Serum alpha-fetoprotein response as a preoperative prognostic indicator in unresectable hepatocellular carcinoma with salvage hepatectomy following conversion therapy: a multicenter retrospective study.

Background: This study evaluates the efficacy of alpha-fetoprotein (AFP) response as a surrogate marker for determining recurrence-free survival (RFS) in patients with unresectable hepatocellular carcinoma (uHCC) who undergo salvage hepatectomy following conversion therapy with tyrosine kinase inhibitor (TKI) and anti-PD-1 antibody-based regimen. Methods: This multicenter retrospective study included 74 patients with uHCC and positive AFP (>20 ng/mL) at diagnosis, who underwent salvage hepatectomy after treatment with TKIs and anti-PD-1 antibody-based regimens. The association between AFP response-defined as a ≥ 80% decrease in final AFP levels before salvage hepatectomy from diagnosis-and RFS post-hepatectomy was investigated. Results: AFP responders demonstrated significantly better postoperative RFS compared to non-responders (P<0.001). The median RFS was not reached for AFP responders, with 1-year and 2-year RFS rates of 81.3% and 70.8%, respectively. In contrast, AFP non-responders had a median RFS of 7.43 months, with 1-year and 2-year RFS rates at 37.1% and 37.1%, respectively. Multivariate Cox regression analysis identified AFP response as an independent predictor of RFS. Integrating AFP response with radiologic tumor response facilitated further stratification of patients into distinct risk categories: those with radiologic remission experienced the most favorable RFS, followed by patients with partial response/stable disease and AFP response, and the least favorable RFS among patients with partial response/stable disease but without AFP response. Sensitivity analyses further confirmed the association between AFP response and improved RFS across various cutoff values and in patients with AFP ≥ 200 ng/mL at diagnosis (all P<0.05). Conclusion: The "20-80" rule based on AFP response could be helpful for clinicians to preoperatively stratify the risk of patients undergoing salvage hepatectomy, enabling identification and management of those unlikely to benefit from this procedure.

Modified Noise-Immune Fuzzy Neural Network for Solving the Quadratic Programming With Equality Constraint Problem.

Quadratic programming with equality constraint (QPEC) problems have extensive applicability in many industries as a versatile nonlinear programming modeling tool. However, noise interference is inevitable when solving QPEC problems in complex environments, so research on noise interference suppression or elimination methods is of great interest. This article proposes a modified noise-immune fuzzy neural network (MNIFNN) model and use it to solve QPEC problems. Compared with the traditional gradient recurrent neural network (TGRNN) and traditional zeroing recurrent neural network (TZRNN) models, the MNIFNN model has the advantage of inherent noise tolerance ability and stronger robustness, which is achieved by combining proportional, integral, and differential elements. Furthermore, the design parameters of the MNIFNN model adopt two disparate fuzzy parameters generated by two fuzzy logic systems (FLSs) related to the residual and residual integral term, which can improve the adaptability of the MNIFNN model. Numerical simulations demonstrate the effectiveness of the MNIFNN model in noise tolerance.

Meta-analysis of the Efficacy of Huoxue Huayu Method Combined With Conventional Western Medicine in the Treatment of Hydrocephalus After Cerebral Hemorrhage.

Context: Hydrocephalus refers to excessive secretion of cerebrospinal fluid, its insufficient absorption, or its blocked circulation and frequently occurs after a cerebral hemorrhage. The mortality and disability rates for cerebral hemorrhage are high. Objective: The study intended to evaluate the clinical efficacy of integrated traditional Chinese and Western medicine in the treatment of hydrocephalus after a cerebral hemorrhage, using systematic screening and analysis of published literature. Design: The research team performed a meta-analysis by searching databases-PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database, and Chinese Biomedical Literature-and collected Chinese and English publications from the establishment of each database until December 2022 discussing studies that used a TCM treatment that promoted blood circulation and removed blood stasis, combined with conventional western medicine, for hydrocephalus after cerebral hemorrhage. The keywords were promoting blood circulation and removing blood stasis, cerebral hemorrhage, and hydrocephalus. The team performed the meta-analysis using RevMan 5.3. Results: The research team found five relevant studies, all of which were randomized controlled trials. The clinical efficacy TCM combined with conventional Western medicine was significantly better than that of other treatments [MD = 1.77, 95% CI (0.23, 3.31), Z = 12.18, P < .001]. The NIHSS score after the integrated treatments also improved significantly more than those of other treatments [MD = -2.54, 95% CI (-4.07, -1.01), Z = 5.16, P < .00001]. Conclusions: Activating blood circulation and removing blood stasis using TCM, combined with conventional Western medicine, can achieve ideal therapeutic effects for patients with hydrocephalus after a cerebral hemorrhage, which can have a positive influence on clinical efficacy and reduce the NIHSS score, and the combined treatments have a clinical value.

