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
AIM: To develop a risk model for Crohn's disease(CD) based on homogeneous population.METHODS: In our study were included 160 CD patients and 209 healthy individuals from Slovenia. The association study was perform...AIM: To develop a risk model for Crohn's disease(CD) based on homogeneous population.METHODS: In our study were included 160 CD patients and 209 healthy individuals from Slovenia. The association study was performed for 112 single nucleotide polymorphisms(SNPs). We generated genetic risk scores(GRS) based on the number of risk alleles using weighted additive model. Discriminatory accuracy was measured by area under ROC curve(AUC). For risk evaluation, we divided individuals according to positive and negative likelihood ratios(LR) of a test, with LR > 5 for high risk group and LR < 0.20 for low risk group.RESULTS: The highest accuracy, AUC of 0.78 was achieved with GRS combining 33 SNPs with optimal sensitivity and specificity of 75.0% and 72.7%, respectively. Individuals with the highest risk(GRS >5.54) showed significantly increased odds of developing CD(OR = 26.65, 95%CI: 11.25-63.15) compared to the individuals with the lowest risk(GRS < 4.57) which is a considerably greater risk captured than in one SNP with the highest effect size(OR = 3.24). When more than 33 SNPs were included in GRS, discriminatory ability was not improved significantly; AUC of all 74 SNPs was 0.76.CONCLUSION: The authors proved the possibility of building accurate genetic risk score based on 33 risk variants on Slovenian CD patients which may serve as a screening tool in the targeted population.展开更多
Fluoride and nitrate enriched groundwater are potential threats to the safety of the groundwater supply that may cause significant effects on human health and public safety,especially in aggregated population areas an...Fluoride and nitrate enriched groundwater are potential threats to the safety of the groundwater supply that may cause significant effects on human health and public safety,especially in aggregated population areas and economic hubs.This study focuses on the high F^(−)and NO_(3)^(−)concentration groundwater in Tongzhou District,Beijing,North China.A total of 36 groundwater samples were collected to analyze the hydrochemical characteristics,elucidate genetic mechanisms and evaluate the potential human health risks.The results of the analysis indicate:Firstly,most of the groundwater samples are characterized by Mg-HCO_(3) and Na-HCO_(3) with the pH ranging from 7.19 to 8.28 and TDS with a large variation across the range 471-2337 mg/L.The NO_(3)^(−)concentration in 38.89%groundwater samples and the F^(−)concentration in 66.67%groundwater samples exceed the permissible limited value.Secondly,F^(−)in groundwater originates predominantly from water-rock interactions and the fluorite dissolution,which is also regulated by cation exchange,competitive adsorption of HCO_(3)−and an alkaline environment.Thirdly,the effect of sewage disposal and agricultural activities have a significant effect on high NO3-concentration,while the high F^(−)concentration is less influenced by anthropogenic activity.The alkaline environment favors nitrification,thus being conducive to the production of NO_(3)^(−).Finally,the health risk assessment is evaluated for different population groups.The results indicate that high NO_(3)^(−)and F^(−)concentration in groundwater would have the largest threat to children’s health.The findings of this study could contribute to the provision of a scientific basis for groundwater supply policy formulation relating to public health in Tongzhou District.展开更多
Background:Cross-sectional evidence and small-scale trials suggest positive effects of stair climbing on cardiometabolic disease and glucose regulation.However,few studies have examined the long-term association betwe...Background:Cross-sectional evidence and small-scale trials suggest positive effects of stair climbing on cardiometabolic disease and glucose regulation.However,few studies have examined the long-term association between stair climbing and the incidence of type 2 diabetes(T2D).We aimed to prospectively evaluate the association of stair climbing with T2D and assess modifications by genetic predisposition to T2D.Methods:We included 451,699 adults(mean age=56.3±8.1 years,mean±SD;55.2%females)without T2D at baseline in the UK Biobank and followed up to March 31,2021.Stair climbing information was collected through the touchscreen questionnaire.Genetic risk score for T2D consisted of 424 single nucleotide polymorphisms.Results:During a median follow up of 12.1 years,14,896 T2D cases were documented.Compared with participants who reported no stair climbing,those who climbed stairs regularly had a lower risk of incident T2D(10-50 steps/day:hazard ratio(HR)=0.95,95%confidence interval(95%CI):0.89-1.00;60-100 steps/day:HR=0.92,95%CI:0.87-0.98;110-150 steps/day:HR=0.86,95%CI:0.80-0.91;>150 steps/day:HR=0.93,95%CI:0.87-0.99,p for trend=0.0007).We observed a significant interaction between stair climbing and genetic risk score on the subsequent T2D risk(p for interaction=0.0004),where the risk of T2D showed a downward trend in subjects with low genetic risk and those who reported stair climbing activity of 110-150 steps/day appeared to have the lowest overall T2D risk among those with intermediate to high genetic risk.Conclusion:A higher number of stairs climbed at home was associated with lower T2D incidence risk,especially among individuals with a low genetic predisposition to T2D.These findings highlight that stair climbing,as incidental physical activity,offers a simple and low-cost complement to public health interventions for T2D prevention.展开更多
