Glyphosate exposure affected longevity-related pathways and reduced survival in asian honey bees (Apis cerana).

Glyphosate (N-(phosphonomethyl)glycine, GLY) ranks among the most extensively used and effective herbicides globally. However, excessive GLY utilization poses a substantial threat to the survival of honey bees (Apis cerana). Here we monitored the survival status of A. cerana treated with GLY, and conducted transcriptome sequencing of the bee gut and head to further explore potential GLY influences at the molecular level. We observed that the mortality rate of bees increased as GLY concentration escalated. Pivotal pathways emerged in response to the GLY treatment, with a substantial number of differentially expressed genes enriched in the longevity regulating pathway - multiple species. This strongly suggested that GLY may influence the physiological behavior of bees by impacting this particular pathway. Moreover, our analysis revealed a notable reduction in the enzymatic activities of CYP450 and AChE in both the bee head and intestines of when exposed to GLY. Conversely, the enzymatic activity of superoxide dismutase (SOD) in the head remained unaffected, whereas in the intestines, it exhibited a significant increase. Additionally, prophenol oxidase (PPO) and glutathione-S-transferases (GSTs) displayed contrasting trends in enzymatic activity in both organs. This study offers valuable insights into how GLY impacted the survival of A. cerana.

Regulation of Primary Cilium Length by O-GlcNAc during Neuronal Development in a Human Neuron Model.

The primary cilium plays critical roles in the homeostasis and development of neurons. Recent studies demonstrate that cilium length is regulated by the metabolic state of cells, as dictated by processes such as glucose flux and O-GlcNAcylation (OGN). The study of cilium length regulation during neuron development, however, has been an area left largely unexplored. This project aims to elucidate the roles of O-GlcNAc in neuronal development through its regulation of the primary cilium. Here, we present findings suggesting that OGN levels negatively regulate cilium length on differentiated cortical neurons derived from human-induced pluripotent stem cells. In neurons, cilium length increased significantly during maturation (after day 35), while OGN levels began to drop. Long-term perturbation of OGN via drugs, which inhibit or promote its cycling, during neuron development also have varying effects. Diminishing OGN levels increases cilium length until day 25, when neural stem cells expand and undergo early neurogenesis, before causing cell cycle exit defects and multinucleation. Elevating OGN levels induces greater primary cilia assembly but ultimately results in the development of premature neurons, which have higher insulin sensitivity. These results indicate that OGN levels and primary cilium length are jointly critical in proper neuron development and function. Understanding the interplays between these two nutrient sensors, O-GlcNAc and the primary cilium, during neuron development is important in paving connections between dysfunctional nutrient-sensing and early neurological disorders.

A Patient with Concurrent Legionella and COVID-19 Infection in a UK District General Hospital.

A 65 year-old gentleman had been brought to our Respiratory Emergency Department for patients with respiratory symptoms and a possible COVID-19 infection with a 3-day history of shortness of breath (SOB), fever, a productive cough of yellow sputum, and right-sided chest pain. The patient had received both vaccinations at the time and initially reported no travel history, although later it was revealed that he had recently stayed at a hotel. He tested positive for COVID-19 and had hyponatremia and a raised procalcitonin, indicating a bacterial infection as well. He had been initiated on our local treatment guidelines for COVID with antibiotics, guided by local hospital guidelines. An atypical pneumonia screen returned a positive result for Legionella urine antigen, and his antibiotic regime was changed accordingly. Our patient deteriorated significantly, and despite being escalated to our intensive care unit (ICU), he unfortunately passed away. Our case highlights the importance of early ICU involvement and escalation of antibiotics in cases of suspected concurrent Legionella and COVID-19 infections.

Effect of Dangfei Liganning capsule on liver X receptor α/steroid regulatory element binding protein-1/fatty acid synthase signal pathway in rats with metabolic- associated fatty liver disease.

