Polymorphisms in PI3K/AKT genes and gene­smoking interaction are associated with susceptibility to tuberculosis.

BACKGROUND: Phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) are involved in the clearance of Mycobacterium tuberculosis (MTB) by macrophages. AIM: This study aimed to investigate the effects of polymorphisms in the PI3K/AKT genes and the gene-smoking interaction on susceptibility to TB. METHODS: This case-control study used stratified sampling to randomly select 503 TB patients and 494 control subjects. Logistic regression analysis was used to determine the association between the polymorphisms and TB. Simultaneously, the marginal structure linear dominance model was used to estimate the gene-smoking interaction. RESULTS: Genotypes GA (OR 1.562), AA (OR 2.282), and GA + AA (OR 1.650) at rs3730089 of the PI3KR1 gene were significantly associated with the risk to develop TB. Genotypes AG (OR 1.460), GG (OR 2.785), and AG + GG (OR 1.622) at rs1130233 of the AKT1 gene were significantly associated with the risk to develop TB. In addition, the relative excess risk of interaction (RERI) between rs3730089 and smoking was 0.9608 (95% CI: 0.5959, 1.3256, p < 0.05), which suggests a positive interaction. CONCLUSION: We conclude that rs3730089 and rs1130233 are associated with susceptibility to TB, and there was positive interaction between rs3730089 and smoking on susceptibility to TB.

Letrozole-stimulated endometrial preparation protocol is a superior alternative to hormone replacement treatment for frozen embryo transfer in women with polycystic ovary syndrome, a cohort study.

BACKGROUND: The current routine endometrial preparation protocol for women with polycystic ovary syndrome (PCOS) is hormone replacement treatment (HRT). Letrozole is rarely used in frozen embryo cycles. Evidence confirming whether letrozole-stimulated (LS) protocol is suitable for frozen embryo transfer in patients with PCOS and for whom is suitable remains lacking. METHODS: This was a retrospective cohort study involving all frozen embryo transfer cycles with LS and HRT for PCOS during the period from Jan 2019 to December 2020 at a tertiary care center. Multivariate Logistic regression was used to analyze the differences in clinical pregnancy rate, live birth rate, miscarriage rate, the incidence of other pregnancy and obstetric outcomes between LS and HRT protocols after adjusting for possible confounding factors. Subgroup analysis was used to explore the population for which LS protocol was suitable. RESULTS: The results of multivariate logistic regression showed that LS was significantly associated with a higher clinical pregnancy rate (70.9% vs. 64.4%;aOR:1.41, 95%CI: 1.18,1.68), live birth rate (60.5% vs. 51.4% aOR:1.49, 95%CI: 1.27,1.76), and a lower risk of miscarriage (14.7% vs. 20.1% aOR: 0.68, 95%CI: 0.53,0.89), hypertensive disorders of pregnancy (6.7% vs. 8.9% aOR: 0.63, 95%CI: 0.42,0.95), and gestational diabetes mellitus (16.7% vs. 20.7% aOR:0.71, 95%CI: 0.53,0.93) than HRT. There were no significant differences in other outcomes such as preterm birth, cesarean delivery, small for gestational age, or large for gestational age between the two endometrial preparation protocols. Subgroup analysis showed that LS had higher live birth rates than HRT in most of the subgroups; in the three subgroups of maternal age ≥ 35 years, menstrual cycle < 35 days, and no insulin resistance, the live birth rates of the two endometrial preparation protocols were comparable. CONCLUSIONS: LS protocol could improve the live birth rate and reduce the incidence of miscarriage, hypertensive disorders of pregnancy and gestational diabetes mellitus in patients with PCOS. LS protocol is suitable for all types of patients with PCOS. LS should be considered the preferred endometrial preparation protocol for women with PCOS.

The association of iron status, supplement iron in the first-trimester pregnancy with gestational diabetes mellitus: A nested case-control study.

