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Accumulating studies have been focused on the independent effects of air pollutants and ambient heat exposure on congenital heart defects (CHDs) but with inconsistent results, and their interactive effect remains unclear. A case-control study including 921 cases and 9210 controls was conducted in Changsha, China in warm season in 2015–2018. The gravidas were assigned monthly averages of daily air pollutants and daily maximum temperature using the nearest monitoring station method and city-wide average method, respectively, during the first trimester of pregnancy. Multivariate logistic regression models were used to estimate the independent effects of each air pollutant and different ambient heat exposure indicators. Their additive joint effects were quantified using attribute proportions of interaction (API). Increasing SO2 consistently increased the risk of CHDs in the first trimester of pregnancy, with aORs ranging from 1.78 to 2.04. CO, NO2 and PM2.5 exposure in the first month of pregnancy, and O3 exposure in the second and third month of pregnancy were also associated with elevated risks of CHDs, with aORs ranging from 1.04 to 1.15. Depending on the ambient heat exposure indicator used, air pollutants showed more apparent synergistic effects (API > 0) with less and moderately intense heat exposure. Maternal exposure to CO, NO2, SO2, PM2.5 and O3 during early pregnancy increased risk of CHDs, and ambient heat exposure may enhance these effects. Our findings help to understand the interactive effect of air pollution with ambient heat exposure on CHDs, which is of vital public health significance.

STUDY QUESTION Can meteorological conditions modify the associations between NO2 and SO2 exposure and congenital limb defects (CLDs) during the first trimester of pregnancy? SUMMARY ANSWER Increases in NO2 and SO2 exposure were consistently associated with higher risks of CLDs during the first trimester of pregnancy; both low- and high-temperature exposure and high air humidity act synergistically with the two air pollutants on CLDs. WHAT IS KNOWN ALREADY Animal studies have indicated air pollutants are associated with CLDs, but corresponding epidemiological studies are limited with equivocal conclusions. Meteorological conditions are closely connected to the generation, diffusion, distribution and even chemical toxicity of air pollutants. STUDY DESIGN, SIZE, DURATION This case–control study included 972 cases of CLDs and 9720 controls in Changsha, China during 2015–2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Cases from the hospital based monitoring system for birth defects (including polydactyly, syndactyly, limb shortening, and clubfoot) and healthy controls from the electronic medical records system were studied. Complete data on daily average NO2 and SO2 concentrations and meteorological variables were obtained from local monitoring stations to estimate monthly individual exposures during the first trimester of pregnancy, using the nearest monitoring station approach for NO2 and SO2 concentrations, and the city-wide average approach for temperature and relative humidity, respectively. The 25th and 75th percentiles of daily mean temperature, as well as the 50th percentile of daily mean relative humidity during the study period were used to classify high- and low-temperature exposure, and high humidity exposure based on existing evidence and local climate characteristics. Multivariate logistic regression models were used to estimate the independent effects per 10 μg/m3 increase in NO2 and SO2 on CLDs, and the attribute proportions of interaction (API) were used to quantify the additive joint effects of air pollutants with meteorological conditions after including a cross product interaction term in the regression models. MAIN RESULTS AND THE ROLE OF CHANCE NO2 and SO2 exposures during the first trimester of pregnancy were consistently and positively associated with overall CLDs and subtypes, with adjusted odd ratios (aORs) ranging from 1.13 to 1.27 for NO2, and from 1.37 to 2.49 for SO2. The effect estimates were generally observed to be the strongest in the first month and then attenuated in the second and third months of pregnancy. Synergistic effects of both low and high temperature in combination with NO2 (with APIs ranging from 0.07 to 0.38) and SO2 (with APIs ranging from 0.18 to 0.51) appeared in the first trimester of pregnancy. Several significant modifying effects by high humidity were also observed, especially for SO2 (with APIs ranging from 0.13 to 0.38). Neither NO2 nor SO2 showed an interactive effect with season of conception. LIMITATIONS, REASONS FOR CAUTION The methods used to estimate individual exposure levels of air pollutants and meteorological factors may lead to the misclassification bias because of the lack of information on maternal activity patterns and residential mobility during pregnancy. Moreover, we were unable to consider several potentially confounding factors, including socioeconomic status, maternal nutrient levels, alcohol use and smoking during early pregnancy due to unavailable data, although previous studies have suggested limited change to the results after when including these factors in the analysis. WIDER IMPLICATIONS OF THE FINDINGS The findings are helpful for understanding the combined effects of air pollution and meteorological conditions on birth defects. Environmental policies and practices should be formulated and implemented to decrease air pollutant emissions and improve meteorological conditions to reduce their harmful effects on pregnancy. Additionally, pregnant women should be suggested to reduce outdoor time when the air quality is poor, especially when ambient temperature is higher or lower than what is comfortable, or when it is excessively humid. STUDY FUNDING/COMPETING INTEREST(S) The study is funded by Major Scientific and Technological Projects for Collaborative Prevention and Control of Birth Defects in Hunan Province (2019SK1012), Major Research and Development Projects in Hunan Province (2018SK2060) and Scientific and Technological Department Projects in Hunan Province (2017SK50802). There are no competing interests. TRIAL REGISTRATION NUMBER N/A.

