarkers are associated with an increased risk of CHD in patients with depression.METHODS We recruited 279 healthy controls and 164 sex-and age-matched patients with depression and collected their clinical characteristics and laboratory values of novel cardiovascular biomarkers.The Framingham CHD risk score was used to assess the CHD risk of all individuals,and the cardiovascular markers related to the CHD risk in patients with depression were analyzed.RESULTS Patients with depression had an increased CHD risk of 5.3%(95%confidence interval:4.470-6.103)and altered novel cardiovascular biomarkers compared to healthy controls,which included lower levels of thyroid stimulating hormone,albumin,total bilirubin,total cholesterol,high-density lipoprotein cholesterol,and higher levels of triglyceride(TG)and uric acid.Further regression analysis showed that illness duration,family history of depression,serum TG,and urea acid levels were significantly correlated with the Framingham risk score in patients with depression.CONCLUSION Patients with depression had a higher CHD risk and that their illness duration,family history of depression,serum TG,and uric acid levels could play important roles in predicting CHD risk.Moreover,elevated CHD risk in patients with depression was not only related to physiological changes caused by depression but also to their genetic susceptibility.展开更多
BACKGROUND Liver grafts from donation after circulatory death(DCD)are associated with a higher risk of early graft dysfunction,determined by the warm ischemia and cold ischemia times.It is essential to have precise cr...BACKGROUND Liver grafts from donation after circulatory death(DCD)are associated with a higher risk of early graft dysfunction,determined by the warm ischemia and cold ischemia times.It is essential to have precise criteria to identify this complication in order to guide therapeutic strategies.AIM To validate different graft and recipient survival scores in patients undergoing liver transplantation(LT)with DCD grafts.METHODS A retrospective and observational unicentric study was conducted on 65 LT patients with grafts obtained from controlled DCD donors from November 2013 to November 2022.The United Kingdom(UK)risk score,early allograft dysfunction(EAD)Olthoff score,and model for early allograft function(MEAF)score were used to evaluate the risk of graft and recipient survival post-transplant.For survival analysis purposes,we used the Kaplan-Meier method,and the differences between subgroups were compared using the log-rank(Mantel-Cox)test.RESULTS Sixty-five patients were included in the study.The UK risk score did not demonstrate predictive capacity for recipient or graft survival.However,in donors aged over 70 years old(18.4%),it significantly predicted graft survival(P<0.05).According to Kaplan-Meier survival curves,graft survival rates at 6 months,2 years,and 5 years in the futility group dramatically decreased to 50%compared to the other groups(log-rank 8.806,P<0.05).The EAD Olthoff and MEAF scores did not demonstrate predictive capacity for recipient or graft survival.Based on Kaplan-Meier survival curves,patients with a MEAF score≥7 had a lower graft survival rate at 6 months,2 years,and 5 years compared to patients with a lower MEAF score(log-rank 4.667,P<0.05).CONCLUSION In our series,both UK DCD risk score and MEAF score showed predictive capability for graft survival.展开更多
Several different approaches are available to clinicians for determining prostate cancer （PCa） risk. The clinical validity of various PCa risk assessment methods utilizing single nucleotide polymorphisms （SNPs） ha...Several different approaches are available to clinicians for determining prostate cancer （PCa） risk. The clinical validity of various PCa risk assessment methods utilizing single nucleotide polymorphisms （SNPs） has been established; however, these SNP-based methods have not been compared. The objective of this study was to compare the three most commonly used SNP-based methods for PCa risk assessment. Participants were men （n = 1654） enrolled in a prospective study of PCa development. Genotypes of 59 PCa risk-associated SNPs were available in this cohort. Three methods of calculating SNP-based genetic risk scores （GRSs） were used for the evaluation of individual disease risk such as risk allele count （GRS-RAC）, weighted risk allele count （GRS-wRAC）, and population-standardized genetic risk score （GRS-PS）. Mean GRSs were calculated, and performances were compared using area under the receiver operating characteristic curve （AUC） and positive predictive value （PPV）. All SNP-based methods were found to be independently associated with PCa （all P 〈 0.05; hence their clinical validity）. The mean GRSs in men with or without PCa using GRS-RAC were 55.15 and 53.46, respectively, using GRS-wRAC were 7.42 and 6.97, respectively, and using GRS-PS were 1.12 and 0.84, respectively （all P 〈 0.05 for differences between patients with or without PCa）. All three SNP-based methods performed similarly in discriminating PCa from non-PCa based on AUC and in predicting PCa risk based on PPV （all P 〉 0.05 for comparisons between the three methods）, and all three SNP-based methods had a significantly higher AUC than family history （all P 〈 0.05）. Results from this study suggest that while the three most commonly used SNP-based methods performed similarly in discriminating PCa from non-PCa at the population level, GRS-PS is the method of choice for risk assessment at the individual level because its value （where 1.0 represents average population risk） can be easily interpreted regardless of the number of risk-associated SNPs used in the calculation.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a common cancer with a poor prognosis.Previous studies revealed that the tumor microenvironment(TME)plays an important role in HCC progression,recurrence,and metastasis,leadi...BACKGROUND Hepatocellular carcinoma(HCC)is a common cancer with a poor prognosis.Previous studies revealed that the tumor microenvironment(TME)plays an important role in HCC progression,recurrence,and metastasis,leading to poor prognosis.However,the effects of genes involved in TME on the prognosis of HCC patients remain unclear.Here,we investigated the HCC microenvironment to identify prognostic genes for HCC.AIM To identify a robust gene signature associated with the HCC microenvironment to improve prognosis prediction of HCC.METHODS We computed the immune/stromal scores of HCC patients obtained from The Cancer Genome Atlas based on the ESTIMATE algorithm.Additionally,a risk score model was established based on Differentially Expressed Genes(DEGs)between high and lowimmune/stromal score patients.RESULTS The risk score model consisting of eight genes was constructed and validated in the HCC patients.The patients were divided into high-or low-risk groups.The genes(Disabled homolog 2,Musculin,C-X-C motif chemokine ligand 8,Galectin 3,B-cell-activating transcription factor,Killer cell lectin like receptor B1,Endoglin and adenomatosis polyposis coli tumor suppressor)involved in our risk score model were considered to be potential immunotherapy targets,and they may provide better performance in combination.Functional enrichment analysis showed that the immune response and T cell receptor signaling pathway represented the major function and pathway,respectively,related to the immune-related genes in the DEGs between high-and low-risk groups.The receiver operating characteristic(ROC)curve analysis confirmed the good potency of the risk score prognostic model.Moreover,we validated the risk score model using the International Cancer Genome Consortium and the Gene Expression Omnibus database.A nomogram was established to predict the overall survival of HCC patients.CONCLUSION The risk score model and the nomogram will benefit HCC patients through personalized immunotherapy.展开更多
To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer’s disease(sAD)and pathological biomarkers in cerebrospinal fluid(CSF),462 sAD patients and 463 age-matched cognitively normal(C...To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer’s disease(sAD)and pathological biomarkers in cerebrospinal fluid(CSF),462 sAD patients and 463 age-matched cognitively normal(CN)controls were genotyped for 35 singlenucleotide polymorphisms(SNPs)that are significantly associated with sAD.Then,the alleles found to be associated with sAD were used to build polygenic risk score(PRS)models to represent the genetic risk.Receiver operating characteristic(ROC)analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset.We measured the CSF levels of Aβ42,Aβ42/Aβ40,total tau(T-tau),and phosphorylated tau(P-tau)in a subgroup(60 sAD and 200 CN participants),and analyzed their relationships with the PRSs.We found that 14 SNPs,including SNPs in the APOE,BIN1,CD33,EPHA1,SORL1,and TOMM40 genes,were associated with sAD risk in our cohort.The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls,and were able to predict the incidence rate of sAD and age at onset.Furthermore,the PRSs were correlated with the CSF levels of Aβ42,Aβ42/Aβ40,T-tau,and P-tau.Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD.As genetic risk profiles vary among populations,large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.展开更多
