Correlation of Maternal Vitamin D Status in Early Pregnancy and Vitamin D Supplementation during Pregnancy with Atopic Dermatitis in Infants: A Prospective Birth Cohort Study.

OBJECTIVE: This study aimed to investigate the association of maternal first-trimester vitamin D levels and vitamin D supplementation during pregnancy with infant atopic dermatitis (AD) and to determine the effect of variables such as mode of conception on the association. METHODS: This study was based on the Shanghai sub-cohort of the International Birth Cohort of China. A total of 4051 woman-infant pairs with singleton pregnancies were recruited. Vitamin D deficiency and insufficiency were defined as serum 25-hydroxyvitamin D concentrations of 25 and 50 nmol/L, respectively. AD in infants was assessed during the first six months using a standardized questionnaire based on the British Working Party criteria. Modified Poisson regression estimated the association between maternal vitamin D status and infant AD. RESULTS: The risk of AD in infants was higher in women with deficient 25-hydroxyvitamin D levels in the first trimester (RR: 1.77, 95% CI: 1.41-2.23). This increased risk was seen in naturally conceived pregnancies, but not in those conceived using assisted reproductive technology (ART). The incidence of AD decreased in infants of mothers who took multi-vitamin (RR: 0.79, 95% CI: 0.67-1.98) and vitamin D supplements (RR: 0.51, 95% CI: 0.37-0.71) compared to those whose mothers did not take any supplements. Maternal vitamin D deficiency had varying effects on AD risk based on passive smoking exposure and breastfeeding patterns. CONCLUSIONS: Our findings highlight the importance of monitoring and supplementing vitamin D during pregnancy, especially in specific maternal populations, to reduce the risk of AD in offspring.

Relationship Between Birth Weight and Asthma Diagnosis: A Cross-Sectional Survey Study Based on the National Survey of Children's Health in the U.S.

OBJECTIVE: To assess the association between birth weight and childhood asthma risk using data from the 2019-2020 National Survey of Children's Health database. DESIGN: Cross-sectional study. SETTING: The USA. PATIENTS: A representative cohort of American children. EXPOSURE: The exposure of this study was birth weight regardless of gestational age. Birth weight was divided into three groups: <1500 g, 1500-2500 g and >2500 g. MAIN OUTCOME MEASURES: Primary outcomes were parent-reported diagnosis of asthma. METHOD: The Rao-Scott χ2 test was used to compare the groups. The main analyses examined the association between birth weight and parent-report asthma in children using univariable and multivariable logistic models adjusting for preterm birth, age, sex, race, family poverty, health insurance, smoking, maternal age. Subgroup analysis was performed based on interaction test. RESULTS: A total of 60 172 children aged 3-17 years were enrolled in this study; of these, 5202 (~8.6%) had asthma. Children with asthma were more likely to be born preterm, with low birth weight (LBW) or very LBW (VLBW). The incidence of asthma was the highest in VLBW children at 20.9% and showed a downward trend with an increase in birth weight class, with rates of 10.7% and 8.1% in the LBW and normal birthweight groups, respectively. Children with VLBW (OR 1.97; 95% CI 1.29 to 3.01) had higher odds of developing asthma in the adjusted analysis model. However, VLBW was only shown to be a risk factor for asthma among Hispanics, black/African-Americans and children between the ages of 6 and 12 years, demonstrating racial and age disparities. CONCLUSIONS: VLBW increases the risk of childhood asthma; however, racial and age disparities are evident.

Examining the relationship between birth weight and attention-deficit hyperactivity disorder diagnosis.

