BACKGROUND Colorectal cancer(CRC)is a major global health burden.The current diagnostic tests have shortcomings of being invasive and low accuracy.AIM To explore the combination of intestinal microbiome composition an...BACKGROUND Colorectal cancer(CRC)is a major global health burden.The current diagnostic tests have shortcomings of being invasive and low accuracy.AIM To explore the combination of intestinal microbiome composition and multi-target stool DNA(MT-sDNA)test in the diagnosis of CRC.METHODS We assessed the performance of the MT-sDNA test based on a hospital clinical trial.The intestinal microbiota was tested using 16S rRNA gene sequencing.This case-control study enrolled 54 CRC patients and 51 healthy controls.We identified biomarkers of bacterial structure,analyzed the relationship between different tumor markers and the relative abundance of related flora components,and distinguished CRC patients from healthy subjects by the linear discriminant analysis effect size,redundancy analysis,and random forest analysis.RESULTS MT-sDNA was associated with Bacteroides.MT-sDNA and carcinoembryonic antigen(CEA)were positively correlated with the existence of Parabacteroides,and alpha-fetoprotein(AFP)was positively associated with Faecalibacterium and Megamonas.In the random forest model,the existence of Streptococcus,Escherichia,Chitinophaga,Parasutterella,Lachnospira,and Romboutsia can distinguish CRC from health controls.The diagnostic accuracy of MT-sDNA combined with the six genera and CEA in the diagnosis of CRC was 97.1%,with a sensitivity and specificity of 98.1%and 92.3%,respectively.CONCLUSION There is a positive correlation of MT-sDNA,CEA,and AFP with intestinal microbiome.Eight biomarkers including six genera of gut microbiota,MT-sDNA,and CEA showed a prominent sensitivity and specificity for CRC prediction,which could be used as a non-invasive method for improving the diagnostic accuracy for this malignancy.展开更多
Background: Cervical cancer remains a significant public health concern in Macao SAR despite the implementation of a cervical cancer screening program and HPV vaccination. To improve early detection, Macao SAR introdu...Background: Cervical cancer remains a significant public health concern in Macao SAR despite the implementation of a cervical cancer screening program and HPV vaccination. To improve early detection, Macao SAR introduced HPV DNA testing alongside cytology (co-testing) as the primary screening method in 2019. This study evaluates the effectiveness of co-testing in identifying cervical precancerous lesions (CIN2+) compared to cytology alone. Methods: We conducted a retrospective analysis of women aged 30 - 65 years who participated in the routine cervical cancer screening program in Macao SAR Primary Healthcare Centers from 2019 to 2022. Data from over 70,000 women were analyzed, comparing the detection rates of CIN2+ through co-testing and cytology alone. Women with abnormal cytology or positive HPV results were referred for colposcopy. Results: The introduction of co-testing led to a significant increase in the detection of CIN2+, particularly in women with atypical squamous cells of undetermined significance (ASCUS) or negative for intraepithelial lesion or malignancy (NILM) cytology results. Between 2019 and 2022, the percentage of women with ASCUS/NILM and any high-risk HPV (hrHPV) positive who were diagnosed with CIN2+ after colposcopy were 24%, 13%, 10% and 7.5% respectively. This highlights the ability of co-testing to identify high-risk individuals who would have been missed by cytology alone. Discussion: Our findings demonstrate the effectiveness of co-testing in improving the sensitivity of cervical cancer screening in Macao SAR. The inclusion of HPV DNA testing allows for better risk stratification of women with ASCUS/NILM cytology, leading to more targeted referrals for colposcopy and timely detection of precancerous lesions. The initial high positive rate in 2019 (24%) might be attributed to the small sample size and potentially reflects a backlog of undiagnosed cases prior to co-testing implementation. Conclusion: The implementation of co-testing in Macao SAR’s cervical cancer screening program significantly improves the early detection of precancerous lesions, particularly in women with ambiguous cytology results. This proactive approach contributes to reducing cervical cancer morbidity and mortality and improving women’s health outcomes in Macao SAR.展开更多