Perioperative safety, oncologic outcome, and risk factors of salvage liver resection for initially unresectable hepatocellular carcinoma converted by transarterial chemoembolization plus tyrosine kinase inhibitor and anti-PD-1 antibody: a retrospective multicenter study of 83 patients.

BACKGROUND: To assess the perioperative safety, oncological outcomes, and determinants influencing the oncological outcomes of salvage liver resection for initially unresectable hepatocellular carcinoma (HCC) rendered resectable through transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies (α-PD-1). METHODS: We retrospectively reviewed data from 83 consecutive patients across six tertiary hospitals who underwent salvage liver resection for initially unresectable HCC following conversion by TACE combined with TKIs and α-PD-1, emphasizing perioperative and oncological outcomes. Multivariate Cox regression analysis was employed to discern independent risk factors for postoperative recurrence-free survival (RFS). RESULTS: The median operative duration was 200 min, with a median blood loss of 400 ml. Intraoperative blood transfusions were necessitated for 27 patients. The overall perioperative complication rate was 48.2%, with a major complication rate of 16.9%. One patient died during the perioperative period due to postoperative liver failure. During the median follow-up period of 15.1 months, 24 patients experienced recurrence, with early and intrahepatic recurrence being the most common. Seven patients died during follow-up. Median RFS was 25.4 months, with 1- and 2-year RFS rates of 68.2% and 61.8%, respectively. Median overall survival was not reached, with 1- and 2-year overall survival rates of 92.2% and 87.3%, respectively. Multivariate Cox regression analysis revealed that pathological complete response (pCR) and intraoperative blood transfusion served as independent prognostic determinants for postoperative RFS. CONCLUSIONS: Our study provides preliminary evidence suggesting that salvage liver resection may be an effective and feasible treatment option for patients with unresectable HCC who achieve resectability after conversion therapy with TACE, TKIs, and α-PD-1. The perioperative safety of salvage liver resection for these patients was manageable and acceptable. However, further research, particularly prospective comparative studies, is needed to better evaluate the potential benefits of salvage liver resection in this patient population.

A Fixed-Time Noise-Tolerance ZNN Model for Time-Variant Inequality-Constrained Quaternion Matrix Least-Squares Problem.

Presently, numerical algorithms for solving quaternion least-squares problems have been intensively studied and utilized in various disciplines. However, they are unsuitable for solving the corresponding time-variant problems, and thus few studies have explored the solution to the time-variant inequality-constrained quaternion matrix least-squares problem (TVIQLS). To do so, this article designs a fixed-time noise-tolerance zeroing neural network (FTNTZNN) model to determine the solution of the TVIQLS in a complex environment by exploiting the integral structure and the improved activation function (AF). The FTNTZNN model is immune to the effects of initial values and external noise, which is much superior to the conventional zeroing neural network (CZNN) models. Besides, detailed theoretical derivations about the global stability, the fixed-time (FXT) convergence, and the robustness of the FTNTZNN model are provided. Simulation results indicate that the FTNTZNN model has a shorter convergence time and superior robustness compared to other zeroing neural network (ZNN) models activated by ordinary AFs. At last, the construction method of the FTNTZNN model is successfully applied to the synchronization of Lorenz chaotic systems (LCSs), which shows the practical application value of the FTNTZNN model.

Application of obstetric nursing-sensitive quality indicators in continuous quality improvement.