Background: Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental condition that is prevalent in children worldwide. We evaluated the potential relationship between birth weight and ADHD using newly released data from the National Survey of Children's Health 2019-2020. Methods: This population-based survey study used parent recollection data that were collected and submitted by 50 states and the District of Columbia to the National Survey of Children's Health database from the National Survey of Children's Health database. Those aged < 3 years and without birth weight or ADHD records were excluded. Children were stratified according to ADHD diagnosis and birth weight: very low birth weight (VLBW, < 1,500 g), low birth weight (LBW, 1,500-2,500 g), and normal birth weight (NBW, ≥ 2,500 g). Multivariable logistic regression was applied to examine the causal association between birth weight and ADHD while controlling for child and household characteristics. Results: The final sample consisted of 60,358 children, of whom 6,314 (9.0%) were reported to have an ADHD diagnosis. The prevalence of ADHD was 8.7% in NBW children, 11.5% in LBW, and 14.4% in VLBW. Compared with NBW children, LBW children [adjusted odds ratio (aOR), 1.32 (95% CI, 1.03-1.68)], and VLBW children [aOR, 1.51 (95% CI, 1.06-2.15)] had a significantly higher risk of ADHD after adjusting all variables. These associations persisted in the male subgroups. Conclusion and relevance: This study found that LBW and VLBW children were at a higher risk of ADHD.

Association of chorioamnionitis with infertility treatment and subsequent neonatal outcomes in the US: a population-based cohort study.

BACKGROUND: Chorioamnionitis (CAM) is a common risk factor for preterm births, resulting in several adverse outcomes. The association between infertility treatment and CAM is unclear. Therefore, this study examined the association between infertility treatment and CAM and described subsequent neonatal outcomes. METHODS: This population-based cohort study used data from the National Vital Statistics System Database. We included women who had a singleton live birth from January 1, 2016 to December 31, 2018. Women-infant pairs were stratified by infertility treatment, and the main outcome was a reported diagnosis of CAM in a checkbox format: clinical CAM or maternal temperature of > 38 °C. Multivariate logistic regression was used to examine the association between infertility treatment and CAM and the effect of infertility treatment on neonatal outcomes in women diagnosed with CAM. RESULTS: The final sample comprised 10,900,495 woman-infant pairs, and 1.4% received infertility treatment. Compared with the natural conception group, women receiving infertility treatment had a significantly higher risk of CAM (adjusted odds ratio [aOR] 1.772 [95% confidence interval {CI}, 1.718-1.827]). Furthermore, newborns exposed to CAM had a higher risk of very low birth weight (VLBW) (aOR, 2.083 [95% CI, 1.664-2.606], P < .001), preterm birth (aOR, 1.497 [95% CI, 1.324-1.693]; P < .001), neonatal intensive care unit admission (aOR, 1.234 [95% CI, 1.156-1.317]; P < .001), and other adverse neonatal outcomes in the infertility treatment group compared with ones conceived naturally. CONCLUSIONS: This study found that women who received infertility treatment had a higher risk of CAM. And CAM deteriorated neonatal outcomes in the infertility treatment group.

Assisted reproductive technology and neurodevelopmental outcomes in offspring: a prospective birth cohort study in East China.

RESEARCH QUESTION: Is ART associated with adverse neurodevelopmental outcome in 12-month-old offspring compared with those conceived through natural conception? DESIGN: In this prospective cohort study, 488 infertile women undergoing ART and 1397 women with natural conception were recruited and followed until their offspring were 12 months old. The primary outcome was the neurodevelopment in the offspring. The association between exposure to ART and Gesell developmental scale scores was investigated using multiple linear regression models after adjusting for confounders. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to verify the results. RESULTS: In total, 18 (3.7%) and 40 (2.9%) children in the ART and natural conception groups, respectively, had been diagnosed with neurodevelopmental delay at 12 months of age. It was found that gross motor, adaptive behaviour, language and total development quotient scores were comparable between the groups. Following multivariate linear regression and IPTW, social behaviour development quotient scores were found to be slightly higher in the ART group than the natural conception group. Higher social behaviour development quotient scores in the ART group were also observed in the male and the singleton subgroups. CONCLUSIONS: At 12 months, offspring born after ART appeared to have similar motor, language and adaptive behaviour skills, and total development quotient scores, to those born after natural conception. However, social behaviour development in 12-month-old infants was slightly higher in those conceived using ART than in naturally conceived offspring, especially in male or singleton infants. These findings may provide new information in evaluating the potential benefits and risks of ART.