Introduction: Anxiety disorders have a lifetime prevalence of 34% with a similar level of heritability (31%) yet lack objective markers that could differentiate patients with underlying conditions. Up to 60%-70% of pa...Introduction: Anxiety disorders have a lifetime prevalence of 34% with a similar level of heritability (31%) yet lack objective markers that could differentiate patients with underlying conditions. Up to 60%-70% of patients with Ehlers-Danlos syndrome have anxiety that meets criteria of generalized anxiety disorder, their clinical-DNA findings worth examining as biomarkers for patients with generalized anxiety. Method: Of the 1899 patients diagnosed with Ehlers-Danlos syndrome, 1261 were systematically evaluated for 80 history and 40 physical findings and separated into 826 who reported anxiety and 435 who did not. The most consistently reported or management-directing 60 of these clinical findings were, along with variations in genes relevant to these disorders, examined for association with anxiety. Results: Among the 30 anxiety- associated findings judged most predictive of Ehlers-Danlos syndrome in patients with anxiety were expected ones of adrenergic stimulation (difficulty concentrating-87% frequency and 1.26 anxiety/no anxiety ratio;chronic fatigue-84%, 1.17;sleep issues 69%, 1.52 that are criteria for generalized anxiety disorder) or of cholinergic suppression (e.g., frequent nausea 64%, 1.26). Less associated but more discriminating for underlying disease were those reflective of neuromuscular impact (e.g., chronic daily headaches 76%, 1.12);hypermobility (e.g., awareness of flexibility 72%, 1.03), or skin changes (e.g., elasticity around jaw 71%, 1.06). Anxiety-associated DNA variants included 54 of 88 in collagen type I/V/VII/IX genes, 14 of 16 in sodium channel SCN9A/10A/ 11A genes, 59 of 85 in POLG/MT-DNA genes, and 21 of 28 in profilaggrin- FLG genes that respectively impacted tissue laxity, sensory neural, autonomic-mitochondrial, and autonomic-inflammatory functions. Conclusion: Analysis of pathogenetic mechanisms in Ehlers-Danlos syndrome selected some 50 clinical-DNA findings useful for its diagnosis in those with generalized anxiety disorders.展开更多
Objective:We aim to assess the clinical performance of cell-free fetal DNA(cffDNA)testing for detecting common fetal aneuploidies as well as subchromosomal deletions/duplications and explore the pregnancy decisions in...Objective:We aim to assess the clinical performance of cell-free fetal DNA(cffDNA)testing for detecting common fetal aneuploidies as well as subchromosomal deletions/duplications and explore the pregnancy decisions in screen-positive cases.Methods:A cohort of 19,531 pregnant women was offered cffDNA testing for detection of trisomies 21,18,and 13(T21,T18,and T13);sex chromosome aneuploidies(SCAs);and subchromosomal deletions/duplications.Screen-positive cases were confirmed by karyotyping and single-nucleotide polymorphism array analysis.Results:A total of 47 cases failed the test.The overall screen-positive rate of chromosomal abnormalities was 1.07%(208/19,484),including 57 cases with T21,18 cases with T18,7 cases with T13,106 cases with SCAs,and 20 cases of subchromosomal deletions/duplications.Positive predictive values were 91.30%(42/46),38.46%(5/13),33.33%(2/6),41.33%(31/75),and 27.78%(5/18),respectively.There was no significant difference in the screening of fetal chromosomal aneuploidies in the high-risk group compared with the low-risk group(P>0.05).All of the pregnant women who had confirmed fetal T21,T18,or T13 terminated their pregnancies,except for a case of T13 mosaic,whereas 45.16%(14/31)of women with fetal SCAs continued their pregnancies.Furthermore,17 pregnant women with positive screens for T21,T18,or T13 without a subsequent diagnosis chose to terminate their pregnancy,whereas 29 of 31 women with SCAs chose to continue their pregnancies.Conclusions:CffDNA testing exhibited good screening accuracy for T21,T18,and T13 and also contributed to detecting fetal SCAs and subchromosomal deletions/duplications.Pregnant women with fetal 47,XXX or 47,XYY were more willing to terminate their pregnancy than those with fetal 45,X or 47,XXY.展开更多
