AIM:To identify the genetic factors underlying anophthalmia and microphthalmia(A/M),and to perform computational analysis to verify the pathophysiological mechanisms of the disease.METHODS:This study investigated a co...AIM:To identify the genetic factors underlying anophthalmia and microphthalmia(A/M),and to perform computational analysis to verify the pathophysiological mechanisms of the disease.METHODS:This study investigated a consanguineous Pakistani family with multiple affected individuals.Clinical evaluations were conducted using A-Scan and ophthalmic B-Scan ultrasonography(B-Scan).To identify the diseasecausing variant,whole exome sequencing(WES)and Sanger sequencing were performed.In silico functional analyses were carried out using AlphaFold(for protein modeling)and ClusPro(for protein docking analysis)tools,and the hydrodynamic properties of the protein were determined via molecular dynamics simulations.RESULTS:Clinical analysis of the five patients revealed severe phenotypes of bilateral anophthalmia.Ocular B-Scan did not detect ocular tissue or intraocular fluid,thus confirming the diagnosis of anophthalmia in all patients.Due to these structural defects,all patients exhibited complete blindness and absence of light perception;additionally,two patients had mild to moderate intellectual disability.Genetic analysis identified a splice site variant[NM_000693.2:c.884-2_885dup;p.(Asp296SerfsTer35)]in the 9^(th)exon of the ALDH1A3 gene.CONCLUSION:The present study expands the genetic spectrum of ALDH1A3 and contributes to establishing the genotype-phenotype correlation for this gene.展开更多
Background:Despite the insights into the role of aldehyde dehydrogenase 1 family member A1(ALDH1A1)in various liver diseases,the expression and its prognostic significance in patients with hepatitis E virus-related ac...Background:Despite the insights into the role of aldehyde dehydrogenase 1 family member A1(ALDH1A1)in various liver diseases,the expression and its prognostic significance in patients with hepatitis E virus-related acute liver failure(HEV-ALF)remain unclear.This study delved into the assessment of serum exosome-derived ALDH1A1 expression and its prognostic implications for HEV-ALF patients.Methods:Between January 2018 and December 2023,a total of 226 individuals with acute hepatitis E(AHE)and 210 patients with HEV-ALF were recruited from member units of Chinese Consortium for the Study of Hepatitis E.According to the number of organ failure,we categorized 210 HEV-ALF patients into three groups:two organs failure(n=131),three organs failure(n=46),and more than three organs failure(n=33).In addition,200 health controls from Suzhou Municipal Hospital were included.Results:The levels of serum exosome-derived ALDH1A1 in HEV-ALF patients were significantly higher than those in AHE patients and health controls(both P<0.05).Furthermore,the levels of serum exosome-derived ALDH1A1 were the highest in more than three organs failure group,followed by three organs failure group and two organs failure group(all P<0.001).Moreover,serum exosome-derived ALDH1A1 was positively correlated with total bilirubin in HEV-ALF patients(r=0.315,P<0.001).The comparisons of serum exosome-derived ALDH1A1 levels in treatment response showed that serum exosome-derived ALDH1A1 levels were decreased in the improvement group,while increased in the fluctuation and deterioration groups(all P<0.001).Moreover,serum exosome-derived ALDH1A1 was an independent risk factor for predicting the 30-day mortality(P<0.001).Furthermore,the area under the receiver operating characteristic curve was 0.943,with the sensitivity of 94.87%and specificity of 87.72%,indicating the robust decision-making ability.However,no significant differences were found in serum exosome-derived ALDH1A1 levels between patients aged<60 and≥60 years old(P=0.131).Conclusions:Serum exosome-derived ALDH1A1 can greatly predict the prognosis of HEV-ALF patients.展开更多
目的研究肿瘤干细胞标记物CD133、CD44、SOX2、OCT4、ALDH1在非小细胞肺癌(NSCLC)组织中的表达及临床意义,为探索非小细胞肺癌肿瘤干细胞提供参考。方法采用免疫组织化学方法检测70例NSCLC组织、14例非癌组织中的CD133、CD44、SOX2、OCT...目的研究肿瘤干细胞标记物CD133、CD44、SOX2、OCT4、ALDH1在非小细胞肺癌(NSCLC)组织中的表达及临床意义,为探索非小细胞肺癌肿瘤干细胞提供参考。方法采用免疫组织化学方法检测70例NSCLC组织、14例非癌组织中的CD133、CD44、SOX2、OCT4、ALDH1蛋白的表达并对结果进行分析。结果 (1)CD133、CD44、SOX2、OCT4、ALDH1在70例NSCLC组织中的阳性表达率分别为88.57%、98.57%、100%、100%、100%,强阳性表达率分别为48.57%、67.14%、67.14%、31.43%、50%;CD133、C C D 4 4在N S C L C与非癌组织中的表达差异存在统计学意义(P均<0.0001),SOX2、OCT4、ALDH1在NSCLC与非癌组织中的表达差异无统计学意义(P均>0.05)。(2)随着病理级别的升高,CD133、CD44、SOX2、OCT4及ALDH1的表达呈上升趋势,分化越低的NSCLC表达上述指标的概率越高,其中CD133、SOX2、OCT4的表达在高、中、低分化组织中差异存在统计学意义(P值分别为0.001、0.040、<0.0001);CD133的表达在吸烟史、分化程度、淋巴结转移、肿瘤分期四个因素上差异存在统计学意义(P值分别为0.033、0.001、0.033、0.046);CD44与SOX2的表达在年龄上的差异存在统计学意义(P值分别为0.001、0.040)。结论 NSCLC组织中CD133、CD44、SOX2、OCT4、ALDH1阳性率高,CD133、CD44的表达明显高于非癌组织;CD133、SOX2、OCT4与NSCLC的恶性程度有关;CD44与SOX2与年龄因素有关。展开更多
基金Supported by Taif University,Taif,Saudi Arabia(TU-DSPP-2024-05).