Prenatal LPS Exposure Promotes Allergic Airway Inflammation via Long Coding RNA NONMMUT033452.2, and Protein Binding Partner, Eef1D.

Epidemiological surveys indicate that intrauterine inflammation increases the risk of asthma in offspring. However, the underlying mechanisms remain largely unknown. Previous studies in BALB/c and C57BL/6 mice showed that prenatal exposure to endotoxins prevented allergic airway inflammation in offspring, which is inconsistent with most clinical observations. In this study, we found that prenatal LPS exposure increased airway resistance and total exfoliated cell counts, eosinophils, and IL-4 concentrations in BAL fluid of ovalbumin-sensitized Institute of Cancer Research (ICR) mice. Importantly, long noncoding RNA (lncRNA) NONMMUT033452.2 was upregulated in the lungs of LPS-exposed ICR offspring. Fluorescence in situ hybridization and cytoplasmic and nuclear fraction analyses revealed that this lncRNA was distributed in both the nuclei and cytoplasm of lung and airway epithelial cells, smooth muscle cells, and fibroblasts. Intranasal administration of NONMMUT033452.2 siRNA markedly alleviated allergic airway inflammation in ovalbumin-sensitized ICR mice. In vitro functional experiments demonstrated that overexpression of NONMMUT033452.2 inhibited the proliferation of lung and bronchiolar epithelial cells and promoted oxidative stress. RNA pull-down assays proved that NONMMUT033452.2 could directly bind Eef1D (eukaryotic translation elongation factor 1 delta). Overexpression of NONMMUT033452.2 induced the redistribution of Eef1D and substantially inhibited the expression of its downstream heat shock genes. NONMMUT033452.2 was also involved in the modulation of IL-1, IL-12, and some key molecules related to asthma, including Npr3 (natriuretic peptide receptor 3), Rac1 (Rac family small GTPase 1), and Nr4a3 (nuclear receptor subfamily 4, group A, member 3). Furthermore, the human lncRNA NONHSAT078603.2 was identified as a functional homolog of NONMMUT033452.2. These findings provide new insight into the pathogenic mechanism underlying asthma development.

EphrinB2 promotes the human aortic smooth muscle cell growth and migration via mediating F-actin remodeling.

OBJECTIVES: To evaluate the potential effect of EphrinB2 in human thoracic aortic dissection (TAD) and to illustrate the mechanisms governing the role of EphrinB2 in the growth of human aortic smooth muscle cells (HASMC). METHODS: In the study, EphrinB2 expression was investigated by qRT-PCR and immunohistochemistry in 12 pairs of TAD and adjacent human tissues. HASMCs were used for in vitro experiments. Next, EphrinB2 overexpression and depletion in HASMCs were established by EphrinB2-overexpressing vectors and small interfering RNA, respectively. The transfection efficiency was evaluated by qRT-PCR and Western blot. The effects of overexpression and depletion of EphrinB2 on cell proliferation, migration, and invasion were tested in vitro. Cell Counting Kit-8, flow cytometry and transwell migration/invasion, and wound healing assay were used to explore the function of EphrinB2 on HASMC cell lines. The relationship between EphrinB2 and F-actin was assessed by Western blot, immunofluorescence, and Co-IP. RESULTS: We found that EphrinB2 was a prognostic biomarker of TAD patients. Moreover, EphrinB2 expression negatively correlated to aortic dissection tissues, and disease incidence of males, suggesting that EphrinB2 might act as a TAD suppressor by promoting proliferation or decreasing apoptosis in HASMC. Next, over-expression of EphrinB2 in HASMC lines drove cell proliferation, migration, and invasion, and inhibited apoptosis while knockdown EphrinB2 showed the opposite phenomenon, respectively. Furthermore, the level of F-actin in mRNA, protein, and distribution in HASMC cell lines highly matched with the expression of EphrinB2, which indicated that EphrinB2 could mediate the HASMC cytoskeleton via inducing F-actin. CONCLUSIONS: In conclusion, our results first provided the pivotal role of EphrinB2 in HASMC proliferation initiated by mediating F-actin and demonstrated a prognostic biomarker and the potential targets for therapy to prevent thoracic aortic dissection.