Colorectal cancer(CRC)is the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide.The leading risk factors for CRC include male gender,age over 50,family history,obesity,tobacco ...Colorectal cancer(CRC)is the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide.The leading risk factors for CRC include male gender,age over 50,family history,obesity,tobacco smoking,alco-hol consumption,and unhealthy diet.CRC screening methods vary considerably between countries and depend on incidence,economic resources and healthcare structure.Important aspects of screening include adherence,which can vary signi-ficantly across ethnic and socioeconomic groups.Basic concepts of CRC screening include pre-stratification of patients by identifying risk factors and then using fecal immunochemical test or guaiac-based fecal occult blood test and/or colono-scopy or radiologic imaging techniques.Technological capabilities for CRC scree-ning are rapidly evolving and include stool DNA test,liquid biopsy,virtual colo-nography,and the use of artificial intelligence.A CRC prevention strategy should be comprehensive and include active patient education along with targeted imple-mentation of screening.展开更多
胎儿游离DNA(cell-free fetal DNA,cff-DNA)存在于孕妇妊娠期外周血中,其为携带胎儿相关遗传信息的DNA片段,可以进行胎儿染色体、基因相关疾病筛查。因其操作风险低、无副作用,目前已被广泛用于无创产前诊断检测(non-invasive prenatal ...胎儿游离DNA(cell-free fetal DNA,cff-DNA)存在于孕妇妊娠期外周血中,其为携带胎儿相关遗传信息的DNA片段,可以进行胎儿染色体、基因相关疾病筛查。因其操作风险低、无副作用,目前已被广泛用于无创产前诊断检测(non-invasive prenatal testing,NIPT)。无创cff-DNA血型检测是运用分子生物学检测cff-DNA血型相关基因,得出胎儿血型结果。以此在妊娠期即可检测出胎母血型是否一致,判断胎儿有无发生血型不合所致胎儿新生儿溶血病(hemolytic disease of the fetus and newborn,HDFN)的风险。展开更多
Objective: To improve the detecting accuracy of chromosomal aneuploidy of fetus by non-invasive prenatal testing (NIPT) using next generation sequencing data of pregnant women’s cell-free DNA. Methods: We proposed th...Objective: To improve the detecting accuracy of chromosomal aneuploidy of fetus by non-invasive prenatal testing (NIPT) using next generation sequencing data of pregnant women’s cell-free DNA. Methods: We proposed the multi-Z method which uses 21 z-scores for each autosomal chromosome to detect aneuploidy of the chromosome, while the conventional NIPT method uses only one z-score. To do this, mapped read numbers of a certain chromosome were normalized by those of the other 21 chromosomes. Average and standard deviation (SD), which are used for calculating z-score of each sample, were obtained with normalized values between all autosomal chromosomes of control samples. In this way, multiple z-scores can be calculated for 21 autosomal chromosomes except oneself. Results: Multi-Z method showed 100% sensitivity and specificity for 187 samples sequenced to 3 M reads while the conventional NIPT method showed 95.1% specificity. Similarly, for 216 samples sequenced to 1 M reads, Multi-Z method showed 100% sensitivity and 95.6% specificity and the conventional NIPT method showed a result of 75.1% specificity. Conclusion: Multi-Z method showed higher accuracy and robust results than the conventional method even at low coverage reads.展开更多
基金Supported by the Medical and Health Research Project of Zhejiang Province,No.2021KY1048 and 2022KY1142Ningbo Health Young Technical Backbone Talents Training Program,No.2020SWSQNGG-02the Key Science and Technology Project of Ningbo City,No.2021Z133.
文摘BACKGROUND Colorectal cancer(CRC)is a major global health burden.The current diagnostic tests have shortcomings of being invasive and low accuracy.AIM To explore the combination of intestinal microbiome composition and multi-target stool DNA(MT-sDNA)test in the diagnosis of CRC.METHODS We assessed the performance of the MT-sDNA test based on a hospital clinical trial.The intestinal microbiota was tested using 16S rRNA gene sequencing.This case-control study enrolled 54 CRC patients and 51 healthy controls.We identified biomarkers of bacterial structure,analyzed the relationship between different tumor markers and the relative abundance of related flora components,and distinguished CRC patients from healthy subjects by the linear discriminant analysis effect size,redundancy analysis,and random forest analysis.RESULTS MT-sDNA was associated with Bacteroides.MT-sDNA and carcinoembryonic antigen(CEA)were positively correlated with the existence of Parabacteroides,and alpha-fetoprotein(AFP)was positively associated with Faecalibacterium and Megamonas.In the random forest model,the existence of Streptococcus,Escherichia,Chitinophaga,Parasutterella,Lachnospira,and Romboutsia can distinguish CRC from health controls.The diagnostic accuracy of MT-sDNA combined with the six genera and CEA in the diagnosis of CRC was 97.1%,with a sensitivity and specificity of 98.1%and 92.3%,respectively.CONCLUSION There is a positive correlation of MT-sDNA,CEA,and AFP with intestinal microbiome.Eight biomarkers including six genera of gut microbiota,MT-sDNA,and CEA showed a prominent sensitivity and specificity for CRC prediction,which could be used as a non-invasive method for improving the diagnostic accuracy for this malignancy.