Background A growing body of studies have investigated the association between air pollution exposure during early pregnancy and the risk of orofacial clefts, but these studies put more emphasis on particulate matter and reported inconsistent results, while research on the independent effects of gaseous air pollutants on orofacial clefts has been quite inadequate, especially in China. Methods A case–control study was conducted in Changsha, China from 2015 to 2018. A total of 446 cases and 4460 controls were included in the study. Daily concentrations of CO, NO2, SO2, O3, PM2.5 and PM10 during the first trimester of pregnancy were assigned to each subject using the nearest monitoring station method. Multivariate logistic regression models were applied to evaluate the associations of monthly average exposure to gaseous air pollutants with orofacial clefts and its subtypes before and after adjusting for particulate matter. Variance inflation factors (VIFs) were used to determine if the effects of gaseous air pollutants could be independent of particulate matter. Results Increase in CO, NO2 and SO2 significantly increased the risk of cleft lip with or without cleft palate (CL/P) in all months during the first trimester of pregnancy, with aORs ranging from 1.39 to 1.48, from 1.35 to 1.61 and from 1.22 to 1.35, respectively. The risk of cleft palate only (CPO) increased with increasing NO2 exposure levels in the first trimester of pregnancy, with aORs ranging from 1.60 to 1.66. These effects sustained and even exacerbated after adjusting for particulate matter. No significant effect of O3 was observed. Conclusions Our study suggested that maternal exposure to CO, NO2, and SO2 during the first trimester of pregnancy might contribute to the development of orofacial clefts, and the associations were potentially independent of particulate matter.

The signal-induced proliferation-associated 1-like 3 (SIPA1L3) gene that encodes a putative Rap GTPase-activating protein (RapGAP) has been associated with congenital cataract and eye development abnormalities. However, our current understanding of the mutation spectrum of SIPA1L3 associated with eye defects is limited. By using whole-exome sequencing plus Sanger sequencing validation, we identified a novel heterozygous c.1871A > G (p.Lys624Arg) variation within the predicted RapGAP domain of SIPA1L3 in the proband with isolated juvenile-onset cataracts from a three-generation Chinese family. In this family, the proband's father and grandmother were also heterozygous for the c.1871A > G variation and affected by cataracts varying in morphology, severity, and age of onset. Sequence alignment shows that the Lys 624 residue of SIPA1L3 is conserved across the species. Based on the resolved structure of Rap1–Rap1GAP complex, homology modeling implies that the Lys 624 residue is structurally homologous to the Lys 194 of Rap1GAP, a highly conserved lysine residue that is involved in the interface between Rap1 and Rap1GAP and critical for the affinity to Rap·GTP. We reasoned that arginine substitution of lysine 624 might have an impact on the SIPA1L3-Rap·GTP interaction, thereby affecting the regulatory function of SIPA1L3 on Rap signaling. Collectively, our finding expands the mutation spectrum of SIPA1L3 and provides new clues to the molecular mechanisms of SIPA1L3-related cataracts. Further investigations are warranted to validate the functional alteration of the p.Lys624Arg variant of SIPA1L3.

Cornelia de Lange syndrome (CdLS) is a genetic disorder characterized by multisystemic malformations. Mutation in the NIPBL gene accounts for nearly 60% of the cases. This study reports the clinical and genetic findings of three cases of CdLS from unrelated Chinese families. Clinically, all the three cases were classified as classic CdLS based on the cardinal (distinctive facial features and limb malformations) and suggestive (developmental delay, growth retardation, microcephaly, hirsutism, etc.) manifestations. SNP array detected a novel de novo heterozygous microdeletion of 0.2 Mb [arr[GRCh37]5p13.2(36848530_37052821) × 1] that spans the first 43 exons of NIPBL in the fetus with nuchal translucency thickening in case 1. Whole-exome sequencing in family trios plus Sanger sequencing validation identified a de novo heterozygous NIPBL c.5566G>A (p.R1856G) mutation in the fetus with intrauterine growth retardation in case 2 and a novel de novo heterozygous NIPBL c.448dupA (p.S150Kfs*23) mutation in the proband (an 8-month-old girl) in case 3. The cases presented in this study may serve as references for increasing our understanding of the mutation spectrum of NIPBL in association with CdLS.

