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Cervical cancer is one of the most common malignant tumors in women, and its morbidity and mortality are increasing year by year worldwide. Therefore, an urgent and challenging task is to identify potential biomarkers for cervical cancer. This study aims to identify the hub genes based on the GEO database and then validate their prognostic values in cervical cancer by multiple databases. By analysis, we obtained 83 co-expressed differential genes from the GEO database (GSE63514, GSE67522 and GSE39001). GO and KEGG enrichment analysis showed that these 83 co-expressed it mainly involved differential genes in DNA replication, cell division, cell cycle, etc.. The PPI network was constructed and top 10 genes with protein-protein interaction were selected. Then, we validated ten genes using some databases such as TCGA, GTEx and oncomine. Survival analysis demonstrated significant differences in CDC45, RFC4, TOP2A. Differential expression analysis showed that these genes were highly expressed in cervical cancer tissues. Furthermore, univariate and multivariate cox regression analysis indicated that CDC45 and clinical stage IV were independent prognostic factors for cervical cancer. In addition, the HPA database validated the protein expression level of CDC45 in cervical cancer. Further studies investigated the relationship between CDC45 and tumor-infiltrating immune cells via CIBERSORT. Finally, gene set enrichment analysis (GSEA) showed CDC45 related genes were mainly enriched in cell cycle, chromosome, catalytic activity acting on DNA, etc. These results suggested CDC45 may be a potential biomarker associated with the prognosis of cervical cancer.

PurposeBreast cancer type 1 susceptibility (BRCA) mutations not only increase breast cancer (BC) risk but also result in poor survival and prognosis for BC patients. This study will analyze the effect and safety of therapeutic regimens for the treatment of BC patients with germline BRCA (gBRCA) mutations by network meta-analysis.MethodsPublic databases were searched from inception to 29 April 2021. Frequentist network meta-analysis was conducted to analyze the benefit of chemotherapy and targeted drug-related strategies.ResultsSeventeen articles were included in the analysis. For progression-free survival (PFS), olaparib (hazard ratio (HR): 0.58; 95% confidence interval (CI): 0.43 – 0.79), platinum (HR: 0.45; 95% CI: 0.22 – 0.89), and talazoparib (HR: 0.54; 95% CI: 0.41 – 0.71) were significantly better than platinum-free chemotherapy (Chemo). The results based on indirect comparisons showed that veliparib (Vel) + platinum + Chemo was also significantly better than Chemo (HR: 0.37; 95% CI: 0.20 – 0.69). For overall survival (OS), olaparib was significantly better than Chemo only in the population who did not receive prior chemotherapy. For pathologic complete response (pCR), bevacizumab+Chemo had a significant advantage over platinum agents (OR: 3.64; 95% CI: 1.07 - 12.39). Olaparib and talazoparib both showed significantly higher objective response rates (ORRs) than Chemo.ConclusionThe PFS results suggested that olaparib, talazoparib, and Vel+platinum agent+Chemo were ideal regimens for overall, TNBC, and advanced BC patients with gBRCA mutations. Whether PARPis are suitable for patients with gBRCA mutations who have received prior platinum therapy still needs to be clarified.

New perinatal care technologies have improved the survival rate of preterm neonates, but the prevalence of bronchopulmonary dysplasia (BPD), one of the most intractable problems in neonatal intensive care unit (NICU), remains unchanged. In present study, high-throughput sequencing (HTS) was performed to detect the expression profiles of long noncoding RNAs (lncRNAs), messenger RNAs (mRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) in hyperoxia-induced BPD mouse model. Significant differentially expressed RNAs were selected and clustered between the BPD group and the control group. The results revealed that expressions of 1778 lncRNAs, 1240 mRNAs, 97 circRNAs, and 201 miRNAs were significantly altered in the BPD group. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to predict the potential functions of differentially expressed RNAs. lncRNA-mRNA and circRNA-miRNA coexpression networks were constructed to detect their association with the pathogenesis of BPD. Our study provides a systematic perspective on the potential function of RNAs during BPD.

