Peripheral Venous Blood Samples Research Articles

Newborn screening and diagnosis for Glucose-6-phosphate dehydrogenase deficiency at Danang Hospital for Women and Children

Background: G6PD deficiency can result in acute hemolysis anemia during times of increased reactive oxygen species production. This study aimed to investigate the rate of high risk among newborns who were screened for G6PD deficiency, as well as some clinical characteristics of those who had this disease at Da Nang Hospital for Women and Children. Materials and Methods: 10,020 newborns were screened for G6PD deficiency using dried heel blood spots,. Samples of peripheral venous blood is drawn from high-risk infants for diagnostic testing. Results: The proportion of high-risk newborns was 1.12%, with boys having a greater incidence than girls (1.71% versus 0.48%). G6PD activity was higher in premature infants than in term infants. G6PD activity was higher in infants having low birth weight (< 2500 g) than in ones having normal birth weight (≥ 2500 g). Only 45.54% of high-risk newborns were tested for diagonosis. Among them, 92.16% had diagnostic confirmation. G6PD deficiency in class II accounts for 31.91%, whereas class III accounts for 68.09%. Boys accounted for 87.23% and jaundice accounted for 82.98% of infants with G6PD deficiency. Only 6.38% of those had a family history of G6PDD deficiency. Conclusion: Da Nang Hospital for Women and Children’s newborn screening programme identified 1.12% of newborns as high risk for G6PD deficiency. Most neonates with G6PD deficiency were in classes II and III, with males being the main gender, and jaundice being the most common symptom. Key words: G6PD deficiency, newborn screening, hell blood, enzyme activity

Evaluation of ocular and genetic findings in patients with Neurofibromatosis Type 1

Neurofibromatosis type 1 (NF1) is an autosomal dominantly inherited disease affecting multiple organ systems and showing many different clinical symptoms. The severity of the disease varies from person to person and progresses gradually over the years. In this study, 17 NF1 patients who had a definite diagnosis were evaluated in terms of genetic, ophthalmological, and nervous system investigations. Approximately 5000 patients who visited medical genetics clinic between 2012 and 2022 are recorded in our archive. In 17 of these patients, a definitive genetic diagnosis was made. In the course of the study, the researchers collected some clinical parameters such as antenatal, intrapartum, and postpartum history and family history. In the family history, the researchers did a detailed pedigree with at least 3 generations of analysis, questioned parental kinship, looked for similar members in families, and identified inheritance patterns of the disorder. Peripheral venous blood samples were taken from the patients and sent to a commercial laboratory for gene panels or WES while the karyotyping was carried out in our laboratory. After obtaining the definitive genetic diagnosis of all patients, we compiled a table with the other parameters we questioned. This study presented the genotype and phenotype findings of NF1 patients. Ophthalmological symptoms in patients were also examined. These new-generation genetic disease diagnosis methods can be routinely used in clinical practice by medical geneticists. The diagnosis of a disease is one step ahead of its treatment. Because if the necessary diagnosis is not made, treatment of the disease is not possible. While this situation was more difficult in the past, nowadays, with the developing technology, diseases can be diagnosed more easily. In NF1 disease, more information can be obtained as a result of genetics, imaging, and examinations of other branches.

Genotype-phenotype correlation study of structural abnormalities in a fetal brain caused by a novel KDM4B variant.

Fetal ventriculomegaly (VM), a common brain structure malformation detected during prenatal ultrasound diagnosis, is associated with an increased risk of neurodevelopmental disorders (NDDs) after birth. KDM4B encodes a lysine-specific demethylase that interacts with histone H3K23me3. Variations in KDM4B are reportedly associated with human NDDs; however, only 11 such patients have been reported. Herein, we report a fetus with VM and agenesis of the corpus callosum (ACC), which suggests that KDM4B plays an important role in fetal brain development. Fetal skin tissue and parental peripheral venous blood samples were collected. Whole-exome and Sanger sequencing were performed to analyze fetal germline variants. Human 293T cells transfected with wild-type or mutant KDM4B were used for western blotting (WB) to analyze protein expression levels. An insertion variant of KDM4B, NM_015015.3: c.2889_2890insGAGAGCATCACGGTGAGCTGTGGGGTGGGGCAGGGGGCGGGGGGAGGCTGGGAGCACAGTGACAACCTGTACCCC, was identified in the fetal tissue; however, the parents carried the wild-type gene. The WB results indicated significantly reduced expression of the mutant protein, likely owing to decreased stability. The structural abnormalities in the brain of the studied fetus may be attributed to an insertion variant of KDM4B. This study highlights the importance of screening for KDM4B variants and considering potential copy number variations when observing VM or ACC in prenatal ultrasound imaging.