OBJECTIVE: To study the mechanism of Dangfei Liganning capsule in the treatment of rats with metabolic associated fatty liver disease (MAFLD). METHODS: Totally 48 specific pathogen free Sprague-Dawley male rats were randomly divided into normal Group, model group, Dangfei Liganning high, moderate, and low-dose groups and Essentiale group which were fed with high fat diet for 8 weeks, and gavage and molding were carried out simultaneously. Dangfei Liganning high, middle and low-dose group were given 0.27, 0.135 and 0.0675 g·kg·d respectively by gavage, Essentiale group was given 0.123 g·kg·d by gavage, the same amount of distilled water was given by gavage in the normal group and the model group. The rats were weighed at the 0th week, 2nd week, 4th week, 6th week and 8th weekend respectively. The rats were sacrificed at the end of the 8th week. Serum levels of alanine aminotransferase (ALT), alanine aminotransferase (AST), triglyceride (TG), total cholesterol (CHO), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL-C), total protein (TP), albumin (Alb), globulin (GLB), total bilirubin (TBIL), direct bilirubin (DBIL), tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) were measured. The levels of liver tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and liver pathology [hematoxylin and eosin (HE) staining, oil red O staining] were detected. The expression levels of liver X receptor α (LXRα), steroid regulatory element binding protein-1 (SREBP-1) and fatty acid synthase (FAS) were detected by immunohistochemistry, Western blot and reverse transcription-polymerase chain reaction reverse transcription-polymerase chain reaction. RESULTS: From the beginning to the 8th week, the growth rate of body weight in the Dangfei Liganning high-dose group was slower than all other groups. There was no significant difference in ALB level in all groups ( 0.05). Compared with the model group, the levels of ALT, AST, LDL-C, TG, CHO, TP, GLB, TBIL, DBIL, IL-6, TNF-α were significantly decreased and HDL-C were significantly increased in Dangfei Liganning high-dose group (0.01, < 0.05). HE and oil red O staining showed that the fatty lesions in rat liver were alleviated, while the expressions of LXRα, SREBP-1, FAS mRNA and protein were significantly decreased (0.01). CONCLUSIONS: Dangfei Liganning capsule can slow down the increase of body weight of MAFLD rats, reduce the levels of transaminase, Lipid and inflammatory factors in MAFLD rats, promote the synthesis of liver protein and bile metabolism, and improve the liver fatty lesion of MAFLD rats, among which the Dangfei Liganning high-dose group is more effective. The mechanism of action may be through blocking LXR-SREBP-1-FAS signal pathway.

Efficacy of Qiancao () and Haipiaoxiao (), a traditional Chinese herb pair, on abnormal uterine bleeding in rats with incomplete abortion.

OBJECTIVE: To investigate the most effective weight ratio of Qiancao () and Haipiaoxiao () used to produce decoction for the treatment of abnormal uterine bleeding (AUB) in rats with incomplete abortion, and to study the possible mechanism. METHODS: The models of AUB were established by incomplete drug abortion with mifepristone and misoprostol in pregnant rats. The therapeutic effects of decoctions made by eight different weight ratios of Qiancao () and Haipiaoxiao () were observed. RESULTS: Statistical analysis revealed that the most effective weight ratio of Qiancao () and Haipiaoxiao () to treat AUB in this study was 2∶1. CONCLUSION: The insights gained from this study would improve understanding of the mechanisms involved in the effect of Qiancao () and Haipiaoxiao () on AUB.

Sterile alpha motif and histidine-aspartic acid domain-containing protein 1 expression and its relationship with T cell activation in human immunodeficiency virus/acquired immune deficiency syndrome patients with lung-spleen deficiency syndrome pattern.

OBJECTIVE: To investigate the relationship between antiviral restriction factor Sterile Alpha Motif and Histidine-Aspartic acid domain-containing protein 1 (SAMHD1) expression and T cell activation, furthermore, identifying objective indexes of lung-spleen deficiency symptom pattern. METHODS: We assessed the profile of T lymphocyte subsets, characteristics of SAMHD1 and human leukocyte antigen DR (HLA-DR) expression in lung-spleen deficiency patients. At the same time, people living with human immunodeficiency virus / acquired immune deficiency syndrome (HIV/AIDS) (PLWHA) without obvious clinical symptoms and healthy donors in this area were used as controls. RESULTS: Immunohematologic indexes lower CD4 count, lower CD4/CD8 ratio and higher SAMHD1 level were found in lung-spleen deficiency patients. Furthermore, we demonstrated a positive relationship between SAMHD1 and HLA-DR level as well as with interferon factor in lung-spleen deficiency syndrome and patients without obvious clinical signs and symptoms groups. CONCLUSIONS: These data indicated the positive relationship between SAMHD1 and T cell activation which further elucidated the role of SAMHD1 in cellular immune response. Furthermore, combination of T lymphocyte subsets counts and SAMHD1 level may be used as clinical and biological reference basis for the differentiation and diagnosis of HIV / AIDS traditional Chinese medicine syndromes.