文摘Background: Cervical cancer remains a significant public health concern in Macao SAR despite the implementation of a cervical cancer screening program and HPV vaccination. To improve early detection, Macao SAR introduced HPV DNA testing alongside cytology (co-testing) as the primary screening method in 2019. This study evaluates the effectiveness of co-testing in identifying cervical precancerous lesions (CIN2+) compared to cytology alone. Methods: We conducted a retrospective analysis of women aged 30 - 65 years who participated in the routine cervical cancer screening program in Macao SAR Primary Healthcare Centers from 2019 to 2022. Data from over 70,000 women were analyzed, comparing the detection rates of CIN2+ through co-testing and cytology alone. Women with abnormal cytology or positive HPV results were referred for colposcopy. Results: The introduction of co-testing led to a significant increase in the detection of CIN2+, particularly in women with atypical squamous cells of undetermined significance (ASCUS) or negative for intraepithelial lesion or malignancy (NILM) cytology results. Between 2019 and 2022, the percentage of women with ASCUS/NILM and any high-risk HPV (hrHPV) positive who were diagnosed with CIN2+ after colposcopy were 24%, 13%, 10% and 7.5% respectively. This highlights the ability of co-testing to identify high-risk individuals who would have been missed by cytology alone. Discussion: Our findings demonstrate the effectiveness of co-testing in improving the sensitivity of cervical cancer screening in Macao SAR. The inclusion of HPV DNA testing allows for better risk stratification of women with ASCUS/NILM cytology, leading to more targeted referrals for colposcopy and timely detection of precancerous lesions. The initial high positive rate in 2019 (24%) might be attributed to the small sample size and potentially reflects a backlog of undiagnosed cases prior to co-testing implementation. Conclusion: The implementation of co-testing in Macao SAR’s cervical cancer screening program significantly improves the early detection of precancerous lesions, particularly in women with ambiguous cytology results. This proactive approach contributes to reducing cervical cancer morbidity and mortality and improving women’s health outcomes in Macao SAR.
文摘Introduction: Anxiety disorders have a lifetime prevalence of 34% with a similar level of heritability (31%) yet lack objective markers that could differentiate patients with underlying conditions. Up to 60%-70% of patients with Ehlers-Danlos syndrome have anxiety that meets criteria of generalized anxiety disorder, their clinical-DNA findings worth examining as biomarkers for patients with generalized anxiety. Method: Of the 1899 patients diagnosed with Ehlers-Danlos syndrome, 1261 were systematically evaluated for 80 history and 40 physical findings and separated into 826 who reported anxiety and 435 who did not. The most consistently reported or management-directing 60 of these clinical findings were, along with variations in genes relevant to these disorders, examined for association with anxiety. Results: Among the 30 anxiety- associated findings judged most predictive of Ehlers-Danlos syndrome in patients with anxiety were expected ones of adrenergic stimulation (difficulty concentrating-87% frequency and 1.26 anxiety/no anxiety ratio;chronic fatigue-84%, 1.17;sleep issues 69%, 1.52 that are criteria for generalized anxiety disorder) or of cholinergic suppression (e.g., frequent nausea 64%, 1.26). Less associated but more discriminating for underlying disease were those reflective of neuromuscular impact (e.g., chronic daily headaches 76%, 1.12);hypermobility (e.g., awareness of flexibility 72%, 1.03), or skin changes (e.g., elasticity around jaw 71%, 1.06). Anxiety-associated DNA variants included 54 of 88 in collagen type I/V/VII/IX genes, 14 of 16 in sodium channel SCN9A/10A/ 11A genes, 59 of 85 in POLG/MT-DNA genes, and 21 of 28 in profilaggrin- FLG genes that respectively impacted tissue laxity, sensory neural, autonomic-mitochondrial, and autonomic-inflammatory functions. Conclusion: Analysis of pathogenetic mechanisms in Ehlers-Danlos syndrome selected some 50 clinical-DNA findings useful for its diagnosis in those with generalized anxiety disorders.