Peripheral Blood CD8+ CD28+ T Cells as an Independent Predictor of Treatment Response and Survival After Concurrent Chemoradiotherapy in Pediatric High-Grade Glioma Patients.

The tumor immune microenvironment influences the efficiency of concurrent chemoradiotherapy (CCRT) in high-grade glioma (HGG). This study investigated peripheral blood T lymphocyte subsets as clinical indicators of therapeutic response and prognosis in pediatric high-grade glioma (pHGG). This retrospective study included 77 patients with postoperative pHGG who were treated concurrently with temozolomide and external beam radiotherapy between January 1, 2012, and December 31, 2018. The median follow-up was 26 (range: 5-106) months. Peripheral venous blood samples were collected before and after CCRT. The proportions of peripheral blood T lymphocytes and their association with treatment outcome and survival were determined. Sixty-four (83.1%) patients achieved complete remission, partial remission, and stable disease, and 13 (16.9%) patients had progressive disease. Higher CD3+ T cell, CD4+ T cell, and CD8+ CD28+ T cell ratios were predictive of better response, while a higher CD8+ CD28- T cell ratio was predictive of poorer response. Binary logistic regression analysis showed that the CD8+ CD28+ T cell ratio was a significant independent predictor of CCRT response (odds ratio [OR] = 53.521, 95% confidence interval [CI] = 4.294-667.119, P = .002). Univariate and multivariate analysis of prognostic factors associated with survival showed that the CD8+ CD28+ T lymphocyte ratio was a significant independent predictor of progression-free survival (hazard ratio [HR] = 1.80, 95% CI = 1.06-3.08, P = .03), but none of the subsets were significantly associated with overall survival. Peripheral blood T lymphocytes have potential as predictors of CCRT response and prognosis in pHGG.

Association of dysglycaemia with persistent infarct core iron in patients with acute ST-segment elevation myocardial infarction

BackgroundDysglycaemia increases the risk of myocardial infarction and subsequent recurrent cardiovascular events. However, the role of dysglycaemia in ischemia/reperfusion injury with development of irreversible myocardial tissue alterations remains poorly understood.In this study we aimed to investigate the association of ongoing dysglycaemia with persistence of infarct core iron and their longitudinal changes over time in patients undergoing primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI). MethodsWe analyzed 348 STEMI patients treated with primary PCI between 2016 and 2021 that were included in the prospective MARINA-STEMI study (NCT04113356). Peripheral venous blood samples for glucose and glycated hemoglobin (HbA1c) measurements were drawn on admission and 4 months after STEMI. Cardiac magnetic resonance (CMR) imaging including T2 * mapping for infarct core iron assessment was performed at both time points. Associations of dysglycaemia with persistent infarct core iron and iron resolution at 4 months were calculated using multivariable regression analysis. ResultsIntramyocardial hemorrhage was observed in 147 (42%) patients at baseline. Of these, 89 (61%) had persistent infarct core iron 4 months after infarction with increasing rates across HbA1c levels (<5.7%: 33%, ≥5.7: 79%). Persistent infarct core iron was independently associated with ongoing dysglycaemia defined by HbA1c at 4 months (OR: 7.87 [95% CI: 2.60–23.78]; p < 0.001), after adjustment for patient characteristics and CMR parameters. The independent association was present even after exclusion of patients with diabetes (pre- and newly diagnosed, n = 16). ConclusionsIn STEMI patients treated with primary PCI, ongoing dysglycaemia defined by HbA1c is independently associated with persistent infarct core iron and a lower likelihood of iron resolution. These findings suggest a potential association between ongoing dysglycaemia and persistent infarct core iron, which warrants further investigation for therapeutic implications.

Accumulation of Inflammatory Mediators in the Normal Pericardial Fluid.

