The correlation between blood lipids and intrahepatic cholestasis syndrome during pregnancy.

BACKGROUND: To analyse changes in lipid levels during the development of intrahepatic cholestasis of pregnancy (ICP) and identify new biomarkers for predicting ICP. METHODS: A retrospective case-control study was conducted to analyse 473 pregnant women who underwent regular prenatal examinations and delivered at the Women and Children's Hospital, School of Medicine, Xiamen University, between June 2020 and June 2023, including 269 normal pregnancy controls and 204 pregnant women with cholestasis. RESULTS: Patients with ICP with gestational diabetes mellitus (GDM) have lower high-density lipoprotein (HDL) levels than in those without GDM. Total bile acid (TBA) levels were significantly higher in pregnant women with GDM than those without. The apolipoprotein A (APOA) level was lower in patients with ICP and hypothyroidism than those without hypothyroidism. TBA levels were significantly higher in pregnant women with hypothyroidism than those without. Triglyceride (TG) levels were significantly higher in patients with preeclampsia (PE) than those without. HDL and APOA levels were lower in women with ICP complicated by preterm delivery than those with normal delivery. The AUC (area under the curve) of the differential diagnosis of cholestasis of pregnancy for the APOA/APOB (apolipoprotein B) ratio was 0.727, with a sensitivity of 85.9% and specificity of 47.5%. CONCLUSIONS: The results suggested that dyslipidaemia is associated with an increased risk of ICP and its complications. The timely detection of blood lipid and bile acid levels can assist in the diagnosis of ICP and effectively prevent ICP and other complications.

Intrahepatic cholestasis of pregnancy (ICP) is recognized as one of the most severe complications during pregnancy. Currently, elevated fasting serum total bile acid (TBA) levels are commonly used as diagnostic markers for ICP. However, it has been observed that women diagnosed with ICP often do not exhibit elevated TBA levels. Additionally, other medical conditions can also lead to increased TBA levels. Our study has revealed a potential correlation between abnormal lipid metabolism and the occurrence and progression of ICP and its associated complications. Specifically, we found that patients with ICP who have higher serum bile acid levels tend to have more disrupted lipid metabolism, as well as a higher risk of complications and adverse pregnancy outcomes. This manuscript is the first to investigate the link between dyslipidemia and ICP, as well as other pregnancy complications. As a result, our findings offer a foundation for the clinical diagnosis and treatment of ICP and its comorbidities during pregnancy, while also highlighting the need for further research in this area.

Management of refined and personalized newborn blood specimen collection.

Background: Iatrogenic blood loss is an important cause of neonatal anemia. In this study, a spreadsheet tool was developed to reduce blood collection, providing a new idea for the prevention of iatrogenic blood loss in newborns. Methods: Based on hematocrit, minimum test volume and dead volume, a new tool was to calculate the minimum blood collection volume and the number of containers required for the test portfolio. We collected data from October 2022 to October 2023 from Xiamen Maternal and Child Health Hospital for analysis and validation. Results: During this year, there were 16,434 patients and 13,696 plasma/serological samples in the neonatology department. Among them, there were 8 test combinations of greater than 1%, and 9490 samples in total. According to the hospital manual, the recommended amount of blood collection is 27,534 ml and 9490 containers. Through the analysis of this tool, total blood collection was 8864.77 ml, marked qnantity of upward containers (closest level to the calculated blood collection volume) was 10301 ml, and the amount of containers was 8835, which decreased by 67.8%, 62.58% and 6.9% respectively. Besides, if the hematocrit information cannot be obtained in advance and the high hematocrit is calculated as 0.8, the recommended amount of blood collection is 14334.3 ml, and the marked amount of the upward container markering is 17340 ml, decreasing by 47.9% and 37.02% respectively. Conclusion: We have developed an auxiliary tool that can manage neonatal blood specimen collection in a fine and personalized way and can be applied among different laboratory instruments by parameters modification.

Maternal and neonatal outcomes and clinical laboratory testing of pregnant women with COVID-19 during the BA.5.2/BF.7 surge.