BACKGROUND The albumin-bilirubin(ALBI)score is an index of liver function recently developed to assess prognosis in patients with hepatocellular carcinoma(HCC).It can detect small changes in liver dysfunction and has ...BACKGROUND The albumin-bilirubin(ALBI)score is an index of liver function recently developed to assess prognosis in patients with hepatocellular carcinoma(HCC).It can detect small changes in liver dysfunction and has been successfully applied to the prediction of survival in patients with non-malignant liver diseases of various etiologies.AIM To investigate the ALBI score for identifying decompensation risk at the 3-year follow-up in patients with compensated cirrhosis.METHODS One-hundred and twenty-three patients with compensated cirrhosis without HCC in King Chulalongkorn Memorial Hospital diagnosed by imaging were retrospectively enrolled from January 2016 to December 2020.A total of 113 patients(91.9%)had Child A cirrhosis with a median model for end-stage liver disease(MELD)score of less than 9.Baseline clinical and laboratory variables and decompensation events were collected.The ALBI score was calculated and validated to classify decompensation risk into low-,middle-,and high-risk groups using three ALBI grade ranges(ALBI grade 1:≤-2.60;grade 2:>-2.60 but≤-1.39;grade 3:>-1.39).Decompensation events were defined as ascites development,variceal bleeding,or grade 3 or 4 hepatic encephalopathy.RESULTS Among 123 cirrhotic patients enrolled,13.8%(n=17)developed decompensating events at a median time of 25[95%confidence interval(CI):17-31]mo.Median baseline ALBI score in compensated cirrhosis was significantly lower than that of patients who developed decompensation events[-2.768(-2.956 to-2.453)vs-2.007(-2.533 to-1.537);P=0.01].Analysis of decompensation risk at 3 years showed that ALBI score had a time-dependent area under the curve(tAUC)of 0.86(95%CI:0.78-0.92),which was significantly better than that of ALBI-Fibrosis-4(ALBI-FIB4)score(tAUC=0.77),MELD score(tAUC=0.66),Child-Pugh score(tAUC=0.65),and FIB-4 score(tAUC=0.48)(P<0.05 for all).The 3-year cumulative incidence of decompensation was 3.1%,22.6%,and 50%in the low-,middle-,and high-risk groups,respectively(P<0.001).The odds ratio for decompensation in patients of the high-risk group was 23.33(95%CI:3.88-140.12,P=0.001).CONCLUSION The ALBI score accurately identifies decompensation risk at the 3-year follow-up in patients with compensated cirrhosis.Those cirrhotic patients with a high-risk grade of ALBI score showed a 23 times greater odds of decompensation.展开更多
The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independ...The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independently reported in two Asian primate research centers.Nevertheless,the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated.Here,we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing.We identified 14558184 single nucleotide polymorphisms(SNPs)from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples.Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers.In addition,SNP and copy number variation(CNV)analyses suggested that the WW domain-containing oxidoreductase(WWOX)and Tyrosine-protein phosphatase nonreceptor type 21(PTPN21)genes may be associated with epilepsy in marmosets.Notably,KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets.This study provides valuable population genomic resources for marmosets in two Asian primate centers.Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers,while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.展开更多
Objective:The heightened prevalence of pulmonary nodules(PN)has escalated its significance as a public health concern.While the precise identification of high-risk PN carriers for malignancy remains an ongoing challen...Objective:The heightened prevalence of pulmonary nodules(PN)has escalated its significance as a public health concern.While the precise identification of high-risk PN carriers for malignancy remains an ongoing challenge,genetic variants hold potentials as determinants of disease susceptibility that can aid in diagnosis.Yet,current understanding of the genetic loci associated with malignant PN(MPN)risk is limited.Methods:A frequency-matched case-control study was performed,comprising 247 MPN cases and 412 benign NP(BNP)controls.We genotyped 11 established susceptibility loci for lung cancer in a Chinese cohort.Loci associated with MPN risk were utilized to compute a polygenic risk score(PRS).This PRS was subsequently incorporated into the diagnostic evaluation of MPNs,with emphasis on serum tumor biomarkers.Results:Loci rs10429489G>A,rs17038564A>G,and rs12265047A>G were identified as being associated with an increased risk of MPNs.The PRS,formulated from the cumulative risk effects of these loci,correlated with the malignant risk of PNs in a dose-dependent fashion.A high PRS was found to amplify the MPN risk by 156%in comparison to a low PRS[odds ratio(OR)=2.56,95%confidence interval(95%CI),1.40−4.67].Notably,the PRS was observed to enhance the diagnostic accuracy of serum carcinoembryonic antigen(CEA)in distinguishing MPNs from BPNs,with diagnostic values rising from 0.716 to 0.861 across low-to high-PRS categories.Further bioinformatics investigations pinpointed rs10429489G>A as an expression quantitative trait locus.Conclusions:Loci rs10429489G>A,rs17038564A>G,and rs12265047A>G contribute to MPN risk and augment the diagnostic precision for MPNs based on serum CEA concentrations.展开更多
Hypertension, obesity, smoking, dyslipidemia, and type 2 diabetes (T2D) are the major risk factors for developing cardiovascular diseases (CVD). Recent studies revealed that taxi-motorbike drivers (TMDs) in Cotonou ha...Hypertension, obesity, smoking, dyslipidemia, and type 2 diabetes (T2D) are the major risk factors for developing cardiovascular diseases (CVD). Recent studies revealed that taxi-motorbike drivers (TMDs) in Cotonou had higher rates of CVD risk factors, but their impacts on cardiovascular events have rarely been studied. The Framingham risk score (FRS) is an algorithm that considers CVD risk factors and estimates the risk of developing CVD in the next 10 years. Our objectives were to assess the 10-year CVD risk predicted by the FRS, and to examine the relationships of 10-year CVD risk with plasma iron and potassium levels among TMDs. We included 134 TMDs (22 - 59 years old) who had no prior diagnosis of CVD or