Age is an important prognostic factor in the outcome of acute coronary syndromes （ACS）. A substantial percentage of patients who ex- perience ACS is more than 75 years old, and they represent the fastest-growing seg...Age is an important prognostic factor in the outcome of acute coronary syndromes （ACS）. A substantial percentage of patients who ex- perience ACS is more than 75 years old, and they represent the fastest-growing segment of the population treated in this setting. These pa- tients present different patterns of responses to pharmacotherapy, namely, a higher ischemic and bleeding risk than do patients under 75 years of age. Our aim was to identify whether the currently available ACS ischemic and bleeding risk scores, which has been validated for the general population, may also apply to the elderly population. The second aim was to determine whether the elderly benefit more from a spe- cific pharmacological regimen, keeping in mind the numerous molecules of antiplatelet and antithrombotic drugs, all validated in the general population. We concluded that the GRACE （Global Registry of Acute Coronary Events） risk score has been extensively validated in the elderly. However, the CRUSADE （Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early imple- mentation of the ACC/AHA Guidelines） bleeding score has a moderate correlation with outcomes in the elderly. Until now, there have not been head-to-head scores that quantify the ischemic versus hemorrhagic risk or scores that use the same end point and timeline （e.g., ischemic death rate versus bleeding death rate at one month）. We also recommend that the frailty score be considered or integrated into the current existing scores to better quantify the overall patient risk. With regard to medical treatment, based on the subgroup analysis, we identified the drugs that have the least adverse effects in the elderly while maintaining optimal efficacy.展开更多
Background Previous studies have demonstrated that micro RNA-204(mi R-204) is involved in atherosclerosis and vascular calcification. However, the value of mi R-204 as the predictive biomarker for cardiovascular disea...Background Previous studies have demonstrated that micro RNA-204(mi R-204) is involved in atherosclerosis and vascular calcification. However, the value of mi R-204 as the predictive biomarker for cardiovascular disease(CVD) remains unclear. We aimed to evaluate the association between the circulating mi R-204 level and ten-year CVD risk based on the Framingham risk score(FRS). Methods In this retrospective study, we enrolled 194 consecutive patients with type 2 diabetes mellitus(T2DM) without CVD in Beijing Anzhen Hospital between January 2015 and September 2016. We used the FRS to evaluate the risk of CVD for each patient. Circulating mi R-204 levels were measured by quantitative real-time polymerase chain reaction. Results Circulating mi R-204 levels were significantly lower in the group of patients(0.49 ± 0.13) at high risk of CVD(FRS > 20%) than in the low(FRS < 10%) and intermediate(FRS: 10%–20%) risk groups(0.87 ± 0.19 and 0.75 ± 0.25, respectively;P < 0.001). FRS was negatively correlated with mi R-204 levels(r =-0.421, P < 0.001). According to multivariate logistic analyses, reduced mi R-204 level was independently associated with an increased risk of CVD after adjusting for conventional risk factors(OR = 0.876, 95% CI: 0.807–0.950, P = 0.001). Receiver-operating characteristic curve analysis showed that the circulating mi R-204 level can predict the high risk of CVD with higher specificity than the traditional risk factor of high systolic blood pressure or the protective factor of high-density lipoprotein cholesterol. Conclusions Our study demonstrated that patients with lower circulating mi R-204 levels were at high risk for CVD. After adjustment for potential confounders, mi R-204 was independently associated with CVD in patients with T2DM.展开更多
Non-alcoholic fatty liver disease(NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma(HCC). Therefore, risk stratificat...Non-alcoholic fatty liver disease(NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma(HCC). Therefore, risk stratification emerges as fundamental in order to optimize human and economic resources, and genetics displays intrinsic characteristics suitable to fulfill this task. According to the available data, heritability estimates for hepatic fat content range from 20% to 70%, and an almost 80% of shared heritability has been found between hepatic fat content and fibrosis. The rs738409 single nucleotide polymorphism(SNP) in patatin-like phospholipase domain-containing protein 3 gene and the rs58542926 SNP in transmembrane 6 superfamily member 2 gene have been robustly associated with NAFLD and with its progression, but promising results have been obtained with many other SNPs. Moreover, there has been proof of the additive role of the different SNPs in determining liver damage, and there have been preliminary experiences in which risk scores created through a few genetic variants, alone or in combination with clinical variables, were associated with a strongly potentiated risk of NAFLD, non-alcoholic steatohepatitis(NASH), NASH fibrosis or NAFLD-HCC. However, to date, clinical translation of genetics in the field of NAFLD has been poor or absent. Fortunately, the research we have done seems to have placed us on the right path: We should rely on longitudinal rather than on cross-sectional studies; we should focus on relevant outcomes rather than on simple liver fat accumulation; and we should put together the genetic and clinical information. The hope is that combined genetic/clinical scores, derived from longitudinal studies and built on a few strong genetic variants and relevant clinical variables, will reach a significant predictive power, such as to have clinical utility for risk stratification at the single patient level and even to esteem the impact of intervention on the risk of disease-related outcomes. Well-structured future studies would demonstrate if this vision can become a reality.展开更多
BACKGROUND Upper gastrointestinal(GI)bleeding is a life-threatening condition with high mortality rates.AIM To compare the performance of pre-endoscopic risk scores in predicting the following primary outcomes:In-hosp...BACKGROUND Upper gastrointestinal(GI)bleeding is a life-threatening condition with high mortality rates.AIM To compare the performance of pre-endoscopic risk scores in predicting the following primary outcomes:In-hospital mortality,intervention(endoscopic or surgical)and length of admission(≥7 d).METHODS We performed a retrospective analysis of 363 patients presenting with upper GI bleeding from December 2020 to January 2021.We calculated and compared the area under the receiver operating characteristics curves(AUROCs)of Glasgow-Blatchford score(GBS),pre-endoscopic Rockall score(PERS),albumin,international normalized ratio,altered mental status,systolic blood pressure,age older than 65(AIMS65)and age,blood tests and comorbidities(ABC),including their optimal cut-off in variceal and non-variceal upper GI bleeding cohorts.We subsequently analyzed through a logistic binary regression model,if addition of lactate increased the score performance.RESULTS All scores had discriminative ability in predicting in-hospital mortality irrespective of study group.AIMS65 score had the best performance in the variceal bleeding group(AUROC=0.772;P<0.001),and ABC score(AUROC=0.775;P<0.001)in the non-variceal bleeding group.However,ABC score,at a cut-off value of 5.5,was the best predictor(AUROC=0.770,P=0.001)of inhospital mortality in both populations.PERS score was a good predictor for endoscopic treatment(AUC=0.604;P=0.046)in the variceal population,while GBS score,(AUROC=0.722;P=0.024),outperformed the other scores in predicting surgical intervention.Addition of lactate to AIMS65 score,increases by 5-fold the probability of in-hospital mortality(P<0.05)and by 12-fold if added to GBS score(P<0.003).No score proved to be a good predictor for length of admission.CONCLUSION ABC score is the most accurate in predicting in-hospital mortality in both mixed and non-variceal bleeding population.PERS and GBS should be used to determine need for endoscopic and surgical intervention,respectively.Lactate can be used as an additional tool to risk scores for predicting inhospital mortality.展开更多