Aberrant methylation of Serpine1 mediates lung injury in neonatal mice prenatally exposed to intrauterine inflammation.

BACKGROUND: Intrauterine inflammation (IUI) alters epigenetic modifications in offspring, leading to lung injury. However, the epigenetic mechanism underlying IUI-induced lung injury remains uncertain. In the present study, we aim to investigate the effect of IUI on lung development, and to identify the key molecule involved in this process and its epigenetic regulatory mechanism. RESULTS: Serpine1 was upregulated in the lung tissue of neonatal mice with IUI. Intranasal delivery of Serpine1 siRNA markedly reversed IUI-induced lung injury. Serpine1 overexpression substantially promoted cell senescence of both human and murine lung epithelial cells, reflected by decreased cell proliferation and increased senescence-associated ß-galactosidase activity, G0/G1 cell fraction, senescence marker, and oxidative and DNA damage marker expression. IUI decreased the methylation level of the Serpine1 promoter, and methylation of the promoter led to transcriptional repression of Serpine1. Furthermore, IUI promoted the expression of Tet1 potentially through TNF-α, while Tet1 facilitated the demethylation of Serpine1 promoter. DNA pull-down and ChIP assays revealed that the Serpine1 promoter was regulated by Rela and Hdac2. DNA demethylation increased the recruitment of Rela to the Serpine1 promoter and induced the release of Hdac2. CONCLUSION: Increased Serpine1 expression mediated by DNA demethylation causes lung injury in neonatal mice with IUI. Therefore, therapeutic interventions targeting Serpine1 may effectively prevent IUI-induced lung injury.

Multilocus Sequence Typing and Antifungal Susceptibility of Vaginal and Non-vaginal Candida glabrata Isolates From China.

Candida glabrata is a common cause of Candida infections. In our present study, we investigated the antifungal susceptibility and molecular epidemiology of vaginal and non-vaginal C. glabrata isolates. Seventy-six vaginal C. glabrata strains isolated from patients with vulvovaginal candidiasis and 57 non-vaginal C. glabrata isolates were collected at two hospitals in Shanghai, China. Antifungal susceptibility was examined using a broth microdilution method. Multilocus sequence typing was used for genotyping. Overall, 28 (21.1%), 28 (21.1%), and 29 (21.8%) C. glabrata isolates were resistant to fluconazole, itraconazole, and voriconazole, respectively. Briefly, 18 (23.7%), 18 (23.7%), and 19 (25%) vaginal strains were resistant to fluconazole, itraconazole, and voriconazole. While the resistance to these antifungals were all 17.5% (10/57) in non-vaginal strains. All isolates retained susceptibility to amphotericin B, and only four non-vaginal isolates were caspofungin resistant. Genotyping identified 17 ST patterns. In non-vaginal samples, the same genotypes appear as in the vaginal samples, except for one genotype (ST-182), while in the vaginal samples more genotypes appear (ST8, ST19, ST45, ST55, ST66, ST80, ST138, and ST17). The most common genotype was ST7 (81 strains), followed by ST10 (14 strains) and ST15 (11 strains). The majority of resistant phenotype strains (25/30, 83.3%) correlated to the predominant genotype (ST7), and the rest belonged to ST3 (2/30, 6.7%), ST10 (1/30, 3.3%), ST19 (1/30, 3.3%), and ST45 (1/30, 3.3%). Our survey revealed cross-resistance in vaginal and non-vaginal C. glabrata isolates. Moreover, there is no genotype associated with the resistance phenotype.

Prenatal inflammation causes obesity and abnormal lipid metabolism via impaired energy expenditure in male offspring.