T2D, and not taking medications affecting iron and potassium homeostasis. Conventional cardiovascular risk factors were used to calculate the 10-year CVD risk, which was categorized as low (20%). FRS > 2%, which corresponded to the 75th percentile of FRS distribution in our study population, was used as a cut-off value to classify participants into two groups. Plasma iron and potassium levels were segregated into tertiles and their associations with 10-year CVD risk were quantified by multivariate-adjusted logistic regression to calculate the odd ratios (ORs) to being above the 75<sup>th</sup> percentile of 10-year CVD risk with the corresponding 95% confidence intervals (CIs). We found that 62.0% of participants had at least one of cardiovascular risk factors. Approximately 97.8% of TMDs had 10-year CVD risk 4.8 mmol/L led to an 83% risk reduction of having 10-year CVD risk > 2% (OR = 0.17, 95% CI: 0.04 - 0.82, P = 0.027). In conclusion, our findings showed that high plasma potassium levels associate with reduced 10-year CVD risk among TMDs. Interventions focused on monitoring of plasma potassium, particularly in those with existing cardiovascular risk factors, may help prevent CVD.展开更多
Genetic variations are associated with individual susceptibility to gastric cancer.Recently,polygenic risk score(PRS)models have been established based on genetic variants to predict the risk of gastric cancer.To asse...Genetic variations are associated with individual susceptibility to gastric cancer.Recently,polygenic risk score(PRS)models have been established based on genetic variants to predict the risk of gastric cancer.To assess the accuracy of current PRS models in the risk prediction,a systematic review was conducted.A total of eight eligible studies consisted of 544842 participants were included for evaluation of the performance of PRS models.The overall accuracy was moderate with Area under the curve values ranging from 0.5600 to 0.7823.Incorporation of epidemiological factors or Helicobacter pylori(H.pylori)status increased the accuracy for risk prediction,while selection of single nucleotide polymorphism(SNP)and number of SNPs appeared to have little impact on the model performance.To further improve the accuracy of PRS models for risk prediction of gastric cancer,we summarized the association between gastric cancer risk and H.pylori genomic variations,cancer associated bacteria members in the gastric microbiome,discussed the potentials for performance improvement of PRS models with these microbial factors.Future studies on comprehensive PRS models established with human SNPs,epidemiological factors and microbial factors are indicated.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 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
The mounting endemic of prescription iatrogenic opioid dependence in pain patients provoked this treatise about an alternative method that can be used to treat pain, improve function and reduce the risk of opioid depe...The mounting endemic of prescription iatrogenic opioid dependence in pain patients provoked this treatise about an alternative method that can be used to treat pain, improve function and reduce the risk of opioid dependence. It is well known that as well as the side effects reported for chronic opioid therapy, genetically predisposed individuals are at risk for opioid dependence. We propose the use of the Genetic Addiction Risk Score (GARS) assessment to identify patients early in treatment who should avoid narcotic pain medications. Primarily, this review will be an exploration of the mechanisms of action of an electrotherapeutic alternative to narcotic treatment that can be used to augment tissue healing and reduce the pain associated with human injuries and neuropathies. This particular electrotherapeutic device was developed at the Electronic Waveform Laboratory in Huntington Beach, California and is called the H-Wave? device. The primary effect of the H-Wave?device is stimulation (HWDS) of small diameter fibers of “red-slow-twitch” skeletal muscle. Mechanisms of action of HWDS have been investigated in both animal and human studies. They include edema reduction, induction of nitric oxide dependent augmented microcirculation and angiogenesis, small muscle contraction that eliminates transcapillary fluid shifts, reducing the painful effects of tetanizing fatigue and gradual loading of healing injured muscle tissue that helps repair and remodeling. A recent metaanalysis found a moderate-to-strong-positive effect of the HWDS in providing pain relief, reducing the requirement for pain medication, with the most robust effect being increased functionality. We are proposing that GARS can be used to identify those at risk of developing opioid dependence and that the need for opioid analgesia can be reduced by use of this electro therapeutic alternative to opioid analgesia in the treatment of pain and injuries.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
AIM: To analyse the association of sleep quality with myopia under different genetic risk(GR) levels.METHODS: A cross-sectional survey of students aged 9-14 y in Wenzhou, China, was conducted. Refraction without cyclo...AIM: To analyse the association of sleep quality with myopia under different genetic risk(GR) levels.METHODS: A cross-sectional survey of students aged 9-14 y in Wenzhou, China, was conducted. Refraction without cycloplegia and ocular parameters were measured. Sleep quality was assessed with the Pittsburgh Sleep Quality Index(PSQI). Seventeen single nucleotide polymorphisms(SNPs) were replicated by association analysis and used to compute the GR score(GRS). Possible confounders were assessed by a questionnaire that collected information about the children and their parents. Generalized linear models were used to analyse the sleep quality, the GR, and their interaction effects on the risk of myopia.RESULTS: Out of 1354 children included in this study, 353(26.07%) had sleep disturbances. The GRS ranged from 4.49 to 12.89 with a mean of 7.74±1.23, and the participants were divided into a low GR group, a moderate GR group and a high GR group according to the GRS quartile. In the generalized linear model, the children with sleep disturbances and high GR had a higher risk of myopia than those without sleep disturbances and with low GR(OR=1.59, 95%CI: 1.12-2.25;OR=1.88, 95%CI: 1.23-2.88, respectively). Compared to those with low GR and SDs, children with high GR with or without SDs had a higher risk of myopia(OR=4.88, 95%CI: 2.03-11.71;OR=1.70, 95%CI: 1.06-2.72, respectively).CONCLUSION: The prevalence of sleep disturbances in elementary school students in Wenzhou was 26.07%. There is a significant interaction between sleep disturbances and a high GR of myopia, suggesting that a high GR of myopia may increase children’s sensitivity to sleep disturbances. This study indicates that children with a high GR of myopia need to achieve adequate sleep duration and excellent sleep quality.展开更多