OBJECTIVE: To verify the effect of obstetric nursing-sensitive quality indicators for continuously improving nursing quality. METHODS: We retrospectively analyzed the obstetric nurse quality in the First Affiliated Hospital of Chongqing Medical University and University-Town Hospital of Chongqing Medical University from October 2019 to September 2020. Nurses and patients in the Obstetrics Department of the First Affiliated Hospital of Chongqing Medical University and University-Town Hospital of Chongqing Medical University were respectively assigned into an experimental group and a control group. High-quality nursing services were provided to patients in both groups. In addition to the high-quality nursing services, the obstetric nurses in the experimental group received training on obstetric nursing-sensitive quality indicators based on the knowledge-attitude-practice model. An obstetric nursing quality evaluation was conducted between the two groups. Continuous quality improvement was achieved using the plan-do-check-act (PDCA) cycle. The nursing quality was reflected by 14 obstetric nursing-sensitive quality indicators and the nurses' job satisfaction was compared between the experimental group and the control group before and after intervention. RESULTS: The information regarding the nurses and parturients, and the nurses' job satisfaction were not significantly different between the two groups before intervention (P>0.05). Except for information regarding the lateral perineotomy at vaginal delivery, there was no significant difference in other obstetric nursing-sensitive quality indicators between the two groups before the intervention. In the experimental group, the rates of early skin-to-skin contact between mothers and infants, early sucking with exclusive breastfeeding during hospitalization, parturient satisfaction with the nurses' work, and nurses' job satisfaction after intervention were better than before (P<0.05). In the experimental group, the rates of neonatal asphyxia/severe neonatal asphyxia and postpartum hemorrhage following vaginal delivery after intervention was significantly lower than before (P<0.05). The experimental group had better outcomes than the control group in the rates of early skin-to-skin contact between mothers and infants, early sucking with exclusive breastfeeding during hospitalization, parturient satisfaction with the nurses' work, and nurses' job satisfaction (P<0.05). CONCLUSION: Obstetric nursing-sensitive quality indicators can be used to improve the nursing quality in continuous quality improvement, which is worthy of promotion in clinics.

Association between Maternal Drug Use and Cytochrome P450 Genetic Polymorphisms and the Risk of Congenital Heart Defects in Offspring.

OBJECTIVE: This study aimed to assess the associations between maternal drug use, cytochrome P450 ( CYP450) genetic polymorphisms, and their interactions with the risk of congenital heart defects (CHDs) in offspring. METHODS: A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020. RESULTS: After adjusting for potential confounding factors, the results show that mothers who used ovulatory drugs (adjusted odds ratio [a OR] = 2.12; 95% confidence interval [ CI]: 1.08-4.16), antidepressants (a OR = 2.56; 95% CI: 1.36-4.82), antiabortifacients (a OR = 1.55; 95% CI: 1.00-2.40), or traditional Chinese drugs (a OR = 1.97; 95% CI: 1.26-3.09) during pregnancy were at a significantly higher risk of CHDs in offspring. Maternal CYP450 genetic polymorphisms at rs1065852 (A/T vs. A/A: OR = 1.53, 95% CI: 1.10-2.14; T/T vs. A/A: OR = 1.57, 95% CI: 1.07-2.31) and rs16947 (G/G vs. C/C: OR = 3.41, 95% CI: 1.82-6.39) were also significantly associated with the risk of CHDs in offspring. Additionally, significant interactions were observed between the CYP450genetic variants and drug use on the development of CHDs. CONCLUSIONS: In those of Chinese descent, ovulatory drugs, antidepressants, antiabortifacients, and traditional Chinese medicines may be associated with the risk of CHDs in offspring. Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development.

Gender of infant and risk of postpartum depression: a meta-analysis based on cohort and case-control studies.

BACKGROUND: It is inconclusive nowadays for the association between infant's gender and their mothers' risk of developing postpartum depression (PPD). In addition, a complete overview is missing. A meta-analysis of cohort and case-control studies was performed to address the question of whether women who gave birth to a female infant were at an increased risk of developing PPD, compared with those giving birth to a male infant. METHODS: Unrestricted searches were conducted, with an end date parameter of 31 January 2018, of PubMed, Embase, Google Scholar, Cochrane Libraries, and Chinese databases, to identify studies that met pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. RESULTS: Twenty-three studies involving 119,736 women were included for analysis. Overall, mothers who gave birth to a female infant experienced a significantly increased risk of developing PPD compared with the reference group (OR = 1.15, 95%CI: 1.01-1.31; p = .03). However, substantial heterogeneity (p < .00001; I2 = 75%) was observed across studies. Relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded consistent results. No evidence of publication bias was observed. CONCLUSIONS: Although the role of potential bias and evidence of heterogeneity should be carefully evaluated, the present study suggests women giving birth to a girl are associated with a higher risk of developing PPD when compared with those giving birth to a boy. Improving family and social communication and reducing gender preference should be important components of any such interventions.Statement of significanceProblem or issue Interestingly, the known risk factors leading to PPD are basically the same in different regions and cultures, but the gender of the infant seems to be an exception.What is already known Some studies conducted in traditional western countries indicated that there is a weak or null association between infant's gender and risk of PPD, while others suggested a positive association. In contrast, studies conducted in Nigeria, India, Turkey and China showed that mothers giving birth to a female infant were at a higher risk of developing PPD.What this paper adds Today, the association between infant's gender and risk of developing postpartum depression (PPD) is still uncertain; additionally, a complete overview is missing. Our study represents the first meta-analysis of risk of PPD associated with infant's gender.

