A novel heterophilic graph diffusion convolutional network for identifying cancer driver genes.

Identifying cancer driver genes plays a curial role in the development of precision oncology and cancer therapeutics. Although a plethora of methods have been developed to tackle this problem, the complex cancer mechanisms and intricate interactions between genes still make the identification of cancer driver genes challenging. In this work, we propose a novel machine learning method of heterophilic graph diffusion convolutional networks (called HGDCs) to boost cancer-driver gene identification. Specifically, HGDC first introduces graph diffusion to generate an auxiliary network for capturing the structurally similar nodes in a biomolecular network. Then, HGDC designs an improved message aggregation and propagation scheme to adapt to the heterophilic setting of biomolecular networks, alleviating the problem of driver gene features being smoothed by its neighboring dissimilar genes. Finally, HGDC uses a layer-wise attention classifier to predict the probability of one gene being a cancer driver gene. In the comparison experiments with other existing state-of-the-art methods, our HGDC achieves outstanding performance in identifying cancer driver genes. The experimental results demonstrate that HGDC not only effectively identifies well-known driver genes on different networks but also novel candidate cancer genes. Moreover, HGDC can effectively prioritize cancer driver genes for individual patients. Particularly, HGDC can identify patient-specific additional driver genes, which work together with the well-known driver genes to cooperatively promote tumorigenesis.

PhenoDriver: interpretable framework for studying personalized phenotype-associated driver genes in breast cancer.

Identifying personalized cancer driver genes and further revealing their oncogenic mechanisms is critical for understanding the mechanisms of cell transformation and aiding clinical diagnosis. Almost all existing methods primarily focus on identifying driver genes at the cohort or individual level but fail to further uncover their underlying oncogenic mechanisms. To fill this gap, we present an interpretable framework, PhenoDriver, to identify personalized cancer driver genes, elucidate their roles in cancer development and uncover the association between driver genes and clinical phenotypic alterations. By analyzing 988 breast cancer patients, we demonstrate the outstanding performance of PhenoDriver in identifying breast cancer driver genes at the cohort level compared to other state-of-the-art methods. Otherwise, our PhenoDriver can also effectively identify driver genes with both recurrent and rare mutations in individual patients. We further explore and reveal the oncogenic mechanisms of some known and unknown breast cancer driver genes (e.g. TP53, MAP3K1, HTT, etc.) identified by PhenoDriver, and construct their subnetworks for regulating clinical abnormal phenotypes. Notably, most of our findings are consistent with existing biological knowledge. Based on the personalized driver profiles, we discover two existing and one unreported breast cancer subtypes and uncover their molecular mechanisms. These results intensify our understanding for breast cancer mechanisms, guide therapeutic decisions and assist in the development of targeted anticancer therapies.

PAX2 is regulated by estrogen/progesterone through promoter methylation in endometrioid adenocarcinoma and has an important role in carcinogenesis via the AKT/mTOR signaling pathway.

Endometrioid adenocarcinoma (EEC) is one of the most common cancers of the female reproductive system. In recent years, much emphasis has been placed on early diagnosis and treatment. PAX2 (Paired box 2) inactivation is reportedly an important biomarker for endometrioid intraepithelial neoplasia (EIN) and EEC. However, the role of PAX2 in EEC carcinogenesis remains unclear. PAX2 expression and associated clinical characteristics were analyzed via The Cancer Genome Atlas, Gene Expression Omnibus, and Cancer Cell Line Encyclopedia databases and clinical paired EIN/EEC tissue samples. Bioinformatic analysis was conducted to identify the putative molecular function and mechanism of PAX2. Cell proliferation, colony formation, cell migration, and invasion assays in vitro, and mouse xenograft models were utilized to study the biological functions of PAX2 in vivo. Pyrosequencing and the demethylating drug 5-Aza-dc were used to verify promoter methylation in clinical tissues and cell lines, respectively. The mechanism underlying the regulatory effect of estrogen (E2) and progesterone (P4) on PAX2 expression was investigated by receptor block assay and double luciferase reporter assay. PAX2 expression was found to be significantly downregulated in EIN and EEC tissues, its overexpression inhibited EEC cell malignant behaviors in vivo and in vitro and inhibited the AKT/mTOR signaling pathway. PAX2 inactivation in EEC was related to promoter methylation, and its expression was regulated by E2 and P4 through their receptors via promoter methylation. Our findings elucidated the expression and function of PAX2 in EEC and have provided hitherto undocumented evidence of the underlying molecular mechanisms. PAX2 expression is suppressed by estrogen prompting its methylation through estrogen receptor. Furthermore, PAX2 regulates the AKT/mTOR signaling pathway to influence EEC progression. © 2024 The Pathological Society of Great Britain and Ireland.

