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There is a consensus that maintenance therapy should be used to prevent relapse of myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (MPO-AAV), but there is a debate about the optimal duration of maintenance therapy. Therefore, the purpose of this study was to determine whether discontinuation of maintenance therapy in MPO-AAV patients who were in long-term stable remission affects relapse, renal survival and patient survival. Seventy-nine patients with MPO-AAV diagnosed at Xiangya hospital from June 2010 to June 2019 who were in stable remission for at least 18 months following maintenance therapy were included. Patient records were retrospectively reviewed, and based on whether patients discontinued maintenance therapy 18 months after commencing maintenance therapy, patients were assigned into either the withdrawal group (n = 26) or maintenance group (n = 53). The endpoint was the percentage of relapse, relapse-free survival, renal survival and patient survival during follow-up. Ten relapses (38.5%) occurred in the withdrawal group (n = 26) and 8 relapses (15.1%) occurred in the maintenance group (n = 53) (p = 0.020). Compared to the withdrawal group, the maintenance group had similar relapse-free survival (log-rank test p = 0.099). But maintenance group had a better renal survival (p = 0.035), with no difference in patient survival or adverse events. This study suggests that discontinuing maintenance therapy at 18 months following induction of sustained remission leads to a significant increase in the percentage of relapse, and decreases renal survival in patients with MPO-AAV, but does not decrease relapse-free survival or patient survival. [ABSTRACT FROM AUTHOR]

Background: Evidence exists that maternal zinc status during pregnancy is linked to adverse pregnancy outcomes including abortion, fetal growth restriction, and neural tube defects. However, it remains unclear whether maternal serum zinc concentration (SZC) during pregnancy is associated with risk of preterm birth.Objective: This study was designed to investigate the association between maternal SZC during pregnancy and risk of preterm birth.Methods: For this substudy of the China-Anhui Birth Cohort Study, 3081 maternal-singleton pairs with detailed birth records and available serum samples were identified. The maternal SZC was determined with flame atomic absorption spectroscopy. A total of 169 preterm births were identified. In this study, the women were divided into tertiles on the basis of their SZC: low (<76.7 μg/dL), medium (76.7-99.6 μg/dL), and high (≥99.7 μg/dL). The ORs for preterm birth were estimated by using multiple logistic regression models.Results: The median SZC was 87.3 μg/dL (range: 11.1-211 μg/dL). Incidences of preterm birth were 7.3% and 6.0% among subjects with low and medium SZCs, respectively, which were significantly higher than 3.1% among subjects with a high SZC [ORs (95% CIs) for low and medium SZCs: 2.45 (1.60, 3.74), P < 0.001, and 2.00 (1.29, 3.09), P < 0.01, respectively]. After adjustment for prepregnancy body mass index, maternal age, time of serum collection, gravidity, parity, and monthly income, adjusted ORs were 2.41 (95% CI: 1.57, 3.70; P < 0.001) and 1.97 (95% CI: 1.27, 3.05; P < 0.01) among subjects with low and medium maternal SZCs.Conclusions: Maternal serum zinc concentration during pregnancy is inversely associated with risk of preterm birth in the Chinese population, and the results are driven by maternal SZC in the first trimester. [ABSTRACT FROM AUTHOR]

Objectives Higher or lower blood pressure may relate to cognitive impairment, whereas the relationship between blood pressure and cognitive impairment among the elderly is not well-studied. The study objective was to determine whether blood pressure is associated with cognitive impairment in the elderly, and, if so, to accurately describe the association. Design Cross-sectional data from the sixth wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) conducted in 2011. Setting Community-based setting in longevity areas in China. Participants A total of 7144 Chinese elderly aged 65 years and older were included in the sample. Measures Systolic blood pressures (SBP) and diastolic blood pressures (DBP) were measured, pulse pressure (PP) was calculated as (SBP) − (DBP) and mean arterial pressures (MAP) was calculated as 1/3(SBP) + 2/3(DBP). Cognitive function was assessed via a validated Mini-Mental State Examination (MMSE). Results Based on the results of generalized additive models (GAMs), U-shaped associations were identified between cognitive impairment and SBP, DBP, PP, and MAP. The cutpoints at which risk for cognitive impairment (MMSE <24) was minimized were determined by quadratic models as 141 mm Hg, 85 mm Hg, 62 mm Hg, and 103 mm Hg, respectively. In the logistic models, U-shaped associations remained for SBP, DBP, and MAP but not PP. Below the identified cutpoints, each 1-mm Hg decrease in blood pressure corresponded to 0.7%, 1.1%, and 1.1% greater risk in the risk of cognitive impairment, respectively. Above the cutpoints, each 1-mm Hg increase in blood pressure corresponded to 1.2%, 1.8%, and 2.1% greater risk of cognitive impairment for SBP, DBP, and MAP, respectively. Conclusion A U-shaped association between blood pressure and cognitive function in an elderly Chinese population was found. Recognition of these instances is important in identifying the high-risk population for cognitive impairment and to individualize blood pressure management for cognitive impairment prevention. [ABSTRACT FROM AUTHOR]