The impact of COVID-19 on pregnant women and newborns continues to be a critical societal concern. However, the majority of research focuses on the disease resulting from the early pandemic variants, without sufficient study on the more recent BA.5.2/BF.7. We retrospectively recruited pregnant women giving birth during the surge of the BA.5.2/BF.7 and analysed the risk impact of COVID-19 on maternal and neonatal outcomes. Furthermore, subjects matched through propensity scores were used for the analysis of clinical laboratory tests. A total of 818 pregnant women were enrolled, among 276 (33.7%) were diagnosed with SARS-CoV-2 during childbirth. COVID-19 significantly increased the risk of a hospital length of stay equal to or greater than seven days and neonatal admission to the neonatal intensive care unit, with an aHR of 2.03 (95% CI, 1.22-3.38) and 1.51 (95% CI, 1.12-2.03), respectively. In the analysis of 462 matched subjects, it was found that subjects infected with SARS-CoV-2 tended slight leucopenia and coagulation abnormalities. We found that during the surge of the BA.5.2/BF.7, COVID-19 increased the risk of maternal and neonatal outcomes among Chinese pregnant women. This finding offers significant insights to guide clinical practices involving pregnant women infected with the recently emerged Omicron subvariants.

Functional testing is a complementary tool for the diagnosis of vaginitis.

OBJECTIVE: Vaginal microbiota evaluation is a methodology widely used in China to diagnose various vaginal inflammatory diseases. Although vaginal microbiota evaluation has many advantages, it is time-consuming and requires highly skilled and experienced operators. Here, we investigated a six-index functional test that analyzed pH, hydrogen peroxide (H2O2), leukocyte esterase (LEU), sialidase (SNA), ß-glucuronidase (GUS), and acetylglucossidase (NAG), and determined its diagnostic value by comparing it with morphological tests of vaginal microbiota. MATERIALS AND METHODS: The research was conducted using data extracted from the Laboratory Information System of Women and Children's Hospital. A total of 4902 subjects, ranging in age from 35.4 ± 9.7 years, were analyzed. During the consultation, a minimum of two vaginal swab specimens per patient were collected for both functional and morphological testing. Fisher's exact was used to analyze data using SPSS. RESULTS: Of the 4,902 patients, 2,454 were considered to have normal Lactobacillus morphotypes and 3,334 were considered to have normal dominant microbiota. The sensitivity and specificity of H2O2-indicating Lactobacillus morphotypes were 91.3% and 25.28%, respectively, while those of pH-indicating Lactobacillus morphotypes were 88.09% and 59.52%, respectively. The sensitivity and specificity of H2O2-indicating dominant microbiota were 91.3% and 25.3%, respectively, while those of pH-indicating dominant microbiota were 86.27% and 64.45%, respectively. The sensitivity and specificity of NAG for vulvovaginal candidiasis were 40.64% and 84.8%, respectively. For aerobic vaginitis, GUS sensitivity was low at 0.52%, while its specificity was high at 99.93%; the LEU sensitivity and specificity values were 94.73% and 27.49%, respectively. Finally, SNA sensitivity and specificity for bacterial vaginosis were 80.72% and 96.78%, respectively. CONCLUSION: Functional tests (pH, SNA, H2O2, LEU) showed satisfactory sensitivity for the detection of vaginal inflammatory diseases. However, these tests lacked specificity, making it difficult to accurately identify specific pathologies. By contrast, NAG and GUS showed excellent specificity in identifying vaginal inflammatory diseases, but their sensitivity was limited. Therefore, functional tests alone are not sufficient to diagnose various vaginal inflammatory diseases. When functional and morphological tests are inconsistent, morphological tests are currently considered the preferred reference method.

Validation of a new kit for preeclampsia screening: A comprehensive analysis.