There is paucity of studies that focus on the composition of pericardial fluid under resting conditions. The purpose of this study is to determine the levels of inflammatory mediators in pericardial fluid and their correlation with plasma levels in patients undergoing elective cardiac surgery. We conducted a prospective cohort study on candidates for elective aortic valve replacement surgery. Pericardial fluid and peripheral venous blood samples were collected after opening the pericardium. Levels of interleukin 1α (IL-1α); interleukin 1β (IL-1β); interleukin 2 (IL-2) interleukin 4 (IL-4); interleukin 6 (IL-6); interleukin 8 (IL8); interleukin 10 (IL10); tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1) epidermal growth factor (EGF), soluble E-selectin, L-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were determined in both pericardial fluid and serum samples. A total of 45 patients with a mean age of 74 years were included of which 66% were males. Serum levels of all study mediators were within normal limits. Serum and pericardial levels of IL-1 α, IL-1 β, IL-2, IL-4, and IL-10 were similar. Levels of VEGF, EGF, VCAM-2, ICAM 1, E-selectin, P-selectin, and L-selectin were significantly lower in pericardial fluid than in serum. However, levels of IL-6, IL-8, TNF-α, IFN-γ, MCP-1, and MCP-1 were significantly higher in the pericardial fluid than in serum. Under normal conditions, the pattern of distribution of different inflammatory mediators in the pericardial fluid does not reflect serum levels. This may either reflect the condition of the underlying myocardium and epicardial fat or the activity of the mesothelial and mononuclear cells present in pericardial fluid.

Haplotype analysis of long-chain non-coding RNA NONHSAT102891 promoter polymorphisms and depression in Chinese individuals: A case-control association study.

Our previous study reported that the single-nucleotide polymorphism (SNP) rs155979 GC in the promoter region of long-chain non-coding RNA (lncRNA) NONHSAT102891 affects depression susceptibility in a Chinese population. To explored associations of two SNPs and haplotypes in the lncRNA NONHSAT102891 promoter region with depression susceptibility in Chinese population. This this case-control association study was approved by the Ethics Committee of Chengdu Medical College (approval number: 201815). Patient diagnosis was based on DSM-IV criteria. We selected a total of 480 patients with depression and 329 healthy controls with no history of psychopathology, and performed genotyping of two SNPs by extracting peripheral venous blood samples from the subjects. The function of the two lncRNA NONHSAT102891 promoter G/C and A/T haplotypes was detected by dual-luciferase reporter assays of human embryonic kidney 293T transfected cells. Stratified analysis of clinical and genotypic characteristics of our cohort showed that the degree of mild depressive episodes associated with the rs6230 TC/CC genotype increased by 1.59 times [TC/CC vs TT: odds ratio (OR) = 1.59, 95% confidence interval (CI): 1.08-2.35, P = 0.019]. The haploid analysis revealed linkage disequilibrium between rs3792747 and rs6230, and the double SNP CG haplotype was more common in the control group compared to case group, indicating that this haplotype significantly reduced the risk of depression (C/G vs T/A: OR = 0.42, 95%CI: 0.21-0.83, P = 0.01). There was no significant difference in the dual-luciferase reporter activity of the G/C and A/T haplotypes compared with the control group (P > 0.05), indicating that the double SNP haplotype has no transcriptional activity. The rs3792747 and rs6230 CG haplotypes of the lncRNA NONHSA T102891 promoter may be related to a reduced risk of depression in the Han Chinese population.

Insufficiency of plasmatic arginine/homoarginine during the initial postoperative phase among patients with tumors affecting the medulla oblongata heightens the likelihood of neurogenic pulmonary oedema following surgery.

This prospective clinical study aims to investigate the fluctuations of neurotransmitters in peripheral venous blood during the perioperative period and to identify independent predictors for postoperative neurogenic pulmonary oedema (NPE) in patients with medulla oblongata-involved tumours. Peripheral venous blood samples of the enroled patients at seven perioperative time points, as well as their medical records and radiologic data were collected. High-performance liquid chromatography-tandem mass spectrometry was utilized to detect the concentrations of 39 neurotransmitters in these samples. The study applied univariate and multivariate generalized estimating equation (GEE) logistic regression analyses to explore independent predictors of postoperative NPE, and one-way repeated-measures ANOVA to compare the concentrations of the same neurotransmitter at different perioperative time points. The study included 36 patients with medulla oblongata-involved tumours from January to December 2019, and found that 13.9% of them experienced postoperative NPE. The absence of intraoperative use of sevoflurane ( P =0.008), decreased concentrations of arginine ( P =0.026) and homoarginine ( P =0.030), and prolonged postoperative tracheal extubation ( P <0.001) were identified as independent risk factors for postoperative NPE in medulla oblongata-involved tumour patients. Pairwise comparison analysis revealed that the perioperative decreases in arginine and homoarginine concentrations mainly occurred within the postoperative 8 h. This study demonstrates that NPE is not uncommon in patients with medulla oblongata-involved tumours. The absence of intraoperative use of sevoflurane, decreased concentrations of plasmatic arginine and homoarginine, and prolonged postoperative tracheal extubation are independent predictors of postoperative NPE. These two neurotransmitters' concentrations dropped mainly within the early postoperative hours and could serve as potential early warning indicators of postoperative NPE in clinical practice.