Biosynthesis of Linear Protein Nanoarrays Using the Flagellar Axoneme.

Applications in biotechnology and synthetic biology often make use of soluble proteins, but there are many potential advantages of anchoring enzymes to a stable substrate, including stability and the possibility for substrate channeling. To avoid the necessity of protein purification and chemical immobilization, there has been growing interest in bio-assembly of protein-containing nanoparticles, exploiting the self-assembly of viral capsid proteins or other proteins that form polyhedral structures. However, these nanoparticles are limited in size, which constrains the packaging and the accessibility of the proteins. An axoneme, the insoluble protein core of the eukaryotic flagellum or cilium, is a highly ordered protein structure that can be several microns in length, orders of magnitude larger than other types of nanoparticles. We show that when proteins of interest are fused to specific axonemal proteins and expressed in living Chlamydomonas reinhardtii cells, they become incorporated into linear arrays, which have the advantages of high protein loading capacity and single-step purification with retention of biomass. The arrays can be isolated as membrane-enclosed vesicles or as exposed protein arrays. The approach is demonstrated for both a fluorescent protein and an enzyme (beta-lactamase), showing that incorporation into axonemes retains protein function in a stable, easily isolated array form.

[Network Meta-analysis of Huoxue Huayu Chinese medicine injections on hypertensive nephropathy].

To assess the clinical efficacy of Huoxue Huayu Chinese medicine injections on hypertensive nephropathy by using Network Meta-analysis method. The relative randomized controlled trials(RCTs) of Huoxue Huayu Chinese medicine injections on hypertensive nephropathy were retrieved from CNKI, WanFang, VIP, SinoMed, PubMed, Cochrane Library and Web of Science in November 2019. Two researchers independently conducted literature screening, data extraction and quality evaluation. The data was analyzed by RevMan 5.3, Stata 15.1, ADDIS 1.16.8 software. Finally, 4 518 patients in 50 RCTs were included, involving 5 kinds of Huoxue Huayu Chinese medicine injections. The five Chinese medicine injections were Breviscapine Injection, Danhong Injection, Sodium Tanshinone Ⅱ_A Sulfonate Injection, Ginkgo Dipyridamole Injection, and Salvianolate Injection. Meta-analysis showed that, in terms of renal function protection, urine protein quantification and serum creatinine of each Chinese medicine injections combined with conventional Western medicine group, except Salvianolate Injection combined with conventional Western medicine group, was significantly lower than those of the conventional Western medicine treatment group. Ginkgo Dipyridamole Injection combined with conventional Western medicine had the best effect in reducing urine protein, and Danhong Injection combined with conventional Western medicine had the best effect in reducing serum creatinine. In terms of blood pressure control, the blood pressure of each Chinese medicine injections combined with conventional Western medicine group, except Breviscapine Injection combined with conventional Western medicine group, was significantly lower than that of conventional Western medicine treatment group. Salvianolate Injection combined with conventional Western medicine had the best effect in reducing blood pressure. In terms of safety, no serious adverse reactions were found in all studies. The five kinds of Huoxue Huayu Chinese medicine injections combined with conventional Western medicine had significantly advantages in the treatment of hypertensive nephropathy. Ginkgo Dipyridamole Injection combined with conventional Western medicine is most likely to be the optimal therapy. However, limited by the quantity and quality of the documents included, the conclusion of this study still needs to be verified by more high-quality, multi-center and large-sample RCT.

Potential Roles of O-GlcNAcylation in Primary Cilia- Mediated Energy Metabolism.

The primary cilium, an antenna-like structure on most eukaryotic cells, functions in transducing extracellular signals into intracellular responses via the receptors and ion channels distributed along it membrane. Dysfunction of this organelle causes an array of human diseases, known as ciliopathies, that often feature obesity and diabetes; this indicates the primary cilia's active role in energy metabolism, which it controls mainly through hypothalamic neurons, preadipocytes, and pancreatic ß-cells. The nutrient sensor, O-GlcNAc, is widely involved in the regulation of energy homeostasis. Not only does O-GlcNAc regulate ciliary length, but it also modifies many components of cilia-mediated metabolic signaling pathways. Therefore, it is likely that O-GlcNAcylation (OGN) plays an important role in regulating energy homeostasis in primary cilia. Abnormal OGN, as seen in cases of obesity and diabetes, may play an important role in primary cilia dysfunction mediated by these pathologies.