Objectives: Preeclampsia is a common pregnancy complication that significantly contributes to maternal mortality, perinatal mortality, and preterm delivery. The sFlt-1/PlGF (fms-like tyrosine kinase-1/placental growth factor) ratio has demonstrated robust diagnostic value for preeclampsia. This study assessed the analytical performance and diagnostic accuracy of a novel quantitative determination kit for sFlt-1 and PlGF for the diagnosis of preeclampsia. Methods: The detection performance of the test kit was validated using the Center for Medical Device Evaluation (CMDE) and Clinical and Laboratory Standards Institute (CLSI) documents. The test results were compared to those of the Elecsys immunoassay (Roche Diagnostics). Independent discovery and validation sets were used to analyze the diagnostic efficacy of the preeclampsia kit. The area under the curve (AUC) for preeclampsia at different gestational ages was calculated. Results: Correlation analysis between the test and Roche kits revealed a strong concordance (sFlt-1: r = 0.9966, P < 0.0001; PlGF: r = 0.9935, P < 0.0001). The AUCs for sFlt-1, PlGF, and the sFlt-1/PlGF ratio in diagnosing preeclampsia were 0.749, 0.795, and 0.834, respectively, in the discovery set and 0.729, 0.811, and 0.831, respectively, in the validation set. The corresponding results from the Roche kit were 0.741, 0.795, and 0.829, respectively, and 0.761, 0.864, and 0.844, respectively. Conclusions: Quantitative sFlt-1 and PlGF kits exhibited high levels of consistency with the Roche kits in terms of quantitative outcomes and diagnostic performance for preeclampsia.

Trends in Respiratory Infectious Pathogens in Children Under the Age of 14 - Xiamen City, Fujian Province, China, 2017-2023.

What is already known about this topic?: Respiratory infections pose a significant burden on public health. Despite recent outbreaks occurring in various locations, there is limited information available on the prevalence trends of multiple common respiratory pathogens in China beyond 2022. What is added by this report?: A retrospective analysis was conducted on respiratory pathogen infections in a Xiamen hospital over a seven-year period. The analysis revealed fluctuating trends, with the number of infections for certain viruses initially decreasing after 2019, only to rebound to previous or higher levels. Recently, there has been an observed collective increase in positive cases for certain pathogens. What are the implications for public health practice?: The study improves understanding of respiratory pathogens, primarily in Xiamen, with potential implications for the improvement of strategies for the prevention and management of respiratory infectious diseases.

Therapeutic vaccine-induced plasma cell differentiation is defective in the presence of persistently high HBsAg levels.

BACKGROUND & AIMS: Mechanisms behind the impaired response of antigen-specific B cells to therapeutic vaccination in chronic hepatitis B virus (HBV) infection remain unclear. The development of vaccines or strategies to overcome this obstacle is vital for advancing the management of chronic hepatitis B. METHODS: A mouse model, denominated as E6F6-B, was engineered to feature a knock-in of a B-cell receptor (BCR) that specifically recognizes HBsAg. This model served as a valuable tool for investigating the temporal and spatial dynamics of humoral responses following therapeutic vaccination under continuous antigen exposure. Using a suite of immunological techniques, we elucidated the differentiation trajectory of HBsAg-specific B cells post-therapeutic vaccination in HBV carrier mice. RESULTS: Utilizing the E6F6-B transfer model, we observed a marked decline in antibody-secreting cells 2 weeks after vaccination. A dysfunctional and atypical pre-plasma cell population (BLIMP-1+ IRF4+ CD40- CD138- BCMA-) emerged, manifested by sustained BCR signaling. By deploying an antibody to purge persistent HBsAg, we effectively prompted the therapeutic vaccine to provoke conventional plasma cell differentiation. This resulted in an enhanced anti-HBs antibody response and facilitated HBsAg clearance. CONCLUSIONS: Sustained high levels of HBsAg limit the ability of therapeutic hepatitis B vaccines to induce the canonical plasma cell differentiation necessary for anti-HBs antibody production. Employing a strategy combining antibodies with vaccines can surmount this altered humoral response associated with atypical pre-plasma cells, leading to improved therapeutic efficacy in HBV carrier mice. IMPACT AND IMPLICATIONS: Therapeutic vaccines aimed at combatting HBV encounter suboptimal humoral responses in clinical settings, and the mechanisms impeding their effectiveness have remained obscure. Our research, utilizing the innovative E6F6-B mouse transfer model, reveals that the persistence of HBsAg can lead to the emergence of an atypical pre-plasma cell population, which proves to be relevant to the potency of therapeutic HBV vaccines. Targeting the aberrant differentiation process of these atypical pre-plasma cells stands out as a critical strategy to amplify the humoral response elicited by HBV therapeutic vaccines in carrier mouse models. This discovery suggests a compelling avenue for further study in the context of human chronic hepatitis B. Encouragingly, our findings indicate that synergistic therapy combining HBV-specific antibodies with vaccines offers a promising approach that could significantly advance the pursuit of a functional cure for HBV.