INTRODUCTION: Obesity has becoming a global health issue. Fetus exposed to adversity in the uterine are susceptible to unhealth stimulus in adulthood. Prenatal inflammation is related to poor neonatal outcomes like neurodevelopmental impairments and respiratory complications. Recent studies suggested prenatal lipopolysaccharide (LPS) exposure could result in metabolic disorders. Thus, we hypothesized that offspring exposed to prenatal inflammation could develop into metabolic disorder. METHODS: The pregnant C57BL/6J mice were intraperitoneally injected with 50 µg/kg LPS or saline only once at GD15. The male offspring were weighted weekly until sacrificed. Indirect calorimetry and body composition were both performed at 9 and 18 weeks old. At 20 weeks old, mice were fasted overnight before collecting blood samples and liver for metabolomics analysis and RNA sequencing, respectively. Differentially expressed genes were further verified by RT-qPCR and western blotting. RESULTS: Prenatal inflammation resulted in obesity with increased fat percentage and decreased energy expenditure in middle-age male offspring. Abnormal lipid accumulation, changes of gene expression profile and upregulation of multi-component mechanistic target of rapamycin complex 1 (mTOR)/Peroxisome proliferator-activated receptor-γ pathway was observed in liver, accompanied with decreased bile acids level, unsaturated fatty acids androgens and prostaglandins in serum. Indirect calorimetry showed increased respiratory exchange rate and deceased spontaneous activity at 9 weeks in LPS group. Impaired energy expenditure was also observed at 18 weeks in LPS group. CONCLUSION: Prenatal LPS exposure led to obesity and abnormal lipid metabolism through impaired energy expenditure.

Serum exosomal miR-451a acts as a candidate marker for pancreatic cancer.

OBJECTIVES: The aim of this study was to explore the diagnostic efficiency of serum exosomal miR-451a as a novel biomarker for pancreatic cancer. METHODS: Serum samples were collected prior to treatment. First, we analyzed microRNA (miRNA) profiles in serum exosomes from eight pancreatic cancer patients and eight healthy volunteers. We then validated the usefulness of the selected exosomal miRNAs as biomarkers in another 191 pancreatic cancer patients, 95 pancreatic benign disease (PB) patients, and 90 healthy controls. RESULTS: The expression of miR-451a in serum-derived exosomes from pancreatic cancer patients was significantly upregulated compared with those from PB patients and healthy individuals. Serum exosomal miR-451a showed excellent diagnostic power in identifying pancreatic cancer patients. In addition, exosomal miR-451a showed a significant association with clinical stage and distant metastasis in pancreatic cancer, and the expression level of serum exosomal miR-451a was sensitive to therapy and relapse. CONCLUSIONS: Serum exosomal miR-451a might serve as a novel diagnostic marker for pancreatic cancer.

Relationship between maternal vitamin D status in the first trimester of pregnancy and maternal and neonatal outcomes: a retrospective single center study.

BACKGROUND: This study aimed to investigate the relationship between maternal serum vitamin D status in the first trimester of pregnancy and maternal as well as neonatal outcomes, considered the prevalence of vitamin D deficiency (serum 25(OH)D < 50 nmol/L) around the world, especially in the pregnant women. METHODS: From January 2015 to December 2016, in this cross-sectional retrospective study, we enrolled women receiving regular prenatal examinations and giving birth in the International Peace Maternity and Child Health Hospital. Cases confirmed as multiple pregnancy, incomplete medical records, and vitamin D level recorded after 13 weeks of gestation were excluded. A total of 23,394 mother-infant pairs were included ultimately. Obstetric and neonatal information were extracted from the database. Maternal serum vitamin D concentration was measured by chemiluminescence microparticle immunoassay. Logistic regression analysis (unadjusted and adjusted models) was used to analyze the association between vitamin D and maternal and neonatal outcomes. RESULTS: The average 25(OH) D concentration was 43.20 ± 0.10 nmol/L; 67.09% of patients were vitamin D deficient(25(OH) D < 50.00 nmol/L), 29.84% were vitamin D insufficient (50 nmol/L ≤ 25(OH)D < 75 nmol/L), 3.07% were sufficient (25(OH)D ≥ 75 nmol/L). The maternal 25(OH)D levels varied with age, pre-pregnancy BMI, season when blood sample was collected, number of previous-pregnancy. Notably, newborns delivered by women with deficient vitamin D status had a higher incidence rate of admission to NICU (Deficiency: 12.20% vs Insufficiency: 10.90% vs Sufficiency: 11.70%, Pbonferroni = .002) and a longer stay (deficiency: 6.2 ± 4.1 days vs insufficiency: 5.9 ± 3.1 days vs sufficiency: 5.1 ± 2.1 days, Pbonferroni = .010). Moreover, maternal vitamin D deficiency was a dependent risk factor for admission to NICU (unadjusted OR = 1.35, 95% CI,1.05-1.74 Pbonferroni = .022; adjusted OR = 1.31, 95% CI,1.010-1.687 Pbonferroni = .042). CONCLUSIONS: Maternal vitamin D deficiency (25(OH) D < 50 nmol/L) was prevalent in eastern coastal China. The incidence rate of GDM as well as preeclampsia was higher in vitamin D insufficient group while vitamin D deficiency group was liable to intrauterine infection when compared with the other two groups. Most importantly, low vitamin D status in the first trimester of pregnancy was a dependent risk factor for admission to NICU. More well-designed perspective researches are necessary to clarify the role of vitamin D in the early stage of pregnancy.