Background Fragile X syndrome (FXS) is the most common inherited form of intellectual disability. Prenatal screening of FXS allows for early identification and intervention. The present study explored the feasibility of FXS carrier screening during prenatal diagnosis for those who were not offered screening early in pregnancy or prior to conception. Methods Pregnant women to be offered amniotic fluid testing were recruited for the free voluntary carrier screening at a single center between August, 2017 and September, 2019. The number of CGG repeats in the 5’ un‐translated region of the fragile X mental retardation gene 1 (FMR1) was determined. Results 4286 of 7000 (61.2%) pregnant women volunteered for the screening. Forty (0.93%), five (0.11%), and three (0.07%) carriers for intermediate mutation (45–54 repeats), premutation (55–200 repeats) and full mutation (>200 repeats) of the FMR1 gene were identified respectively. None of the detected premutation alleles were inherited by the fetuses. Of the three full mutation carrier mothers, all had a family history and one transmitted a full mutation allele to her male fetus. Conclusion Implementation of FXS carrier screening during prenatal diagnosis may be considered for the need to increase screening for FXS., The present study explored the feasibility of FXS carrier screening during prenatal diagnosis for those who were not offered screening early in pregnancy or prior to conception. Implementation of FXS carrier screening during prenatal diagnosis may be considered for the need to increase screening for FXS.

Atopic dermatitis (AD) is a chronic inflammatory skin disease common among infants and children. It is associated with a high risk of allergies, asthma, and mental health problems. Attempts have been made to use probiotics in clinical interventions for AD.Our objective was to perform an updated meta-analysis of recently published studies to evaluate the effect of probiotics in the prevention and treatment of AD in children and to further understand the role of probiotics in AD interventions in the clinic.We searched the PubMed/MEDLINE, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang databases with prespecified selection criteria from inception of each database to 11 January 2020. No language restrictions were applied.A total of 25 studies were included in our meta-analysis. Of these, 14 were prevention studies (with 3049 children enrolled) and 11 were treatment studies (with 816 children enrolled). One treatment study was excluded after the sensitivity analysis. From the 14 prevention studies included, the pooled relative risk ratio of AD in those treated with probiotics versus placebo was 0.70 [95% confidence interval (CI) 0.57-0.84; P = 0.0002]. Subgroup analyses showed that only mixed strains of probiotics had a significant effect on lowering the incidence of AD. Probiotics administered solely to infants did not prevent the development of AD, but effects were significant when probiotics were administered to both pregnant mothers and their infants or solely to pregnant mothers. In studies with treatment durations 6 months, the incidence of AD decreased significantly; a similar effect was achieved when the treatment duration was 6 months. Meta-analysis of the ten treatment studies showed a significant decrease in the weighted mean difference (WMD) in Scoring Atopic Dermatitis (SCORAD) index values in the probiotics group compared with the control group (WMD, - 7.23; 95% CI - 10.59 to - 3.88; P 0.0001). Subgroup analyses showed that both single-strain and mixed-strain probiotics had a significant effect on improving SCORAD values. Studies with participants aged 1 year (P = 0.07) reported no significant results. In studies with treatment periods 8 weeks, SCORAD values seemed to decrease more than in studies with treatment periods 8 weeks. However, the subgroup difference was only statistically significant when the analysis was performed according to participant age in prevention studies.Our updated meta-analysis demonstrates that interventions with probiotics potentially lower the incidence of AD and relieve AD symptoms in children, particularly when treating infants and children aged ≥ 1 year with AD. Interventions with mixed-strain probiotics tended to have better preventive and curative effects. Probiotics administered solely to infants appeared to produce negative preventive effects. Different intervention durations might also affect clinical outcomes. However, given the insignificant subgroup differences, except for treatment by participant age, and the moderate heterogeneity among the studies, these conclusions should be interpreted with caution, and more powerful randomized controlled trials using standardized measurements should be conducted to assess the long-term effects of probiotics.

