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OBJECTIVE@#To explore the genetic etiology and related factors in 1 065 women with spontaneous abortions.@*METHODS@#All patients have presented at the Center of Prenatal Diagnosis of Nanjing Drum Tower Hospital from January 2018 to December 2021. Chorionic villi and fetal skin samples were collected, and the genomic DNA was assayed by chromosomal microarray analysis (CMA). For 10 couples with recurrent spontaneous abortions but normal CMA results for abortive tissues, non-in vitro fertilization-embryo transfer (IVF-ET) pregnancies and no previous history of live births and no structural abnormalities of the uterus, peripheral venous blood samples were collected. Genomic DNA was subjected to trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing and bioinformatics analysis. Multifactorial unconditional logistic regression analysis was carried out to analyze the factors that may affect chromosomal abnormality in spontaneous abortions, such as the age of the couple, number of previous spontaneous abortions, IVF-ET pregnancy and history of live birth. The incidence of chromosomal aneuploidies in spontaneous abortions during the first trimester was compared in young or advanced-aged patients by chi-square test for liner trend.@*RESULTS@#Among the 1 065 spontaneous abortion patients, 570 cases (53.5%) of chromosomal abnormalities were detected in spontaneous abortion tissues, which included 489 cases (45.9%) of chromosomal aneuploidies and 36 cases (3.4%) of pathogenic/likely pathogenic copy number variations (CNVs). Trio-WES results have revealed one homozygote variant and one compound heterozygote variants in two pedigrees, both of which were inherited from the parents. One likely pathogenic variant was detected in the patient from two pedigrees. Multifactorial unconditional Logistic regression analysis suggested that age of patient was an independent risk factor of chromosome abnormalities (OR = 1.122, 95%CI: 1.069-1.177, P < 0.001), the number of previous abortions and IVF-ET pregnancy were independent protective factors for chromosomal abnormalities (OR = 0.791, 0.648; 95%CI: 0.682-0.916, 0.500-0.840; P = 0.002, 0.001), whilst the age of husband and history of live birth were not (P > 0.05). The incidence of aneuploidies in the abortive tissues has decreased with the number of previous spontaneous abortions in young patients (χ² = 18.051, P < 0.001), but was not significantly correlated with the number of previous spontaneous abortions in advanced-aged patients with spontaneous abortions (P > 0.05).@*CONCLUSION@#Chromosomal aneuploidy is the main genetic factor for spontaneous abortion, though CNVs and genetic variants may also underlie its genetic etiology. The age of patients, number of previous abortions and IVF-ET pregnancy are closely associated with chromosome abnormalities in abortive tissues.
Subject(s)
Pregnancy , Humans , Female , Aged , Abortion, Spontaneous/genetics , DNA Copy Number Variations , Chromosome Aberrations , Chromosome Disorders/genetics , Aneuploidy , Abortion, Habitual/geneticsABSTRACT
Objective:To investigate the RHD genotypes of RhD-negative pregnant women and explore the optimum strategy for fetal RHD screening among this population in the region. Methods:This prospective study recruited 33 cases of RhD-negative singleton pregnancies at ≥12 weeks of gestation in Nanjing Drum Tower Hospital from March to November 2021. On the basis of RHD genotyping, quantitative real-time polymerase chain reaction (PCR) was used to amplify the exons 5 and 10 of RHD gene in the circulating cell-free DNA of RhD-negative pregnant women harboring whole RHD gene deletion and RHD-CE(2-9)- D. High-throughput sequencing was performed to detect chr1:25648453 locus from circulating cell-free DNA in plasma of RhD-negative pregnant women harboring RHD 1227A mutation to screen the fetal RhD blood group. Neonatal umbilical cord blood samples were collected for verifying fetal RHD genotyping. Descriptive statistical analysis was used. Results:Whole RHD gene deletion homozygous genotype ( n=20, 60.6%), RHD-CE(2-9) -D/whole RHD gene deletion heterozygous genotype ( n=5, 21.2%), RHD 1227A/whole RHD gene deletion heterozygous genotype ( n=7, 15.2%) and RHD 711delC/whole RHD gene deletion heterozygous genotype ( n=1) were identified in the 33 RhD-negative pregnant women. In the 25 cases with whole RHD gene deletion homozygous genotype or RHD-CE(2-9)- D/whole RHD gene deletion heterozygous genotype, 22 fetuses were RhD-positive and three were RhD-negative based on prenatal screening, which were confirmed by the neonatal serological test results after birth. In the seven cases carrying RHD 1227A/whole RHD gene deletion heterozygous genotype, all fetuses were RhD-positive, which were consistent with the results of serological detection after delivery. The case harboring RHD 711delC/whole RHD gene deletion heterozygous genotype did not receive fetal RHD screening. Conclusions:This study suggests that whole RHD gene deletion homozygous genotype is the most common allele in RhD-negative population in this area, followed by RHD 1227A/whole RHD gene deletion heterozygous genotype and RHD- CE(2-9)- D/whole RHD gene deletion heterozygous genotype. For women with whole RHD gene deletion homozygous genotype, RHD- CE(2-9)- D, or RHD 1227A mutation, fetal RHD screening with quantitative real-time PCR and high-throughput sequencing are important for the management of RhD-negative pregnant women.