The Relationship and Clinical Significance of Hepc-20, LpPLA2, PTX3, and Acute Myocardial Infarction in Patients with Varying Degrees of Coronary Artery Disease.

Objective: This study aimed to investigate the association between hepcidin-20 (Hepc-20), lipoprotein-associated phospholipase A2 (LpPLA2), pentraxin 3 (PTX3), acute myocardial infarction (AMI) occurrence, the severity of coronary artery lesions, and their predictive effectiveness. Methods: A total of 100 patients diagnosed and treated for AMI at our hospital between January 2021 and January 2022 were included in the AMI group. Based on the severity of coronary artery lesions determined by the Gensini score, patients were divided into the mild group and the moderate-to-severe group. Additionally, 100 healthy individuals were selected as control samples and included in the normal group. Serum levels of Hepc-20, LpPLA2, and PTX3 were compared, and receiver operating characteristic curves (ROC curves) were constructed to analyze the predictive efficacy of these biomarkers for AMI occurrence and the degree of coronary artery disease. Results: Compared to the normal group, the AMI group exhibited significantly increased serum levels of Hepc-20, LpPLA2, and PTX3 (P < .05). The sensitivity and specificity of serum Hepc-20, LpPLA2, and PTX3 in predicting AMI occurrence and the severity of coronary artery lesions were >60.00%, and the Area Under Curve (AUC) was >0.70. Moreover, compared to the mild group, the moderate-to-severe group showed significantly higher serum levels of Hepc-20, LpPLA2, and PTX3 (P < .05). Hepc-20, LpPLA2, and PTX3 demonstrated positive correlations with the severity of coronary artery lesions (P < .05). Conclusions: The levels of Hepc-20, LpPLA2, and PTX3 are elevated abnormally in AMI patients and positively associated with the degree of coronary artery disease. Hepc-20, LpPLA2, and PTX3 have the potential to serve as sensitive and accurate predictors of AMI occurrence and the severity of coronary artery disease, thereby warranting their clinical application.

The risk factors for Group B Streptococcus colonization during pregnancy and influences of intrapartum antibiotic prophylaxis on maternal and neonatal outcomes.

BACKGROUND: Group B Streptococcus (GBS), also referred as Streptococcus agalactiae, is one of the leading causes of life-threatening invasive diseases such as bacteremia, meningitis, pneumonia and urinary tract infection in pregnant women and neonates. Rates of GBS colonization vary by regions, but large-sample studies on maternal GBS status are limited in southern China. As a result, the prevalence of GBS among pregnant women and its associated risk factors and the efficacy of intrapartum antibiotic prophylaxis (IAP) intervention in preventing adverse pregnancy and neonatal outcomes remain poorly understood in southern China. METHODS: To fill this gap, we retrospectively analyzed demographic and obstetrical data of pregnant women who have undergone GBS screening and delivered between 2016 and 2018 in Xiamen, China. A total of 43,822 pregnant women were enrolled and only a few GBS-positive women did not receive IAP administration. Possible risk factors for GBS colonization were assayed by univariate and multivariate logistic regression analysis. Generalized linear regression model was applicated to analyze whether IAP is one of the impact factors of the hospital length of stay of the target women. RESULTS: The overall GBS colonization rate was 13.47% (5902/43,822). Although women > 35 years old (P = 0.0363) and women with diabetes mellitus (DM, P = 0.001) had a higher prevalence of GBS colonization, the interaction between ages and GBS colonization was not statistically significant in Logistic Regression analysis (adjusted OR = 1.0014; 95% CI, 0.9950, 1.0077). The rate of multiple births was significantly dropped in GBS-positive group than that of GBS-negative group (P = 0.0145), with no significant difference in the rate of fetal reduction (P = 0.3304). Additionally, the modes of delivery and the incidences of abortion, premature delivery, premature rupture of membranes, abnormal amniotic fluid and puerperal infection were not significantly different between the two groups. The hospitalization stays of the subjects were not influenced by GBS infection. As for neonatal outcomes, the cases of fetal death in maternal GBS-positive group did not statistically differ from that in maternal GBS-negative group. CONCLUSION: Our data identified that pregnant women with DM are at high risk of GBS infection and IAP is highly effective in prevention of adverse pregnancy and neonatal outcomes. This stressed the necessity of universal screening of maternal GBS status and IAP administration to the target population in China, and women with DM should be considered as priorities.