Abstract Arsenic is an environmental toxicant. The association of gestational arsenic exposure with adverse pregnant outcomes remains controversial. This study was to investigate the association of serum As level with adverse pregnant outcomes in a large Chinese cohort population. Total 3194 mother-and-infant pairs were recruited from the China-Anhui Birth Cohort Study. Maternal serum arsenic (As) concentration was measured using hydride generation-atomic fluorescence spectrometry. Subjects were divided into L-As group and H-As group in accordance to the 75th percentile of serum As concentration. The associations of serum As level during gestation with adverse pregnant outcomes were analyzed. The incidence of small-for-gestational-age (SGA) newborns was elevated in H-As group compared to L-As group (9.9% vs 7.6%, P =.044). After controlling confounders and stratified analysis, the adjusted OR for SGA was significant only in girls with H-As but not in boys. Moreover, the incidence of preterm delivery (PTD) was elevated in H-As group compared to L-As group (7.0% vs 4.8%, P =.016). Further analysis found that the adjusted OR for moderate-to-late PTD was 1.47 (95%CI: 1.03, 2.09; P =.034) in H-As group as compared with L-As group. These results indicate that maternal serum As level during gestation is positively associated with adverse pregnant outcomes. Graphical abstract Unlabelled Image Highlights • Maternal As exposure during pregnancy elevates the risks of SGA infants and preterm birth. • Maternal As exposure during pregnancy only elevates the risks of SGA girls, but not boys. • Maternal As exposure elevates the risks of moderate-to-late preterm birth. [ABSTRACT FROM AUTHOR]

Abstract: Osteopetrosis is a rare genetically heterogeneous disorder of bone metabolism characterized by increased skeleton density. In the past, standard methods for genetic diagnosis of osteopetrosis have primarily been performed by candidate gene screening and positional cloning. However, these methods are time and labor consumptive; and the genetic basis of approximately 30% of the cases is yet to be elucidated. Here, we employed whole exome sequencing of two affected individuals from an osteopetrosis family to identify a candidate mutation in CLCN7 (Y99C). It was identified from a total of 1757 and 1728 genetic variations found in either patient, which were then distilled using filtering strategies and confirmed using Sanger sequencing. We identified this mutation in six family members, while not in population matched controls. This mutation was previously found in osteopetrosis patients by other researchers. Our evolutionary analysis also indicated that it is under extremely high selective pressure, and is likely to be critical for the correct function of ClC-7, and thus is likely to be the responsible cause of disease. Collectively, our data further indicated that mutation (Y99C) may be a cause of osteopetrosis, and highlights the use of whole exome sequencing as a valuable approach to identifying disease mutations in a cost and time efficient manner. [Copyright &y& Elsevier]

Thallium (Tl), a ubiquitous environmental toxicant, can cross the placental barrier during pregnancy. However, the effects of prenatal Tl exposure on placental function are currently unclear. Based on the Ma'anshan Birth Cohort study, we examined whether long-term prenatal Tl exposure was associated with placental inflammation. Tl concentrations were quantified in serum samples (n = 7050) from 2515 pregnancy during each trimester, placental inflammatory cytokine mRNA expression was assessed in 2519 placenta tissues. Geometric mean values of serum Tl concentrations were 63.57, 63.63 and 48.71 ng/L for the first, second and third trimesters, respectively. After adjustment for potential confounders, serum Tl concentration was positively associated with CD68 (β: 0.30; 95% CI: 0.05, 0.56) in the first trimester and TNF-α (β: 0.12; 95% CI: 0.01, 0.23), IL-6 (β: 0.15; 95% CI: 0.05, 0.25) and CD68 (β: 0.25; 95% CI: 0.10, 0.39) in the third trimester, however was negatively associated with IL-4 (β: −0.21; 95% CI: −0.41, −0.01) and CD206 (β: −0.23; 95% CI: −0.45, −0.02) in the first trimester. Repeated measures analysis showed that TNF-α, IL-6 and CD68 increased by 0.11 (95% CI: 0.01, 0.21), 0.12 (0.15, 95% CI: 0.05, 0.25), 0.22 (95% CI: 0.10, 0.39), respectively, with each 1ln-transformed Tl increase in total samples. Gender-specific analyses revealed that these associations were largely driven by male offspring. In addition, immunohistochemistry revealed that nuclear NF-κB p65 expression increased in placenta tissue. The results of this prospective cohort study provide longitudinal evidence that prenatal Tl exposure induces a placental inflammatory response in the Chinese population. Image 1 • We measured 11 inflammatory cytokine mRNAs expression to observe local immune activation in the placenta. • Elevated Tl concentrations were associated with increased placental TNF-α, IL6 and CD68 mRNA expression in longitudinal analysis. • Our findings suggest that prenatal Tl exposure may induce the placenta inflammation response via NF-κB activation. [ABSTRACT FROM AUTHOR]