Genetic risk score （GRS） based on disease risk-associated single nucleotide polymorphisms （SNPs） is an informative tool that can be used to provide inherited information for specific diseases in addition to family...Genetic risk score （GRS） based on disease risk-associated single nucleotide polymorphisms （SNPs） is an informative tool that can be used to provide inherited information for specific diseases in addition to family history, However, it is still unknown whether only SNPs that are implicated in a specific racial group should be used when calculating GRSs. The objective of this study is to compare the performance of race-specific GRS and nonrace-specitic GRS for predicting prostate cancer （PCa） among 1338 patients underwent prostate biopsy in Shanghai, China. A race-specific GRS was calculated with seven PCa risk-associated SNPs implicated in East Asians （GRS7）, and a nonrace-specific GRS was calculated based on 76 PCa risk-associated SNPs implicated in at least one racial group （GRS76）. The means of GRS7 and GRS76 were 1.19 and 1.85, respectively, in the study population. Higher GRS7 and GRS76 were independent predictors for PCa and high-grade PCa in univariate and multivariate analyses. GRS7 had a better area under the receiver-operating curve （AUC） than GRS76 for discriminating PCa （0.602 vs 0.573） and high-grade PCa （0.603 vs 0.575） but did not reach statistical significance. GRS7 had a better （up to 13% at different cutoffs） positive predictive value （PPV） than GRS76. In conclusion, a race-specific GRS is more robust and has a better performance when predicting PCa in East Asian men than a GRS calculated using SNPs that are not shown to be associated with East Asians.展开更多
Prostate cancer （PCa） testing is recommended by most authoritative groups for high-risk men including those with a family history of the disease. However, family history information is often limited by patient knowl...Prostate cancer （PCa） testing is recommended by most authoritative groups for high-risk men including those with a family history of the disease. However, family history information is often limited by patient knowledge and clinician intake, and thus, many men are incorrectly assigned to different risk groups. Alternate methods to assess PCa risk are required. In this review, we discuss how genetic variants, referred to as PCa-risk single-nucleotide polymorphisms, can be used to calculate a genetic risk score （GRS）. GRS assigns a relatively unique value to all men based on the number of PCa-risk SNPs that an individual carries. This GRS value can provide a more precise estimate of a man＇s PCa risk. This is particularly relevant in situations when an individual is unaware of his family history. In addition, GRS has utility and can provide a more precise estimate of risk even among men with a positive family history. It can even distinguish risk among relatives with the same degree of family relationships. Taken together, this review serves to provide support for the clinical utility of GRS as an independent test to provide supplemental information to family history. As such, GRS can serve as a platform to help guide-shared decision-making processes regarding the timing and frequency of PCa testing and biopsies.展开更多
Current issues related to prostate cancer （PCa） clinical care （e.g., over-screening, over-diagnosis, and over-treatment of nonaggressive PCa） call for risk assessment tools that can be combined with family history...Current issues related to prostate cancer （PCa） clinical care （e.g., over-screening, over-diagnosis, and over-treatment of nonaggressive PCa） call for risk assessment tools that can be combined with family history （FH） to stratify disease risk among men in the general population. Since 2007, genome-wide association studies （GWASs） have identified more than 100 SNPs associated with PCa susceptibility. In this review, we discuss （1） the validity of these PCa risk-associated SNPs, individually and collectively; （2） the various methods used for measuring the cumulative effect of multiple SNPs, including genetic risk score （GRS）; （3） the adequate number of SNPs needed for risk assessment; （4） reclassification of risk based on evolving numbers of SNPs used to calculate genetic risk, （5） risk assessment for men from various racial groups, and （6） the clinical utility of genetic risk assessment. In conclusion, data available to date support the clinical validity of PCa risk-associated SNPs and GRS in risk assessment among men with or without FH. PCa risk-associated SNPs are not intended for diagnostic use; rather, they should be used the same way as FH. Combining GRS and FH can significantly improve the performance of risk assessment. Improved risk assessment may have important clinical utility in targeted PCa testing. However, clinical trials are urgently needed to evaluate this clinical utility as well as the acceptance of GRS by patients and physicians.展开更多
Background Sarcopenia is a risk factor for metabolic disorders and cardiovascular disease, but the association between sarcopenia and cardiovascular risk factors according to age and obesity status in the general popu...Background Sarcopenia is a risk factor for metabolic disorders and cardiovascular disease, but the association between sarcopenia and cardiovascular risk factors according to age and obesity status in the general population remains unknown. We thus investigated these associations in the Korean population. Methods We included 8,958 and 8,518 subjects from the fifth Korean National Health and Nutrition Examination Survey （KNHANES） （from 2010 and 2011, respectively）. The study was restricted to participants 〉 20 years old who had completed the health examination survey, including whole body dual-energy X-ray absorptiometry scans. After exclusion, 7,366 subjects （3,188 men, 4,178 women） were included in our final analysis. Age was categorized according to three age groups （20-39, 40-59, mad 〉 60 years）, and subjects were catego- rized according to their sarcopenic and obesity status. Cardiovascular risk was assessed with Framingham risk score （FRS）. Results The sarco- penic obese group had a higher FRS than the non-sarcopenic obese group, which had a higher FRS than the non-sarcopenic non-obese group. Age-wise, the 20-39 year-old group showed a non-significant association between sarcopenia and FRS. In the 40-59 year-old group, regardless of obesity status, sarcopenic subjects had a higher FRS than non-sarcopenic subjects. In the 〉 60 year-old group, sarcopenic subjects had a higher FRS than non-sarcopenic subjects for the non-obese group. Conclusions Sarcopenia was associated with cardiovascular disease and may be an early predictor of its susceptibility in both elderly and middle-aged subjects. Thus, management of sarcopenia is necessary to prevent cardiovascu- lar disease.展开更多
BACKGROUND Disease-related single nucleotide polymorphisms(SNPs)based genetic risk score(GRS)has been proven to provide independent inherited risk other than family history in multiple cancer types.AIM To evaluate the...BACKGROUND Disease-related single nucleotide polymorphisms(SNPs)based genetic risk score(GRS)has been proven to provide independent inherited risk other than family history in multiple cancer types.AIM To evaluate the potential of GRS in the prediction of pancreatic cancer risk.METHODS In this case-control study(254 cases and 1200 controls),we aimed to evaluate the association between GRS and pancreatic ductal adenocarcinoma(PDAC)risk in the Chinese population.The GRS was calculated based on the genotype information of 18 PDAC-related SNPs for each study subject(personal genotyping information of the SNPs)and was weighted by external odd ratios(ORs).RESULTS GRS was significantly different in cases and controls(1.96±3.84 in PDACs vs 1.09±0.94 in controls,P<0.0001).Logistic regression revealed GRS to be associated with PDAC risk[OR=1.23,95%confidence interval(CI):1.13-1.34,P<0.0001].GRS remained significantly associated with PDAC(OR=1.36,95%CI:1.06-1.74,P=0.015)after adjusting for age and sex.Further analysis revealed an association of increased risk for PDAC with higher GRS.Compared with low GRS(<1.0),subjects with high GRS(2.0)were 99%more likely to have PDAC(OR:1.99,95%CI:1.30-3.04,P=0.002).Participants with intermediate GRS(1.0-1.9)were 39%more likely to have PDAC(OR:1.39,95%CI:1.03-1.84,P=0.031).A positive trend was observed(P trend=0.0006).CONCLUSION GRS based on PDAC-associated SNPs could provide independent information on PDAC risk and may be used to predict a high risk PDAC population.展开更多