[Effects of Human Immunodeficiency Virus-positive Mothers Receiving Antiretroviral Therapy to Prevent Mother-to-child Transmission on the Growth and Development of 18-month-old Children in Lingshan County of Guangxi].

Objective To evaluate the effects of antiretroviral therapy(ART)for the prevention of mother-to-child transmission(PMTCT)of acquired immune deficiency syndrome(AIDS)on the growth and development of 18-month-old children born by human immunodeficiency virus(HIV)-positive pregnant women in Lingshan County,Guangxi Zhuang Autonomous Region,and provide scientific evidence for improving the ART medication plan for PMTCT.Methods Lingshan County,ranking the first in the HIV-epidemic counties of Guangxi,was selected as the research site.According to the design of retrospective case-control study,we assigned all the subjects into the case group and the control group:(1)The case group included the HIV-positive pregnant women who had received ART for PMTCT and their HIV-negative infants in Lingshan County from 2010 to 2017.The historical cards and PMTCT data of them were collected from the national PMTCT database.(2)The control group included the healthy pregnant women and their healthy babies born in the Lingshan Maternity and Infant Hospital in 2017,and the children's growth and development data were collected.The stunted growth in children was defined as at least one of the three main indicators of body height,body weight,and head circumference below the normal range.Results The number of HIV-positive mothers and their infants in the case group was 391 and 368,respectively,and 87.21%(341/391)and 95.38%(351/368)of mothers and infants respectively received ART medication.The HIV positive rate,mortality rate,and mother-to-child transmission rate of 18-month-old children were 1.36%(5/368),4.35%(16/368),and 2.01%(5/249),respectively.The incidence of stunted growth of 18-month-old children in the case group and the control group was 42.12%(155/368)and 23.06%(101/438),respectively,with significant difference(χ2=33.520,P<0.001).Conclusion After HIV-positive mothers in Lingshan County of Guangxi received ART for PMTCT,the incidence of growth stunting in 18-month-old children increased.

[The Establishment and Identification of Acute Myeloid Leukemia NOD-SCID-IL2rg-/-Mice Model by Using Luciferase-Expressing KG1a Cells].

OBJECTIVE: To establish the in vivo traceable acute myeloid leukemia mice model with Luciferase-Expressing KG1a Cells. METHODS: KG1a cells with stable luciferase gene expression (called as KG1a-Luc cells) were constructed by lentivirus transfection, then sifted out by puromycin. Eighteen male NOD-SCID-IL2rg-/-mice aged 8 to 12 weeks were randomly and equally divided into two groups: the control group and the KG1a-Luc group. The mice in KG1a-Luc group were injected with 200 µl PBS containing 5×106 KG1a-Luc cells through tail veins, and the mice in control group were injected with 200 µl PBS only. The bioluminescence imaging technology was used to monitor the tumor burden in vivo. The peripheral blood of the mice in both groups was analyzed by flow cytometry. After the mice were sacrificed, there were pathologic evaluations: bone marrow and spleens made into smears, and livers sliced to get paraffin sections. The survival time of the mice in the two groups was recorded and compared. RESULTS: KG1a cells expressing luciferase stably were successfully obtained. The tumor luminescence wildly spread at day 17 captured by in vivo imaging. The KG1a-Luc tumor cells could be detected in the peripheral blood of the mice, with the average percentage of (16.27±6.66)%. The morphology and pathology result showed that KG1a-Luc cells infiltrate was detected in bone marrow, spleens and livers. The survival time of the KG1a-Luc mice was notably shorter as compared with those in the control group, the median survival time was 30.5 days (95%CI: 0.008-0.260). CONCLUSION: The acute myeloid leukemia NOD-SCID-IL2rg-/-mouse model was successfully established by tail vein injection of 5×106 KG1a-Luc cells.

Butorphanol alleviates lipopolysaccharide-induced inflammation and apoptosis of cardiomyocytes via activation of the κ-opioid receptor.