The aim of this study was to develop a simple and reliable method to detect Mycobacterium tuberculosis complex (MTBC) and verify its clinical application preliminarily. A loop-mediated isothermal amplification method coupled with lateral flow biosensor (LAMP-LFB) assay, was developed and evaluated for detection of MTBC. Two sets of primers, which targeted IS6110 and IS1081 sequences of MTBC, were designed for establishment of multiplex LAMP-LFB assay. The amplicons were labelled with biotin and fluorescein isothiocyanate (FITC) by adding FITC labelled primer and biotin-14-dATP and biotin-14-dCTP and could be visualized using LFB. The optimal reaction conditions of multiplex LAMP-LFB assay confirmed were 66°C for 50 min. The analytical sensitivity of multiplex LAMP-LFB is 10 fg of genomic templates using pure culture, and no cross-reactivity with other common bacteria and non-tuberculous mycobacteria strains was obtained. A total of 143 clinical samples collected from 100 TB patients (62 definite TB cases and 38 probable TB cases) and 43 non-TB patients were used for evaluating the feasibility of multiplex LAMP-LFB assay. The multiplex LAMP-LFB (82.0%, 82/100) showed higher sensitivity than culture (47.0%, 47/100, P < 0.001) and Xpert MTB/RIF (54.0%, 54/100, P < 0.001). Importantly, the multiplex LAMP-LFB assay detected additional 28 probable TB cases, which increased the percentage of definite TB cases from 62.0% (62/100) to 90.0% (90/100). The specificity of multiplex LAMP-LFB assay in patients without TB was 97.7% (42/43). Therefore, multiplex LAMP-LFB assay is a simple, reliable, and sensitive method for MTBC detection, especially in probable TB cases and resource limited settings.

The lack of efficacious vaccines against Mycobacterium tuberculosis (MTB) infection is a limiting factor in the prevention and control of tuberculosis (TB), the leading cause of death from an infectious agent. Improvement or replacement of the BCG vaccine with one that reliably protects all age groups is urgent., The lack of efficacious vaccines against Mycobacterium tuberculosis (MTB) infection is a limiting factor in the prevention and control of tuberculosis (TB), the leading cause of death from an infectious agent. Improvement or replacement of the BCG vaccine with one that reliably protects all age groups is urgent. Concerns exist that antigens currently being evaluated are too homogeneous. To identify new protective antigens, we screened 1,781 proteins from a high-throughput proteome-wide protein purification study for antigenic activity. Forty-nine antigens (34 previously unreported) induced antigen-specific gamma interferon (IFN-γ) release from peripheral blood mononuclear cells (PBMCs) derived from 4,452 TB and suspected TB patients and 167 healthy donors. Three (Rv1485, Rv1705c, and Rv1802) of the 20 antigens evaluated in a BALB/c mouse challenge model showed protective efficacy, reducing lung CFU counts by 66.2%, 75.8%, and 60%, respectively. Evaluation of IgG2a/IgG1 ratios and cytokine release indicated that Rv1485 and Rv1705c induce a protective Th1 immune response. Epitope analysis of PE/PPE protein Rv1705c, the strongest candidate, identified a dominant epitope in its extreme N-terminal domain accounting for 90% of its immune response. Systematic preclinical assessment of antigens Rv1485 and Rv1705c is warranted.

In recent years, the obese and overweight population has increased rapidly, which has become a worldwide public health problem. However, effective medication is lacking. Our previous study identified a novel peptide, PDBSN (GLSVADLAESIMKNL), that could significantly restrict adipocyte differentiation in vitro, but its in vivo function has not been determined. Thus, in this study, we encapsulated the peptide into liposomes attached with two ligands (visceral-adipose-tissue-targeting peptide and cell-penetrating peptide) to improve stability and specificity. We then tested the peptide’s function in HFD (high-fat diet)-induced obese mice and found that PDBSN could reduce weight gain and improve insulin resistance as well as lipid homeostasis. These results suggest that PDBSN may be a potential candidate for anti-obesity drug discovery.