BACKGROUND The Khorana risk score(KRS)has poor predictive value for cancer-associated thrombosis in a single tumor type but is associated with early all-cause mortality from cancer.Evidence for the association between...BACKGROUND The Khorana risk score(KRS)has poor predictive value for cancer-associated thrombosis in a single tumor type but is associated with early all-cause mortality from cancer.Evidence for the association between KRS and all-cause mortality in Japanese patients with gastric and colorectal cancer is limited.AIM To investigate whether KRS was independently related to all-cause mortality in Japanese patients with gastric and colorectal cancer after adjusting for other covariates and to shed light on its temporal validity.METHODS Data from Dryad database were used in this study.Patients in the Gastroen-terology Department of Sapporo General Hospital,Sapporo,Japan,were enrolled.The starting and ending dates of the enrollment were January 1,2008 and January 5,2015,respectively.The cutoff date for follow-up was May 31,2016.The inde-pendent and dependent(target)variables were the baseline measured using the KRS and final all-cause mortality,respectively.The KRS was categorized into three groups:Low-risk group(=0 score),intermediate-risk group(1-2 score),and high-risk group(≥3 score).RESULTS Men and patients with Eastern Cooperative Oncology Group Performance Status(ECOG PS)≥2 displayed a higher 2-year risk of death than women and those with ECOG PS 0-1 in the intermediate/high risk group for KRS.The higher the score,the higher the risk of early death;however,the relevance of this independent prediction decreased with longer survival.The overall survival of each patient was recorded via real-world follow-up and retrospective observations,and this study yielded the overall relationship between KRS and all-cause mortality.CONCLUSION The prechemotherapy baseline of KRS was independently associated with all-cause mortality within 2 years;however,this independent predictive relationship weakened as survival time increased.展开更多
BACKGROUND Genetic variants of Helicobacter pylori(H. pylori) are involved in gastric cancer occurrence. Single nucleotide polymorphisms(SNPs) of H. pylori that are associated with gastric cancer have been reported. T...BACKGROUND Genetic variants of Helicobacter pylori(H. pylori) are involved in gastric cancer occurrence. Single nucleotide polymorphisms(SNPs) of H. pylori that are associated with gastric cancer have been reported. The combined effect of H. pylori SNPs on the risk of gastric cancer remains unclear.AIM To assess the performance of a polygenic risk score(PRS) based on H. pylori SNPs in predicting the risk of gastric cancer.METHODS A total of 15 gastric cancer-associated H. pylori SNPs were selected. The associations between these SNPs and gastric cancer were further validated in 1022 global strains with publicly available genome sequences. The PRS model was established based on the validated SNPs. The performance of the PRS for predicting the risk of gastric cancer was assessed in global strains using quintiles and random forest(RF) methods. The variation in the performance of the PRS among different populations of H. pylori was further examined.RESULTS Analyses of the association between selected SNPs and gastric cancer in the global dataset revealed that the risk allele frequencies of six SNPs were significantly higher in gastric cancer cases than non-gastric cancer cases. The PRS model constructed subsequently with these validated SNPs produced significantly higher scores in gastric cancer. The odds ratio(OR) value for gastric cancer gradually increased from the first to the fifth quintile of PRS, with the fifth quintile having an OR value as high as 9.76(95% confidence interval: 5.84-16.29). The results of RF analyses indicated that the area under the curve(AUC) value for classifying gastric cancer and non-gastric cancer was 0.75, suggesting that the PRS based on H. pylori SNPs was capable of predicting the risk of gastric cancer. Assessing the performance of the PRS among different H. pylori populations demonstrated that it had good predictive power for cancer risk for hp Europe strains, with an AUC value of 0.78.CONCLUSION The PRS model based on H. pylori SNPs had a good performance for assessment of gastric cancer risk. It would be useful in the prediction of final consequences of the H. pylori infection and beneficial for the management of the infection in clinical settings.展开更多
The Systemic Arterial Hypertension (SAH) stands out among the chronic non-transmissible pathologies that impact the cause and/or aggravation of cardiovascular diseases (CVD) on a global level, as the disease is an und...The Systemic Arterial Hypertension (SAH) stands out among the chronic non-transmissible pathologies that impact the cause and/or aggravation of cardiovascular diseases (CVD) on a global level, as the disease is an underestimated disorder due to non-perceptive symptoms and associated with factors and risk markers of another CVD. Therefore, establishing the risk of progression and aggravation of the SAH, according the Framingham Risk Score (FRS), allows to reducing morbidity and improving preventative measures for DCVs. This observational and transversal study approaches the data collection of patient records at the Health Family Strategy of Senhor do Bonfim, BA, which established differences by descriptive and inferential statistical analysis (correlation and regression). The aspects of hypertension associated with risk factors for atherosclerosis were analyzed, determining the risk of developing cardiovascular events in 10 years by FRS. From 432 families, 746 patients were selected, of which 340 are hypertensive individuals (SAH = 45.57%) and 406 (NSAH = 54.42%) non-hypertensives. Among the SAH the majority (31.17%) was in the age range of 63 - 77, but, in both groups, women were in stronger number. There was greater prevalence in SAH for all the characteristics analyzed, smoking (13.20%), sedentary (29.41%) and cardiovascular accident (22.60%). The SAH group is more susceptive to the CVD progress in 10 years by FRS (P < 0.0001 ANOVA). In the NSAH group, there were significant associations among all the variables analyzed as was expected, without differences between the linear correlation and regression, indicating the physio-metabolic equilibrium of the factors and markers evaluated by FRS. Already in SAH group, despite the correlations have been significant too, the regression analysis revealed that only Total Cholesterol (P = 0.0086);LDL (P < 0.0001), Glucose (P < 0.0006) and Age (P < 0.0001) have significative association with FRS. So, these factors and markers deserve more attention upon the health staff of Health Family Strategy, in the SAH course at studied population, attempt the highest cardiovascular risk by FRS (2.5 to 2.8 times) to SAH. The monitoring of high-risk patients should prioritize the lifestyle changes, employing preventive measures to SAH and CVD and atherosclerosis.展开更多
基金funded,in part,by the National Natural Science Fund (NSFC,China) under award number 81900382supported,in part,by the Yang talents Program of Beijing (QML20200302)Beijing Municipal Natural Science Foundation (7222072).
文摘Background Biomarkers-based prediction of long-term risk of acute coronary syndrome(ACS)is scarce.We aim to develop a risk score integrating clinical routine information(C)and plasma biomarkers(B)for predicting long-term risk of ACS patients.Methods We included 2729 ACS patients from the OCEA(Observation of cardiovascular events in ACS patients).The earlier admitted 1910 patients were enrolled as development cohort;and the subsequently admitted 819 subjects were treated as valida-tion cohort.We investigated 10-year risk of cardiovascular(CV)death,myocardial infarction(MI)and all cause death in these pa-tients.Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was de-rived using main part of these variables.Results During 16,110 person-years of follow-up,there were 238 CV death/MI in the development cohort.The 7 most import-ant predictors including in the final model were NT-proBNP,D-dimer,GDF-15,peripheral artery disease(PAD),Fibrinogen,ST-segment elevated MI(STEMI),left ventricular ejection fraction(LVEF),termed as CB-ACS score.C-index of the score for predica-tion of cardiovascular events was 0.79(95%CI:0.76-0.82)in development cohort and 0.77(95%CI:0.76-0.78)in the validation co-hort(5832 person-years of follow-up),which outperformed GRACE 2.0 and ABC-ACS risk score.The CB-ACS score was also well calibrated in development and validation cohort(Greenwood-Nam-D’Agostino:P=0.70 and P=0.07,respectively).Conclusions CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS.This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.