Homologous booster immunization with an inactivated vaccine induced robust antibody response in healthcare workers: A retrospective study.

Coronavirus Disease 2019 (Covid-19) severely impacted the health, society, and economy around the world. With declining protective efficacy of primary vaccination and the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, a Covid-19 booster vaccination is being fully implemented globally. Many people received three doses of BBIBP-CorV inactivated vaccine in China and other developing countries. However, the antibody response and immune persistence of the homologous BBIBP-CorV booster vaccination is yet to be thoroughly evaluated, as previous studies focused within one month after the third dose. In this study, 97 participants were enrolled to analyze the antibody response and immune persistence within 6 months as well as the safety within 7 days after the third-dose of homologous BBIBP-CorV inactivated vaccine. The seroconversion rate for total antibody against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein were both 100% at month 1 and month 6 after the third dose. The IgG against the RBD of the SARS-CoV-2 S protein seroconversion rate increased from 42.27% before the third dose to 100% 1 month after the third dose and then slightly decreased to 98.97% 5 months later. Positive IgM against the RBD of the SARS-CoV-2 S protein was rare and was observed in only one participant at month 1 after the third dose. The neutralizing antibody levels at month 1 and month 6 after the third dose increased 63.32-fold and 13.16-fold compared with those before the third dose, and the positive rate for neutralizing antibody was still 100% at month 6 after the third dose. Importantly, the antibody responses induced by the vaccine and immune persistence were not affected by sex or age. No serious adverse reactions were reported. Total antibody and IgG against the RBD of the SARS-CoV-2 S protein were highly correlated with neutralizing antibody, suggesting that total antibody and IgG against the RBD of the SARS-CoV-2 S protein could be used as predictors for neutralizing antibody. In conclusion, the third dose of homologous BBIBP-CorV inactivated vaccine induced a robust antibody response and moderate immune persistence. These finding are of great significance for development future vaccination strategies.

Evaluating the value of anti-SARS-CoV-2 antibody detection and neutralizing responses with euvirus: A population of 10776 close contacts in the epidemic of Fujian.

BACKGROUND: Nucleic acid detection represents limitations due to its false-negative rate and technical complexity in the COVID-19 pandemic. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests are widely spread all over the world presently. However, there is no report on the effectiveness of anti-SARS-CoV-2 antibody testing methods in China. METHODS: We gathered 10776 serum samples from close contacts of the SARS-CoV-2 infections in Fujian of China and used 2 chemiluminescence immunoassays (Wantai Bio., Yahuilong Bio.) and 2 lateral flow immunoassays (Lizhu Bio. and Dongfang Bio.) to perform the anti-SARS-CoV-2 antibody tests in China. RESULTS: The 4 antibody tests have great diagnostic value for infected or uninfected, especially in the neutralizing antibodies tests, the AUC can reach 0.939 (Wantai Bio.) and 0.916 (Yahuilong Bio.). Furthermore, we used pseudoviruses and euvirus neutralization assay to validate the effectiveness of these antibody test, the results of pseudoviruses neutralization assay or euvirus neutralization assay shows a considerable correlation with the 4 antibody detection respectively, particularly in euvirus neutralization assay, neutralizing antibodies detected by Wantai Bio. or Yahuilong Bio., the correlation can get the level of 0.93 or 0.82. CONCLUSIONS: The findings of this study demonstrate that the detections of antibodies have profound value in the diagnosis of COVID-19.

Effectiveness of SARS-CoV-2-inactivated vaccine and the correlation to neutralizing antibodies: A test-negative case-control study.