Revealing spatiotemporal inequalities, hotspots, and determinants in healthcare resource distribution: insights from hospital beds panel data in 2308 Chinese counties.

BACKGROUND: Ensuring universal health coverage and equitable access to health services requires a comprehensive understanding of spatiotemporal heterogeneity in healthcare resources, especially in small areas. The absence of a structured spatiotemporal evaluation framework in existing studies inspired us to propose a conceptual framework encompassing three perspectives: spatiotemporal inequalities, hotspots, and determinants. METHODS: To demonstrate our three-perspective conceptual framework, we employed three state-of-the-art methods and analyzed 10 years' worth of Chinese county-level hospital bed data. First, we depicted spatial inequalities of hospital beds within provinces and their temporal inequalities through the spatial Gini coefficient. Next, we identified different types of spatiotemporal hotspots and coldspots at the county level using the emerging hot spot analysis (Getis-Ord Gi* statistics). Finally, we explored the spatiotemporally heterogeneous impacts of socioeconomic and environmental factors on hospital beds using the Bayesian spatiotemporally varying coefficients (STVC) model and quantified factors' spatiotemporal explainable percentages with the spatiotemporal variance partitioning index (STVPI). RESULTS: Spatial inequalities map revealed significant disparities in hospital beds, with gradual improvements observed in 21 provinces over time. Seven types of hot and cold spots among 24.78% counties highlighted the persistent presence of the regional Matthew effect in both high- and low-level hospital bed counties. Socioeconomic factors contributed 36.85% (95% credible intervals [CIs]: 31.84-42.50%) of county-level hospital beds, while environmental factors accounted for 59.12% (53.80-63.83%). Factors' space-scale variation explained 75.71% (68.94-81.55%), whereas time-scale variation contributed 20.25% (14.14-27.36%). Additionally, six factors (GDP, first industrial output, local general budget revenue, road, river, and slope) were identified as the spatiotemporal determinants, collectively explaining over 84% of the variations. CONCLUSIONS: Three-perspective framework enables global policymakers and stakeholders to identify health services disparities at the micro-level, pinpoint regions needing targeted interventions, and create differentiated strategies aligned with their unique spatiotemporal determinants, significantly aiding in achieving sustainable healthcare development.

Gentamicin promoted the production of CD4+CD25+ Tregs via the STAT5 signaling pathway in mice sepsis.

BACKGROUND: Increasing studies have reported that gentamicin (GNT) plays an essential role in sepsis; however, its underlying mechanism is still unclear. In this study, we investigated the mechanism of GNT in sepsis. RESULTS: We observed that GNT enhanced survival and alleviated inflammatory injuries of the lungs, liver, kidneys, and intestines in mice with sepsis. Furthermore, regulatory T cells (Tregs) showed enhanced inhibitory function, and pro-inflammatory cytokines IL-1ß, TNF-α, and IL-2 and anti-inflammatory cytokine IL-10 showed decreased and increased peritoneal fluid levels, respectively, after treatment with GNT. GNT showed enhanced phosphorylation of signal transducer and activator of transcription 5 (p-STAT5) in Tregs in vivo and in vitro. The STAT5 inhibitor restrained the increased functional changes of Tregs and reduced inflammatory responses induced by GNT in vitro. Moreover, the STAT5 inhibitor reversed GNT-mediated impacts on survival and inflammation, and the percentage, apoptosis, and phenotypic and functional changes of Tregs in neonatal sepsis. CONCLUSIONS: Our study revealed that GNT regulates the function of Tregs via the STAT5 signaling pathway, alleviating inflammatory injuries, and provides novel evidence in the treatment of neonatal sepsis.