Gastroesophageal reflux disease(GERD) is a common gastrointestinal disorder with an increasing prevalence. GERD develops when the reflux of stomach contents causes troublesome typical and atypical symptoms and/or comp...Gastroesophageal reflux disease(GERD) is a common gastrointestinal disorder with an increasing prevalence. GERD develops when the reflux of stomach contents causes troublesome typical and atypical symptoms and/or complications. Several risk factors of GERD have been identified and evaluated over the years, including a considerable amount of genetic factors. Multiple mechanisms are involved in the pathogenesis of GERD including:(1) motor abnormalities, such as impaired lower esophageal sphincter(LES) resting tone, transient LES relaxations, impaired esophageal acid clearance and delayed gastric emptying; and(2) anatomical factors, such as hiatal hernia and obesity. Genetic contribution seems to play a major role in GERD and GERD-related disorders development such Barrett's esophagus and esophageal adenocarcinoma. Twin and family studies have revealed an about 31% heritability of the disease. Numerous single-nucleotide polymorphisms in various genes like FOXF1, MHC, CCND1, anti-inflammatory cytokine and DNA repair genes have been strongly associated with increased GERD risk. GERD, Barrett'sesophagus and esophageal adenocarcinoma share several genetic loci. Despite GERD polygenic basis,specific genetic loci such as rs10419226 on chromosome 19, rs2687201 on chromosome 3, rs10852151 on chromosome 15 and rs520525 on the paired related homeobox 1 gene have been mentioned as potential risk factors. Further investigation on the risk genes may elucidate their exact function and role and demonstrate new therapeutic approaches to this increasingly common disease.展开更多
Adenocarcinoma of small intestines(SBA) is a relatively rare malignancy with poor outcomes due to delayed diagnosis.Fifty percent of patients have metastases on presentation and therefore early detection and treatment...Adenocarcinoma of small intestines(SBA) is a relatively rare malignancy with poor outcomes due to delayed diagnosis.Fifty percent of patients have metastases on presentation and therefore early detection and treatment offers the best long term outcomes.Certain genetic polyposis syndromes and familial diseases are associatedwith increased risks for SBA.These include familial adenomatous polyposis(FAP),Lynch syndromes(LS),Juvenile polyposis syndrome,Peutz-Jeghers syndrome,Crohn's disease(CD) and celiac disease.Mutations in APC gene,Mismatch repair genes,STK11 gene,and SMAD4 gene have been implicated for the genetic diseases respectively.While there are no specific inherited genetic mutations for CD,genome-wide association studies have established over 140 loci associated with CD.CpG island mutations with defects in mismatch repair genes have been identified in celiac disease.Significant diagnostic advances have occurred in the past decade and intuitively,it would seem beneficial to use these advanced modalities for surveillance of these patients.At present it is debatable and no clear data exists to support this approach except for established guidelines to diagnose duodenal polyps in FAP,and LS.Here we discuss the genetic alterations,cancer risks,signaling mechanisms and briefly touch the surveillance modalities available for these genetic and clinical syndromes.English language articles from Pub Med/Medline and Embase was searched were collected using the phrases "small-bowel adenocarcinoma,genetics,surveillance,familial adenomatous polyposis,lynch syndromes,Peutz-Jeghers syndrome,juvenile polyposis syndrome,CD and celiac disease".Figures,tables and schematic diagram to illustrate pathways are included in the review.展开更多
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AIM: To develop a risk model for Crohn's disease(CD) based on homogeneous population.METHODS: In our study were included 160 CD patients and 209 healthy individuals from Slovenia. The association study was performed for 112 single nucleotide polymorphisms(SNPs). We generated genetic risk scores(GRS) based on the number of risk alleles using weighted additive model. Discriminatory accuracy was measured by area under ROC curve(AUC). For risk evaluation, we divided individuals according to positive and negative likelihood ratios(LR) of a test, with LR > 5 for high risk group and LR < 0.20 for low risk group.RESULTS: The highest accuracy, AUC of 0.78 was achieved with GRS combining 33 SNPs with optimal sensitivity and specificity of 75.0% and 72.7%, respectively. Individuals with the highest risk(GRS >5.54) showed significantly increased odds of developing CD(OR = 26.65, 95%CI: 11.25-63.15) compared to the individuals with the lowest risk(GRS < 4.57) which is a considerably greater risk captured than in one SNP with the highest effect size(OR = 3.24). When more than 33 SNPs were included in GRS, discriminatory ability was not improved significantly; AUC of all 74 SNPs was 0.76.CONCLUSION: The authors proved the possibility of building accurate genetic risk score based on 33 risk variants on Slovenian CD patients which may serve as a screening tool in the targeted population.