A novel APC mutation associated with Gardner syndrome in a Chinese family

Gardner syndrome (GS) is a specific form of familial adenomatous polyposis (FAP), which manifests as colorectal polyps, multiple osteomas and soft tissue tumors, and in the oral cavity as osteomas of the jaws, odontomas, and abnormal tooth counts. The underlying cause of GS is attributed to mutations in the APC gene. Mutations in this gene disrupt the normal functioning of the protein and lead to the development of GS. To further investigate GS, a family affected by the syndrome was selected from Dongguan, Guangdong Province. The family members underwent a comprehensive survey, which involved collecting clinical data and peripheral venous blood samples. The samples were then used for genetic analysis. Whole exome sequencing (WES) and Sanger sequencing techniques were utilized to screen and identify specific mutation sites in the APC gene. The clinical findings for the GS family included the presence of gastrointestinal polyps and odontomas. After analyzing the genetic sequencing results, a novel mutation site c.4266dupA on the APC gene was found in the patients, which leading to the APC protein truncation. As a result of this study, it is suggested that odontoma may be an early indicator of GS. Additionally, the identification of this novel mutation site in the APC gene expands the known spectrum of genetic mutations associated with the disease. This discovery has significant implications for the early diagnosis of GS, thus enabling timely intervention to reduce the risk of developing colon cancer and other related diseases.

Pro-Inflammatory Biomarkers and Progression of Atherosclerosis in Patients with Myocardial Infarction with Non-Obstructive Coronary Artery Disease: 1-Year Follow-Up.

Samples of peripheral venous blood were collected upon admission and on days 2, 4, and 7 of hospitalization and after 1 year. An extended multiplex analysis was performed in blood serum. Multidetector-computed tomography coronary angiography was performed on day 7 and 1 year after acute myocardial infarction to assess the progression of atherosclerosis. The level of high-sensitive C-reactive protein (hsCRP) was elevated upon admission in MINOCA patients compared to MI-CAD patients (p = 0.05), but it was comparable in two groups at other time points and did not exceed the reference range after 1 year. Despite comparable levels of cytokines CXCL-6, LIGHT, CCL-8, and endocan-1 in patients in both groups, MINOCA patients had a greater increase in pro-inflammatory cytokines PlGF, oncostatin M, IL-20, and CCL-15 sVCAM-1 in the early post-infarction period and in CCL-21, sVCAM-1, oncostatin M, and PlGF after 1 year. We observed significant differences in the dynamics of the following biomarkers between patients with MI-CAD and MINOCA: the dynamics of concentrations of CCL21 (p = 0.002), LIGHT (p = 0.03), and endocan-1 (p = 0.03) after 1 year compared to day 1 in MI-CAD and MINOCA patients was opposite, while the dynamics of CXCL6 (p = 0.04) and endocan-1 (p = 0.02) differed between groups when evaluated after 1 year compared to day 7 of the early post-infarction period. In the MINOCA group, factors associated with atherosclerosis progression were concentrations of sVCAM-1 and CCL-21, while in the MI-CAD group, concentrations of CCL-8 and CXCL6 were the main determinants of atherosclerosis progression. This small study showed that MINOCA and MI-CAD patients exhibited differences in a pro-inflammatory biomarker profile in the early post-infarction period and after 1-year follow-up, which implies distinct inflammatory pathways involved in atherogenesis during MINOCA. The key factors that were associated with atherosclerosis progression in MINOCA patients are sVCAM-1 and CCL-21, which may suggest a complex genesis of atherosclerosis progression due to structurally altered plaques and changes in the microcirculatory bed. In MI-CAD patients, CCL-8 and CXCL-6 were the key biomarkers associated with atherosclerosis progression. Further large-scale studies are required to confirm our data.