基金supported by the Key Research and Development Program of the Ministry of Science and Technology of China(grant number:2016YF0900605)the Key Research and Development Program of Hebei Province(grant number:192777129D)+1 种基金the Joint Fund for Iron and Steel of the Natural Science Foundation of Hebei Province(grant number:H2016209058)the National Natural Science Foundation for Regional Joint Fund of China(grant number:U22A20364)。
文摘Objective We aimed to investigate the patterns of fasting blood glucose(FBG)trajectories and analyze the relationship between various occupational hazard factors and FBG trajectories in male steelworkers.Methods The study cohort included 3,728 workers who met the selection criteria for the Tanggang Occupational Cohort(TGOC)between 2017 and 2022.A group-based trajectory model was used to identify the FBG trajectories.Environmental risk scores(ERS)were constructed using regression coefficients from the occupational hazard model as weights.Univariate and multivariate logistic regression analyses were performed to explore the effects of occupational hazard factors using the ERS on FBG trajectories.Results FBG trajectories were categorized into three groups.An association was observed between high temperature,noise exposure,and FBG trajectory(P<0.05).Using the first quartile group of ERS1 as a reference,the fourth quartile group of ERS1 had an increased risk of medium and high FBG by 1.90and 2.21 times,respectively(odds ratio[OR]=1.90,95%confidence interval[CI]:1.17–3.10;OR=2.21,95%CI:1.09–4.45).Conclusion An association was observed between occupational hazards based on ERS and FBG trajectories.The risk of FBG trajectory levels increase with an increase in ERS.
基金supported by grants from the National Natural Science Foundation of China(No.82173593,32300473)Guangzhou Science and Technology Project(No.2025A04J4537,2025A04J4696)+1 种基金Guangdong Basic and Applied Basic Research Foundation(No.2023A1515220053)Postdoctoral Science Foundation of Jiangsu Province(No.2021K524C).
文摘Objective:Neuroblastoma is the most common extracranial solid tumor in children and has complex genetic underpinnings.Previous genome-wide association studies(GWASs)have identified many loci associated with neuroblastoma susceptibility;however,their application in risk prediction for Chinese children has not been systematically explored.This study seeks to enhance neuroblastoma risk prediction by validating these loci and evaluating their performance in polygenic risk models.Methods:We validated 35 GWAS-identified neuroblastoma susceptibility loci in a cohort of Chinese children,consisting of 402 neuroblastoma patients and 473 healthy controls.Genotyping these polymorphisms was conducted via the TaqMan method.Univariable and multivariable logistic regression analyses revealed the genetic loci significantly associated with neuroblastoma risk.We constructed polygenic risk models by combining these loci and assessed their predictive performance via area under the curve(AUC)analysis.We also established a polygenic risk scoring(PRS)model for risk prediction by adopting the PLINK method.Results:Fourteen loci,including ten protective polymorphisms from CASC15,BARD1,LMO1,HSD17B12,and HACE1,and four risk variants from BARD1,RSRC1,CPZ and MMP20 were significantly associated with neuroblastoma risk.Compared with single-gene model,the 8-gene model(AUC=0.72)and 13-gene model(AUC=0.73)demonstrated superior predictive performance.Additionally,a PRS incorporating six significant loci achieved an AUC of 0.66,effectively stratifying individuals into distinct risk categories regarding neuroblastoma susceptibility.A higher PRS was significantly associated with advanced International Neuroblastoma Staging System(INSS)stages,suggesting its potential for clinical risk stratification.Conclusions:Our findings validate multiple loci as neuroblastoma risk factors in Chinese children and demonstrate the utility of polygenic risk models,particularly the PRS,in improving risk prediction.These results suggest that integrating multiple genetic variants into a PRS can enhance neuroblastoma risk stratification and potentially improve early diagnosis by guiding targeted screening programs for high-risk children.
基金Supported by the National Natural Science Foundation of China,No.82301737.
文摘BACKGROUND The prevalence of coronary heart disease(CHD)is higher in patients with depression than in the general population.Recently,multiple novel biomarkers have been proposed to predict CHD risk,and these factors have been reported to be altered in patients with depression.AIM To explore whether these new biomarkers are associated with an increased risk of CHD in patients with depression.METHODS We recruited 279 healthy controls and 164 sex-and age-matched patients with depression and collected their clinical characteristics and laboratory values of novel cardiovascular biomarkers.The Framingham CHD risk score was used to assess the CHD risk of all individuals,and the cardiovascular markers related to the CHD risk in patients with depression were analyzed.RESULTS Patients with depression had an increased CHD risk of 5.3%(95%confidence interval:4.470-6.103)and altered novel cardiovascular biomarkers compared to healthy controls,which included lower levels of thyroid stimulating hormone,albumin,total bilirubin,total cholesterol,high-density lipoprotein cholesterol,and higher levels of triglyceride(TG)and uric acid.Further regression analysis showed that illness duration,family history of depression,serum TG,and urea acid levels were significantly correlated with the Framingham risk score in patients with depression.CONCLUSION Patients with depression had a higher CHD risk and that their illness duration,family history of depression,serum TG,and uric acid levels could play important roles in predicting CHD risk.Moreover,elevated CHD risk in patients with depression was not only related to physiological changes caused by depression but also to their genetic susceptibility.
文摘BACKGROUND Liver grafts from donation after circulatory death(DCD)are associated with a higher risk of early graft dysfunction,determined by the warm ischemia and cold ischemia times.It is essential to have precise criteria to identify this complication in order to guide therapeutic strategies.AIM To validate different graft and recipient survival scores in patients undergoing liver transplantation(LT)with DCD grafts.METHODS A retrospective and observational unicentric study was conducted on 65 LT patients with grafts obtained from controlled DCD donors from November 2013 to November 2022.The United Kingdom(UK)risk score,early allograft dysfunction(EAD)Olthoff score,and model for early allograft function(MEAF)score were used to evaluate the risk of graft and recipient survival post-transplant.For survival analysis purposes,we used the Kaplan-Meier method,and the differences between subgroups were compared using the log-rank(Mantel-Cox)test.RESULTS Sixty-five patients were included in the study.The UK risk score did not demonstrate predictive capacity for recipient or graft survival.However,in donors aged over 70 years old(18.4%),it significantly predicted graft survival(P<0.05).According to Kaplan-Meier survival curves,graft survival rates at 6 months,2 years,and 5 years in the futility group dramatically decreased to 50%compared to the other groups(log-rank 8.806,P<0.05).The EAD Olthoff and MEAF scores did not demonstrate predictive capacity for recipient or graft survival.Based on Kaplan-Meier survival curves,patients with a MEAF score≥7 had a lower graft survival rate at 6 months,2 years,and 5 years compared to patients with a lower MEAF score(log-rank 4.667,P<0.05).CONCLUSION In our series,both UK DCD risk score and MEAF score showed predictive capability for graft survival.
文摘Several different approaches are available to clinicians for determining prostate cancer （PCa） risk. The clinical validity of various PCa risk assessment methods utilizing single nucleotide polymorphisms （SNPs） has been established; however, these SNP-based methods have not been compared. The objective of this study was to compare the three most commonly used SNP-based methods for PCa risk assessment. Participants were men （n = 1654） enrolled in a prospective study of PCa development. Genotypes of 59 PCa risk-associated SNPs were available in this cohort. Three methods of calculating SNP-based genetic risk scores （GRSs） were used for the evaluation of individual disease risk such as risk allele count （GRS-RAC）, weighted risk allele count （GRS-wRAC）, and population-standardized genetic risk score （GRS-PS）. Mean GRSs were calculated, and performances were compared using area under the receiver operating characteristic curve （AUC） and positive predictive value （PPV）. All SNP-based methods were found to be independently associated with PCa （all P 〈 0.05; hence their clinical validity）. The mean GRSs in men with or without PCa using GRS-RAC were 55.15 and 53.46, respectively, using GRS-wRAC were 7.42 and 6.97, respectively, and using GRS-PS were 1.12 and 0.84, respectively （all P 〈 0.05 for differences between patients with or without PCa）. All three SNP-based methods performed similarly in discriminating PCa from non-PCa based on AUC and in predicting PCa risk based on PPV （all P 〉 0.05 for comparisons between the three methods）, and all three SNP-based methods had a significantly higher AUC than family history （all P 〈 0.05）. Results from this study suggest that while the three most commonly used SNP-based methods performed similarly in discriminating PCa from non-PCa at the population level, GRS-PS is the method of choice for risk assessment at the individual level because its value （where 1.0 represents average population risk） can be easily interpreted regardless of the number of risk-associated SNPs used in the calculation.