Severe acute respiratory syndrome coronavirus 2 breakthrough infection in highly vaccinated populations raises study on the effectiveness for inactivated vaccine, including effectiveness of the vaccine dose, the continuance of effectiveness, the effectiveness against severe/critical coronavirus disease 2019 and against secondary attacks. A population of 10 870 close contacts were investigated in a Delta variant's epidemic. The effectiveness of vaccination was estimated in a test-negative case-control study. In addition, serum was used to detect neutralizing antibodies, to explore their correlation to effectiveness. The vaccine effectiveness (VE) values were estimated for populations aged 12 years or older. The overall adjusted VE was 56.2% and a two-dose vaccine was more effective than a one-dose vaccine (56.7% vs. 43.8%). In addition, the population that got the second dose vaccine within 2 months showed higher VE than the population vaccinated for longer than 2 months (61.5% vs. 52.3%). Among the population who vaccinated 2 doses or within 2 months, a higher level of neutralizing antibodies was observed. For infected cases, vaccinated populations showed lower rates of transmission (2.63% vs. 4.36%). Further, those vaccinated cases, who were not found causing transmission, had a higher level of antibodies. The study provided a full view of the effectiveness of inactivated vaccines in a real-world setting. The time-related VE against infection and lower transmission of breakthrough vaccinated cases were observed, which may indicate that a necessity of a booster vaccine to maintain the effectiveness and high level of neutralizing antibody.

Evaluation of strategies for identification of infants with pathogenic glucose-6-phosphate dehydrogenase variants in China.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which is caused by pathogenic variants of G6PD that result in decreased G6PD activity, is an X-linked inherited inborn error of metabolism that occurs worldwide. Individuals with G6PD deficiency and heterozygous females with normal G6PD activity (i.e., all individuals with pathogenic G6PD variants) are at risk of developing hemolytic anemia under increased oxidative challenge. However, this risk can be minimized by timely diagnosis. Currently, two assays are used to diagnose G6PD deficiency in China: evaluation of enzymatic activity and targeted genotyping. In terms of identification of all individuals with pathogenic G6PD variants, the performance and cost of different diagnostic strategies (isolated or combined evaluation of G6PD activity and G6PD genotyping) can vary, and these factors should be comprehensively evaluated. In this study, we examined 555 infants (437 males and 118 females) who were positive for the newborn screening of G6PD deficiency. We first evaluated the diagnostic performances of enzymatic testing and targeted genotyping. Both assays attained 100% specificities and positive predictive values for both male and female infants. In contrast, the sensitivities and negative predictive values (NPVs) of the diagnostic tests were different for male and female infants. For male infants, the sensitivities were 99.8 and 98.3%, and the NPVs were 94.1% and 69.6%, for enzymatic testing and targeted genotyping, respectively. For female infants, the sensitivities were 62.5% and 97.9%, and the NPVs were 37.9% and 91.7%, for enzymatic testing and targeted genotyping, respectively. We also evaluated the cost of the five different diagnostic strategies. The combination of G6PD activity testing of all infants, followed by genotyping of female infants with normal G6PD activity, attained high diagnostic sensitivity (99.8%) at a low cost (8.60 USD per diagnosed case). In the future, simultaneous examination of G6PD activity and whole-exon or whole-gene G6PD sequencing could become a standard clinical practice. Our data provide references for clinical practice on the standardization of current and future interventions for G6PD deficiency in China.

Molecular Evolution of Attachment Glycoprotein (G) and Fusion Protein (F) Genes of Respiratory Syncytial Virus ON1 and BA9 Strains in Xiamen, China.

Monitoring viral transmission and analyzing the genetic diversity of a virus are imperative to better understand its evolutionary history and the mechanism driving its evolution and spread. Especially, effective monitoring of key antigenic mutations and immune escape variants caused by these mutations has great scientific importance. Thus, to further understand the molecular evolutionary dynamics of respiratory syncytial virus (RSV) circulating in China, we analyzed nasopharyngeal swab specimens derived from hospitalized children ≤5 years old with acute respiratory tract infections (ARIs) in Xiamen during 2016 to 2019. We found that infants under 6 months of age (52.0%) were the main population with RSV infection. The prevalent pattern "BBAA" of RSV was observed during the epidemic seasons. RSV ON1 and BA9 genotypes were the dominant circulating strains in Xiamen. Interestingly, we observed four Xiamen-specific amino acid substitution combinations in the G protein and several amino acid mutations primarily occurring at antigenic sites Ø and V in the F protein. Our analyses suggest that introduction of new viruses and local evolution are shaping the diversification of RSV strains in Xiamen. This study provides new insights on the evolution and spread of the ON1 and BA9 genotypes at local and global scales. IMPORTANCE Monitoring the amino acid diversity of the RSV G and F genes helps us to find the novel genotypes, key antigenic mutations affecting antigenicity, or neutralizing antibody-resistant variants produced by natural evolution. In this study, we analyzed the molecular evolution of G and F genes from RSV strains circulating in Xiamen, China. These data provide new insights on local and global transmission and could inform the development of control measures for RSV infections.