Sepsis-induced myocardial dysfunction is a leading cause of the high mortality rates associated with sepsis. The aim of the present study was to investigate the effect of butorphanol on sepsis-induced cardiomyocyte dysfunction. Lipopolysaccharide (LPS) was used to induce H9C2 cardiomyocytes to establish an in vitro sepsis model. The effect of butorphanol on the viability of LPS-induced H9C2 cells was analyzed using a Cell Counting Kit-8 assay. The levels of tumor necrosis factor-α, interleukin (IL)-1ß and IL-6 were detected using ELISA. Western blotting was used to analyze the expression levels of inflammation-and apoptosis-related proteins. Cell apoptosis was measured using a TUNEL assay. The expression levels of κ-opioid receptor (KOR) were analyzed using reverse transcription-quantitative PCR analysis and western blotting. Following LPS induction, the levels of inflammatory cytokines and proapoptotic proteins were found to be upregulated in H9C2 cells, while butorphanol treatment downregulated these levels. The expression levels of KOR were also upregulated following butorphanol treatment in LPS-induced H9C2 cells. Addition of the KOR inhibitor, nor-binaltorphimine, alleviated the inhibitory effects of butorphanol on inflammation and apoptosis in LPS-induced H9C2 cells. In conclusion, the findings of the present study provided evidence indicating that butorphanol may alleviate LPS-induced inflammation and apoptosis in cardiomyocytes by upregulating KOR expression, which may provide a novel insight into the potential therapeutic effects of butorphanol and its underlying mechanism of action.

[Association between maternal reduced folate carrier gene polymorphisms and congenital heart disease in offspring: a case-control study].

OBJECTIVE: To study the association between maternal reduced folate carrier (RFC) gene polymorphisms and congenital heart disease (CHD) in offspring. METHODS: A hospital-based case-control study was conducted. The mothers of 683 infants with CHD who attended the Department of Cardiothoracic Surgery, Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group. The mothers of 740 healthy infants without any deformity who attended the hospital during the same period of time were enrolled as the control group. A questionnaire survey was performed to collect the exposure data of subjects. Venous blood samples of 5 mL were collected from the mothers for genetic polymorphism detection. A multivariate logistic regression analysis was used to evaluate the association of RFC gene polymorphisms and their haplotypes with CHD. A generalized multifactor dimensionality reduction method was used to analyze gene-gene interactions. RESULTS: After control for confounding factors, the multivariate logistic regression analysis showed that maternal RFC gene polymorphisms at rs2236484 (AG vs AA:OR=1.91, 95%CI:1.45-2.51; GG vs AA: OR=1.96, 95%CI:1.40-2.75) and rs2330183 (CT vs CC:OR=1.39, 95%CI:1.06-1.83) were significantly associated with the risk of CHD in offspring. The haplotypes of G-G (OR=1.21, 95%CI:1.03-1.41) and T-G (OR=1.25, 95%CI:1.07-1.46) in mothers significantly increased the risk of CHD in offspring. The interaction analysis showed significant gene-gene interactions between different SNPs of the RFC gene in CHD (P < 0.05). CONCLUSIONS: Maternal RFC gene polymorphisms and interactions between different SNPs are significantly associated with the risk of CHD in offspring.

Association analysis of maternal MTHFR gene polymorphisms and the occurrence of congenital heart disease in offspring.

BACKGROUND: Although many studies showed that the risk of congenital heart disease (CHD) was closely related to genetic factors, the exact pathogenesis is still unknown. Our study aimed to comprehensively assess the association of single nucleotide polymorphisms (SNPs) of maternal MTHFR gene with risk of CHD and its three subtypes in offspring. METHODS: A case-control study involving 569 mothers of CHD cases and 652 health controls was conducted. Thirteen SNPs were detected and analyzed. RESULTS: Our study showed that genetic polymorphisms of maternal MTHFR gene at rs4846052 and rs1801131 were significantly associated with risk of CHD in the homozygote comparisons (TT vs. CC at rs4846052: OR = 7.62 [95%CI 2.95-19.65]; GG vs. TT at rs1801131: OR = 5.18 [95%CI 2.77-9.71]). And six haplotypes of G-C (involving rs4846048 and rs2274976), A-C (involving rs1801133 and rs4846052), G-T (involving rs1801133 and rs4846052), G-T-G (involving rs2066470, rs3737964 and rs535107), A-C-G (involving rs2066470, rs3737964 and rs535107) and G-C-G (involving rs2066470, rs3737964 and rs535107) were identified to be significantly associated with risk of CHD. Additionally, we observed that a two-locus model involving rs2066470 and rs1801131 as well as a three-locus model involving rs227497, rs1801133 and rs1801131 were significantly associated with risk of CHD in the gene-gene interaction analyses. For three subtypes including atrial septal defect, ventricular septal defect and patent ductus arteriosus, similar results were observed. CONCLUSIONS: Our study indicated genetic polymorphisms of maternal MTHFR gene were significantly associated with risk of fetal CHD in the Chinese population. Additionally, there were significantly interactions among different SNPs on risk of CHD. However, how these SNPs affect the development of fetal heart remains unknown, and more studies in different ethnic populations and with a larger sample are required to confirm these findings.