AIMS: The objective of this study was to examine whether the level of iron and iron supplements in the first-trimester pregnancy is associated with gestational diabetes mellitus (GDM). METHODS: This was a nested case-control study using data from an established cohort in the Hunan Provincial Maternal and Child Health Hospital (HPMCHH) in South China. A total of 119 patients with GDM and 238 controls were enrolled in the study. Iron status indicators were tested in early pregnancy. Information on iron supplements use was collected by questionnaires. Binary logistic regression was used to obtain odds ratio (OR). The relative excess risk of interaction (RERI) was applied to evaluate the interaction. RESULTS: We observed that pregnant women with normal ferritin levels (≥30 ng/ml) and iron supplements were associated with a 3.701-fold increased risk of GDM (OR: 3.701, 95% CI: 1.689-8.112) compared with the ferritin <30 ng/ml and without iron supplements group. Similarly, pregnant women with normal serum iron (SI) levels (≥9 µmol/L) and iron supplements were associated with a 5.447-fold increased risk of GDM (OR: 5.447, 95% CI: 2.246-13.209) compared with the SI < 9 µmol/L and without iron supplement group. We found an additive interaction between ferritin and iron supplements on the presence of GDM (RERI: 1.164, 95%CI: 0.333-1.994) and SI and iron supplements on the risk of GDM (RERI: 6.375, 95%CI: 4.494-8.256). CONCLUSION: Pregnant women with normal ferritin or SI levels and iron supplements could significantly increase the risks for GDM.

The impact of blastocyst freezing and biopsy on the association of blastocyst morphological parameters with live birth and singleton birthweight.

OBJECTIVE: To explore whether the associations of 3 blastocyst morphological parameters, namely, degree of blastocyst expansion (expansion), appearance of trophectoderm (TE) and inner cell mass, with live birth and singleton birth weight are influenced by blastocyst freezing and biopsy. DESIGN: A retrospective study. SETTING: An assisted reproductive technology center. PATIENT(S): 28,515 single blastocyst transfer cycles between January 2014 and August 2019. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Live birth and singleton birth weight. RESULT(S): Blastocyst transfer cycles were divided into 4 groups: biopsied blastocyst cycles (biopsied-blast), thawed blastocyst cycles (thawed-blast), blastocyst from thawed cleavage embryo cycles (blast-thawed-D3), and fresh blastocyst cycles (fresh-blast). Subgroup analyses by blastocyst stage (day 5 and day 6) were performed in thawed-blast and blast-thawed-D3. Because almost all blastocysts were biopsied on day 6 and fresh blastocysts were transferred on day 5, the biopsied-blast and fresh-blast were not divided into subgroups. First, the associations between blastocyst morphological parameters and live birth were analyzed. To explore the effect of freezing, we compared day-5 frozen cycles (thawed-blast) vs. day-5 fresh cycles (including fresh-blast and blast-thawed-D3) and day 6 frozen cycles (thawed-blast) vs. day-6 fresh cycles (blast-thawed-D3). Inner cell mass and TE were associated with live birth for day 5 embryos, and only TE affected live birth for day-6 embryos. The associations were the same in frozen cycles and fresh cycles. To explore the effect of biopsy, we compared day-6 biopsied cycles (biopsied-blast) vs. day-6 nonbiopsied cycles (including thawed-blast and blast-thawed-D3). All the 3 parameters were associated with live birth in biopsied-blast, whereas only TE was associated with live birth in nonbiopsied cycles. In addition, the associations between blastocyst morphological parameters and singleton birthweight were analyzed. In the 6 subgroups, expansion stage of day-6 embryos in biopsied-blast and TE grade of day-6 embryos in thawed-blast were associated with birth weight, and there are no associations in other subgroups. CONCLUSION(S): The association of blastocyst morphological parameters with live birth may be affected by blastocyst biopsy and/or genetic testing, and its association with birth weight may be affected by blastocyst freezing and biopsy and/or genetic testing.

Prognostic significance and immune characteristics of CMTM4 in hepatocellular carcinoma.