基金supported by the project of China Geological Survey(Grant No.DD20221677-2)the fundamental research funds of Chinese Academy of Geological Sciences Basal Research Fund(Grant No.JKYQN202307).
文摘Fluoride and nitrate enriched groundwater are potential threats to the safety of the groundwater supply that may cause significant effects on human health and public safety,especially in aggregated population areas and economic hubs.This study focuses on the high F^(−)and NO_(3)^(−)concentration groundwater in Tongzhou District,Beijing,North China.A total of 36 groundwater samples were collected to analyze the hydrochemical characteristics,elucidate genetic mechanisms and evaluate the potential human health risks.The results of the analysis indicate:Firstly,most of the groundwater samples are characterized by Mg-HCO_(3) and Na-HCO_(3) with the pH ranging from 7.19 to 8.28 and TDS with a large variation across the range 471-2337 mg/L.The NO_(3)^(−)concentration in 38.89%groundwater samples and the F^(−)concentration in 66.67%groundwater samples exceed the permissible limited value.Secondly,F^(−)in groundwater originates predominantly from water-rock interactions and the fluorite dissolution,which is also regulated by cation exchange,competitive adsorption of HCO_(3)−and an alkaline environment.Thirdly,the effect of sewage disposal and agricultural activities have a significant effect on high NO3-concentration,while the high F^(−)concentration is less influenced by anthropogenic activity.The alkaline environment favors nitrification,thus being conducive to the production of NO_(3)^(−).Finally,the health risk assessment is evaluated for different population groups.The results indicate that high NO_(3)^(−)and F^(−)concentration in groundwater would have the largest threat to children’s health.The findings of this study could contribute to the provision of a scientific basis for groundwater supply policy formulation relating to public health in Tongzhou District.
基金supported by the National Key Research and Development Program of China(grant number 2020YFC2006300)the Young Scientists Fund of the National Natural Science Foundation of China(grant number 82103835)。
文摘Background:Cross-sectional evidence and small-scale trials suggest positive effects of stair climbing on cardiometabolic disease and glucose regulation.However,few studies have examined the long-term association between stair climbing and the incidence of type 2 diabetes(T2D).We aimed to prospectively evaluate the association of stair climbing with T2D and assess modifications by genetic predisposition to T2D.Methods:We included 451,699 adults(mean age=56.3±8.1 years,mean±SD;55.2%females)without T2D at baseline in the UK Biobank and followed up to March 31,2021.Stair climbing information was collected through the touchscreen questionnaire.Genetic risk score for T2D consisted of 424 single nucleotide polymorphisms.Results:During a median follow up of 12.1 years,14,896 T2D cases were documented.Compared with participants who reported no stair climbing,those who climbed stairs regularly had a lower risk of incident T2D(10-50 steps/day:hazard ratio(HR)=0.95,95%confidence interval(95%CI):0.89-1.00;60-100 steps/day:HR=0.92,95%CI:0.87-0.98;110-150 steps/day:HR=0.86,95%CI:0.80-0.91;>150 steps/day:HR=0.93,95%CI:0.87-0.99,p for trend=0.0007).We observed a significant interaction between stair climbing and genetic risk score on the subsequent T2D risk(p for interaction=0.0004),where the risk of T2D showed a downward trend in subjects with low genetic risk and those who reported stair climbing activity of 110-150 steps/day appeared to have the lowest overall T2D risk among those with intermediate to high genetic risk.Conclusion:A higher number of stairs climbed at home was associated with lower T2D incidence risk,especially among individuals with a low genetic predisposition to T2D.These findings highlight that stair climbing,as incidental physical activity,offers a simple and low-cost complement to public health interventions for T2D prevention.