MTIM affects retinal ganglion cells through PI3K/AKT signaling pathway.

OBJECTIVE: Retinal ganglion cells (RGCs) are the main cells that form vision in the retina. MT1M is involved in the occurrence and progression of various diseases. However, the role of MTIM in RGCs cells remains unclear. MATERIALS AND METHODS: RGCs were cultured in vitro and randomly divided into control group, MT1M group (transfected with MT1M-pcDNA3.1 plasmid), and MT1M siRNA group (transfected with MT1M siRNA) followed by measuring MT1M and NT-3 expression by real time PCR and Western blot, cell proliferation by MTT assay, secretion of IL-2 and IL-6 by enzyme-linked immunosorbent assay (ELISA), SOD activity and ROS content. In addition, expression of PI3K/AKT signaling pathway protein was detected by Western blot. RESULTS: MT1M expression in MT1M group was significantly increased, which promoted cell proliferation, increased NT-3 expression, and decreased Caspase 3 activity and IL-2 and IL-6 secretion. Meanwhile, SOD activity was increased, ROS content was decreased and PI3K/AKT protein phosphorylation was elevated. The differences were statistically significant compared with control group (p < 0.05). MT1M siRNA decreased MT1M expression, inhibited cell proliferation, decreased NT-3, and increased Caspase 3 activity and IL-2 and IL-6 secretion. In addition, MT1M siRNA decreased SOD activity, increased ROS content and reduced PI3K/AKT protein phosphorylation. Compared with control group, the differences were statistically significant (p < 0.05). CONCLUSIONS: Up-regulation of MT1M can inhibit RGC cell apoptosis and inflammation, and promote RGC cell proliferation through the PI3K/AKT signaling pathway.

Reconstruction of lymphatic vessels in the mouse tail after cupping therapy.

BACKGROUND: The aim of the study was to investigate the regulatory mechanism of local lymphatic reconstruction after cupping therapy in a mouse model. MATERIALS AND METHODS: The lymphatic reconstruction process in the mouse tail after cupping therapy as well as the expression levels of the vascular endothelial identification molecule CD34, prospero homeobox protein 1 (PROX1), and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) were investigated for a duration of 4 days through immunohistochemistry experiments. RESULTS: On day 1 after cupping therapy, the CD34+ and LYVE-1+ cell densities were significantly increased, and the formed CD34+LYVE-1+ tubular structure started to express PROX1. This was followed by a decrease in both the CD34+ and LYVE-1+ stem cell densities to basal levels on the second day after cupping therapy. Both the CD34+ and LYVE-1+ cell densities subsequently increased again on the third day after cupping therapy. The increase in the LYVE-1+ density was accompanied by tubular structure formation, which is characteristic of lymphangiogenesis. In addition, the colocalisation of CD34+ and LYVE-1+ cells by immunohistochemistry suggests that the CD34+ stem cells differentiated into new lymphatic endothelial cells. CONCLUSIONS: Our findings indicate that the mechanism underlying the therapeutic effect of cupping therapy involves upregulation of vascular and lymphatic endothelial markers (CD34+, LYVE-1+, and CD34+LYVE-1+) in local tissues, which in turn promotes local new lymphatic vessel formation through the expression of PROX1.

O-GlcNAcylation Regulates Primary Ciliary Length by Promoting Microtubule Disassembly.

The sensory organelle cilium is involved in sensing and transducing important signaling cascades in almost all cells of our body. These ciliary-mediated pathways affect cellular homeostasis and metabolisms profoundly. However, it is almost completely unknown whether the cellular metabolic state affects the assembly of cilia. This study is to investigate how O-linked ß-N-acetylglucosamine (O-GlcNAc), a sensor of cellular nutrients, regulates the cilia length. Pharmacologic or genetic inhibition of O-GlcNAcylation led to longer cilia, and vice versa. Further biochemical assays revealed that both α-tubulin and HDAC6 (histone deacetylase 6) were O-GlcNAcylated in vivo. In vitro enzymatic assays showed that O-GlcNAcylation of either tubulin or HDAC6 promoted microtubule disassembly, which likely in turn caused ciliary shortening. Taken together, these results uncovered a negative regulatory role of O-GlcNAc in modulating the ciliary microtubule assembly. The cross talk between O-GlcNAc and cilium is likely critical for fine-tuning the cellular response to nutrients.