Pyrogallol and Fluconazole Interact Synergistically In Vitro against Candida glabrata through an Efflux-Associated Mechanism.

Candida glabrata is currently the first or second most commonly encountered non-albicans Candida species worldwide. The potential severity of Candida resistance mandates the discovery of novel antifungal agents, including those that can be used in combination therapies. In this study, we evaluated the in vitro interactions of pyrogallol (PG) and azole drugs against 22 clinical C. glabrata isolates. The potential mechanism underlying the synergism between PG and fluconazole (FLC) was investigated by the rhodamine 6G efflux method and quantitative reverse transcription (qRT)-PCR analysis. In susceptibility tests, PG showed strong synergism with FLC, itraconazole (ITC), and voriconazole (VRC), with fractional inhibitory concentration index values of 0.18 to 0.375 for PG+FLC, 0.250 to 0.750 for PG+ITC, and 0.141 to 0.750 for PG+VRC. Cells grown in the presence of PG+FLC exhibited reduced rhodamine 6G extrusion and significantly downregulated expression of the efflux-related genes CgCDR1, CgCDR2, and CgPDR1 compared with cells grown in the presence of PG or FLC alone. PG did not potentiate FLC when tested against a ΔCgpdr1 strain. Restoration of a functional CgPDR1 allele also restored the synergism. These results indicate that PG is an antifungal agent that synergistically potentiates the activity of azoles. Furthermore, PG appears to exert its effects by inhibiting efflux pumps and downregulating CgCDR1, CgCDR2, and CgPDR1, with CgPDR1 probably playing a crucial role in this process.

Synergistic Effect of Pseudolaric Acid B with Fluconazole Against Resistant Isolates and Biofilm of Candida tropicalis.

PURPOSE: Candida tropicalis (C. tropicalis) has emerged as an important fungal pathogen due to its increasing resistance to conventional antifungal agents, especially fluconazole (FLC). Pseudolaric acid B (PAB), a herbal-originated diterpene acid from Pseudolarix kaempferi Gordon, has been reported to possess inhibitory activity against fungus. The present study aims to investigate the antifungal effect of PAB alone and in combination with FLC on planktonic and biofilm cells of C. tropicalis. METHODS: The antifungal activity of PAB against planktonic isolates was evaluated alone and in combination with FLC using the chequerboard microdilution method and growth curve assay. The anti-biofilm effects were quantified by tetrazolium (XTT) reduction assay, which were further confirmed by scanning electron microscopy (SEM) and fluorescent microscope to observe morphological changes of biofilm treated with PAB and FLC. RESULTS: It was revealed that PAB alone exhibited similar inhibitory activity against FLC-resistant and FLC-susceptible strains with median MIC ranging from 8 to 16 µg/mL. When administered in combination, synergism was observed in all (13/13) FLC-resistant and (2/9) FLC-susceptible strains with FICI ranging from 0.070 to 0.375. Moreover, the concomitant use of PAB and FLC exhibited a strong dose-dependent synergistic inhibitory effect on the early and mature biofilm, eliminating more than 80% biofilm formation. SEM found that PAB, different from azoles, could significantly inhibit spore germination and destroy the cell integrity causing cell deformation, swelling, collapse and outer membrane perforation. CONCLUSION: PAB was highly active against FLC-resistant isolates and biofilm of C. tropicalis, particularly when combined with FLC. These findings suggest that PAB may have potential as a novel antifungal agent with different targets from azole drugs.