The effects of ultra-high temperature (UHT) (140 °C, 10 s) and packages on quality and shelf life of baked purple sweet potato nectar (BPSPN) were evaluated in this study. UHT did not change pH, titratable acidity (TA), centrifugal sediment ratio, viscosity, lightness, redness, particle size distribution (PSD) character of D(4,3), reducing sugar, total phenols and antioxidant capacity, but lightly reduced browning degree, ascorbic acid and total anthocyanins while increased PSD character of D(3,2). UHT treatment succeed in assuring the microbial safety at 4 °C for 28 days, total aerobic bacteria in different packing materials did not shown statistical tendency (P

// Gang Tang 1, 2 , Yunpeng Zhen 1, 2 , Wanqin Xie 3 , Yinlei Wang 1, 2 , Feiran Chen 1, 2 , Chuan Qin 1, 2 , Han Yang 1, 2 , Zhiyong Du 1, 2 , Zhonghua Shen 1, 2 , Bo Zhang 1, 2 , Zhouliang Wu 1, 2 , Dawei Tian 1, 2 and Hailong Hu 1, 2 1 Department of Urology, The Second Hospital of Tianjin Medical University, Hexi District, Tianjin 300211, China 2 Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China 3 Key Laboratory of Genetics and Birth Health of Hunan Province, The Family Planning Research Institute of Hunan Province, Changsha, Hunan 410126, China Correspondence to: Dawei Tian, email: jianshi001@126.com Hailong Hu, email: hhllove2004@163.com Keywords: HPR; T1G3 bladder cancer; PFS; OS; CSS Received: June 28, 2016 Accepted: November 12, 2017 Epub: January 03, 2018 Published: April 06, 2018 ABSTRACT Objective: To investigate the prognostic role of hematological biomarkers, especially hemoglobin-platelet ratio (HPR) in the oncological outcomes in stage 1 and grade 3 (T1G3) bladder cancer. Materials and Methods: We identified 457 T1G3 bladder cancer patients who underwent transurethral resection of the bladder (TURB) between 2009 and 2014. Based on hematological parameters (hemoglobin-platelet ratio (HPR), hemoglobin, and platelet counts), recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) and cancer-specific survival (CSS) were analyzed by using Kaplan-Meier analysis. Multivariate Cox regression model was adopted to identify the predictors of oncological outcomes. Results: Kaplan-Meier survival analysis showed that low HPR ( 240 x 10 3 /μl) were correlated with poor OS. Low HPR, but not low hemoglobin and high platelet counts, is associated with worse PFS. Low HPR and low hemoglobin, but not elevated platelet counts, are associated with worse CSS. However, no significant difference was observed in RFS according to any of these hematological markers. On multivariate analysis, low HPR (HR = 1.27, 95% CI = 0.81–1.75, P = 0.030), low hemoglobin (HR = 1.20, 95% CI = 0.79–1.84, P = 0.028) and elevated platelet counts (HR = 1.07, 95% CI = 0.72–1.32, P = 0.038) were significantly associated with OS. Low hemoglobin (HR = 1.08, 95% CI = 0.68–1.82, P = 0.041) was significantly linked with CSS. Particularly, low HPR was identified as an independent predictor of PFS (HR = 1.16, 95% CI = 0.97–1.49, P = 0.033) and CSS (HR = 1.14, 95% CI = 0.87–1.78, P = 0.029). Conclusions: Preoperative HPR can be taken into account as a factor predictive of oncological outcomes for T1G3 bladder cancer, particularly disease progression and mortality outcomes.

Key Clinical Message We report two heterozygous carriers of c.464A>G variation in the GJB2 gene in a Chinese pedigree. The proband with hearing loss most likely inherited the c.464A>G variation from his mother who also carries heterozygous c.79G>A variation and has normal hearing. The pathological significance of c.464A>G variation remains to be determined.