[Expression of long non-coding RNA linc00467 in childhood acute myeloid leukemia and its role in drug resistance].

OBJECTIVE: To study the expression and function of long non-coding RNA linc00467 in childhood acute myeloid leukemia (AML). METHODS: Bone marrow samples were collected from 5 children with AML who were diagnosed from May 2016 to June 2018. Normal bone marrow samples based on bone marrow examination were collected from 3 children as controls. Quantitative real-time PCR was used to measure the expression of linc00467 in the two groups. A lentivirus system was used to achieve overexpression of linc00467 in AML cells (HL-60) (linc00467 overexpression group), and empty vector expressing green fluorescent protein (GFP) was transfected into AML cells to establish a GFP control group. A lentivirus system was used to insert an interfering sequence into AML cells (sh-linc00467 interfering group), and a random sequence was inserted to establish an sh-NC control group. Cell proliferation and resistance to doxorubicin were observed for all groups. RESULTS: Compared with the normal control group, the children with AML had a significant increase in linc00467 (P=0.018). Overexpression and interference with linc00467 expression had no significant effect on cell proliferation. Compared with the GFP control group, the linc00467 overexpression group had a significant increase in the viability of HL-60 cells at the adriamycin concentrations of 0.1, 0.2, 0.3, 0.4, and 0.5 µg/mL (P<0.05). Compared with the sh-NC control group, the sh-linc00467 interfering group had a significant reduction in the viability of HL-60 cells at the adriamycin concentrations of 0.1, 0.2, 0.3, 0.4, and 0.5 µg/mL (P<0.05). Compared with the untreated group, the adriamycin treatment group had a significant increase in the expression of linc00467 in HL-60 cells (P<0.05). CONCLUSIONS: This study reveals the biological function of linc00467 to promote the resistance to adriamycin in AML, which provides a basis for developing new therapeutic drugs for AML.

The short-term association between air pollution and childhood asthma hospital admissions in urban areas of Hefei City in China: A time-series study.

BACKGROUND: The impacts of air pollution on asthma attacks have become a hotspot. Previous studies mainly focused on the developed countries or cities. There have been very limited studies in less-developed region to quantify the effects of air pollutants on asthma admissions in children. This study aims to assess the short-term impact of air pollutants on asthma hospital admissions for children in Hefei, China. METHODS: Poisson generalized linear regression combined with distributed lag non-linear model (DLNM) were applied to investigate the effects of air pollutants on daily childhood hospital admissions of asthma from 2015 to 2016, controlling for meteorological factors. Subgroup analyses by sex and age were performed. RESULTS: There were a total of 17,227 asthma admissions during 2015-2016. We found positive correlations between childhood asthma hospital visits and concentrations of NO2, O3, PM10 and PM2.5. Significantly, NO2 exhibited robust positive correlations with cumulative effects 1.551 (95% CI: 1.306-1.841, lag0-3 days) in single-pollutant model and 1.580 (95% CI: 1.315-1.899, lag0-3 days) in multiple-pollutant model. CONCLUSIONS: Air pollutants had adverse effects on childhood asthma. NO2 presented the greatest effect, followed by PM2.5. Results will be important for health authority and guardians to realize the severity of air pollution on the increased risk of asthma, so as to develop relevant strategies and health interventions to meet the challenges of childhood asthma and reduce air pollution.