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Objective To explore impacts of social support and coping styles on self-perceived burden of patients with spinal cord injury. Methods A total of 150 patients with spinal cord injury were investigated using Self-Perceived Burden Scale, Social Support Rating Scale, and Medical Coping Modes Questionnaire by cross-sectional survey method. Results The total score of self-perceived burden was at a moderate level and the average score was (33.98±10.76) points. Resignation of coping style had directly positive effect on self-perceived burden, path coefficient was 0.19, subjective support, support utilization had directly negative effect on SPB, path coefficient were-0.18,-0.21;objective support exerted directly negative influence on self-perceived burden through resignation of coping style. In other words, the resignation of coping style played a mediating role between social support and self-perceived burden, effect size was 0.034. Conclusions Most of patients with spinal cord injury suffer from moderate self-perceived burden. Objective support, subjective support, support utilization and the resignation of coping style are the important factors that affect self-perceived burden.
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<p><b>BACKGROUND</b>Most patients with epilepsy want to learn as much as possible about the disease, and many have turned to the internet for information. Patients are likely to use information obtained from the internet to control their epilepsy, but little is known about the accuracy of this information. In this survey, we have assessed the feasibility and usability of internet-based interventions for the treatment of epilepsy.</p><p><b>METHODS</b>Data were collected from an internet search. Different search terms were used to obtain general information on epilepsy together with information about medication, types of epilepsy, treatment, women's health, and other information. The accuracy of the information was evaluated by a group of experts.</p><p><b>RESULTS</b>A total of 1320 web pages were assessed. The majority were websites related to health. A large number (80.2%) of web pages contained content related to the search term. A significant number of web pages 450/1058 (42.5%) claimed to provide information from a credible source; however, only 206/1058 (19.5%) of the information was accurate and complete; 326/1058 (30.8%) was accurate but incomplete; 328/1058 (31.0%) was correct but nonstandard, and 198/1058 (18.8%) was inaccurate. The authenticity of the information was not significantly different between the two search engines (χ2 = 0.009, P = 0.924). No significant difference was observed in the information obtained from a specialist or nonspecialist source (χ2 = 7.538, P = 0.057). There was also no correlation between the quality of the information and the priority (χ2 = 6.880, P = 0.076).</p><p><b>CONCLUSIONS</b>Searching for information about epilepsy on the internet is convenient, but the information provided is not reliable. Too much information is inaccurate or for advertisement purposes, and it is difficult for patients to find the useful information. Turning to the internet for medical knowledge may be harmful. Physicians should be aware that their patients may search for information on the internet and guide them to safe, reputable websites.</p>
Subject(s)
Humans , Chi-Square Distribution , Epilepsy , Internet , SoftwareABSTRACT
Background Heidelberg Retinal Tomograph (HRT) has been widely used in clinical diagnosis of glaucomatous optic neuropathy,importantly,the measurement results of HRT may be affected by myopia.Therefore,studying the effect of different refractive status and axial length on structural parameters of the optic disc is important.Objective This study was to evaluate the influence of refractive error and axial length to optic nerve head parameter measured by HRT.Methods The parents who participate in Guangzhou Twin Study were enrolled in this investigation from July 2006 to August 2011.The regular eye examinations,including visual acuity,slit lamp,fundus,auto-refraction,HRT-Ⅲ and intraocular lens (IOL) Master,were performed on all the subjects.Thc data from right eyes of subjects were collected and analyzed.The linear correlation analysis and multiple linear regression analysis were applied to analyze the correlation between HRT optic papilla configuration parameter and equivalent sphere and ocular axis length.Results A pilot prospective series cases observational study was designed.1748subjects were enrolled in this study.The disc area (DA) (P=0.021),rim area (RA) (P＜0.001),rim volume (RV) (P＜0.001),mean retinal nerve fiber layer