A multicenter study was performed to evaluate the value of testing gastric aspirate (GA) with Xpert MTB/RIF Ultra assay (Ultra) for childhood tuberculosis (TB) detection in China. In total, 129 children with active TB and 173 children without TB were enrolled. The sensitivity of Ultra in bacteriologically confirmed TB and probable TB cases was 87.5% (42/48) and 44.4% (36/81), respectively. The specificity of Ultra was high (99.4%, 172/173). When Ultra, culture, and acid-fast bacilli outcomes were integrated as a composite reference standard, the percentage of children with definite TB increased from 37., A multicenter study was performed to evaluate the value of testing gastric aspirate (GA) with Xpert MTB/RIF Ultra assay (Ultra) for childhood tuberculosis (TB) detection in China. In total, 129 children with active TB and 173 children without TB were enrolled. The sensitivity of Ultra in bacteriologically confirmed TB and probable TB cases was 87.5% (42/48) and 44.4% (36/81), respectively. The specificity of Ultra was high (99.4%, 172/173). When Ultra, culture, and acid-fast bacilli outcomes were integrated as a composite reference standard, the percentage of children with definite TB increased from 37.2% (48/129) to 67.4% (87/129). The sensitivity of Ultra is 80.0% (40/50) in children aged

Islets damage is a major abnormality underling diabetes. Recent studies suggested the value of exosomes in diagnosis. This study aimed to investigate the impact of injury factors on the miRNA profiles of islet exosomes and determine whether circulating exosomal miRNAs is suitable as biomarkers of islets damage. Islets were isolated from ICR mice and induced injury in vitro by mixed cytokines (Tumor Necrosis Factor-α, Interleukin -1β and Interferon-γ) or streptozotocin (STZ), and exosomes were derived from the cultural supernatant. Using miRNA microarray analysis, we found 22 and 11 differentially expressed miRNAs in islet exosomes of STZ and cytokines treatment, respectively, including 6 miRNAs as the intersection of two injured conditions. Thereinto, mmu-miR-375-3p and mmu-miR-129-5p could be validated by qRT-PCR. Then, Serum exosomes were isolated from STZ injected mice and subjects with various glucose metabolism states and diabetic duration. qRT-PCR demonstrated exosomal mmu-miR-375-3p dramatically increased in serum of STZ treated mouse prior to the disturbance of blood glucose and insulin. In human serum exosomes, hsa-miR-375-3p was elevated in new-onset diabetes patients. Overall, our results suggest that injury factors changed miRNA profiles of exosomes derived from islets and exosomal miR-375-3p showed promising potential as a biomarker of islets damage.

T2DM is a global health problem that seriously lowers the quality of life and insulin resistance makes a considerable contribution to the pathophysiology of T2DM. Long noncoding RNAs (lncRNAs) have emerged as important regulators in glucose and lipid metabolism. However, comprehensive analysis of lncRNAs in db/db mice skeletal muscle and their potential roles involved in skeletal muscle insulin resistance (IR) remains poorly characterized. Here, we identified 331 lncRNAs, 172 upregulated and 159 downregulated (|fold change|>2, q

Over the past decades, the epidemic of childhood obesity has greatly increased, and it has recently become a global public health concern. Methylation, serving as a crucial regulator of the gene-environment interaction, has exhibited a strong association with obesity. In this study, we aimed to evaluate the relationship between DNA methylation and childhood obesity, and further uncover the potential association of aberrantly methylated genes with obesity. DNA samples of peripheral blood leukocytes from three obese subjects (mean BMI: 21.67) and 4 age/sex matched controls (mean BMI: 14.92) were subjected to Infinium Human Methylation 450 Bead Array analysis. A total of more than 4 85 000 methylation sites were identified across the genome, and 226 methylated CpGs (DMCpGs) were differentially methylated between these two groups. Subsequent Gene Ontology (GO) and KEGG Pathway analyses showed that these DMCpGs were mainly engaged in immunity and lipoprotein metabolism, indicating their physiological significance. Further verification of the candidate CpG sites within the HDAC4, RAX2, APOA5, CES1, and SLC25A20 gene loci, were performed using bisulfite sequencing PCR (BSP) in a cohort of 42 controls and 39 obese cases. The results revealed that methylation levels within HDAC4 and RAX2 loci were positively associated with obesity, while the methylation levels of loci within APOA5 and CES1 loci were negatively correlated with obesity. Thus, alterations in methylation of CpG sites of specific genes may contribute to childhood obesity, which provide novel insights into the aetiology of obesity.