A novel compound heterozygous mutation in VARS2 in a newborn with mitochondrial cardiomyopathy: a case report of a Chinese family.

BACKGROUND: Genetic defects in the mitochondrial aminoacyl-tRNA synthetase are important causes of mitochondrial disorders. VARS2 is one of the genes encoding aminoacyl-tRNA synthetases. Recently, an increasing number of pathogenic variants of VARS2 have been reported. CASE PRESENTATION: We report the novel compound heterozygous pathogenic VARS2 mutations c.643 C > T (p. His215Tyr) and c.1354 A > G (p. Met452Val) in a female infant who presented with poor sucking at birth, poor activity, hyporeflexia, hypertonia, persistent pulmonary hypertension of newborn (PPHN), metabolic acidosis, severe lactic acidosis, expansion and hypertrophic cardiomyopathy. These heterozygous mutations were carried individually by the proband's parents and elder sister; the two mutations segregated in the family and were the cause of the disease in the proband.The c.643 C > T (p. His215Tyr) mutation was not described in the ExaC, GNomAD and 1000 Genomes Project databases, and the frequency of c.1354 A > G (p. Met452Val) was < 0.001 in these gene databases.The two mutated amino acids were located in a highly conserved region of the VARS2 protein that is important for its interaction with the cognate tRNA. The two missense mutations were predicted by online tools to be damaging and deleterious. CONCLUSIONS: Our report expands the spectrum of known pathogenicVARS2 variants associated with mitochondrial disorders in humans.VARS2 deficiency may cause a severe neonatal presentation with structural cardiac abnormalities.

Mutations within the major hydrophilic region (MHR) of Hepatitis B virus from individuals with simultaneous HBsAg and anti-HBs in Guangzhou, Southern China.

The mechanism of the coexistence of HBsAg and anti-HBs is still unclear. This study investigated the variations located in the major hydrophilic region (MHR) of HBV from individuals with simultaneous HBsAg and anti-HBs in Guangzhou, southern China. Among 4455 samples analyzed, 179 (4.02%) patients were discovered with both HBsAg and anti-HBs. Finally, 44 individuals with concurrent HBsAg and anti-HBs (defined as group I), and 88 patients with positive HBsAg and negative anti-HBs (defined as group II, served as control) were enrolled in the study. The number of residue changes per 100 residues within the MHR in group I was 7.1 times more frequent than group II (P < 0.001) and was discovered mostly in the MHR1 (aa99-119) (P < 0.001). Two or more residue changes in the MHR were discovered in 15 patients (34.1%) of group I, but were found in only one (1.1%) patient of group II (P < 0.001). The most common variants in group I were at positions s101Q, s133M, s126T/I, s131T, s145G, s120P, and s129Q. In addition, sQ101 K, sT131N, and sM133L were more frequently discovered in group I with significant difference (P < 0.05). In chronic hepatitis B (CHB) patients, the simultaneous of HBsAg and anti-HBs were accompanied with an increase of MHR variants, and suggested that the HBsAg mutants were selected by naturally acquired anti-HBs during chronic carriage.

Prevalence of S gene mutations within the major hydrophilic region of hepatitis B virus in patients in Dongguan, southern China.