BIODOSIMETRY AND BIODOSIMETRY NETWORKS FOR MANAGING RADIATION EMERGENCY.

Biological dosimetry enables individual dose reconstruction in the case of unclear or inconsistent radiation exposure situations, especially when a direct measurement of ionizing radiation is not or is no longer possible. To be prepared for large-scale radiological incidents, networking between well-trained laboratories has been identified as a useful approach for provision of the fast and trustworthy dose assessments needed in such circumstances. To this end, various biodosimetry laboratories worldwide have joined forces and set up regional and/or nationwide networks either on a formal or informal basis. Many of these laboratories are also a part of global networks such as those organized by World Health Organization, International Atomic Energy Agency or Global Health Security Initiative. In the present report, biodosimetry networks from different parts of the world are presented, and the partners, activities and cooperation actions are detailed. Moreover, guidance for situational application of tools used for individual dosimetry is given.

The relationship between soluble CD40 ligand level and atherosclerosis in white-coat hypertension.

This study was designed to examine the distribution of plasma soluble CD40 ligand (sCD40L), and its relationship with carotid intima-media thickness (CIMT) in healthy controls and subjects with white-coat hypertension (WCH) or hypertension (HT). Thirty-five patients with HT, 35 patients with WCH, and 35 healthy controls were enrolled. The normal group (CIMT < 0.9 mm), subclinical atherosclerosis group (0.9 mm ≤ CIMT < 1.2 mm) and atherosclerosis group (CIMT ≥ 1.2 mm) were grouped based on the value of CIMT. The highest level of sCD40L was observed in HT group, followed by WCH group and healthy controls. The level of sCD40L was significantly increased in atherosclerosis group compared with subclinical atherosclerosis group and healthy controls. In the WCH group, sCD40L level was significantly and positively correlated with CIMT and systolic blood pressure. Multiple logistic regression indicated that sCD40L was a risk factor for increased CIMT (odds ratio, 1.504; 95% confidence interval, 1.054-1.956, P < 0.001). The data provided evidence that sCD40L levels in subjects with WCH and HT were significantly and consistently higher than those in healthy controls. SCD40L may represent a potential non-invasive atherosclerosis marker in WCH patients.

Difference in resting-state fractional amplitude of low-frequency fluctuation between bipolar depression and unipolar depression patients.

OBJECTIVE: To investigate the difference in fractional amplitude of low-frequency fluctuation (fALFF) of localized brain activities in the resting-state between bipolar depression and unipolar depression patients and to find biological markers that differentiate the two groups of patients. PATIENTS AND METHODS: Thirteen patients with bipolar depression, 15 patients with unipolar depression, and 16 healthy control subjects that were matched in age and years of education were subjected to 3.0 T resting-state functional magnetic resonance scans. The values of whole brain fALFF were calculated and statistical analysis was performed. RESULTS: The fALFF-values of the right inferior temporal gyrus, left cerebellar posterior lobe, right middle temporal gyrus, left inferior frontal gyrus/insula, right inferior frontal gyrus/insula, left lingual gyrus and right middle temporal gyrus of the three groups showed significant differences (p < 0.05). Compared with the healthy control (HC) group, the fALFF-values of the unipolar depression (UD) patient group significantly increased in the right superior temporal gyrus, left insula, left inferior frontal gyrus, right inferior frontal gyrus, right supramarginal gyrus and right medial frontal gyrus but significantly decreased in the right medial occipital gyrus, left frontal lobe, right superior parietal lobule; the fALFF-values of the bipolar depression (BD) patient group significantly decreased in the left cerebellum posterior lobe, right lingual gyrus, left lingual gyrus, right middle temporal gyrus, left middle temporal gyrus, and left superior frontal gyrus and significantly increased in the right inferior frontal gyrus and left insula compared to those of the HC group; compared with those of the UD group, the fALFF-values of the BD group significantly decreased in the left middle occipital gyrus, right middle temporal gyrus, left middle frontal gyrus, and left medial frontal gyrus. CONCLUSIONS: The brain activities of BD and UD patients in the resting-state exhibit abnormalities, which differ between the two groups of patients.

What is the association of hypothyroidism with risks of cardiovascular events and mortality? A meta-analysis of 55 cohort studies involving 1,898,314 participants.