Genetic testing and prenatal diagnosis for two Chinese pedigrees affected with Alport syndrome due to variants of COL4A5 gene

To analysis variants of COL4A5 gene in two Chinese pedigrees affected with Alport syndrome (AS) and provide prenatal diagnosis for them. Two unrelated ethnic Han Chinese pedigrees who had visited the First Affiliated Hospital of Zhengzhou University respectively in September 2018 and January 2020 were selected as the study subjects. Clinical data were collected, and genomic DNA was extracted from peripheral venous blood and amniotic fluid samples for genetic testing. Following next generation sequencing, candidate variants of the COL4A5 gene were verified by Sanger sequencing and bioinformatic analysis. The gender of the fetuses was determined by the presence of sex-determining region on Y (SRY). Genetic testing revealed that the proband and a fetus from pedigree 1 had both harbored a c.2723G>A (p.Gly908Glu) variant in exon 32 of the COL4A5 gene, whilst the proband and a fetus from pedigree 2 had both harbored a c.3817G>A (p.Gly1273Asp) variant in exon 44 of the COL4A5 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as likely pathogenic (PP2+PM2_Supporting). Following exclusion of maternal contamination, PCR amplification of the SRY region indicated that both fetuses were males. The c.2723G>A (p.Gly908Glu) and c.3817G>A (p.Gly1273Asp) variants of the COL4A5 gene probably underlay the AS in the two pedigrees. Detection of the SRY region can reliably identify the fetal sex, which is conducive to the prenatal diagnosis. Above results have also enriched the mutational spectrum of the COL4A5 gene and provided a reference for correlating the genotype and phenotype of the AS.

Genetic analysis of a Chinese pedigree affected with Congenital dysfibrinogenemia due to variant of FGG gene

To explore the coagulation deficit and genetic basis for a Chinese pedigree affected with Congenital dysfibrinogenemia (CD). Peripheral venous blood samples of the proband and her family members (including 4 individuals from three generations) were subjected to routine blood test and assays of liver and kidney functions and viral hepatitis to exclude related diseases. Clauss method and DFg-PT method were used to determine the fibrinogen activity (Fg:C), and an immunoturbidimetric assay was used to determine the level of fibrinogen antigen (Fg:Ag). All of the exons (22 in total) and their flanking sequences of the FGA, FGB and FGG genes were amplified by PCR and directly sequenced. Variants in the coding regions of the three genes and transcriptional splicing sites were screened by using Mutation SurveyorTM software. The Clauss method showed that Fg:C was significantly reduced in the proband and her father, whilst her mother and son were normal. With the DFg-PT method, the proband, her parents and son were all within the normal range. The Fg:C/Fg:Ag ratio of the proband and her father was lower than 0.7, whilst her mother and son were above 0.7. No significant change in the prothrombin time, activated partial thromboplastin clotting time and thrombin time was noted. Two genetic variants were detected, which included a homozygous missense variant in the FGA gene [c.991A>G (p.Thr331Ala)], which was predicted to be benign, and a heterozygous missense variant of the γ chain of the FGG gene [c.1211C>G (p.Ser404Phe)], which is located in a conserved region and unreported in the CLINVAR/HGMD/EXAC/1000G databases and literature. This pedigree has conformed to the autosomal dominant inheritance of CD. The c.1211C>T (p.Ser404Phe) missense variant of the γ chain of the FGG gene probably underlay the pathogenesis of CD in this pedigree. The variant was unreported previously and named as "Fibrinogen Harbin II Ser404Phe".

Association of dysglycaemia with persistent infarct core iron in patients with acute ST-segment elevation myocardial infarction

Abstract Background Dysglycaemia increases the risk of myocardial infarction and subsequent recurrent cardiovascular events. However, the role of dysglycaemia in ischemia/reperfusion injury with development of irreversible myocardial tissue alterations remains poorly understood. Objectives To investigate the association of dysglycaemia with persistence of infarct core iron and their longitudinal changes over time in patients undergoing primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI). Methods We analyzed 348 STEMI patients treated with primary PCI between 2016 and 2021 that were included in a prospective observational study. Peripheral venous blood samples for glucose and glycated hemoglobin (HbA1c) measurements were drawn on admission and 4 months after STEMI. Cardiac magnetic resonance (CMR) imaging including T2* mapping for infarct core iron assessment was performed at both time points. Associations of dysglycaemia with persistent infarct core iron and iron resolution at 4 months were calculated using multivariable regression analysis. Results Persistent infarct core iron was present in 89 (26%) patients (HBA1c &amp;lt;5.7%: 16%, 5.7-6.4: 37%, ≥6.5: 34%) and was independently associated with HbA1c levels (OR: 1.64 [95% CI: 1.11-2.42]; p=0.01), but not glucose levels on admission. The independent association was present even after exclusion of patients with diabetes (pre- and newly diagnosed, n=42). Infarct core iron resolution was observed in 34 (14%) patients and was independently associated with HbA1c levels at 4 months (OR: 0.51 [95% CI: 0.28-0.93]; p=0.03). Conclusions In STEMI patients treated with primary PCI, dysglycaemia is independently associated with persistent infarct core iron and impaired iron resolution at 4 months. Persistent infarct core iron might represent a mechanistic driver for adverse outcome and a potential therapeutic target in patients with altered glycemic status suffering acute STEMI.