HBsAg point mutations within the major hydrophilic region (MHR) have frequently been reported to be associated with diagnostic failure, vaccine escape and immunotherapy escape. However, the prevalence of escape mutations in chronic hepatitis B (CHB) patients has not been systematically studied in patients from southern China within the past decade. This study aimed to determine the prevalence of escape mutations within the MHR of hepatitis B virus in patients in Dongguan, southern China. Between June 2015 and May 2016, 391 patients who were chronically infected with HBV were enrolled in the study, including 240 patients with the genotype B strain and 151 with the genotype C strain. The most frequent mutated position was s126 (4.3%), followed by s100 (3.3%), s101 (2.8%), s133 (2.8%), s145 (2.3%), s120 (2.0%) and s129 (1.8%). Furthermore, the mutations sY100C, sQ101R/K, sS114A, sP120T, sT/I126A/N/S, sQ129R, sM133L/T/S and sG145R/A were prevalent in at least one genotype, with a frequency higher than 1%, which indicated that these mutations were relatively common. In addition, sQ101K/R was found only in genotype C isolates (P < 0.05), and sT126A was only discovered in genotype B isolates (P = 0.047), indicating that such mutations were genotype-associated mutations. Notably, combinations of escape mutations within the MHR were also frequently discovered in genotypes B (5.0%) and C (6.6%), with no significant difference (P = 0.498). These results indicated that we should increase the surveillance HBsAg mutations among HBV-infected patients in China.

Antimicrobial resistance in bacterial pathogens among hospitalized children with community acquired lower respiratory tract infections in Dongguan, China (2011-2016).

BACKGROUND: Bacterial pathogens are a major cause of childhood community acquired lower respiratory tract infections (CA-LRTIs), and few data described the impact of antimicrobial resistance on children with CA-LRTIs. This study aims to investigate the antimicrobial resistance in common bacterial agents among hospitalized children with CA-LRTIs between 2011 and 2016 in Dongguan, China. METHODS: Sputum samples were collected from hospitalized children (0-5 years old) with CA-LRTIs in Dongguan Children's Hospital. Bacterial pathogens were detected using traditional culture methods, and disc diffusion tests were used to determine antibiotic resistance. RESULTS: Among the 2360 samples analyzed, 342 (14.5%) were positive for bacterial infection. The most prevalent pathogen was MSSA (2.3%), followed by MRSA (1.5%), E. coli (1.7%), E. coli ESBLs (1.2%), K. pneumonia ESBLs (1.5%), K. pneumonia (1.4%) and S. pneumonia (1.3%). Of the hospitalized patients with bacteria causing of CA-LRTIs, 90.1% were less than 1-year-old. MSSA and MRSA were more commonly isolated in infants less than 3 months. E. coli, K. pneumonia and K. pneumonia ESBLs were more common bacteria causing CA-LRTIs in infants less than 1 month. Resistance levels to penicillins, fluoroquinolones, macrolides, cephalosporins, carbapenems and vancomycin varied in different bacteria. CONCLUSIONS: S. aureus, E coli and K. pneumonia were the common bacterial isolates recovered from chidren with CA-LTRIs during 2011-2015. Age group of under 1 year old was at a high risk of bacterial infections. Many isolates showed antibiotic resistance level was associated with antibiotic usage in clinic. Increasing surveillance of antibiotic resistance is urgently needed and develops better strategies to cure the antibiotic abuse in China.

Impact of short-term temperature variability on emergency hospital admissions for schizophrenia stratified by season of birth.

Diurnal temperature range (DTR) and temperature change between neighboring days (TCN) are important meteorological indicators closely associated with global climate change. However, up to date, there have been no studies addressing the impacts of both DTR and TCN on emergency hospital admissions for schizophrenia. We conducted a time-series analysis to assess the relationship between temperature variability and daily schizophrenia onset in Hefei, an inland city in southeast China. Daily meteorological data and emergency hospital admissions for schizophrenia from 2005 to 2014 in Hefei were collected. After stratifying by season of birth, Poisson generalized linear regression combined with distributed lag nonlinear model (DLNM) was used to examine the relationship between temperature variability and schizophrenia, adjusting for long-term trend and seasonality, mean temperature, and relative humidity. Our analysis revealed that extreme temperature variability may increase the risk for schizophrenia onset among patients born in spring, while no such association was found in patients born in summer and autumn. In patients born in spring, the relative risks of extremely high DTR comparing the 95th and 99th percentiles with the reference (50th, 10 °C) at 3-day lag were 1.078 (95 % confidence interval (CI) 1.025-1.135) and 1.159 (95 % CI 1.050-1.279), respectively. For TCN effects, only comparing 99th percentile with reference (50th, 0.7 °C) was significantly associated with emergency hospital admissions for schizophrenia (relative risk (RR) 1.111, 95 % CI 1.002-1.231). This study suggested that exposure to extreme temperature variability in short-term may trigger later days of schizophrenia onset for patients born in spring, which may have important implications for developing intervention strategies to prevent large temperature variability exposure.