Associations and interaction effects of maternal smoking and genetic polymorphisms of cytochrome P450 genes with risk of congenital heart disease in offspring: A case-control study.

ABSTRACT: To assess associations and interactions of maternal smoking and cytochrome P450 (CYP450) genetic variants with the developments of congenital heart disease (CHD) and specific subtypes.A case-control study of 654 cases and 666 controls was conducted from November 2017 to March 2020. The exposures of interest were maternal active and passive smoking before/in the early pregnancy and CYP450 genetic polymorphisms. Data were analyzed using the Chi-square test and logistic regression analysis.After adjusting for the potential confounding factors, our study showed maternal active (ORadj = 2.34, 95%CI: 1.19-4.60) or passive (ORadj = 1.76, 95%CI: 1.34-2.31) smoking before pregnancy, passive smoking in the early pregnancy (ORadj = 3.05, 95%CI: 2.26-4.12), as well as polymorphisms of CYP450 at rs1065852 (G/A vs G/G: ORadj = 1.46, 95%CI: 1.07-1.99; A/A vs G/G: ORadj = 1.63, 95%CI: 1.15-2.33) and rs16947 (A/A vs G/G: ORadj = 3.61, 95%CI: 2.09-6.23), were significantly associated with risk of total CHD in offspring. Similar results were also found for some subtypes of CHD. Additionally, significant interactions between maternal smoking and CYP450 genes on the risk of CHD were observed.Maternal smoking and CYP450 genetic variants were associated with increased risk of CHD and specific subtypes in offspring. And the effects of CYP450 genes on CHD may be modified by maternal smoking.

Association of maternal folate use and reduced folate carrier gene polymorphisms with the risk of congenital heart disease in offspring.

Although it is generally recognized that genetic and environmental factors are associated with the risk of congenital heart disease (CHD), the mechanism remains largely uncertain. This study aimed to investigate the association of maternal folate use, the time when folate use was started, and polymorphisms of the reduced folate carrier (RFC1) gene with the risk of CHD in offspring of Chinese descent, which can help provide new insight into the etiology of folate-related birth defects. A case-control study of 683 mothers of CHD patients and 740 mothers of healthy children was performed. The present study showed that mothers who did not use folate were at a significantly increased risk of CHD (OR=2.04; 95% CI: 1.42-2.93). When compared with those who started using folate prior to conception, mothers who started using folate from the first trimester of pregnancy (OR=1.90; 95% CI: 1.43-2.54) or from the second trimester of pregnancy (OR=8.92; 95% CI: 4.20-18.97) had a significantly higher risk of CHD. Maternal RFC1 gene polymorphisms at rs2236484 (AG vs AA: OR=1.79 [95% CI: 1.33-2.39]; GG vs AA: OR=1.64 [95% CI: 1.15-2.35]) and rs2330183 (CT vs CC: OR=1.54 [95% CI: 1.14-2.09]) were also significantly associated with CHD risk. Additionally, the risk of CHD was significantly decreased among mothers who had variant genotypes but used folate when compared with those who had variant genotypes and did not use folate.Conclusion: In those of Chinese descent, maternal folate use and the time when use started are significantly associated with the risk of CHD in offspring. Furthermore, maternal folate supplementation may help to offset some of the risks of CHD in offspring due to maternal RFC1 genetic variants. What is Known: • Folate use could help prevent CHD, but the relationship between the time when folate use is started and CHD has not received sufficient attention. • Studies have assessed the associations of folate metabolism-related genes with CHD, but genes involved in cellular transportation of folate, such as the RFC1 gene, have not garnered enough attention. What is New: • In those of Chinese descents, the time when folate use is started is significantly associated with the risk of CHD in offspring. • Maternal RFC1 polymorphisms were significantly associated with the risk of CHD. • Folate supplementation may help to offset some risks of CHD due to RFC1 genetic variants.