基金Supported by National Natural Science Foundation of China,No.81972255,No.81772597 and No.81672412Guangdong Natural Science Foundation,No.2017A030311002+4 种基金Guangdong Science and Technology Foundation,No.2017A020215196Fundamental Research Funds for the Central Universities of Sun YatSen University,No.17ykpy44Science Foundation of Jiangxi,No.20181BAB214002Education Department Science and Technology Foundation of Jiangxi,No.GJJ170936Grant from Guangdong Science and Technology Department,No.2017B030314026
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a common cancer with a poor prognosis.Previous studies revealed that the tumor microenvironment(TME)plays an important role in HCC progression,recurrence,and metastasis,leading to poor prognosis.However,the effects of genes involved in TME on the prognosis of HCC patients remain unclear.Here,we investigated the HCC microenvironment to identify prognostic genes for HCC.AIM To identify a robust gene signature associated with the HCC microenvironment to improve prognosis prediction of HCC.METHODS We computed the immune/stromal scores of HCC patients obtained from The Cancer Genome Atlas based on the ESTIMATE algorithm.Additionally,a risk score model was established based on Differentially Expressed Genes(DEGs)between high and lowimmune/stromal score patients.RESULTS The risk score model consisting of eight genes was constructed and validated in the HCC patients.The patients were divided into high-or low-risk groups.The genes(Disabled homolog 2,Musculin,C-X-C motif chemokine ligand 8,Galectin 3,B-cell-activating transcription factor,Killer cell lectin like receptor B1,Endoglin and adenomatosis polyposis coli tumor suppressor)involved in our risk score model were considered to be potential immunotherapy targets,and they may provide better performance in combination.Functional enrichment analysis showed that the immune response and T cell receptor signaling pathway represented the major function and pathway,respectively,related to the immune-related genes in the DEGs between high-and low-risk groups.The receiver operating characteristic(ROC)curve analysis confirmed the good potency of the risk score prognostic model.Moreover,we validated the risk score model using the International Cancer Genome Consortium and the Gene Expression Omnibus database.A nomogram was established to predict the overall survival of HCC patients.CONCLUSION The risk score model and the nomogram will benefit HCC patients through personalized immunotherapy.
基金supported by the National Basic Research Development Programof Ministry of Science and Technology of China (2016YFC1306401)the National Natural Science Foundation of China (91749206)。
文摘To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer’s disease(sAD)and pathological biomarkers in cerebrospinal fluid(CSF),462 sAD patients and 463 age-matched cognitively normal(CN)controls were genotyped for 35 singlenucleotide polymorphisms(SNPs)that are significantly associated with sAD.Then,the alleles found to be associated with sAD were used to build polygenic risk score(PRS)models to represent the genetic risk.Receiver operating characteristic(ROC)analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset.We measured the CSF levels of Aβ42,Aβ42/Aβ40,total tau(T-tau),and phosphorylated tau(P-tau)in a subgroup(60 sAD and 200 CN participants),and analyzed their relationships with the PRSs.We found that 14 SNPs,including SNPs in the APOE,BIN1,CD33,EPHA1,SORL1,and TOMM40 genes,were associated with sAD risk in our cohort.The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls,and were able to predict the incidence rate of sAD and age at onset.Furthermore,the PRSs were correlated with the CSF levels of Aβ42,Aβ42/Aβ40,T-tau,and P-tau.Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD.As genetic risk profiles vary among populations,large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.
文摘Age is an important prognostic factor in the outcome of acute coronary syndromes （ACS）. A substantial percentage of patients who ex- perience ACS is more than 75 years old, and they represent the fastest-growing segment of the population treated in this setting. These pa- tients present different patterns of responses to pharmacotherapy, namely, a higher ischemic and bleeding risk than do patients under 75 years of age. Our aim was to identify whether the currently available ACS ischemic and bleeding risk scores, which has been validated for the general population, may also apply to the elderly population. The second aim was to determine whether the elderly benefit more from a spe- cific pharmacological regimen, keeping in mind the numerous molecules of antiplatelet and antithrombotic drugs, all validated in the general population. We concluded that the GRACE （Global Registry of Acute Coronary Events） risk score has been extensively validated in the elderly. However, the CRUSADE （Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early imple- mentation of the ACC/AHA Guidelines） bleeding score has a moderate correlation with outcomes in the elderly. Until now, there have not been head-to-head scores that quantify the ischemic versus hemorrhagic risk or scores that use the same end point and timeline （e.g., ischemic death rate versus bleeding death rate at one month）. We also recommend that the frailty score be considered or integrated into the current existing scores to better quantify the overall patient risk. With regard to medical treatment, based on the subgroup analysis, we identified the drugs that have the least adverse effects in the elderly while maintaining optimal efficacy.
基金the National Natural Scientific Foundation of China (No. 81573744 & No. 81973841)。
文摘Background Previous studies have demonstrated that micro RNA-204(mi R-204) is involved in atherosclerosis and vascular calcification. However, the value of mi R-204 as the predictive biomarker for cardiovascular disease(CVD) remains unclear. We aimed to evaluate the association between the circulating mi R-204 level and ten-year CVD risk based on the Framingham risk score(FRS). Methods In this retrospective study, we enrolled 194 consecutive patients with type 2 diabetes mellitus(T2DM) without CVD in Beijing Anzhen Hospital between January 2015 and September 2016. We used the FRS to evaluate the risk of CVD for each patient. Circulating mi R-204 levels were measured by quantitative real-time polymerase chain reaction. Results Circulating mi R-204 levels were significantly lower in the group of patients(0.49 ± 0.13) at high risk of CVD(FRS > 20%) than in the low(FRS < 10%) and intermediate(FRS: 10%–20%) risk groups(0.87 ± 0.19 and 0.75 ± 0.25, respectively;P < 0.001). FRS was negatively correlated with mi R-204 levels(r =-0.421, P < 0.001). According to multivariate logistic analyses, reduced mi R-204 level was independently associated with an increased risk of CVD after adjusting for conventional risk factors(OR = 0.876, 95% CI: 0.807–0.950, P = 0.001). Receiver-operating characteristic curve analysis showed that the circulating mi R-204 level can predict the high risk of CVD with higher specificity than the traditional risk factor of high systolic blood pressure or the protective factor of high-density lipoprotein cholesterol. Conclusions Our study demonstrated that patients with lower circulating mi R-204 levels were at high risk for CVD. After adjustment for potential confounders, mi R-204 was independently associated with CVD in patients with T2DM.
文摘Non-alcoholic fatty liver disease(NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma(HCC). Therefore, risk stratification emerges as fundamental in order to optimize human and economic resources, and genetics displays intrinsic characteristics suitable to fulfill this task. According to the available data, heritability estimates for hepatic fat content range from 20% to 70%, and an almost 80% of shared heritability has been found between hepatic fat content and fibrosis. The rs738409 single nucleotide polymorphism(SNP) in patatin-like phospholipase domain-containing protein 3 gene and the rs58542926 SNP in transmembrane 6 superfamily member 2 gene have been robustly associated with NAFLD and with its progression, but promising results have been obtained with many other SNPs. Moreover, there has been proof of the additive role of the different SNPs in determining liver damage, and there have been preliminary experiences in which risk scores created through a few genetic variants, alone or in combination with clinical variables, were associated with a strongly potentiated risk of NAFLD, non-alcoholic steatohepatitis(NASH), NASH fibrosis or NAFLD-HCC. However, to date, clinical translation of genetics in the field of NAFLD has been poor or absent. Fortunately, the research we have done seems to have placed us on the right path: We should rely on longitudinal rather than on cross-sectional studies; we should focus on relevant outcomes rather than on simple liver fat accumulation; and we should put together the genetic and clinical information. The hope is that combined genetic/clinical scores, derived from longitudinal studies and built on a few strong genetic variants and relevant clinical variables, will reach a significant predictive power, such as to have clinical utility for risk stratification at the single patient level and even to esteem the impact of intervention on the risk of disease-related outcomes. Well-structured future studies would demonstrate if this vision can become a reality.