thickness (mRNFLt) (P＜0.001) and retinal nerve fiber layer cross section area (RNFLcsa) in the high myopia were greater than those of the emmetropic group,with significant difference between the two groups (P＜0.001).However,the cup area (CA),cup/disk area ratio (C/DAR) and cup volume (CV) were less in the high myopic group than those of the emmetropic group (P=0.004,P＜0.001 and P＜O.001),respectively.In the mild-moderatc myopic group,the RV,mRNFLt and RNFLcsa were greater than those of the emmetropic group (all of the P value less than 0.001),but the numbers of DA,CA,C/DAR,and CV were less than those of the emmetropic group,the differences were significant and their P valuables were 0.038,＜ 0.001,＜0.001 and 0.001 respectively.The differences of structure parameters between the hyperopia group and the emmetropic group were not statistically significant (P＞0.05).The DA,CA,RA,C/DAR,CV,RV,mean cup depth (MCD),maximum cup depth (MxCD),cup shape measure (CSM),mRNFLt and RNTLcsa were (2.04±0.43) mm2,(0.49±0.34) mm2,(1.55 ± 0.34) mm2,0.23-0.13,(0.11 ± 0.12) mm3,(0.45 ± 0.19) mm3,(0.21 ± 0.09) mm,(0.60±0.21) mm,-0.21 ± 0.07,(0.29 ± 0.07) mm and (1.46 ± 0.36)mm2,respectively,in the 1748 eyes of 1748 subjects.No significant correlation was found between the DA value with SE (r=-0.032,P =0.186).However,weaker positive correlations were seen between the CA,C/DAR,CV,MCD,MxCD with SE (r=0.139,0.163,0.130,0.004,0.054,P＜ 0.05) and negative correlation between RA,RV,mRNFLt and RNFLcsa with SE (r =-0.178,-0.331,0.241,-0.239,P＜0.001).With the increase of the ocular axial length,the DA,RA,RV,mRNFLt and RNFLcsa values were enlarged,and the CV value was smaller.With the increase of CA,the RA,C/DAR,CV,RV,MCD,MxCD,CSM and RNFLcsa values elevated,but mRNFLt value was decreased.Conclusions Refractive error is not associated with DA,but the measuring results are different among various refractive groups.Refractive error,ocular axial length and DA affect the measuring result of HRT.
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Background Normal adult optic disc rim width follows inferior ≥ superior ≥ nasal ≥ temporal (ISNT) rule.Analysis of the optic disc structural parameters with Heidelberg retina tomograph (HRT) can understand whether ISNT principle is suitable to other optic disc structure parameters.Objective This study was to investigate the characteristics of optic nerve head structure parameters in normal Chinese adults.Methods The parents of twins who participated Guangzhou Twin Eye Study were enrolled in Zhongshan Ophthalmic Center from 2006 June to 2011 August.All subjects received the routine eye examinations,including visual acuity,slit lamp microscope,direct ophthalmoscope examination,auto-refraction examination and HRT Ⅲ examination.All data from the right eyes were collected and analyzed.HRT values from different quadrants of optical nerve head were compared with one-way analysis of variance,and the multiple comparison between quadrants was carried out by Bonferroni test.The differences of optical nerve head parameters in different gender were analyzed using independent sample t test and Bland-Altman test.Results In this study,1672 eyes of 1672 subjects were included,with the 759 male and 913 female persons and average age of (41.8±5.3)years.No significant differences were seen in the disc area (DA)between the superior and inferior,as well as the nasal and temporal quadrants among the subjects (P＞0.05).In addition,there were not significantly different in the rim area (RA) between the superior and nasal disc as well as the rim volume (RV) among the inferior,superior and nasal disc (P＞O.05).However,significant differences were found in the cup area (CA),cup/disk area ratio (C/DAR),cup volume (CV),mean cupdepth (MCD),maximum cup depth (MxCD),height variation contour (HVC),cup shape measure (CSM),mean retinal nerve fiber layer thickness (mRNFLT) and retinal nerve fiber layer cross section area (RNFLcsa) among the different quadrants (P＜0.001).The local differences from only DA and RA complied with an ordination of the ISNT rule.The values of DA,CA,C/DAR,CV,MCD,MxCD from male individuals were higher,but those of the RV,HVC,mRNFLT RNFLcsa were lower in comparison with female individuals.Nevertheless,all the differences were ＜ 0.1 with a maximal mean difference in DA and CA (both 0.07 mm2).Conclusions The optical nerve head configurations measured by HRT have different distributing characteristics in four quadrants in normal adults.Most parameters show the higher values in the inferior and superior than those in nasal and temporal of disc,but DA and RA meet ISNT rule.The differences of most parameters between male and female subjects can be ignored.