基金supported by the Shanghai Municipal Health Bureau(grants 20174Y0199 and 201740096)Shanghai Clinical and Medical Center of Key Programs(2017ZZ01016)。
文摘Objective:We aim to assess the clinical performance of cell-free fetal DNA(cffDNA)testing for detecting common fetal aneuploidies as well as subchromosomal deletions/duplications and explore the pregnancy decisions in screen-positive cases.Methods:A cohort of 19,531 pregnant women was offered cffDNA testing for detection of trisomies 21,18,and 13(T21,T18,and T13);sex chromosome aneuploidies(SCAs);and subchromosomal deletions/duplications.Screen-positive cases were confirmed by karyotyping and single-nucleotide polymorphism array analysis.Results:A total of 47 cases failed the test.The overall screen-positive rate of chromosomal abnormalities was 1.07%(208/19,484),including 57 cases with T21,18 cases with T18,7 cases with T13,106 cases with SCAs,and 20 cases of subchromosomal deletions/duplications.Positive predictive values were 91.30%(42/46),38.46%(5/13),33.33%(2/6),41.33%(31/75),and 27.78%(5/18),respectively.There was no significant difference in the screening of fetal chromosomal aneuploidies in the high-risk group compared with the low-risk group(P>0.05).All of the pregnant women who had confirmed fetal T21,T18,or T13 terminated their pregnancies,except for a case of T13 mosaic,whereas 45.16%(14/31)of women with fetal SCAs continued their pregnancies.Furthermore,17 pregnant women with positive screens for T21,T18,or T13 without a subsequent diagnosis chose to terminate their pregnancy,whereas 29 of 31 women with SCAs chose to continue their pregnancies.Conclusions:CffDNA testing exhibited good screening accuracy for T21,T18,and T13 and also contributed to detecting fetal SCAs and subchromosomal deletions/duplications.Pregnant women with fetal 47,XXX or 47,XYY were more willing to terminate their pregnancy than those with fetal 45,X or 47,XXY.
文摘Colorectal cancer(CRC)is the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide.The leading risk factors for CRC include male gender,age over 50,family history,obesity,tobacco smoking,alco-hol consumption,and unhealthy diet.CRC screening methods vary considerably between countries and depend on incidence,economic resources and healthcare structure.Important aspects of screening include adherence,which can vary signi-ficantly across ethnic and socioeconomic groups.Basic concepts of CRC screening include pre-stratification of patients by identifying risk factors and then using fecal immunochemical test or guaiac-based fecal occult blood test and/or colono-scopy or radiologic imaging techniques.Technological capabilities for CRC scree-ning are rapidly evolving and include stool DNA test,liquid biopsy,virtual colo-nography,and the use of artificial intelligence.A CRC prevention strategy should be comprehensive and include active patient education along with targeted imple-mentation of screening.
文摘胎儿游离DNA(cell-free fetal DNA,cff-DNA)存在于孕妇妊娠期外周血中,其为携带胎儿相关遗传信息的DNA片段,可以进行胎儿染色体、基因相关疾病筛查。因其操作风险低、无副作用,目前已被广泛用于无创产前诊断检测(non-invasive prenatal testing,NIPT)。无创cff-DNA血型检测是运用分子生物学检测cff-DNA血型相关基因,得出胎儿血型结果。以此在妊娠期即可检测出胎母血型是否一致,判断胎儿有无发生血型不合所致胎儿新生儿溶血病(hemolytic disease of the fetus and newborn,HDFN)的风险。
文摘Objective: To improve the detecting accuracy of chromosomal aneuploidy of fetus by non-invasive prenatal testing (NIPT) using next generation sequencing data of pregnant women’s cell-free DNA. Methods: We proposed the multi-Z method which uses 21 z-scores for each autosomal chromosome to detect aneuploidy of the chromosome, while the conventional NIPT method uses only one z-score. To do this, mapped read numbers of a certain chromosome were normalized by those of the other 21 chromosomes. Average and standard deviation (SD), which are used for calculating z-score of each sample, were obtained with normalized values between all autosomal chromosomes of control samples. In this way, multiple z-scores can be calculated for 21 autosomal chromosomes except oneself. Results: Multi-Z method showed 100% sensitivity and specificity for 187 samples sequenced to 3 M reads while the conventional NIPT method showed 95.1% specificity. Similarly, for 216 samples sequenced to 1 M reads, Multi-Z method showed 100% sensitivity and 95.6% specificity and the conventional NIPT method showed a result of 75.1% specificity. Conclusion: Multi-Z method showed higher accuracy and robust results than the conventional method even at low coverage reads.