文摘BACKGROUND Upper gastrointestinal(GI)bleeding is a life-threatening condition with high mortality rates.AIM To compare the performance of pre-endoscopic risk scores in predicting the following primary outcomes:In-hospital mortality,intervention(endoscopic or surgical)and length of admission(≥7 d).METHODS We performed a retrospective analysis of 363 patients presenting with upper GI bleeding from December 2020 to January 2021.We calculated and compared the area under the receiver operating characteristics curves(AUROCs)of Glasgow-Blatchford score(GBS),pre-endoscopic Rockall score(PERS),albumin,international normalized ratio,altered mental status,systolic blood pressure,age older than 65(AIMS65)and age,blood tests and comorbidities(ABC),including their optimal cut-off in variceal and non-variceal upper GI bleeding cohorts.We subsequently analyzed through a logistic binary regression model,if addition of lactate increased the score performance.RESULTS All scores had discriminative ability in predicting in-hospital mortality irrespective of study group.AIMS65 score had the best performance in the variceal bleeding group(AUROC=0.772;P<0.001),and ABC score(AUROC=0.775;P<0.001)in the non-variceal bleeding group.However,ABC score,at a cut-off value of 5.5,was the best predictor(AUROC=0.770,P=0.001)of inhospital mortality in both populations.PERS score was a good predictor for endoscopic treatment(AUC=0.604;P=0.046)in the variceal population,while GBS score,(AUROC=0.722;P=0.024),outperformed the other scores in predicting surgical intervention.Addition of lactate to AIMS65 score,increases by 5-fold the probability of in-hospital mortality(P<0.05)and by 12-fold if added to GBS score(P<0.003).No score proved to be a good predictor for length of admission.CONCLUSION ABC score is the most accurate in predicting in-hospital mortality in both mixed and non-variceal bleeding population.PERS and GBS should be used to determine need for endoscopic and surgical intervention,respectively.Lactate can be used as an additional tool to risk scores for predicting inhospital mortality.
基金This work was in part supported by grants from the Key Project of the National Science Foundation of China to Jianfeng Xu （81130047）, the National Key Basic Research Program Grant 973 of China to Jianfeng Xu （2012CB518301）, the National Natural Science Foundation of China （Grant No. 81402339） to Rong Na, the intramural grants from Huashan Hospital Fudan University to Rong Na. This study is also partially supported by the Ellrodt-Schweighauser Family Chair of Cancer Genomic Research of NorthShore University HealthSystem to JX. Finally, We would like to thank all the subjects included in this study.
文摘Genetic risk score （GRS） based on disease risk-associated single nucleotide polymorphisms （SNPs） is an informative tool that can be used to provide inherited information for specific diseases in addition to family history, However, it is still unknown whether only SNPs that are implicated in a specific racial group should be used when calculating GRSs. The objective of this study is to compare the performance of race-specific GRS and nonrace-specitic GRS for predicting prostate cancer （PCa） among 1338 patients underwent prostate biopsy in Shanghai, China. A race-specific GRS was calculated with seven PCa risk-associated SNPs implicated in East Asians （GRS7）, and a nonrace-specific GRS was calculated based on 76 PCa risk-associated SNPs implicated in at least one racial group （GRS76）. The means of GRS7 and GRS76 were 1.19 and 1.85, respectively, in the study population. Higher GRS7 and GRS76 were independent predictors for PCa and high-grade PCa in univariate and multivariate analyses. GRS7 had a better area under the receiver-operating curve （AUC） than GRS76 for discriminating PCa （0.602 vs 0.573） and high-grade PCa （0.603 vs 0.575） but did not reach statistical significance. GRS7 had a better （up to 13% at different cutoffs） positive predictive value （PPV） than GRS76. In conclusion, a race-specific GRS is more robust and has a better performance when predicting PCa in East Asian men than a GRS calculated using SNPs that are not shown to be associated with East Asians.
文摘Prostate cancer （PCa） testing is recommended by most authoritative groups for high-risk men including those with a family history of the disease. However, family history information is often limited by patient knowledge and clinician intake, and thus, many men are incorrectly assigned to different risk groups. Alternate methods to assess PCa risk are required. In this review, we discuss how genetic variants, referred to as PCa-risk single-nucleotide polymorphisms, can be used to calculate a genetic risk score （GRS）. GRS assigns a relatively unique value to all men based on the number of PCa-risk SNPs that an individual carries. This GRS value can provide a more precise estimate of a man＇s PCa risk. This is particularly relevant in situations when an individual is unaware of his family history. In addition, GRS has utility and can provide a more precise estimate of risk even among men with a positive family history. It can even distinguish risk among relatives with the same degree of family relationships. Taken together, this review serves to provide support for the clinical utility of GRS as an independent test to provide supplemental information to family history. As such, GRS can serve as a platform to help guide-shared decision-making processes regarding the timing and frequency of PCa testing and biopsies.
文摘Current issues related to prostate cancer （PCa） clinical care （e.g., over-screening, over-diagnosis, and over-treatment of nonaggressive PCa） call for risk assessment tools that can be combined with family history （FH） to stratify disease risk among men in the general population. Since 2007, genome-wide association studies （GWASs） have identified more than 100 SNPs associated with PCa susceptibility. In this review, we discuss （1） the validity of these PCa risk-associated SNPs, individually and collectively; （2） the various methods used for measuring the cumulative effect of multiple SNPs, including genetic risk score （GRS）; （3） the adequate number of SNPs needed for risk assessment; （4） reclassification of risk based on evolving numbers of SNPs used to calculate genetic risk, （5） risk assessment for men from various racial groups, and （6） the clinical utility of genetic risk assessment. In conclusion, data available to date support the clinical validity of PCa risk-associated SNPs and GRS in risk assessment among men with or without FH. PCa risk-associated SNPs are not intended for diagnostic use; rather, they should be used the same way as FH. Combining GRS and FH can significantly improve the performance of risk assessment. Improved risk assessment may have important clinical utility in targeted PCa testing. However, clinical trials are urgently needed to evaluate this clinical utility as well as the acceptance of GRS by patients and physicians.
文摘Background Sarcopenia is a risk factor for metabolic disorders and cardiovascular disease, but the association between sarcopenia and cardiovascular risk factors according to age and obesity status in the general population remains unknown. We thus investigated these associations in the Korean population. Methods We included 8,958 and 8,518 subjects from the fifth Korean National Health and Nutrition Examination Survey （KNHANES） （from 2010 and 2011, respectively）. The study was restricted to participants 〉 20 years old who had completed the health examination survey, including whole body dual-energy X-ray absorptiometry scans. After exclusion, 7,366 subjects （3,188 men, 4,178 women） were included in our final analysis. Age was categorized according to three age groups （20-39, 40-59, mad 〉 60 years）, and subjects were catego- rized according to their sarcopenic and obesity status. Cardiovascular risk was assessed with Framingham risk score （FRS）. Results The sarco- penic obese group had a higher FRS than the non-sarcopenic obese group, which had a higher FRS than the non-sarcopenic non-obese group. Age-wise, the 20-39 year-old group showed a non-significant association between sarcopenia and FRS. In the 40-59 year-old group, regardless of obesity status, sarcopenic subjects had a higher FRS than non-sarcopenic subjects. In the 〉 60 year-old group, sarcopenic subjects had a higher FRS than non-sarcopenic subjects for the non-obese group. Conclusions Sarcopenia was associated with cardiovascular disease and may be an early predictor of its susceptibility in both elderly and middle-aged subjects. Thus, management of sarcopenia is necessary to prevent cardiovascu- lar disease.