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Long-term endurance training or physical activity has been confirmed not only to improve physical performance, but to bring about an obvious beneficial effect on human health; however, the mechanism of this effect is not clear. The most studied health adaptations in skeletal muscle response to endurance exercise are increased muscle glycogen level and insulin sensitivity, fiber type transformation toward oxidative myofibers, and increased mitochondrial content/function. Mitochondria are dynamic organelles in eukaryotic cells critical in physical performance and disease occurrence. The mitochondrial life cycle spans biogenesis, maintenance, and clearance. Exercise training may promote each of these processes and confer positive impacts on skeletal muscle contractile and metabolic functions. This review focused on the regulation of these processes by endurance exercise and discussed its potential benefits in health and disease. We presented evidence suggesting that exercise training potentiates not only the biogenesis of mitochondria but also the removal of old and unhealthy mitochondria through mitochondrial quality control.
Subject(s)
Humans , Adaptation, Physiological , Exercise , Mitochondria , Physiology , Muscle Contraction , Muscle, Skeletal , PhysiologyABSTRACT
<p><b>OBJECTIVE</b>To establish the high-resolution melting curve (HRM) approach for genotyping CYP2C9*3 (1075A/C, rs1057910) and VKORC1 (-1639A/G, rs9923231) and explore its value on estimation of the Warfarin initial dose in comparison with various traditional genotyping methods.</p><p><b>METHODS</b>CYP2C9*3 (1075A/C, rs1057910) and VKORC1 (-1639A/G, rs9923231) genotyping was detected in 100 patients receiving Warfarin therapy by the newly developed HRM method and traditional genotyping methods including PCR-restriction fragment length polymorphism (PCR-RFLP), TaqMan probe and DNA sequencing.</p><p><b>RESULTS</b>The results of the genotypes obtained from above mentioned methods to detect CYP2C9*3 (1075A/C, rs1057910) and VKORC1 (-1639A/G, rs9923231) were similar and consistent. The HRM method is simpler, more economical, and faster compared to the traditional methods. The frequencies of the VKORC1-1639 AA, AG, GG genotypes from these 100 clinical samples were 73 (73%), 23 (23%), 4 (4%), respectively; Frequencies of the CYP2C9 1075 AA, AC, CC genotypes were 94(94%), 6 cases (6%), 0, respectively.</p><p><b>CONCLUSIONS</b>HRM approach can effectively detect CYP2C9*3 (1075A/C, rs1057910) and VKORC1 (-1639A/G, rs9923231) polymorphisms and this method is simpler, more economical, and faster compared to the traditional methods for detecting CYP2C9*3 (1075A/C, rs1057910) and VKORC1 (-1639A/G, rs9923231) polymorphisms.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Aryl Hydrocarbon Hydroxylases , Genetics , Cytochrome P-450 CYP2C9 , Dose-Response Relationship, Drug , Freezing , Genotype , Genotyping Techniques , Mixed Function Oxygenases , Genetics , Polymorphism, Restriction Fragment Length , Vitamin K Epoxide Reductases , Warfarin , Therapeutic UsesABSTRACT
<p><b>OBJECTIVE</b>To investigate the association between rs751141 gene polymorphisms in EPHX2 gene and essential hypertension in Kazak and Han in Xinjiang.</p><p><b>METHODS</b>A total of 267 essential hypertensive patients in Kazaks, 368 essential hypertensive patients in Hans, 284 normotensive controls in Kazaks and 348 normotensive controls in Hans were enrolled in this study. TaqMan assay was used to detect the rs751141 G/A gene polymorphisms of EPHX2 gene.</p><p><b>RESULTS</b>The rs751141 G/A genotype frequencies for GA + AA genotypes was 40.2 percent in essential hypertensive subjects and 52.0 percent in control subjects in Hans, respectively. The genotype frequencies were significant difference between the two groups in Hans in Xinjiang (P < 0.01). The rs751141G/A gene polymorphism had no significant difference between essential hypertensive patients and normotensive controls in Kazaks in Xinjiang (P > 0.05).</p><p><b>CONCLUSION</b>The essential hypertension in Kazaks in Xinjiang is not associated with rs751141G/A gene polymorphism of EPHX2 gene, but the essential hypertension in Hans in Xinjiang is associated with rs751141G/A allele gene polymorphism of EPHX2 gene. A type of rs751141 allele gene polymorphism may be the independent protective factor of essential hypertension in Hans in Xinjiang.</p>
Subject(s)
Adult , Humans , Middle Aged , Alleles , Asian People , Genetics , China , Epidemiology , Epoxide Hydrolases , Genetics , Gene Frequency , Genotype , Hypertension , Epidemiology , Genetics , Polymorphism, Single NucleotideABSTRACT