Impact of weather factors on hand, foot and mouth disease, and its role in short-term incidence trend forecast in Huainan City, Anhui Province.

Hand, foot, and mouth disease (HFMD) is one of the most common communicable diseases in China, and current climate change had been recognized as a significant contributor. Nevertheless, no reliable models have been put forward to predict the dynamics of HFMD cases based on short-term weather variations. The present study aimed to examine the association between weather factors and HFMD, and to explore the accuracy of seasonal auto-regressive integrated moving average (SARIMA) model with local weather conditions in forecasting HFMD. Weather and HFMD data from 2009 to 2014 in Huainan, China, were used. Poisson regression model combined with a distributed lag non-linear model (DLNM) was applied to examine the relationship between weather factors and HFMD. The forecasting model for HFMD was performed by using the SARIMA model. The results showed that temperature rise was significantly associated with an elevated risk of HFMD. Yet, no correlations between relative humidity, barometric pressure and rainfall, and HFMD were observed. SARIMA models with temperature variable fitted HFMD data better than the model without it (sR 2 increased, while the BIC decreased), and the SARIMA (0, 1, 1)(0, 1, 0)52 offered the best fit for HFMD data. In addition, compared with females and nursery children, males and scattered children may be more suitable for using SARIMA model to predict the number of HFMD cases and it has high precision. In conclusion, high temperature could increase the risk of contracting HFMD. SARIMA model with temperature variable can effectively improve its forecast accuracy, which can provide valuable information for the policy makers and public health to construct a best-fitting model and optimize HFMD prevention.

Molecular epidemiology of the enteroviruses associated with hand, foot and mouth disease/herpangina in Dongguan, China, 2015.

Enteroviruses (EVs) are the etiological agents involved in most cases of hand, foot and mouth disease (HFMD) and herpangina (HA). Information on the epidemiology profiles of EVs in China is very limited, as the present surveillance system of China focuses on CAV16 and EV71, and no published data are available in Dongguan. The aim of this study is to determine the prevalence of EVs among patients with HFMD and HA in Dongguan, China, during 2015. A total of 271 clinical stool specimens that were clinically determined to be positive for enteroviruses were genotyped by semi-nested polymerase chain reaction (PCR) for the VP1 genes of EVs. The results showed that a total of 14 enterovirus genotypes were identified among HFMD and HA patients in this study. CVA6 was the most common genotype for HFMD, and CVA2 accounted for the majority of HA cases in this study. Sequence and phylogenetic analysis showed that all of the CVA6 and CVA2 strains identified in our study displayed a close genetic relationship to strains identified in other cities in China. This study also demonstrates that there are associations between particular causative enterovirus genotypes and some clinical symptoms, which may provide useful information for improving case prevention, diagnosis and treatment of HFMD and HA.

Impacts of temperature change on ambulance dispatches and seasonal effect modification.