文摘AIM:To identify the genetic factors underlying anophthalmia and microphthalmia(A/M),and to perform computational analysis to verify the pathophysiological mechanisms of the disease.METHODS:This study investigated a consanguineous Pakistani family with multiple affected individuals.Clinical evaluations were conducted using A-Scan and ophthalmic B-Scan ultrasonography(B-Scan).To identify the diseasecausing variant,whole exome sequencing(WES)and Sanger sequencing were performed.In silico functional analyses were carried out using AlphaFold(for protein modeling)and ClusPro(for protein docking analysis)tools,and the hydrodynamic properties of the protein were determined via molecular dynamics simulations.RESULTS:Clinical analysis of the five patients revealed severe phenotypes of bilateral anophthalmia.Ocular B-Scan did not detect ocular tissue or intraocular fluid,thus confirming the diagnosis of anophthalmia in all patients.Due to these structural defects,all patients exhibited complete blindness and absence of light perception;additionally,two patients had mild to moderate intellectual disability.Genetic analysis identified a splice site variant[NM_000693.2:c.884-2_885dup;p.(Asp296SerfsTer35)]in the 9^(th)exon of the ALDH1A3 gene.CONCLUSION:The present study expands the genetic spectrum of ALDH1A3 and contributes to establishing the genotype-phenotype correlation for this gene.
基金supported by grants from the National Nat-ural Science Foundation of China(82272396)Suzhou Med-ical and Health Science and Technology Innovation Project(SKY2022057)。
文摘Background:Despite the insights into the role of aldehyde dehydrogenase 1 family member A1(ALDH1A1)in various liver diseases,the expression and its prognostic significance in patients with hepatitis E virus-related acute liver failure(HEV-ALF)remain unclear.This study delved into the assessment of serum exosome-derived ALDH1A1 expression and its prognostic implications for HEV-ALF patients.Methods:Between January 2018 and December 2023,a total of 226 individuals with acute hepatitis E(AHE)and 210 patients with HEV-ALF were recruited from member units of Chinese Consortium for the Study of Hepatitis E.According to the number of organ failure,we categorized 210 HEV-ALF patients into three groups:two organs failure(n=131),three organs failure(n=46),and more than three organs failure(n=33).In addition,200 health controls from Suzhou Municipal Hospital were included.Results:The levels of serum exosome-derived ALDH1A1 in HEV-ALF patients were significantly higher than those in AHE patients and health controls(both P<0.05).Furthermore,the levels of serum exosome-derived ALDH1A1 were the highest in more than three organs failure group,followed by three organs failure group and two organs failure group(all P<0.001).Moreover,serum exosome-derived ALDH1A1 was positively correlated with total bilirubin in HEV-ALF patients(r=0.315,P<0.001).The comparisons of serum exosome-derived ALDH1A1 levels in treatment response showed that serum exosome-derived ALDH1A1 levels were decreased in the improvement group,while increased in the fluctuation and deterioration groups(all P<0.001).Moreover,serum exosome-derived ALDH1A1 was an independent risk factor for predicting the 30-day mortality(P<0.001).Furthermore,the area under the receiver operating characteristic curve was 0.943,with the sensitivity of 94.87%and specificity of 87.72%,indicating the robust decision-making ability.However,no significant differences were found in serum exosome-derived ALDH1A1 levels between patients aged<60 and≥60 years old(P=0.131).Conclusions:Serum exosome-derived ALDH1A1 can greatly predict the prognosis of HEV-ALF patients.
文摘目的研究肿瘤干细胞标记物CD133、CD44、SOX2、OCT4、ALDH1在非小细胞肺癌(NSCLC)组织中的表达及临床意义,为探索非小细胞肺癌肿瘤干细胞提供参考。方法采用免疫组织化学方法检测70例NSCLC组织、14例非癌组织中的CD133、CD44、SOX2、OCT4、ALDH1蛋白的表达并对结果进行分析。结果 (1)CD133、CD44、SOX2、OCT4、ALDH1在70例NSCLC组织中的阳性表达率分别为88.57%、98.57%、100%、100%、100%,强阳性表达率分别为48.57%、67.14%、67.14%、31.43%、50%;CD133、C C D 4 4在N S C L C与非癌组织中的表达差异存在统计学意义(P均<0.0001),SOX2、OCT4、ALDH1在NSCLC与非癌组织中的表达差异无统计学意义(P均>0.05)。(2)随着病理级别的升高,CD133、CD44、SOX2、OCT4及ALDH1的表达呈上升趋势,分化越低的NSCLC表达上述指标的概率越高,其中CD133、SOX2、OCT4的表达在高、中、低分化组织中差异存在统计学意义(P值分别为0.001、0.040、<0.0001);CD133的表达在吸烟史、分化程度、淋巴结转移、肿瘤分期四个因素上差异存在统计学意义(P值分别为0.033、0.001、0.033、0.046);CD44与SOX2的表达在年龄上的差异存在统计学意义(P值分别为0.001、0.040)。结论 NSCLC组织中CD133、CD44、SOX2、OCT4、ALDH1阳性率高,CD133、CD44的表达明显高于非癌组织;CD133、SOX2、OCT4与NSCLC的恶性程度有关;CD44与SOX2与年龄因素有关。
基金supported by Natural Science Foundation of Yunnan Science and Technology Committee(2007C223M2009CD)Natural Science Foundation of Yunnan Provincial Department of Education(07Z10336)