Luteinizing Hormone/Human Chorionic Gonadotropin Receptor N312S Single-Nucleotide Polymorphism and Its Impact on Clinical and Reproductive Outcomes in Assisted Reproductive Technology: A Prospective Cohort Study.

Objective The aim of this study was to determine the genotypic distribution of luteinizing hormone/human chorionic gonadotropin receptor (LHCGR) N312S single-nucleotide polymorphism (SNP) and to investigate its impact on clinical and reproductive outcomes in infertile Indian women undergoing assisted reproductive technology (ART). Study design and settings This was a prospective cohort study conducted at a tertiary care university hospital. Subjects and methods Infertile women aged between 21 and 40 years undergoing ART with an antagonist protocol were enrolled in this study. A 2-ml sample of peripheral venous blood was collected from each woman and genotyped for the LHCGR N312S SNP. Participants were divided into three groups based on their SNP: NN, NS, and SS. All subjects underwent controlled ovarian hyperstimulation (COH) through a gonadotropin-releasing hormone (GnRH) antagonist protocol and intracytoplasmic sperm injection (ICSI). Of the 140 women recruited based on selection criteria, 128 underwent embryo transfer. We compared the genotypic distribution of the LHCGR N312S SNP, baseline characteristics, clinical outcomes, and reproductive outcomes in ART among the three groups. Data were analyzed using IBM SPSS Statistics for Windows, Version 29 (Released 2022; IBM Corp., Armonk, New York, United States). The chi-square test and Fisher-Irwin test were employed to evaluate significant differences among the qualitative categorical variables. A p-value of less than 0.05 was considered statistically significant. Results Among the test subjects, 19.3% were homozygous for the LHCGR N312 SNP (NN group), 38.6% were heterozygous (NS group), and 42.1% were homozygous for the LHCGR S312 SNP (SS group). Baseline characteristics were similar among the three groups. In terms of ovarian reserve tests, significantly lower anti-Müllerian hormone (AMH) levels were observed in the SS group compared to the NS and NN groups (2.8 ± 2.1 vs. 3.2 ± 2.5 vs. 4.3 ± 3.3; p=0.03). No significant differences were observed in COH outcomes such as duration of stimulation, total gonadotropin requirement, oocyte yield, or the number of good-quality embryos among the three groups. The cumulative pregnancy rate (82.9% vs. 50.0% vs. 38.2%, p=0.0005), cumulative clinical pregnancy rate (78.8% vs. 44.7% vs. 34.5%, p = 0.0005), and cumulative live birth rate (50.0% vs. 20.2% vs. 20.0%, p=0.005) were significantly higher in the NN group than in the NS and SS groups. Conclusion The study's findings suggest that LHCGR N312 may help predict reproductive outcomes in ART, which may aid in providing better counseling to infertile couples. We need more studies on individualized/personalized COH using pharmacogenomics for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) supplementation based on combined FSH and LH receptor SNP and to assess their effects on ART outcomes.

Angiotensin-Converting Enzyme (ACE) gene polymorphism and arterial blood pressure among the Tawang Monpa of Eastern Himalayan Mountains: Is there a signature of natural selection?

The present paper aims to characterize the Angiotensin-converting enzyme (ACE) genotype, with particular emphasis on its association with arterial oxygen saturation, arterial blood pressure, hemoglobin [Hb] concentration, and ventilatory measures among the Tawang Monpa, a high-altitude native population of the Eastern Himalaya, India. A cross-sectional sample of 168Monpa participants from Tawang town, Arunachal Pradesh, India, was selected who live at an altitude of ∼3,200 meters (m) above sea level. For each participant, height, weight, and skinfold thickness were measured, based on which body mass index (BMI, kg/m2) and percentage of body fat (%BF) were calculated. Physiological measures, such as the transcutaneous arterial oxygen saturation (SaO2), hemoglobin [Hb] concentration, forced vital capacity (FVC), forced expiratory volume in 1-second (FEV1), and systemic arterial blood pressure were measured. First, the peripheral venous blood samples (four ml) were drawn, and then white blood cells were separated for the ACE genotyping of each participant. Unlike high-altitude natives from Peru and Ladakh, who exhibit high frequencies of II homozygotes, the Tawang Monpa shows a significantly high frequency of ID heterozygotes (p<0.0001). In addition, no significant association was identified between ACE gene polymorphism and arterial blood pressure, oxygen saturation at rest, vital capacity, or [Hb] concentration. The results suggest that the association of the ACE gene with resting SaO2 is inconsistent across native populations living under hypobaric hypoxia. Further, ACE I/D gene polymorphism may not be under natural selection in specific native populations, including Tawang Monpa, for their adaptation to high-altitude hypoxia.