Association of maternal gut microbiota and plasma metabolism with congenital heart disease in offspring: a multi-omic analysis.

Congenital heart disease (CHD) is the most common congenital disorder diagnosed in newborns. Although lots of related studies have been published, yet the pathogenesis has not been fully elucidated. A growing body of evidence indicates perturbations of the gut microbiota may contribute in a significant way to the development of obesity and diabetes. Given that maternal obesity and diabetes are well-known risk factors for CHD, maternal gut microbiota may be considered as one of the environmental factors involved in the pathogenesis of CHD. The object of this study is to explore the association between maternal gut microbiota and risk of congenital heart disease (CHD) in offspring, as well as the possible mechanisms linking gut microbiota and disease risk. A case-control study was conducted in mothers of infants with CHD (n = 101) and mothers of infants without CHD (n = 95). By applying 16S rRNA gene sequencing and metabolic approaches to 196 stool and plasma samples, we determined microbiome and metabolome profiles in mothers of infants with CHD and controls, and their association with risk of CHD in offspring. The gut microbiome of mothers of infants with CHD was characterized with lower alpha-diversity and distinct overall microbial composition compared with mothers of infants without CHD. A distinct different metabolic profile was found between mothers of infants with CHD and controls. After controlling for the possible confounders, thirty-four bacterial genera and fifty-three plasma metabolites showed distinct abundances between the two groups. The results of the Spearman correlation analyses revealed a great number of significant correlations between the abundant bacterial genera and differentially expressed metabolites. In particular, the genus Bifidobacterium and Streptococcus showed comparable moderate positive correlations with a range of metabolites that involved in lipid metabolism pathway. Our findings suggest that perturbations of maternal gut microbiota and plasma metabolites may be associated with risk of CHD in offspring, and co-variation between microbiota and metabolites may play a part in the linkage between gut microbiota and risk of CHD in offspring.

Male sperm quality and risk of recurrent spontaneous abortion in Chinese couples: A systematic review and meta-analysis.

OBJECTIVE: To assess the association of conventional semen parameters and sperm DNA fragmentation with risk of recurrent spontaneous abortion (RSA). DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENTS: Total 1,690 male partners of women with RSA, and 1,337 male partners of fertile control women. INTERVENTIONS: Case-control or cohort studies were determined by searching PubMed, Google Scholar, Cochrane Libraries, China Biology Medicine disc, Chinese Scientific Journals Fulltext Database, China National Knowledge Infrastructure, and Wanfang Database. RSA was defined as two or more previous pregnancy losses. The fertile women refer to the reproductive women who have had at least a normal pregnancy history and no history of abortion. MAIN OUTCOME MEASURES: This study included eight outcome measures: semen volume(ml), semen pH value, sperm density(106/ml), sperm viability (%), sperm progressive motility rate (%), normal sperm morphology rate (%), sperm deformity rate(%), sperm DNA fragmentation index (DFI) (%). The summary measures were reported as standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS: Finally, twenty-four studies were included for analysis. Overall, male partners of women with RSA had a significantly lower level of sperm density (SMD = -0.53, 95%CI: - 0.75 to -0.30), sperm viability (SMD = -1.03, 95%CI: - 1.52 to -0.54), sperm progressive motility rate (SMD = -0.76, 95%CI:-1.06 - -0.46), and normal sperm morphology rate (SMD =  -0.56, 95%CI: - 0.99 to -0.12), and had a significantly higher rate of sperm deformity rate (SMD = 1.29, 95%CI: 0.60 - 1.97), and sperm DFI (SMD = 1.60, 95%CI: 1.04 to 2.17), when compared with the reference group. However, there were no statistically significant differences for semen volume (SMD = -0.03, 95%CI: -0.14 - 0.08) and semen pH value (SMD =  -0.23, 95% CI: -0.50 to 0.05) among 2 groups. CONCLUSIONS: The results of this analysis support an association of sperm density, sperm viability, sperm progressive motility rate, normal sperm morphology rate, sperm deformity rate, as well as sperm DFI with RSA. However, given the significant heterogeneity between studies and the lack of more detailed data on the subjects, further large-scale prospective studies are needed.

Associations of maternal diabetes mellitus and adiponectin gene polymorphisms with congenital heart disease in offspring: A case-control study.