Angiogenesis is important in the development of solid tumors. Vasohibin-1 (VASH-1) is an endothelium-derived protein that acts as an inhibitor of angiogenesis in many different types of cancer. However, the expression of VASH-1 and its clinical value in bladder cancer remain unknown. The current study analyzed the expression of VASH-1, as well as the expression of the angiogenesis-related factors vascular endothelial growth factor-A, hypoxia inducible factor-1α and cluster of differentiation 34 in bladder cancer tissues from 50 patients using immunohistochemistry. The associations between the expression of these factors and the clinicopathological characteristics of the patients were assessed. The current study demonstrated that VASH-1 is primarily expressed in the cytoplasm of bladder cancer cells and in a fraction of vascular endothelial cells. Furthermore, the expression of VASH-1 was positively associated with the tumor stage (P0.05). Spearman rank correlation tests indicated that levels of those four factors were positively correlated with each other. Kaplan-Meier analysis indicated that high expression of these four factors was significantly associated with lower 5-year overall survival and progression-free survival rates. Collectively, the results of the current study suggest that VASH-1 is clinically significant in bladder cancer and its high expression may predict the progression and prognosis of patients with bladder cancer. The present study also implies that VASH-1 may be a novel target for vascular targeting therapy.

Objective Anti–citrullinated protein antibodies (ACPAs) are highly specific for rheumatoid arthritis (RA). However, the molecular basis for ACPA production is still unclear. The purpose of this study was to determine if circulating plasmablasts from RA patients produce ACPAs and whether Porphyromonas gingivalis facilitates the generation of ACPAs. Methods Using a single-cell antibody cloning approach, we generated 217 and 110 monoclonal recombinant antibodies from circulating plasmablasts from 7 RA patients and 4 healthy controls, respectively. Antibody reactivity with citrullinated antigens was tested by a second-generation anti–cyclic citrullinated peptide (anti-CCP) kit and by enzyme-linked immunosorbent assays (ELISAs) against citrullinated human antigens. Antibody reactivity with P gingivalis was tested by ELISAs against outer membrane antigens (OMAs) and citrullinated enolase from P gingivalis. Results Approximately 19.5% of plasmablast-derived antibodies from anti-CCP–positive RA patients, but none from 1 anti-CCP–negative RA patient or the healthy controls, specifically recognized citrullinated antigens. The immunoglobulin genes encoding these ACPAs were highly mutated, with increased ratios of replacement mutations to silent mutations, suggesting the involvement of active antigen selection in ACPA generation. Interestingly, 63% of the ACPAs cross-reacted with OMAs and/or citrullinated enolase from P gingivalis. The reactivity of ACPAs against citrullinated proteins from P gingivalis was confirmed by immunoblotting and mass spectrometry. Furthermore, some germline-reverted ACPAs retained their reactivity with P gingivalis antigens but completely lost their reactivity with citrullinated human antigens. Conclusion These results suggest that circulating plasmablasts in RA patients produce ACPAs and that this process may be facilitated by anti–P gingivalis immune responses.

Tongue squamous cell carcinoma (TSCC) is the most common type of oral carcinoma. Mitochondrial DNA (mtDNA) is a circular DNA molecule of 16,569 bp, which functionally encompasses a regulatory non-coding region (D-loop) and 37 encoding genes that correspond to 13 subunits of respiratory chain complexes (I, III, IV and V), 22 transfer RNAs and 2 ribosomal (r)RNAs. Recently, mtDNA has been implicated as a mutation hotspot in various tumors. However, to our knowledge mtDNA alteration in TSCC has not been investigated to date. In the present study, the mitochondrial genomes of tongue carcinoma, adjacent non-cancerous tissue and peripheral blood samples from 8 patients with TSCC were sequenced and aligned with the revised Cambridge Reference Sequence. Overall, only one synonymous mutation, which mapped to the NADH:ubiquinone oxidoreductase core subunit 5 gene, was observed in the tongue carcinoma sample from a single patient. A further 21 polymorphisms were identified, including six in the non-coding region (D-loop), five in Complex I, three in Complex III, two in Complex IV, two in Complex V and three in rRNA. In addition, mitochondrial microsatellite instability (mtMSI) was detected in 2/8 tongue carcinoma samples, and localized in the D310 region. These variations, particularly the polymorphisms and mtMSI, imply that the mitochondrial genome may be a hotspot of genome alteration in tongue cancer. Further investigation is expected to reveal the role of mtDNA alteration in TSCC development, as well as its clinical implications.