Redox Status and Telomere-Telomerase System Biomarkers in Patients with Acute Myocardial Infarction Using a Principal Component Analysis: Is There a Link?

In the present study, we examined redox status parameters in arterial and venous blood samples, its potential to predict the prognosis of acute myocardial infarction (AMI) patients assessed through its impact on the comprehensive grading SYNTAX score, and its clinical accuracy. Potential connections between common blood biomarkers, biomarkers of redox status, leukocyte telomere length, and telomerase enzyme activity in the acute myocardial infarction burden were assessed using principal component analysis (PCA). This study included 92 patients with acute myocardial infarction. Significantly higher levels of advanced oxidation protein products (AOPP), superoxide anion (O2•-), ischemia-modified albumin (IMA), and significantly lower levels of total oxidant status (TOS) and total protein sulfhydryl (SH-) groups were found in arterial blood than in the peripheral venous blood samples, while biomarkers of the telomere-telomerase system did not show statistical significance in the two compared sample types (p = 0.834 and p = 0.419). To better understand the effect of the examined biomarkers in the AMI patients on SYNTAX score, those biomarkers were grouped using PCA, which merged them into the four the most contributing factors. The "cholesterol-protein factor" and "oxidative-telomere factor" were independent predictors of higher SYNTAX score (OR = 0.338, p = 0.008 and OR = 0.427, p = 0.035, respectively), while the ability to discriminate STEMI from non-STEMI patients had only the "oxidative-telomere factor" (AUC = 0.860, p = 0.008). The results show that traditional cardiovascular risk factors, i.e., high total cholesterol together with high total serum proteins and haemoglobin, are associated with severe disease progression in much the same way as a combination of redox biomarkers (pro-oxidant-antioxidant balance, total antioxidant status, IMA) and telomere length.

Clinical characteristics and genetic analysis of a Chinese pedigree affected with Alström syndrome

To explore the clinical characteristics and genetic etiology of a Chinese pedigree affected with Alström syndrome. A pedigree with 5 members affected with Alström syndrome who had visited the First Affiliated Hospital of Zhengzhou University in February 2021 was selected as the study subject. Clinical data of the pedigree were collected, and peripheral venous blood samples were collected for the extraction of genomic DNA. Genetic testing was carried out for the eldest daughter and third son through whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. The eldest daughter (14 years old) and the third son (11 years old) both had congenital nystagmus, amblyopia, growth retardation and type 2 diabetes. WES revealed that both had harbored homozygous c.3538A>T (p.Lys1180*) variant of the ALMS1 gene. Sanger sequencing confirmed that the father, mother, and second daughter were all heterozygous carriers. Based on the Guidelines for Genetic Variation and the Technical Standards for Interpretation and Reporting of Primary Copy Number Variations, the variant was predicted as pathogenic (PVS1+PM2_Supporting+PP4). The homozygous c.3538A>T (p.Lys1180*) variant of the ALSM1 gene probably underlay the Alström syndrome in this pedigree, which has provided a reference for the clinical treatment.

Identification of Potential Abnormal Methylation-Modified Genes in Coronary Artery Ectasia.

Coronary artery ectasia (CAE) is an easily recognized abnormality of coronary artery anatomy and morphology. However, its pathogenesis remains unclear. This study aimed to identify abnormal methylation-modified genes in patients with CAE, which could provide a research basis for CAE. Peripheral venous blood samples from patients with CAE were collected for RNA sequencing to identify differentially expressed genes (DEGs), followed by functional enrichment. Then, the DNA methylation profile of CAE was downloaded from GSE87016 (HumanMethylation450 BeadChip data, involving 11 cases and 12 normal controls) to identify differentially methylated genes (DMGs). Finally, after taking interaction genes between DEGs and DMGs, abnormal methylation-modified genes were identified, followed by protein-protein interaction analysis and expression validation using reverse transcriptase polymerase chain reaction. A total of 152 DEGs and 4318 DMGs were obtained from RNA sequencing and the GSE87016 dataset, respectively. After taking interaction genes, 9 down-regulated DEGs due to hypermethylation and 11 up-regulated DEGs due to hypomethylation were identified in CAE. A total of 10 core abnormal methylation-modified genes were identified, including six down-regulated DEGs due to hypermethylation (netrin G1, ADAM metallopeptidase domain 12, immunoglobulin superfamily member 10, sarcoglycan dela, Dickkopf WNT signaling pathway inhibitor 3, and GATA binding protein 6), and four up-regulated DEGs due to hypomethylation (adrenomedullin, ubiquitin specific peptidase 18, lymphocyte antigen 6 family member E, and MX dynamin-like GTPase 1). Some signaling pathways were identified in patients with CAE, including cell adhesion molecule, O-glycan biosynthesis, and the renin-angiotensin system. Abnormal methylation-modified DEGs involved in signaling pathways may be involved in CAE development.