BACKGROUND: Whether hypothyroidism is an independent risk factor for cardiovascular events is still disputed. We aimed to assess the association between hypothyroidism and risks of cardiovascular events and mortality. METHODS: We searched PubMed and Embase from inception to 29 February 2016. Cohort studies were included with no restriction of hypothyroid states. Priori main outcomes were ischemic heart disease (IHD), cardiac mortality, cardiovascular mortality, and all-cause mortality. RESULTS: Fifty-five cohort studies involving 1,898,314 participants were identified. Patients with hypothyroidism, compared with euthyroidism, experienced higher risks of IHD (relative risk (RR): 1.13; 95% confidence interval (CI): 1.01-1.26), myocardial infarction (MI) (RR: 1.15; 95% CI: 1.05-1.25), cardiac mortality (RR: 1.96; 95% CI: 1.38-2.80), and all-cause mortality (RR: 1.25; 95% CI: 1.13-1.39); subclinical hypothyroidism (SCH; especially with thyrotropin level ≥10 mIU/L) was also associated with higher risks of IHD and cardiac mortality. Moreover, cardiac patients with hypothyroidism, compared with those with euthyroidism, experienced higher risks of cardiac mortality (RR: 2.22; 95% CI: 1.28-3.83) and all-cause mortality (RR: 1.51; 95% CI: 1.26-1.81). CONCLUSIONS: Hypothyroidism is a risk factor for IHD and cardiac mortality. Hypothyroidism is associated with higher risks of cardiac mortality and all-cause mortality compared with euthyroidism in the general public or in patients with cardiac disease.

Analysis of Human Papillomavirus Infection in 16,320 Patients From a Gynecology Clinic in Central South China.

OBJECTIVE: This study aimed to investigate the relationship between persistent human papillomavirus (HPV) infection and cervical lesion. METHODS: Clinical data of 16,320 patients who visited our clinic between January 2009 and December 2013 were collected. Retrospective analysis was performed to analyze the overall HPV infection and compare the infection rates of different subtypes among different age groups, to reveal the relationship between persistent HPV infection and cervical cytology. RESULTS: The overall prevalence of HPV was 26.54%. The most common genotypes were HPV 52, HPV 16, HPV 58, CP8304, and HPV 53. The highest overall high-risk HPV prevalence was found in women older than 60 years, and the lowest prevalence was found in women between the ages of 30 and 39 years. There was no significant difference in low-risk HPV prevalence among different age groups (p = .693). The HPV clearance rate after 1 year among those with initial positive test was 87.65%. The constituent ratios of high- or low-risk HPV subtypes were not significantly different (p = .545) between nonpersistent-positive and persistent-positive (PP) groups. Conversely, the constituent ratios of singe- or multi-type HPV infection were significantly different (p < .05) between these 2 groups. The most common subtypes in PP group were HPV 16, 52, 58, CP8304, and 33. The occurrence rates of atypical squamous cells of undetermined significance, high-grade squamous intraepithelial lesion, and squamous cell carcinoma in the PP group significantly increased (p < .05). CONCLUSIONS: Persistent HPV infections are mainly caused by multiple types of HPV and high-risk HPV. Our region should particularly pay attention to the prevention and treatment of HPV 16, 52, and 58.

Association between MTHFR C677T polymorphism and congenital heart disease. A family-based meta-analysis.

Congenital heart disease (CHD) is the most common type of birth defect. It is suspected that polymorphisms in folate metabolism are associated with an increased risk of CHD, but the conclusion remains unclear. Studies have reported that the MTHFR C677T polymorphism was associated with the development of structural congenital heart malformations. The objective of this study was to conduct a meta-analysis of available studies to identify common polymorphisms in the MTHFR gene in children with CHD and their mothers and to test for an association between genotype and disease. In all, 19 eligible studies comprising 4,219 cases and 20,123 controls were included in this meta-analysis. A significant association was found between the MTHFR C677T polymorphism and CHD risk (OR: 1.26; 95 % CI = 1.06-1.51; p = 0.009) with no strong evidence of heterogeneity (I(2) = 39 %) in the fetal analysis. In the maternal analysis, the MTHFR C677T polymorphism was significantly associated with CHD risk (OR = 1.52; 95 % CI = 1.09-2.11; p = 0.01) with significant heterogeneity (I(2) = 63 %).