The aim of this study was to identify and compare the peptidomic profiles of lung tissues from neonatal mice with and without bronchopulmonary dysplasia (BPD). Hyperoxia was used to establish the BPD mouse model. Lung tissues obtained on postnatal day (PND) 9 were processed for analysis via histological staining and label-free liquid chromatography-mass spectrometry (LC-MS/MS). Histological analysis of the lung sections from the BPD group showed significant alveolar simplification and aberrant pulmonary vascularization. We identified 3,704 total peptides, of which 63 were differentially expressed in the lung tissues from the BPD group compared with those from the control group. Within this subset, 31 peptides were downregulated, and 32 peptides were upregulated. Bioinformatics analysis suggested several potential roles of the differentially expressed peptides in the pathophysiological process of BPD. In summary, this study highlights novel peptide candidates, and provides new insights for further understanding the molecular mechanism of BPD development.

Whether the maternal vitamin D deficiency is associated with infant birth weight is still an argument. Here, we performed a nested case-control study (545 women who subsequently delivered infant with macrosomia and 1090 controls) to evaluate the association of the maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations with risk of macrosomia. We measured the serum 25(OH)D concentrations by enzyme immunoassays. Logistic regression analysis, receiver-operator characteristic curve analysis and graphical nomogram were used for the statistical analyses. Among women who delivered infant with macrosomia, 71.2% of the women had serum 25(OH)D concentrations P P for trend = 0.001). We also observed a threshold for 25(OH)D of 50.0 nmol/L for delivering infant with macrosomia and a predictive accuracy of the 25(OH)D concentrations included panel, with an area under the ROC curve of 0.712 for delivering infant with macrosomia. In conclusion, maternal serum 25(OH)D

The novel obesity-associated protein Phosphotyrosine Interaction Domain containing 1 (PID1) inhibits insulin-PI3K/Akt signaling pathway and insulin-stimulated glucose uptake in vitro. In this study, we generated fat tissue-specific aP2-PID1 transgenic (aP2-PID1tg) mice and PID1 knockout (PID1-/-) mice to explore how PID1 affects glucose metabolism in vivo. We observed insulin resistance and impaired insulin-PI3K/Akt signaling in aP2-PID1tg mice. Consistent with these data, the PID1-/- mice displayed improved glucose tolerance and insulin sensitivity under chow diet, with increased Akt phosphorylation in white adipose tissue (WAT). We further demonstrated that PID1 could interact with low density lipoprotein receptor-related protein 1 (LRP1) but not the insulin receptor (IR) in adipocytes, and its overexpression could lead to decreased GLUT4 level. Our results thus indentify PID1 as a critical regulator of glucose metabolism in adipocytes.