Circular RNAs (circRNAs) as a family of non-coding RNAs are increasingly recognized regarding their biogenesis, regulatory roles in gene expression and clinic significance in developmental diseases and cancers. In this study, we aim to identify circRNAs that may be associated with clinicopathological characteristics of patients with bladder cancer. The circRNAs databases CircBase and circ2 Traits were used to seek circRNAs reported to bladder cancer. The expression levels of the circRNA of interest in paired samples of tumor tissue and adjacent normal mucosa from 61 patients with bladder cancer were detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and statistically analyzed. Database search shows that circASXL1 (circBase ID: hsa_circ_0001136) transcribed from the ASXL1 gene locus is among the circRNAs with altered expressions in bladder cancer. Results showed that the expression level of circASXL1 was significantly higher in bladder cancer tissues compared to that in adjacent noncancerous tissues (P

Genome-wide association studies (GWAS) have identified a number of genetic variants associated with risk of bladder cancer in populations of European descent. Here, we assessed association of two of these variants, rs11892031 (2q37.1 region) and rs401681 (5p15.33 region) in a Chinese case-control study, which included 367 bladder cancer cases and 420 controls. We found that the AC genotype of rs11892031 was associated with remarkably decreased risk of bladder cancer (adjusted odds ratio (OR), 0.27, 95% confidence interval (CI), 0.09–0.81, p = 0.019), compared with the AA genotype of rs11892031, and that CT/CC genotypes of rs401681 were associated with significantly increased risk of bladder cancer (adjusted OR, 1.79, 95% CI, 1.10–2.91, p = 0.02), compared with the TT genotype of rs401681. We further conducted stratification analysis to examine the correlation between single nucleotide polymorphism (SNP) rs11892031/rs401681 and tumor grade/stage. Results showed that heterogeneity in ORs of tumor categories was not significant for either rs11892031 or rs401681 (p &gt, 0.05), indicating that the two SNPs seemingly do not associate with tumor grade and stage of bladder cancer in our study population. The present study suggests that the SNPs rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population. Future analyses will be conducted with more participants recruited in a case-control study.

It has been recognized for a long time that engagement of B cell antigen receptors (BCRs) on immature B cells or mature B cells leads to completely opposite cell fate decisions. The underlying mechanism remains unclear. Here, we show that crosslinking of BCRs on human EU12μHC+immature B cells resulted in complete internalization of cell surface BCRs. After loss of cell surface BCRs, restimulation of EU12μHC+cells showed impaired Ca2+flux, delayed SYK phosphorylation, and decreased CD19 and FOXO1 phosphorylation, which differ from those in mature Daudi or Ramos B cells with partial internalization of BCRs. In contrast, sustained phosphorylation and reactivation of ERK upon restimulation were observed in the EU12μHC+cells after BCR internalization. Taken together, these results show that complete internalization of cell surface BCRs in EU12μHC+cells specifically alters the downstream signaling events, which may favor receptor editing versus cell activation.

Background Robot-assisted partial nephrectomy (RAPN) has been widely used worldwide, to determine whether RAPN is a safe and effective alternative to open partial nephrectomy (OPN) via the comparison of RANP and OPN. Methods A comprehensive literature search was performed within the databases including PubMed, Cochrane Library, and Embase updated on 30 September 2015. Summary data with their corresponding 95 % confidence intervals (CIs) were calculated using a random effects or fixed effects model. Heterogeneity and publication bias were also evaluated. Results A total of 16 comparative studies including 3024 cases were used for this meta-analysis. There are no significant differences in the demographic characteristic between the two groups, but the age was lower and the tumor size was smaller for the RAPN group. RAPN had a longer operative time and warm ischemia time but which showed less estimated blood loss, hospital stay, and perioperative complications. No differences existed in the margin status, the change of glomerular filtration rate, transfusion rate, and conversion rate between the two groups. There was no significant publication bias. Conclusions RAPN offered a lower rate of perioperative complications, less estimated blood loss, and shorter length of hospital stay than OPN, suggesting that RAPN can be an effective alternative to OPN. Well-designed prospective randomized controlled trials will be helpful in validating our findings.

Lipid transfer proteins in plants are believed to be involved in many processes of cell physiology and development. In this work, a full-length cDNA encoding a novel lipid transfer protein, designated BcLTP was isolated from Brassica chinensis. At least two copies of BcLTP are present in whole genome of B. chinensis, and its transcripts preferably accumulate in second-year organs, implying its role in reproductive growth stage. The 118 amino acid sequence deduced from a 354 bp open reading frame (ORF) shares common features with other members of plants LTPs family. A putative signal peptide at the N terminus was tested for secretion function by the yeast signal sequence trap (YSST) system, and further confirmed by vesicular and extracellular localization of YFP fusion protein. A highly conserved CaM binding site at C terminus was found and the binding properties with two representative CaM isoforms, one is convergent AtCaM2, one is divergent SCaM5, were determined by gel overlay. We found that convergent AtCaM2 prefer high concentration of Ca(2+) for binding BcLTP, while SCaM5 does not depend on Ca(2+ )concentration too much for binding BcLTP. The lipid binding feature of BcLTP was demonstrated using florescence-marked 1-pyrenedodecanoic acid, which can be enhanced by AtCaM2 in Ca(2+ )dependent manner and by SCaM5 in either presence or absence of Ca(2+). The collected data suggest that BcLTP may secrete and combine extracellular CaM isoforms, which in turn, facilitate lipid binding of BcLTP via Ca(2+) mediated signaling.