Mechanisms of azole resistance in clinical isolates of Candida glabrata from two hospitals in China.

Purpose: Candida glabrata has emerged as the second or third most common non-albicans species responsible for an increasing number of systemic infections. Moreover, its high-level of resistance to azole is associated with a high mortality rate. This study aimed to evaluate nosocomial infections and resistance characteristics of C. glabrata and to explore the mechanism of azole resistance in C. glabrata. Patients and methods: Fifty-nine clinical C. glabrata isolates were collected from two hospitals in China. The susceptibility of the strains to antifungal agents was determined by both the ATB Fungus 3 strip and CLSI M27 broth microdilution method. Efflux of rhodamine 6G was examined to evaluate the effects of efflux pumps. The expression levels of CgCDR1, CgCDR2, CgSNQ2, CgERG11, and CgPDR1 were examined by real-time PCR. The sequences of CgERG11 and CgPDR1 were determined by PCR-based DNA sequencing. Results: All 59 isolates of C. glabrata were susceptible to flucytosine and amphotericin B. Twelve (20.3%) isolates were determined to be fluconazole-resistant, whereas 13 (22.0%) and 27 (45.7%) isolates were categorized as non-wild-type for itraconazole and voriconazole, respectively. Efflux pumps in azole-resistant isolates showed stronger effects than those in azole-susceptible-dose dependent isolates, which is consistent with the significant upregulation of CgCDR1 and CgCDR2 (P<0.05), whereas no obvious differences were found for CgSNQ2, CgERG11, and CgPDR1 (P>0.05). Sequencing of CgERG11 showed no alteration favoring the hypothesis that CgERG11 is not involved in the azole resistance of C. glabrata. Four CgPDR1 missense mutations were found in azole-resistant isolates, of which the high frequency of the CgPDR1 mutation, A848V, has not been reported previously. Conclusion: Efflux pump function is the main mechanism of resistance to fluconazole in our collected clinical isolates of C. glabrata, and further studies of the related gene disruption and genome-wide expression are needed to verify the function.

Infective endocarditis with antineutrophil cytoplasmic antibody: report of 13 cases and literature review.

OBJECTIVE: Chronic infections tend to induce the production of antineutrophil cytoplasmic antibody (ANCA). Infective endocarditis (IE) has been reported to exhibit positive ANCA tests and to mimic ANCA-associated vasculitis, which may lead to a misdiagnosis and inappropriate treatment. The aim of this study was to clarify whether there is any difference in the clinical features between ANCA-positive IE and ANCA-negative IE. METHODS: A retrospective study was carried out on 39 IE patients whose proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA levels were measured. After dividing the patients into ANCA-positive and ANCA-negative IE, we compared their clinical features. RESULTS: we compared 13 ANCA-positive IE patients with 26 ANCA-negative IE patients. All 13 ANCA-positive IE patients were proteinase-3-ANCA positive. Compared with the ANCA-negative IE group, the prevalence of edema of the lower extremities, the serum lactate dehydrogenase (LDH) level and positive blood cultures rate were higher in ANCA-positive IE group, but there was no significant difference in other clinical features. CONCLUSION: Therefore, if a patient presents with fever, arthralgia, skin rash and is ANCA-positive, appropriate steps should be taken to exclude infection (especially IE) before confirming the diagnosis of ANCA-associated vasculitis and embarking on long-term immunosuppressive therapy.