文摘BACKGROUND The albumin-bilirubin(ALBI)score is an index of liver function recently developed to assess prognosis in patients with hepatocellular carcinoma(HCC).It can detect small changes in liver dysfunction and has been successfully applied to the prediction of survival in patients with non-malignant liver diseases of various etiologies.AIM To investigate the ALBI score for identifying decompensation risk at the 3-year follow-up in patients with compensated cirrhosis.METHODS One-hundred and twenty-three patients with compensated cirrhosis without HCC in King Chulalongkorn Memorial Hospital diagnosed by imaging were retrospectively enrolled from January 2016 to December 2020.A total of 113 patients(91.9%)had Child A cirrhosis with a median model for end-stage liver disease(MELD)score of less than 9.Baseline clinical and laboratory variables and decompensation events were collected.The ALBI score was calculated and validated to classify decompensation risk into low-,middle-,and high-risk groups using three ALBI grade ranges(ALBI grade 1:≤-2.60;grade 2:>-2.60 but≤-1.39;grade 3:>-1.39).Decompensation events were defined as ascites development,variceal bleeding,or grade 3 or 4 hepatic encephalopathy.RESULTS Among 123 cirrhotic patients enrolled,13.8%(n=17)developed decompensating events at a median time of 25[95%confidence interval(CI):17-31]mo.Median baseline ALBI score in compensated cirrhosis was significantly lower than that of patients who developed decompensation events[-2.768(-2.956 to-2.453)vs-2.007(-2.533 to-1.537);P=0.01].Analysis of decompensation risk at 3 years showed that ALBI score had a time-dependent area under the curve(tAUC)of 0.86(95%CI:0.78-0.92),which was significantly better than that of ALBI-Fibrosis-4(ALBI-FIB4)score(tAUC=0.77),MELD score(tAUC=0.66),Child-Pugh score(tAUC=0.65),and FIB-4 score(tAUC=0.48)(P<0.05 for all).The 3-year cumulative incidence of decompensation was 3.1%,22.6%,and 50%in the low-,middle-,and high-risk groups,respectively(P<0.001).The odds ratio for decompensation in patients of the high-risk group was 23.33(95%CI:3.88-140.12,P=0.001).CONCLUSION The ALBI score accurately identifies decompensation risk at the 3-year follow-up in patients with compensated cirrhosis.Those cirrhotic patients with a high-risk grade of ALBI score showed a 23 times greater odds of decompensation.
基金supported by the National Natural Science Foundation of China (82001372)National Key Research and Development Program of China (2018YFE0126700)+3 种基金Shanghai Jiao Tong University 2030 Initiative (WH510363001-7)Shanghai Municipal Commission of Science and Technology Program (21dz2210100)Shanghai Education Commission Research and Innovation Program (2019-01-07-00-02-E00037)a National Institutes of Health (NIH)grant (5R01HG002385)to E.E.E。
文摘The common marmoset(Callithrix jacchus)has emerged as a valuable nonhuman primate model in biomedical research with the recent release of high-quality reference genome assemblies.Epileptic marmosets have been independently reported in two Asian primate research centers.Nevertheless,the population genetics within these primate centers and the specific genetic variants associated with epilepsy in marmosets have not yet been elucidated.Here,we characterized the genetic relationships and risk variants for epilepsy in 41 samples from two epileptic marmoset pedigrees using whole-genome sequencing.We identified 14558184 single nucleotide polymorphisms(SNPs)from the 41 samples and found higher chimerism levels in blood samples than in fingernail samples.Genetic analysis showed fourth-degree of relatedness among marmosets at the primate centers.In addition,SNP and copy number variation(CNV)analyses suggested that the WW domain-containing oxidoreductase(WWOX)and Tyrosine-protein phosphatase nonreceptor type 21(PTPN21)genes may be associated with epilepsy in marmosets.Notably,KCTD18-like gene deletion was more common in epileptic marmosets than control marmosets.This study provides valuable population genomic resources for marmosets in two Asian primate centers.Genetic analyses identified a reasonable breeding strategy for genetic diversity maintenance in the two centers,while the case-control study revealed potential risk genes/variants associated with epilepsy in marmosets.
基金supported by the National Natural Science Foundation of China(No.82073628,81871876 and 82173609).