Ambulance dispatch is a proxy of acute health outcomes, and growing epidemiological evidence documented its relation to extreme temperature events. Research, however, on short-term temperature change and ambulance dispatches is scarce. We aimed to investigate the effect of short-term temperature change on ambulance dispatches and potential modification by season. Daily data on ambulance dispatch and weather factors were collected in Huainan, a Chinese inland city from December 2011 through December 2013. A Poison generalized linear regression model combined with distributed lag nonlinear model was constructed to examine the association of temperature change between neighboring days (TCN) with ambulance dispatches. The effect modification by season was also examined. There were 48,700 ambulance attendances during the study period. A statistically significant association of TCN with ambulance dispatches was observed. Temperature rise between neighboring days (TCN > 0) was associated with elevated adverse risk of ambulance dispatches, and the effects appeared to be acute (lag0, on the current day) and could last for at least a week, while temperature drop between neighboring days (TCN < 0) had a protective effect. For a 1 °C increase of TCN at lag0 and lag06 (on the 7-day moving average), the risk of ambulance dispatches increased by 2 % (95 % CI 1-3 %) and 7 (95 % CI 1-13 %), respectively. Extreme TCN increase (95th percentile, 3.3 °C vs. 0 °C) at lag0 and lag05 was accompanied by 6 (95 % CI 3-8 %) and 27 % (95 % CI 12-44 %) increase in ambulance dispatches. Ambulance dispatches were more vulnerable to extremely great temperature rise in summer and autumn. TCN was adopted for the first time to quantify the impact of short-term temperature change on ambulance dispatches. Temperature drop between neighboring days (TCN < 0) had a protective effect on ambulance dispatches, while temperature rise between neighboring days (TCN > 0) could acutely trigger the increase in ambulance dispatches, and TCN effect differs by season.

Asthma and Risk of Stroke: A Systematic Review and Meta-analysis.

BACKGROUND: Several studies have suggested that asthma is associated with an increased risk of stroke. However, the results are inconsistent. The aim of this study is to investigate the relation of asthma and the risk of stroke through a systematic review and meta-analysis of published research. METHODS: Pertinent studies were identified by a search of the PubMed and the Web of Science databases to June 2015. Study-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using fixed-effect or random-effect models when appropriate. Associations were tested in subgroups representing different participants and study characteristics. Publication bias was assessed with Egger's test. RESULTS: Five articles comprising 524,637 participants and 6031 stroke cases were eligible for inclusion. Asthma was associated significantly with increased risk of stroke, and the pooled HR was 1.32 (95% CI: 1.13, 1.54, I(2)=80.4%). Subgroup analyses revealed that the association between asthma and stroke risk was stronger among female patients (HR = 1.42, 95% CI: 1.15-1.76) and prospective cohort study design (HR = 1.52, 95% CI: 1.21-1.91). CONCLUSION: Asthma is associated with a significantly increased risk of stroke. This finding may have clinical and public health importance.

Prenatal antibiotic use and risk of childhood wheeze/asthma: A meta-analysis.

BACKGROUND: Existing body of knowledge suggests that antibiotic use during pregnancy was inconsistently associated with childhood wheeze/asthma. The aim of this study was to determine whether exposure to antibiotic during pregnancy could increase the risk for childhood wheeze/asthma using a comprehensive meta-analysis. METHODS: PubMed, MEDLINE, and China National Knowledge Infrastructure (CNKI) were systematically searched for studies up to September 10, 2014, and additional studies were found by searching reference lists of relevant articles. For this meta-analysis, cohort studies and case-control studies assessing the association between antibiotic use during pregnancy and risk of childhood wheeze/asthma were included. Extracted data were mainly pooled using random-effects model. Study quality was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). RESULTS: Ten studies were identified in final analysis. Pooling analysis of these studies showed an OR of 1.20 (95% CI, 1.13-1.27) for wheeze/asthma. After excluding case-control studies and prospective studies without achieving high scores on the NOS, the pooled OR was 1.18 (95% CI, 1.11-1.26). We found the risk of antibiotic use and pooled ORs of wheeze/asthma were 1.09 (95% CI, 0.92-1.29) for the first trimester, 1.14 (95% CI, 1.01-1.29) for the second trimester, and 1.33 (95% CI, 1.11-1.60) for the third trimester, respectively. CONCLUSIONS: This meta-analysis suggests that antibiotic exposure during pregnancy may increase the risk of wheeze/asthma in childhood. Besides, the risk of developing wheeze/asthma in childhood was marked during last two trimesters of pregnancy. Future studies of large-size and prospective cohorts which adequately address concerns for confounder bias are needed to examine the relationship between antibiotic use and risk of childhood asthma.