Association of MTHFR 677C > T gene polymorphism with neonatal defects: a meta-analysis of 81444 subjects.

This meta-analysis was performed to clarify controversial associations of the MTHFR 677 C > T gene polymorphism in maternal and foetal tissue with neonatal defects. It was reported the association of MTHFR 677 C > T gene polymorphism with frequencies of neonatal defects including congenital heart disease (CHD), neural tube defects (NTD), non-syndromic cleft lip and palate (NSCL/P), and Down syndrome (DS). Depending on the neonatal defect subtypes, MTHFR 677 C > T gene polymorphism was associated with NTD, CHD (except for codominant mode of inheritance (TC/CC) and dominant mode of inheritance (TT + TC/CC); p = .167 and p = .054, respectively), DS, and NSCL/P (codominant mode of inheritance (TC/CC), p = .032) in the maternal group. However, in the neonatal group, the MTHFR 677 C > T gene polymorphism was only associated with the frequency of NTD and CHD. Maternal and neonatal MTHFR 677 C > T gene polymorphisms appear to be associated with neonatal defects but differ by defect types.IMPACT STATEMENTWhat is already known on this subject? Neonatal defects are a signifcant problem and are related to genes involved in the metabolism of homocysteine and folate.What do the results of this study add? The MTHFR 677C > T polymorphism in maternal and neonatal subjects was significantly associated with neonatal defects. When the neonatal subjects were stratified based on disease, the maternal MTHFR 677C > T polymorphism was found to be significantly correlated with all four neonatal defects. In contrast, the polymorphism in newborns was significantly associated with neural tube defects.What are the implications of these findings for clinical practice and/or further research? We believe that our study makes a significant contribution to the literature because it collectively analysed neural tube defects, congenital heart disease, cleft lip and palate, and Down syndrome in relation to the 677C > T polymorphism of MTHFR. Thus, we anticipate that this study will serve as a valuable resource for future investigations of neonatal defect prevention and maternal inheritance in newborn diseases.

IGFBP1 inhibits the invasion, migration, and apoptosis of HTR-8/SVneo trophoblast cells in preeclampsia.

OBJECTIVE: To investigate the effects and underlying mechanisms of IGFBP1 on the biological functions of trophoblasts in simulated preeclampsia. METHODS: IGFBP1 expression in placenta was determined by immunohistochemistry. HTR-8/SVneo cells were stimulated with/without IGFBP1-overexpression and hypoxia-reoxygenation, and the proliferation, invasion, migration, and apoptosis were detected by CCK8, transwell, and flow cytometry, respectively. RESULTS: IGFBP1 expression was increased in placenta of preeclampsia. IGFBP1 overexpression inhibited proliferation, invasion, migration, and apoptosis of HTR-8/SVneo cells and induced MMP-26 expression with/without hypoxia-reoxygenation challenge. CONCLUSION: IGFBP1 affects biological functions of trophoblasts, and it may play a role in pathophysiology of preeclampsia by inducing MMP-26.

A Novel de novo Mutation in EBF3 Associated With Hypotonia, Ataxia, and Delayed Development Syndrome in a Chinese Boy.