Tetrahydrobiopterin (BH4) is an essential cofactor for all three nitric oxide synthase (NOS isoforms), which plays an important role in vascular diseases. GTP cyclohydrolase 1 (GCH 1) is the first-step and rate-limiting enzyme for BH4 biosynthesis in its de novo pathway. Common GCH1 gene variant C+243T in the 3'-untranslated region predicts NO excretion. The present study examined the predictive role of GCH 1 gene 3'-UTR C+243T variant in the long-term outcome of ischemic stroke. A total of 142 patients with first-onset ischemic stroke were recruited and detected for genotype of GCH1 3'-UTR C+243T by a TaqMan SNP Genotyping assay. Subsequent vascular events and death were determined over a 5-year follow-up period. The frequency of GCH1 3'-UTR +243 C/T or T/T genotype was significantly increased in patients with endpoint events as compared with those without events (74% vs 57.8%, P=0.06). Cox regression survival analysis indicated that an increased probability of death or new vascular events was found in patients with GCH1 3'-UTR +243 C/T or T/T genotype compared with those with GCH1 3'-UTR C/C genotype (40.6% vs 25.5%), GCH1 3'-UTR +243 C/T or T/T genotype relative to GCH1 3'-UTR C/C genotype was associated with the increased risk of death or vascular events even after adjustment for other risk factors (OR=2.171, 95% CI: 1.066-4.424, P=0.033). It was concluded that GCH1 3'-UTR C+243T variant was an independent predictor of worsening long-term outcomes in patients with first-onset ischemic stroke.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , 3' Untranslated Regions , Genetics , Brain Ischemia , Genetics , GTP Cyclohydrolase , Genetics , Nitric Oxide , Metabolism , Prognosis , Risk Factors , Stroke , Diagnosis , GeneticsABSTRACT
Tetrahydrobiopterin (BH4) is an essential cofactor for all three nitric oxide synthase (NOS isoforms), which plays an important role in vascular diseases. GTP cyclohydrolase 1 (GCH 1) is the first-step and rate-limiting enzyme for BH4 biosynthesis in its de novo pathway. Common GCH1 gene variant C+243T in the 3'-untranslated region predicts NO excretion. The present study examined the predictive role of GCH 1 gene 3'-UTR C+243T variant in the long-term outcome of ischemic stroke. A total of 142 patients with first-onset ischemic stroke were recruited and detected for genotype of GCH1 3'-UTR C+243T by a TaqMan SNP Genotyping assay. Subsequent vascular events and death were determined over a 5-year follow-up period. The frequency of GCH1 3'-UTR +243 C/T or T/T genotype was significantly increased in patients with endpoint events as compared with those without events (74% vs 57.8%, P=0.06). Cox regression survival analysis indicated that an increased probability of death or new vascular events was found in patients with GCH1 3'-UTR +243 C/T or T/T genotype compared with those with GCH1 3'-UTR C/C genotype (40.6% vs 25.5%), GCH1 3'-UTR +243 C/T or T/T genotype relative to GCH1 3'-UTR C/C genotype was associated with the increased risk of death or vascular events even after adjustment for other risk factors (OR=2.171, 95% CI: 1.066-4.424, P=0.033). It was concluded that GCH1 3'-UTR C+243T variant was an independent predictor of worsening long-term outcomes in patients with first-onset ischemic stroke.
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KCNK17 is a member of the acid-sensitive subfamily of tandem pore K(+) channels, which are open at all membrane potentials an red contribute to cellular resting membrane potential. Recent genome-wide study (GWA) has shown that variants within KCNK17 confer genetic susceptibility for increasing ischemic stroke. In an effort to discover additional polymorphism(s), we scrutinized the genetic polymorphisms in the KCNK17. By direct DNA sequencing in 32 individuals, we identified nine sequence variants within the 16 kb of whole KCNK17 gene: one in exon1, one in intron and seven in the promoter region. Haplotypes, their frequencies and linkage disequilibrium coefficients (D'), among polymorphisms were estimated. All the polymorphisms in the 5'-flanking region (SNP2-SNP7) being in complete (or nearly complete) association with each other in the promoter region maybe produce synergistic effect to regulate the expression of KCNK17 gene and then have an influence on the pathogenesis of cerebrovascular diseases. The common haplotypes were observed comprising 88.9% of the total haplotypes in the same block. Bioinformatic analysis predicted several potential transcriptional factors binding sites by SNP -95, -134, -596 and -846. However, these binding sites need to be experimentally verified. The information concerning genetic polymorphisms of KCNK17 gene might provide valuable information for future genetic studies of diseases.