Synchronous small cell neuroendocrine carcinoma of the cervix and immature ovarian teratoma: A case report and literature review.

The onset of two synchronous primary malignancies of the female genital tract is uncommon; therefore, the simultaneous occurrence of cervical small cell neuroendocrine carcinoma and ovarian immature teratoma is rare. The present study describes the case of a woman with cervical small cell neuroendocrine carcinoma complicated by ovarian immature teratoma. The clinical manifestations, and the histopathological and immunophenotypic features of the patient are recorded. Furthermore, all PubMed-indexed cases of synchronous primary malignancies in both the cervix and ovary have been briefly summarized.

Long non-coding RNA JPX promotes endometrial carcinoma progression via janus kinase 2/signal transducer and activator of transcription 3.

Introduction: Although LncRNA JPX has been linked to a number of malignancies, it is yet unknown how it relates to endometrial carcinoma (EC). Investigating the expression, functional activities, and underlying molecular processes of lncRNA JPX in EC was the goal of this work. Methods: RT-qPCR was used to examine the differences in lncRNA/microRNA (miRNA, miR)/mRNA expression between normal cervical and EC tissues or cells. Cell Counting Kit-8, flow cytometry, and transwell were used to evaluate the association between lncRNA JPX/miR-140-3p/phosphoinositide-3-kinase catalytic subunit α (PIK3CA) in Ishikawa and JEC cell lines. The impact of JPX on the downstream janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 signaling pathway was investigated using Western blot analysis. Results: When comparing EC tissues to nearby normal tissues, JPX expression is markedly increased in EC tissues, with greater expression in advanced-stage EC. Furthermore, compared to normal epithelial cells, EC cell lines have higher levels of JPX expression. In Ishikawa and JEC endometrial cancer cell lines, we used siRNA-mediated suppression of JPX to find lower cell viability, increased apoptosis, cell cycle arrest, and reduced migration and invasion. We next verified that miR-140-3p binds to downstream target cells to impede the transcription and translation of PIK3CA, which in turn prevents the growth of Ishikawa and JEC cells. JPX functions as a ceRNA to adsorb miR-140-3p. This procedure required controlling JAK2/STAT3, a downstream signal. Conclusion: JPX enhances the development of Ishikawa and JEC cells and activates downstream JAK2/STAT3 signal transduction via the miR-140-3p/PIK3CA axis, offering a possible therapeutic target for the treatment of EC.

Elastic, Piezoelectric Coefficients, and Internal Frictions of a Single Alpha-Quartz Crystal Determined by Partial-Electrode Electromechanical Impedance Spectroscopy.

In this work, all independent elastic coefficients, piezoelectric coefficients, and internal frictions of a single alpha-quartz crystal are determined at room temperature using our recently proposed partial-electrode electromechanical impedance spectroscopy (PE-EMIS). In PE-EMIS, the rectangular parallelepiped quartz sample with two small partial electrodes fabricated on a corner is self-excited/sensed. The conductance spectrum (equivalent to the acoustic resonance spectrum) measured by an impedance analyzer under a free boundary condition is noiseless, allowing the first 100 eigenmodes ranging from 50 to 310 kHz to be accurately fit. To avoid mode misidentification, the off-plane displacement distributions of the quartz sample under different eigenmodes are determined using a scanned-laser vibrometer. The resonance spectrum measured by a traditional sandwich-like resonant ultrasound spectroscopy (RUS) apparatus is also presented for comparison, and the results show that the clamping force in sandwich-like RUS shifts the sample's resonance frequencies, causing 13% and 75% overestimations for the piezoelectric coefficients e11 and e14, respectively. In comparison with the RUS, our proposed PE-EMIS is more effective and convenient and will be widely used for characterization of piezoelectric crystals.