OBJECTIVE: Global developmental delay has markedly high phenotypic and genetic heterogeneity, and is a great challenge for clinical diagnosis. Hypotonia, ataxia, and delayed development syndrome (HADDS), first reported in 2017, is one type of global development delay. The aim of the present study was to investigate the genetic etiology of a Chinese boy with global developmental delay. METHODS: We combined clinical and imaging phenotyping with trio whole-exome sequencing and Sanger sequencing to the patient and his clinically unaffected parents. A luciferase reporter and immunofluorescence were performed to detect the effect of mutation on transcriptional activity and subcellular localization. RESULTS: The patient presented with several previously unreported symptoms in the patients with HADDS, including hemangiomas, mild hearing abnormalities and tracheomalacia. A novel EBF3 c.589A > G missense mutation (p.Asn197Asp, p.N197D) was identified in the patient but not in his parents. By constructing the plasmid and transfecting HEK293T cells, EBF3-N197D mutant showed impaired activation of luciferase reporter expression of the p21 promoter, and the mutant affected its entry into the nucleus. CONCLUSION: To the best of our knowledge, this is the first report of EBF3 pathogenic mutation which associated with HADDS in the Chinese population. Our results expand the phenotypes and pathogenic mutation spectrum of HADDS, thus potentially facilitating the clinical diagnosis and genetic counseling of HADDS patients.

Meta-analysis: association of homocysteine with recurrent spontaneous abortion.

We analyzed the differences in serum homocysteine levels between patients with a history of recurrent spontaneous abortion (RSA) and those who had not experienced pregnancy-related complications. To this end, we retrieved literature and data on the association of RSA and serum homocysteine levels published before September 1st 2019 from the PubMed, EMBASE, China National Knowledge Infrastructure, and Wanfang databases. We further narrowed our literature review by focusing on peer-reviewed and full-text literature reporting on studies that used similar research methods and provided raw data or means and standard deviations while reporting results. Utilizing Stata 12.0 for a combined statistical analysis of the data, we assessed the quality of the included literature using the Newcastle Ottawa Scale. Patients who experienced RSA had higher serum homocysteine levels than the controls, with the difference being statistically significant (p < .05). High serum homocysteine levels may be an important risk factor for RSA, indicating that homocysteine may be useful as a noninvasive marker for the diagnosis of recurrent abortions.

Methylation of CYP1A1 and VKORC1 promoter associated with stable dosage of warfarin in Chinese patients.

OBJECTIVE: To investigate the association between DNA methylation and the stable warfarin dose through genome-wide DNA methylation analysis and pyrosequencing assay. METHOD: This study included 161 patients and genome-wide DNA methylation analysis was used to screen potential warfarin dose-associated CpGs through Illumina Infinium HumanMethylation 450 K BeadChip; then, the pyrosequencing assay was used to further validate the association between the stable warfarin dose and alterations in the methylation of the screened CpGs. GenomeStudio Software and R were used to analyze the differentially methylated CpGs. RESULTS: The methylation levels of CpGs surrounding the xenobiotic response element (XRE) within the CYP1A1 promoter, differed significantly between the different dose groups (P < 0.05), and these CpGs presented a positive correlation (r> 0, P < 0.05) with an increase in the stable dose of warfarin. At the VKORC1 promoter, two CpGs methylation levels were significantly different between the differential dose groups (P < 0.05), and one CpG (Chr16: 31106793) presented a significant negative correlation (r <  0, P <  0.05) among different dose (low, medium, and high) groups. CONCLUSION: This is a novel report of the methylation levels of six CpGs surrounding the XRE within the CYP1A1 promoter and one differential CpG at the VKORC1 promoter associated with stable warfarin dosage; these methylation levels might be applied as molecular signatures for warfarin.

The role of DNA methylation in syndromic and non-syndromic congenital heart disease.

Congenital heart disease (CHD) is a common structural birth defect worldwide, and defects typically occur in the walls and valves of the heart or enlarged blood vessels. Chromosomal abnormalities and genetic mutations only account for a small portion of the pathogenic mechanisms of CHD, and the etiology of most cases remains unknown. The role of epigenetics in various diseases, including CHD, has attracted increased attention. The contributions of DNA methylation, one of the most important epigenetic modifications, to CHD have not been illuminated. Increasing evidence suggests that aberrant DNA methylation is related to CHD. Here, we briefly introduce DNA methylation and CHD and then review the DNA methylation profiles during cardiac development and in CHD, abnormalities in maternal genome-wide DNA methylation patterns are also described. Whole genome methylation profile and important differentially methylated genes identified in recent years are summarized and clustered according to the sample type and methodologies. Finally, we discuss the novel technology for and prospects of CHD-related DNA methylation.