ABSTRACT: This study aimed at assessing the association of maternal diabetes mellitus (DM), the adiponectin gene (APM1) gene polymorphisms, and their interactions with risk of congenital heart disease (CHD) in offspring.A case-control study of 464 mothers of CHD patients and 504 mothers of healthy children was conducted.After adjusting for potential confounding factors, our study suggested that mothers with gestational DM (GDM) during this pregnancy (adjusted odds ratio [aOR = 2.96]), GDM in previous pregnancy experiences (aOR = 3.16), and pregestational DM in the 3 months before this pregnancy (aOR = 4.52) were at a significantly higher risk of CHD in offspring, when compared with those without any diabetes. The polymorphisms of maternal APM1 gene at rs1501299 (T/T vs G/G: aOR = 3.45; T/G vs G/G: aOR = 1.73) and rs2241766 (G/G vs T/T, aOR = 3.36; G/T vs T/T, aOR = 1.93) were significantly associated with risk of CHD in offspring. In addition, significant interactions between maternal DM and the APM1 genetic variants on the development of CHD were found.Our findings indicate that maternal DM, APM1 gene genetic variants, and their interactions are significantly associated with risk of CHD in offspring. However, more studies in different ethnic populations and with a larger sample and prospective design are required to confirm our findings.

Cellulose nanocrystal assisted trace silver nitrate to synthesize green silver nanocomposites with antibacterial activity.

Cellulose nanocrystals (CNCs) with silver nanoparticles (AgNPs) are used for applications ranging from chemical catalysis to environmental remediation, and generation of smart electronics and biological medicine such as antibacterial agents. To reduce the synthesis cost of AgNPs and environmental pollution, microwave-assisted generation of AgNPs on the CNC surface (AgNPs@CNC) has been found to be useful, because microwave reaction has the advantages of simple reaction conditions, short reaction time and high reaction efficiency. The silver ions (Ag+) could be added to the CNC suspension and placed in the microwave reactor for a few minutes to produce AgNPs. AgNP generation was affected by factors such as the concentrations of Ag+ and CNC, and the power of the microwave, as well as the time of reaction. In this study, we used trace amounts of AgNO3 to rapidly synthesize AgNPs using a green microwave-based method instead of Tollen's reagent, and the antibacterial activity of the T1 sample showed that only using 0.03 mM (∼0.01 wt%) AgNO3 to synthesize AgNPs@CNC could achieve good antibacterial properties.

Association of maternal dietary intakes and CBS gene polymorphisms with congenital heart disease in offspring.

BACKGROUND: Although it is generally acknowledged that genetic and environmental factors are associated with risk of congenital heart disease (CHD), the causes are not fully understood. This study aimed at assessing the association of maternal dietary intakes, genetic variants of cystathionine beta synthase (CBS) gene and their interactions with risk of CHDs in offspring. METHOD: A hospital-based case-control study of 464 mothers with CHD infants and 504 control mothers of health infant was performed. The exposures of interest were maternal dietary intakes in early pregnancy, single nucleotide polymorphisms (SNPs) of CBS gene. RESULTS: More frequent intake of pickled vegetables (adjusted odds ratio[aOR] = 1.81; 95% confidence interval[CI]: 1.38-2.37), smoked foods (aOR = 2.00; 95%CI: 1.53-2.60), barbecued foods (aOR = 1.63; 95%CI: 1.19-2.25) and fried foods (aOR = 1.57; 95%CI: 1.22-2.03) were associated with higher risk of CHD, while salted eggs (aOR = 0.20; 95%CI: 0.12-0.33), fish and shrimp (aOR = 0.34; 95%CI: 0.27-0.44), fresh fruits (aOR = 0.49; 95%CI: 0.37-0.66), and milk products (aOR = 0.54; 95%CI: 0.45-0.65) were associated with lower risk of CHD. The SNPs of CBS gene at rs2851391 (T/T vs C/C: aOR = 1.91, 95%CI: 1.15-3.15) and rs234714 (T/T vs C/C: aOR = 2.22, 95%CI: 1.32-3.73) significantly increased the risk of CHD. Additionally, significant interaction effects between maternal dietary intakes and CBS genetic variants on CHD risks were observed. CONCLUSIONS: Maternal dietary factors, CBS genetic variants and their interactions were significantly associated with risk of CHD in offspring. However, it is still unclear how these factors jointly work in the development of CHD, and more studies with larger samples and prospective design are required.