Long noncoding RNAs (lncRNAs) have been implicated playing important roles in human urologic cancers. In the present study, microarray analysis was initially performed to screen the differentially expressed lncRNAs between bladder cancer tissues and paired adjacent non-cancerous tissues (n = 3). Subsequent qRT-PCR validation was conducted using tissue samples from 95 patients with bladder cancer. Results showed that the expression level of lncRNA-n336928 (noncode database ID: n336928) was significantly higher in bladder cancer tissues compared to that in adjacent noncancerous tissues (P

This study aimed to determine the molecular mechanism by which the oncogenic micoRNA-21 (miR-21) functions in bladder cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed that the expression of miR-21 considerably increased in primary cancer tissue compared with that in the paired adjacent noncancerous tissue and that in normal bladder mucosa. Knockdown of miR-21 by using antisense oligonucleotide significantly suppressed the proliferation and migration of bladder cancer cells (J82 and RT112). Mechanism studies showed that downregulation of miR-21 resulted in cell cycle arrest at the G1 phase and upregulation of the tumor suppressor PTEN (phosphatase and tensin homologue) and p53 phosphorylation at Ser46. The p53 phosphorylation at Ser15 and the whole level of p53 acetylation remained unchanged in response to miR-21 knockdown. MicroRNA-21 regulates proliferation and migration of bladder cancer cells and cross talk with PTEN and p53 in bladder cancer.

VH replacement provides a unique RAG-mediated recombination mechanism to edit nonfunctional IgH genes or IgH genes encoding self-reactive BCRs and contributes to the diversification of Ab repertoire in the mouse and human. Currently, it is not clear how VH replacement is regulated during early B lineage cell development. In this article, we show that cross-linking BCRs induces VH replacement in human EU12 μHC+ cells and in the newly emigrated immature B cells purified from peripheral blood of healthy donors or tonsillar samples. BCR signaling–induced VH replacement is dependent on the activation of Syk and Src kinases but is inhibited by CD19 costimulation, presumably through activation of the PI3K pathway. These results show that VH replacement is regulated by BCR-mediated signaling in human immature B cells, which can be modulated by physiological and pharmacological treatments.

Nan Sha,1,2,* Hao Xu,1,2,* Tao Chen,1,2,* Da-wei Tian,1,2 Wan-qin Xie,3 Lin-Guo Xie,1,2 Yu Zhang,1,2 Chen Xing,1,2 Xiao-teng Liu,1,2 Zhong-Hua Shen,1,2 Zhou-Liang Wu,1,2 Hai-Long Hu1,2 Chang-Li Wu1,2 1Department of Urology, The Second Hospital of Tianjin Medical University, 2Tianjin Key Laboratory of Urology, Tianjin Institute of Urology, Tianjin, 3Key Laboratory of Genetics and Birth Health of Hunan province, Family Planning Research Institute of Hunan Province, Changsha, Hunan, People’s Republic of China *These authors contributed equally tothis work Objective: The objective of this article was to summarize the relationship between some components of metabolic syndrome (MetS) and the histopathologic findings in bladder cancer in a Chinese population. Methods: We retrospectively analyzed data of 323 patients from the Department of Urology, Second Hospital of Tianjin Medical University between January 2012 and January 2014. All the patients were diagnosed with bladder cancer for the first time. Age, height, weight, histologic stage, grade, the presence of hypertension, diabetes mellitus, and body mass index were evaluated. The 2009 American Joint Committee on Cancer TNM staging system was used, with Ta and T1 tumors accepted as lower stage and T2, T3, and T4 tumors as higher stage bladder cancers. Also, pathologists assigned tumor grade according to the 1973 World Health Organization grading system. Noninvasive papillary urothelial neoplasms of low malignant potential were regarded as low grade. Analyses were completed using chi-square tests and logistic regression analysis. Results: Of the 323 patients, 164 had hypertension, 151 had diabetes mellitus, and 213 had a body mass index ≥25 kg/m2. MetS was significantly associated with histologic grade (P