To evaluate the effects of maternal vitamin D deficiency on body fat and adipogenesis in offspring rats, and explore the potential mechanism, we constructed a vitamin D deficient rat model and performed metabolic activity evaluation, body fat monitoring, biochemical analysis, adipogenesis assay, methylation microarray and RNA-seq for their offspring rats. We found the weight of vitamin D deficient (VDD) offspring was gradually higher than that of control (CLT) offspring, and the difference was significant since 10 weeks old. When compared with CTL offspring, the 24 h heat production, peak blood glucose, adipose tissue volume and blood lipid indexes were significantly increased in VDD offspring at 14 weeks old. Moreover, a significant increase in proliferation rate and number of lipid droplets for pre-adipocytes was also observed in VDD offspring group. DNA methylation profiling showed that compared to CTL group, 608 promoters and 204 CpG islands were differentially methylated in the VDD group, involving 305 genes. When combined with the results of RNA-seq, 141 genes of the methylated genes were differentially expressed. In conclusion, vitamin D deficiency during pregnancy may promote the proliferation and differentiation of pre-adipocytes, which may be associated with methylation alterations of genes, ultimately leading to offspring obesity.

The purposes of this study are to investigate the prevalence of nonresponsive feeding practice (NRFP) and child's eating behavior (CEB) and to explore the hypothetical association between child's weight status, NRFP and CEB for 1- to 6-year-old children. In this study, 2423 caregivers of 1- to 6-year-old children are from the Nanjing Maternal and Child Health Hospital who completed the self-report questionnaires about their NRFP and CEB as well as their children's sociodemographic data. Chi-square test and multiple regression analyses were used to examine the correlation between child's weight status and NRFP and CEB. The total prevalence of overweight and obesity was 15.2 and 7.3%, respectively. High prevalence of CEB problems and NRFP was detected at 2- and 5-year-old children. Moreover, maternal NRFP was significantly positively associated with CEB. The regression and correlation analysis revealed CEB and maternal NRFP are closely associated with BMI. For instance, refusing new food (OR = 3.57, 95%CI, 1.37-9.33, 1.5-year-old) and restriction (OR = 3.01, 95%CI, 1.34-6.76) are likely to be associated with underweight. Preferring junk food (OR = 4.892, 95%CI, 1.71-14.01, 1-year-old) and inattention (OR = 2.24, 95%CI, 1.16-4.35, 1-year-old) are prone to be overweight and obese, and pressure (OR = 0.23, 95%CI, 0.06-0.91, 1-year-old) is less likely to be associated with underweight.The findings provide strong evidence for the correlation between NRFR and CEB, and this indicates that prevention and intervention of unhealthy weight should start in early life. However, further research is necessary to gain an understanding of the impact of NRFP on CEB and weight. What is known: • Responsive feeding practice is crucial to the formation of eating behavior, and poor practice is associated with the current epidemics of childhood obesity and underweight. What is new: • The findings provide a strong evidence for the correlation between NRFR and CEB. • This finding indicates that NRFR and CEB are associated with child's unhealthy weight.

Mycoplasma pneumoniae (M. pneumoniae) is responsible for pneumonia, and is a causative agent of other respiratory tract infections (e.g., bronchiolitis and tracheobronchitis). Herein, we established and applied a multiple cross displacement amplification (MCDA) coupled with a nanoparticle-based lateral flow biosensor (LFB) assay (MCDA–LFB) for rapid, simple, and reliable detection of target pathogen. A set of 10 primers was designed based on M. pneumoniae-specific P1 gene, and optimal reaction conditions were found to be 30 min at 65°C. The detection results were visually reported using a biosensor within 2 min. The M. pneumoniae–MCDA–LFB method specifically detected only M. pneumoniae templates, and no cross-reactivity was generated from non-M. pneumoniae isolates. The analytical sensitivity for this assay was 50 fg of genomic templates in the pure cultures, as obtained from colorimetric indicator and real-time turbidimeter analysis. The assay was applied to 197 oropharyngeal swab samples collected from children highly suspected of M. pneumoniae infection, and compared to culture-based method and real-time PCR assay. The detection rates of M. pneumoniae using a culture-based method, real-time PCR assay, and MCDA–LFB assay were 8.1%, 33.0%, and 52.3%, respectively, which indicated that the MCDA–LFB assay was superior to the culture-based method and real-time PCR method for detection of target agent. Using this protocol, 25 min for rapid template extraction followed by MCDA reaction (30 min) combined with LFB detection (2 min) resulted in a total assay time of ~60 min. In conclusion, the MCDA–LFB assay established in this report was a simple, rapid, sensitive, and reliable assay to detect M. pneumoniae strains, and can be used as a potential diagnostic tool for M. pneumoniae in basic and clinical laboratories.