ASSESSMENT OF SARS-COV-2 SPECIFIC B-CELL IMMUNE MEMORY: EVIDENCE FOR PERSISTENCE UP TO 1 YEAR POST-INFECTION

Background: SARS-CoV-2, the virus responsible for COVID-19 pandemic, has posed huge global health challenges. Understanding the immune response to SARS-CoV-2 infection, and in particular – the role of B cells in the generation of immune memory is crucial for assessing the durability of protective immunity. Materials and Methods: In this longitudinal prospective study, individuals who had recovered from SARS-CoV-2 infection were included. Peripheral venous blood samples were collected at three time intervals post symptom onset (PSO): 1-3 mo, 4-8 mo, and 9-12 mo. The humoral immune response was evaluated by measuring anti-SARS-CoV-2 IgG, virus-neutralizing antibody activity, total S1-specific B-cells, and B cell subpopulations. Results: The levels of anti-SARS-CoV-2 specific IgG antibodies decreased from 390.3 to 204.5 BAU/ml in the first 6-8 months PSO but did not significantly decrease further until the 12 th mo (126.6 BAU/ml). Virus-neutralizing antibodies (activity decreased by 20.4% between the 1st and 6-8th mos but remained relatively stable thereafter and could be detected up to 12 months PSO. In peripheral blood, the amount of S1-specific plasmablasts was highest one month after COVID-19 infection, and the level of memory B cells at 6 months. Those were detected even 12 months PSO, albeit in smaller quantities. Conclusion: The study provides evidence for the persistence of SARS-CoV-2-specific B-cell immune memory up to 1year post-infection. The presence of virus-specific memory B cells and plasmablasts suggests potential for sustained protection against reinfection. Further research is needed to elucidate the role of B-cell immune memory in preventing infection and to understand the individual variations of immune response.

Prenatal diagnosis of two fetuses with Xp22.31 microdeletion syndrome indicated by non-invasive prenatal testing

To assess the value of non-invasive prenatal testing (NIPT) for detecting fetal chromosomal microdeletion/microduplication syndromes by carrying out prenatal diagnoses for two fetuses with Xp22.31 microdeletion indicated by NIPT. Two pregnant women suspected for fetal Xp22.31 microdeletion syndrome who presented at Zaozhuang Maternal and Child Health Care Hospital on December 5, 2017 and October 15, 2020 were selected as the study subjects. Clinical data of the two women were collected, and peripheral venous blood samples were collected for NIPT testing. Amniotic fluid samples were taken for G-banding chromosomal karyotyping analysis and copy number variation sequencing (CNV-seq) for fetus 1, while G-banding chromosomal karyotyping and single nucleotide polymorphism microarray analysis (SNP array) were carried out for fetus 2. Peripheral venous blood samples of couple 1 were collected for CNV-seq to verify the origin of copy number variation . NIPT indicated that fetus 1 had harbored a 1.3 Mb deletion in the Xp22.31 region, while G-banding chromosomal karyotyping had found no abnormality. CNV-seq analysis verified the fetus to be seg[GRCh37]del(X)(p22.31)chrX:g.6800001_7940000del, with a 1.14 Mb deletion at Xp22.31, which was derived from its mother. NIPT indicated that fetus 2 had harbored a 1.54 Mb deletion in the Xp22.31 region, while G-banding chromosomal karyotyping had found no abnormality. SNP array analysis indicated arr[GRCh37]Xp22.31(6458940_8003247)×0, with a 1.54 Mb deletion in Xp22.31 region. NIPT not only has a good performance for detecting fetal trisomies 21, 18 and 13, but also has the potential for detecting chromosomal microdeletion/microduplications. For high risk fetuses indicated by NIPT, prenatal diagnosis needs to be carry out to verify the chromosomal abnormalities.