Yu Zhang,1,* Linguo Xie,1,* Tao Chen,1,* Wanqin Xie,2 Zhouliang Wu,1 Hao Xu,1 Chen Xing,1 Nan Sha,1 Zhonghua Shen,1 Yunkai Qie,1 Xiaoteng Liu,1 Hailong Hu,1 Changli Wu1 1Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, 2Key Laboratory of Genetics and Birth Health of Hunan Province, The Family Planning Research Institute of Hunan Province, Changsha, People’s Republic of China *These authors contributed equally to this work Objective: The management of stage 1 and grade 3 (T1G3) bladder cancer continues to be controversial. Although the transurethral resection of bladder tumor (TURBT) followed by intravesical chemotherapy is a conservative strategy for treatment of T1G3 bladder cancer, a relatively high risk of tumor recurrence and progression remains regarding the therapy. This study aimed to compare the efficacy of intravenous chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder cancer after TURBT surgery. Methods: We retrospectively reviewed the cases of 457 patients who were newly diagnosed with T1G3 bladder urothelial carcinoma between January 2009 and March 2014. After TURBT, 281 patients received intravesical chemotherapy alone, whereas 176 patients underwent intravesical chemotherapy in combination with intravenous chemotherapy. Tumor recurrence and progression were monitored periodically by urine cytology and cystoscopy in follow-up. Recurrence-free survival and progression-free survival of the two chemotherapy strategies following TURBT were analyzed. Univariable and multivariable Cox hazards analyses were performed to predict the prognostic factors for tumor recurrence and progression. Results: The tumor recurrence rate was 36.7% for patients who received intravesical chemotherapy alone after TURBT, compared with 19.9% for patients who received intravenous chemotherapy combined with intravesical chemotherapy after TURBT (P

MicroRNAs are small non-coding RNAs of approximately 22 nucleotides in length, and play important regulatory roles in normal heart development and the pathogenesis of heart diseases. Recently, a few prospective studies have implicated the diagnostic role of microRNAs in congenital heart defects (CHD).This review retrieved the research articles in PubMed focusing on the altered microRNAs in cardiac tissue or serum of patients with CHD versus healthy normal controls, as well as the studies exploring circulating microRNAs as potential biomarkers for (fetal) CHD.Most of the studies of interest were conducted in recent years, implicating that the topic in this review is a newly emerging field and is drawing much attention. Moreover, a number of differentially expressed microRNAs between CHD specimens and normal controls have been reported.Circulating microRNAs may serve as potential biomarkers for diagnosis of CHD in the future, with more efforts paving the road to the aim.

Although plant non-specific lipid transfer proteins (ns-LTPs) are characterized by their ability to bind and transfer a broad range of hydrophobic ligands in vitro, their biological functions in vivo remain unclear. Recently, it has been proposed that ns-LTPs may play a key role in plant defense mechanisms, particularly during the induction of systemic acquired resistance, however, very little is known about the regulation in this process. We report that the binding of maize non-specific lipid transfer protein (Zm-LTP) to calmodulin (CaM) is in a calcium-independent manner. To better understand the interaction mechanism between Zm-LTP and CaM, the CaM-binding site of Zm-LTP was mapped to the region of amino acids 46-60. Point mutations indicate that four amino acid residues, R46, R47, K54 and R58, in this region are crucial for binding. Furthermore, we tested the effects of CaM on the lipid-binding activity of Zm-LTP in the presence of Ca(2+), EGTA, N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide and trifluoperazine respectively. We also investigated the structural features of CaM-binding motifs in LTPs from different species and strong differences were observed. Taken together, our results suggest that the interaction with CaM could be a common feature of plant LTPs. The identification and characterization of CaM-binding domain of LTPs should provide new insights into the mechanism by which the physiological functions of LTPs are regulated.

Water resource is crucial for human survival. And fresh-water is the constraint for the development of China. In order to realize the sustainable development, we build three mathematical models for determining an effective, feasible and cost-efficient water strategy to meet the projected water demand of China in 2025. These models are as following: model of the cost of water transfer, model of the water price and the model of desalination plant construction cost. All the models are based on the forecast of the water demand and supply of China in 2025. Based on the result of these models, we propose some advice about the water strategy to meet the water demand of China in 2025, such as: building desalination plants in the coastal provinces which are lack of water, carrying out the inter-basin water transfer projects in the middle of China, setting a reasonable water price based on the market economy and et al.©JASEM