Krüppel-like factor 4 (KLF4), a key transcription factor, acts as a multifunctional player involved in the progression of numerous aggressive cancers. The proteasome-dependent pathway is one of the main modalities in controlling KLF4 abundance at a posttranslational level. Although some of the ubiquitin ligases have been identified, the deubiquitinases of KLF4 and the regulatory function remain unexplored. Here, by screening ubiquitin-specific proteases that may interact with KLF4, we found ubiquitin-specific peptidase 10 (USP10) as a deubiquitinating enzyme for KLF4. Forced expression of USP10 remarkably increases KLF4 protein level by blocking the latter degradation, whereas the depletion of USP10 promotes KLF4 degradation and thus enhances tumorigenesis. Loss of USP10 in mice downregulates KLF4 expression and accelerates Kras(G12D)-driven lung adenocarcinoma initiation and progression. In addition, our data revealed that KLF4 can facilitate the transcription of tumor suppressor TIMP3 by directly binding to the TIMP3 promoter. Clinically, reduction of USP10 expression, concomitant with decreased KLF4 and TIMP3 abundance in carcinoma tissue, predicts poor prognosis of lung cancer patient. Taken together, our results demonstrate that USP10 is a critical regulator of KLF4, pinpointing USP10-KLF4-TIMP3 axis as a promising therapeutic target in lung cancer.

The purpose of this study was to investigate the pathophysiology and discover novel predictors of neonatal respiratory distress syndrome (NRDS) from a peptidomics perspective.Comparative profiling of umbilical cord blood from NRDS and control patients was performed by liquid chromatography tandem mass spectrometry technology. The underlying biological functions of the differentially expressed peptides (DEPs) were predicted by Gene Ontology (GO) and KEGG pathway analyses. The interactions of DEPs and their precursor proteins were explored by ingenuity pathway analysis (IPA). The sources and stability of DEPs were determined by online databases, including UniProt, SMART and ProtParam tool.A total of 251 DEPs were identified, of which 139 peptides were upregulated, and 112 peptides were downregulated (fold change ≥2.0, P 0.05). These DEPs were predicted to be associated with respiratory failure, atelectasis, and morphogenesis of endothelial cells. These processes indicated that DEPs may play a role in NRDS. Among them, eleven stable DEPs might be used as preclinical biomarkers.Our findings improve our understanding of NRDS and facilitate the discovery of candidate diagnostic biomarkers for NRDS from the perspective of peptidomics.

Scope Human milk can prevent the development of necrotizing enterocolitis (NEC). Human milk is rich in cargo-carrying exosomes that participate in intercellular communication. This study investigated the effects of term and preterm human milk-derived exosomes, and elucidated their lipid expression profiles. Methods and results Milk from healthy mothers is collected who have delivered full-term or preterm infants, and exosomes are isolated and quantified. Administration of term and preterm milk exosomes significantly enhances epithelial proliferation and migration in vitro, and ameliorates the severity of NEC in vivo. A total of 395 lipids are identified in term and preterm human milk-derived exosomes. Bioinformatics analysis and western blotting reveal that top 50 lipids regulate intestinal epithelial cell function via the Extracellular-Signal-Regulated Kinase/Mitogen Activated Protein Kinase (ERK/MAPK) pathway. Conclusion This study reveals for the first time the lipidomic complexities in exosomes derived from preterm and term milk. The results provide novel mechanistic insight on how human milk prevents the development of NEC.