文摘Objective:The heightened prevalence of pulmonary nodules(PN)has escalated its significance as a public health concern.While the precise identification of high-risk PN carriers for malignancy remains an ongoing challenge,genetic variants hold potentials as determinants of disease susceptibility that can aid in diagnosis.Yet,current understanding of the genetic loci associated with malignant PN(MPN)risk is limited.Methods:A frequency-matched case-control study was performed,comprising 247 MPN cases and 412 benign NP(BNP)controls.We genotyped 11 established susceptibility loci for lung cancer in a Chinese cohort.Loci associated with MPN risk were utilized to compute a polygenic risk score(PRS).This PRS was subsequently incorporated into the diagnostic evaluation of MPNs,with emphasis on serum tumor biomarkers.Results:Loci rs10429489G>A,rs17038564A>G,and rs12265047A>G were identified as being associated with an increased risk of MPNs.The PRS,formulated from the cumulative risk effects of these loci,correlated with the malignant risk of PNs in a dose-dependent fashion.A high PRS was found to amplify the MPN risk by 156%in comparison to a low PRS[odds ratio(OR)=2.56,95%confidence interval(95%CI),1.40−4.67].Notably,the PRS was observed to enhance the diagnostic accuracy of serum carcinoembryonic antigen(CEA)in distinguishing MPNs from BPNs,with diagnostic values rising from 0.716 to 0.861 across low-to high-PRS categories.Further bioinformatics investigations pinpointed rs10429489G>A as an expression quantitative trait locus.Conclusions:Loci rs10429489G>A,rs17038564A>G,and rs12265047A>G contribute to MPN risk and augment the diagnostic precision for MPNs based on serum CEA concentrations.
文摘Hypertension, obesity, smoking, dyslipidemia, and type 2 diabetes (T2D) are the major risk factors for developing cardiovascular diseases (CVD). Recent studies revealed that taxi-motorbike drivers (TMDs) in Cotonou had higher rates of CVD risk factors, but their impacts on cardiovascular events have rarely been studied. The Framingham risk score (FRS) is an algorithm that considers CVD risk factors and estimates the risk of developing CVD in the next 10 years. Our objectives were to assess the 10-year CVD risk predicted by the FRS, and to examine the relationships of 10-year CVD risk with plasma iron and potassium levels among TMDs. We included 134 TMDs (22 - 59 years old) who had no prior diagnosis of CVD or T2D, and not taking medications affecting iron and potassium homeostasis. Conventional cardiovascular risk factors were used to calculate the 10-year CVD risk, which was categorized as low (20%). FRS > 2%, which corresponded to the 75th percentile of FRS distribution in our study population, was used as a cut-off value to classify participants into two groups. Plasma iron and potassium levels were segregated into tertiles and their associations with 10-year CVD risk were quantified by multivariate-adjusted logistic regression to calculate the odd ratios (ORs) to being above the 75<sup>th</sup> percentile of 10-year CVD risk with the corresponding 95% confidence intervals (CIs). We found that 62.0% of participants had at least one of cardiovascular risk factors. Approximately 97.8% of TMDs had 10-year CVD risk 4.8 mmol/L led to an 83% risk reduction of having 10-year CVD risk > 2% (OR = 0.17, 95% CI: 0.04 - 0.82, P = 0.027). In conclusion, our findings showed that high plasma potassium levels associate with reduced 10-year CVD risk among TMDs. Interventions focused on monitoring of plasma potassium, particularly in those with existing cardiovascular risk factors, may help prevent CVD.
基金Supported by the National Natural Science Foundation of China,No.31870777.
文摘Genetic variations are associated with individual susceptibility to gastric cancer.Recently,polygenic risk score(PRS)models have been established based on genetic variants to predict the risk of gastric cancer.To assess the accuracy of current PRS models in the risk prediction,a systematic review was conducted.A total of eight eligible studies consisted of 544842 participants were included for evaluation of the performance of PRS models.The overall accuracy was moderate with Area under the curve values ranging from 0.5600 to 0.7823.Incorporation of epidemiological factors or Helicobacter pylori(H.pylori)status increased the accuracy for risk prediction,while selection of single nucleotide polymorphism(SNP)and number of SNPs appeared to have little impact on the model performance.To further improve the accuracy of PRS models for risk prediction of gastric cancer,we summarized the association between gastric cancer risk and H.pylori genomic variations,cancer associated bacteria members in the gastric microbiome,discussed the potentials for performance improvement of PRS models with these microbial factors.Future studies on comprehensive PRS models established with human SNPs,epidemiological factors and microbial factors are indicated.
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.
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The mounting endemic of prescription iatrogenic opioid dependence in pain patients provoked this treatise about an alternative method that can be used to treat pain, improve function and reduce the risk of opioid dependence. It is well known that as well as the side effects reported for chronic opioid therapy, genetically predisposed individuals are at risk for opioid dependence. We propose the use of the Genetic Addiction Risk Score (GARS) assessment to identify patients early in treatment who should avoid narcotic pain medications. Primarily, this review will be an exploration of the mechanisms of action of an electrotherapeutic alternative to narcotic treatment that can be used to augment tissue healing and reduce the pain associated with human injuries and neuropathies. This particular electrotherapeutic device was developed at the Electronic Waveform Laboratory in Huntington Beach, California and is called the H-Wave? device. The primary effect of the H-Wave?device is stimulation (HWDS) of small diameter fibers of “red-slow-twitch” skeletal muscle. Mechanisms of action of HWDS have been investigated in both animal and human studies. They include edema reduction, induction of nitric oxide dependent augmented microcirculation and angiogenesis, small muscle contraction that eliminates transcapillary fluid shifts, reducing the painful effects of tetanizing fatigue and gradual loading of healing injured muscle tissue that helps repair and remodeling. A recent metaanalysis found a moderate-to-strong-positive effect of the HWDS in providing pain relief, reducing the requirement for pain medication, with the most robust effect being increased functionality. We are proposing that GARS can be used to identify those at risk of developing opioid dependence and that the need for opioid analgesia can be reduced by use of this electro therapeutic alternative to opioid analgesia in the treatment of pain and injuries.