文摘BACKGROUND Disease-related single nucleotide polymorphisms(SNPs)based genetic risk score(GRS)has been proven to provide independent inherited risk other than family history in multiple cancer types.AIM To evaluate the potential of GRS in the prediction of pancreatic cancer risk.METHODS In this case-control study(254 cases and 1200 controls),we aimed to evaluate the association between GRS and pancreatic ductal adenocarcinoma(PDAC)risk in the Chinese population.The GRS was calculated based on the genotype information of 18 PDAC-related SNPs for each study subject(personal genotyping information of the SNPs)and was weighted by external odd ratios(ORs).RESULTS GRS was significantly different in cases and controls(1.96±3.84 in PDACs vs 1.09±0.94 in controls,P<0.0001).Logistic regression revealed GRS to be associated with PDAC risk[OR=1.23,95%confidence interval(CI):1.13-1.34,P<0.0001].GRS remained significantly associated with PDAC(OR=1.36,95%CI:1.06-1.74,P=0.015)after adjusting for age and sex.Further analysis revealed an association of increased risk for PDAC with higher GRS.Compared with low GRS(<1.0),subjects with high GRS(2.0)were 99%more likely to have PDAC(OR:1.99,95%CI:1.30-3.04,P=0.002).Participants with intermediate GRS(1.0-1.9)were 39%more likely to have PDAC(OR:1.39,95%CI:1.03-1.84,P=0.031).A positive trend was observed(P trend=0.0006).CONCLUSION GRS based on PDAC-associated SNPs could provide independent information on PDAC risk and may be used to predict a high risk PDAC population.
文摘BACKGROUND The Khorana risk score(KRS)has poor predictive value for cancer-associated thrombosis in a single tumor type but is associated with early all-cause mortality from cancer.Evidence for the association between KRS and all-cause mortality in Japanese patients with gastric and colorectal cancer is limited.AIM To investigate whether KRS was independently related to all-cause mortality in Japanese patients with gastric and colorectal cancer after adjusting for other covariates and to shed light on its temporal validity.METHODS Data from Dryad database were used in this study.Patients in the Gastroen-terology Department of Sapporo General Hospital,Sapporo,Japan,were enrolled.The starting and ending dates of the enrollment were January 1,2008 and January 5,2015,respectively.The cutoff date for follow-up was May 31,2016.The inde-pendent and dependent(target)variables were the baseline measured using the KRS and final all-cause mortality,respectively.The KRS was categorized into three groups:Low-risk group(=0 score),intermediate-risk group(1-2 score),and high-risk group(≥3 score).RESULTS Men and patients with Eastern Cooperative Oncology Group Performance Status(ECOG PS)≥2 displayed a higher 2-year risk of death than women and those with ECOG PS 0-1 in the intermediate/high risk group for KRS.The higher the score,the higher the risk of early death;however,the relevance of this independent prediction decreased with longer survival.The overall survival of each patient was recorded via real-world follow-up and retrospective observations,and this study yielded the overall relationship between KRS and all-cause mortality.CONCLUSION The prechemotherapy baseline of KRS was independently associated with all-cause mortality within 2 years;however,this independent predictive relationship weakened as survival time increased.
基金Supported by the National Natural Science Foundation of China,No. 31870777。
文摘BACKGROUND Genetic variants of Helicobacter pylori(H. pylori) are involved in gastric cancer occurrence. Single nucleotide polymorphisms(SNPs) of H. pylori that are associated with gastric cancer have been reported. The combined effect of H. pylori SNPs on the risk of gastric cancer remains unclear.AIM To assess the performance of a polygenic risk score(PRS) based on H. pylori SNPs in predicting the risk of gastric cancer.METHODS A total of 15 gastric cancer-associated H. pylori SNPs were selected. The associations between these SNPs and gastric cancer were further validated in 1022 global strains with publicly available genome sequences. The PRS model was established based on the validated SNPs. The performance of the PRS for predicting the risk of gastric cancer was assessed in global strains using quintiles and random forest(RF) methods. The variation in the performance of the PRS among different populations of H. pylori was further examined.RESULTS Analyses of the association between selected SNPs and gastric cancer in the global dataset revealed that the risk allele frequencies of six SNPs were significantly higher in gastric cancer cases than non-gastric cancer cases. The PRS model constructed subsequently with these validated SNPs produced significantly higher scores in gastric cancer. The odds ratio(OR) value for gastric cancer gradually increased from the first to the fifth quintile of PRS, with the fifth quintile having an OR value as high as 9.76(95% confidence interval: 5.84-16.29). The results of RF analyses indicated that the area under the curve(AUC) value for classifying gastric cancer and non-gastric cancer was 0.75, suggesting that the PRS based on H. pylori SNPs was capable of predicting the risk of gastric cancer. Assessing the performance of the PRS among different H. pylori populations demonstrated that it had good predictive power for cancer risk for hp Europe strains, with an AUC value of 0.78.CONCLUSION The PRS model based on H. pylori SNPs had a good performance for assessment of gastric cancer risk. It would be useful in the prediction of final consequences of the H. pylori infection and beneficial for the management of the infection in clinical settings.
文摘The Systemic Arterial Hypertension (SAH) stands out among the chronic non-transmissible pathologies that impact the cause and/or aggravation of cardiovascular diseases (CVD) on a global level, as the disease is an underestimated disorder due to non-perceptive symptoms and associated with factors and risk markers of another CVD. Therefore, establishing the risk of progression and aggravation of the SAH, according the Framingham Risk Score (FRS), allows to reducing morbidity and improving preventative measures for DCVs. This observational and transversal study approaches the data collection of patient records at the Health Family Strategy of Senhor do Bonfim, BA, which established differences by descriptive and inferential statistical analysis (correlation and regression). The aspects of hypertension associated with risk factors for atherosclerosis were analyzed, determining the risk of developing cardiovascular events in 10 years by FRS. From 432 families, 746 patients were selected, of which 340 are hypertensive individuals (SAH = 45.57%) and 406 (NSAH = 54.42%) non-hypertensives. Among the SAH the majority (31.17%) was in the age range of 63 - 77, but, in both groups, women were in stronger number. There was greater prevalence in SAH for all the characteristics analyzed, smoking (13.20%), sedentary (29.41%) and cardiovascular accident (22.60%). The SAH group is more susceptive to the CVD progress in 10 years by FRS (P < 0.0001 ANOVA). In the NSAH group, there were significant associations among all the variables analyzed as was expected, without differences between the linear correlation and regression, indicating the physio-metabolic equilibrium of the factors and markers evaluated by FRS. Already in SAH group, despite the correlations have been significant too, the regression analysis revealed that only Total Cholesterol (P = 0.0086);LDL (P < 0.0001), Glucose (P < 0.0006) and Age (P < 0.0001) have significative association with FRS. So, these factors and markers deserve more attention upon the health staff of Health Family Strategy, in the SAH course at studied population, attempt the highest cardiovascular risk by FRS (2.5 to 2.8 times) to SAH. The monitoring of high-risk patients should prioritize the lifestyle changes, employing preventive measures to SAH and CVD and atherosclerosis.