Scope Human breast milk has been shown to prevent necrotizing enterocolitis (NEC). Although exosomes have been identified in breast milk, their function and components have not been fully addressed. This study is conducted to elucidate the differences in peptidomic complexities between preterm and term milk exosomes. Methods and results Breast milk samples are collected from healthy lactating mothers who have delivered term and preterm infants. Exosomes are separated and quantified. The protective effects of purified exosomes against NEC are investigated both in vitro and in vivo. The peptidomic complexities in term and preterm milk exosomes are analyzed by iTRAQ LC-MS/MS to screen differentially expressed exosomal peptides. Preterm milk exosomes administration significantly enhances proliferation and migration of intestinal epithelial cells compared with term milk exosomes. A total of 70 peptides are found to be significantly modulated in preterm milk samples compared to term milk samples. Of these, 47 peptides are upregulated, and 23 peptides are downregulated. Bioinformatics analysis suggests several potential regulatory roles of the altered peptides in intestinal epithelial cell function. Conclusion These results reveal the differences for the first time in peptidomic complexities between preterm and term milk exosomes. Milk exosome administration might be a promising prevention for NEC.

Background/Aims: Vitamin D deficiency has been shown to be associated with a greater prevalence of anemia in various healthy and diseased populations by a great deal of observational studies. However, less work has been done to explore this association in pregnant women. The aim of this study was to evaluate the association between maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations and risk of gestational anemia in a large, nested case-control study. Methods: The serum 25(OH)D concentrations was measured by enzyme immunoassay in 775 pregnant women affected with anemia and 1550 controls. Logistic regression analysis was conducted to assess the association of 25(OH)D concentrations with risk of gestational anemia. Results: We found the 25(OH)D concentrations was significantly lower in women affected with anemia than in controls. Logistic regression analyses showed that women with 25(OH)D concentrations < 25.0 nmol/L, from 25.0 to 37.4 nmol/L and from 37.5 to 49.9 nmol/L all had increased risk of anemia when compared with women with concentrations from 50.0 to 74.9 nmol/L. And the risk of anemia was significantly increased with the decreasing concentrations of the serum 25(OH)D in a dose-dependent manner (P for trend = 0.012). For women with concentrations < 50.0 nmol/L, they had an 80% increase in anemia risk (95% CI = 1.45-2.25) after adjustment for confounders. We also observed a nonlinear relationship between the serum 25(OH)D and anemia, with a threshold for 25(OH)D of 50.0 nmol/L existed for anemia. Conclusion: Maternal serum 25(OH)D < 50.0 nmol/L may be a risk factor for gestational anemia, and it should be monitored for the high-risk pregnant women.

Genome-wide association studies (GWASs) have revealed the worldwide heterogeneity of genetic factors in tuberculosis (TB) susceptibility. Despite having the third highest global TB burden, no TB-related GWAS has been performed in China. Here, we performed the first three-stage GWAS on TB in the Han Chinese population. In the stage 1 (discovery stage), after quality control, 691 388 SNPs present in 972 TB patients and 1537 controls were retained. After replication on an additional 3460 TB patients and 4862 controls (stages 2 and 3), we identified three significant loci associated with TB, the most significant of which was rs4240897 (logistic regression P = 1.41 × 10-11, odds ratio = 0.79). The aforementioned three SNPs were harbored by MFN2, RGS12 and human leukocyte antigen class II beta chain paralogue encoding genes, all of which are candidate immune genes associated with TB. Our findings provide new insight into the genetic background of TB in the Han Chinese population.

To evaluate the maternal serum 25(OH)D concentrations and its association with gestational diabetes and other pregnancy outcomes.zMethods:In our nested case-control study, 4718 pregnancy women were included, who were attending second- and third-trimester screening in Nanjing, China. Serum 25(OH)D concentrations were tested by enzyme-linked immunoassay, and the pregnancy and birth outcomes were obtained via electronic medical record collection and information extraction. The associations of 25(OH)D concentrations with gestational diabetes and other pregnancy outcomes were assessed by logistic regression analysis. And receiver-operator characteristic curve analysis was also conducted.For the total population, the median (IQR) concentrations of 25(OH)D was 43.7 (35.5-57.9) nmol lLow 25(OH)D concentrations (50.0 nmol l