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.
基金Supported by the National Natural Science Foundation of China(No.81873683)。
文摘AIM: To analyse the association of sleep quality with myopia under different genetic risk(GR) levels.METHODS: A cross-sectional survey of students aged 9-14 y in Wenzhou, China, was conducted. Refraction without cycloplegia and ocular parameters were measured. Sleep quality was assessed with the Pittsburgh Sleep Quality Index(PSQI). Seventeen single nucleotide polymorphisms(SNPs) were replicated by association analysis and used to compute the GR score(GRS). Possible confounders were assessed by a questionnaire that collected information about the children and their parents. Generalized linear models were used to analyse the sleep quality, the GR, and their interaction effects on the risk of myopia.RESULTS: Out of 1354 children included in this study, 353(26.07%) had sleep disturbances. The GRS ranged from 4.49 to 12.89 with a mean of 7.74±1.23, and the participants were divided into a low GR group, a moderate GR group and a high GR group according to the GRS quartile. In the generalized linear model, the children with sleep disturbances and high GR had a higher risk of myopia than those without sleep disturbances and with low GR(OR=1.59, 95%CI: 1.12-2.25;OR=1.88, 95%CI: 1.23-2.88, respectively). Compared to those with low GR and SDs, children with high GR with or without SDs had a higher risk of myopia(OR=4.88, 95%CI: 2.03-11.71;OR=1.70, 95%CI: 1.06-2.72, respectively).CONCLUSION: The prevalence of sleep disturbances in elementary school students in Wenzhou was 26.07%. There is a significant interaction between sleep disturbances and a high GR of myopia, suggesting that a high GR of myopia may increase children’s sensitivity to sleep disturbances. This study indicates that children with a high GR of myopia need to achieve adequate sleep duration and excellent sleep quality.
文摘Gastroesophageal reflux disease(GERD) is a common gastrointestinal disorder with an increasing prevalence. GERD develops when the reflux of stomach contents causes troublesome typical and atypical symptoms and/or complications. Several risk factors of GERD have been identified and evaluated over the years, including a considerable amount of genetic factors. Multiple mechanisms are involved in the pathogenesis of GERD including:(1) motor abnormalities, such as impaired lower esophageal sphincter(LES) resting tone, transient LES relaxations, impaired esophageal acid clearance and delayed gastric emptying; and(2) anatomical factors, such as hiatal hernia and obesity. Genetic contribution seems to play a major role in GERD and GERD-related disorders development such Barrett's esophagus and esophageal adenocarcinoma. Twin and family studies have revealed an about 31% heritability of the disease. Numerous single-nucleotide polymorphisms in various genes like FOXF1, MHC, CCND1, anti-inflammatory cytokine and DNA repair genes have been strongly associated with increased GERD risk. GERD, Barrett'sesophagus and esophageal adenocarcinoma share several genetic loci. Despite GERD polygenic basis,specific genetic loci such as rs10419226 on chromosome 19, rs2687201 on chromosome 3, rs10852151 on chromosome 15 and rs520525 on the paired related homeobox 1 gene have been mentioned as potential risk factors. Further investigation on the risk genes may elucidate their exact function and role and demonstrate new therapeutic approaches to this increasingly common disease.
文摘Adenocarcinoma of small intestines(SBA) is a relatively rare malignancy with poor outcomes due to delayed diagnosis.Fifty percent of patients have metastases on presentation and therefore early detection and treatment offers the best long term outcomes.Certain genetic polyposis syndromes and familial diseases are associatedwith increased risks for SBA.These include familial adenomatous polyposis(FAP),Lynch syndromes(LS),Juvenile polyposis syndrome,Peutz-Jeghers syndrome,Crohn's disease(CD) and celiac disease.Mutations in APC gene,Mismatch repair genes,STK11 gene,and SMAD4 gene have been implicated for the genetic diseases respectively.While there are no specific inherited genetic mutations for CD,genome-wide association studies have established over 140 loci associated with CD.CpG island mutations with defects in mismatch repair genes have been identified in celiac disease.Significant diagnostic advances have occurred in the past decade and intuitively,it would seem beneficial to use these advanced modalities for surveillance of these patients.At present it is debatable and no clear data exists to support this approach except for established guidelines to diagnose duodenal polyps in FAP,and LS.Here we discuss the genetic alterations,cancer risks,signaling mechanisms and briefly touch the surveillance modalities available for these genetic and clinical syndromes.English language articles from Pub Med/Medline and Embase was searched were collected using the phrases "small-bowel adenocarcinoma,genetics,surveillance,familial adenomatous polyposis,lynch syndromes,Peutz-Jeghers syndrome,juvenile polyposis syndrome,CD and celiac disease".Figures,tables and schematic diagram to illustrate pathways are included in the review.