BACKGROUND: Previous study has shown that chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family member 4 (CMTM4) can bind and maintain programmed cell death ligand 1 (PD-L1) expression to promote tumor progression by alleviating the suppression of tumor-specific T cell activity, suggesting its potential role in tumor immunotherapy. However, the role of CMTM4 in tumor immunity has not been well clarified, especially in hepatocellular carcinoma (HCC). METHODS: The protein expression of CMTM4/PD-L1/CD4/CD8 was detected by immunohistochemistry (IHC) detection in 90 cases of HCC tissues. The mRNA expression profiles and related prognosis data were obtained from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC). Two immune therapy cohorts were from Imvigor210 and GSE176307. RESULTS: Though the single protein expression of CMTM4, PD-L1, CD4 or CD8 in HCC tissues by IHC detection didn't show a significant relationship with the prognosis of HCC patients, we found that high co-expression of CMTM4/PD-L1/CD4 showed a good prognosis of HCC patients. Further Timer 2.0 analysis identified that HCC patients with high expression of CMTM4/PD-L1 and high infiltration of CD4+ T cells had a better overall survival than those with low infiltration of CD4+ T cells. Moreover, a series of bioinformatics analyses revealed that CMTM4-related genes posed important effects on prognosis and immunity in HCC patients, and CMTM4 had a positive correlation with infiltration of CD4+ and CD8+ T cells in HCC. At last, we used two immunotherapy cohorts to verify that the combination of CMTM4 with PD-L1 could improve the prognosis of tumor patients underwent immunotherapy. CONCLUSIONS: CMTM4 and PD-L1 co-expression with T cell infiltration shows prognostic significance in HCC, suggesting combined effect from multiple proteins should be considered in HCC treatment.

Betel quid chewing and oral potential malignant disorders and the impact of smoking and drinking: A meta-analysis.

BACKGROUND: Oral potential malignant disorders (OPMDs) are a precancerous condition of oral disease. Several studies have found that betel quid chewing, smoking and alcohol drinking might be the risk factors of OPMDs. But the relationships of them, especially their interaction are still inconclusive. AIM: To evaluate the relationship between betel quid chewing and OPMDs and to explore the interaction of smoking and alcohol drinking on the relationship. METHODS: We searched PubMed, Web of Science, Embase and the Cochrane Library databases with items complete until January 2021 for relevant studies. The research data were extracted according to the inclusion criteria. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the effect size. Subgroup analysis was performed to assess interactions between exposures and OPMDs. Relative excess risk of interaction (RERI) was used to estimate the size of interaction. RESULTS: Nine articles were selected in the final meta-analysis. The results showed that betel quid chewing (pooled OR: 8.70, 95%CI: 5.18-14.61), alcohol consumption (pooled OR: 1.95, 95%CI: 1.5-2.55), and smoking (pooled OR:4.35, 95%CI: 3.06-6.2) could significantly increase the risk of OPMDs compared to individuals without these behaviors. Smoking and alcohol drinking synergistically increased the association between betel quid chewing and OPMDs (pooled OR(BQ+SM):14.38, 95%CI: 7.14-28.95; pooled OR(BQ+DK): 11.12, 95%CI: 8.00-15.45, respectively). The RERI(BQ+SM) and RERI(BQ+DK) were 2.33 and 1.47, respectively. CONCLUSION: The synergistic effects between smoking/drinking and betel quid highlights the importance of focusing on individuals with multiple exposures. Further study should be conducted to confirm these interactions.

hsa-miR-9-5p-Mediated TSPAN9 Downregulation Is Positively Related to Both Poor Hepatocellular Carcinoma Prognosis and the Tumor Immune Infiltration.

Tetraspanins (TSPANs) play crucial roles in cell adhesion, migration, and metastasis of human cancer. However, there is no study in revealing the aspects of TSPAN9 traits and its functions in hepatocellular carcinoma (HCC) prognosis. Our study is the first to portray the TSPAN9 expression in HCC tissues with immunohistochemistry (IHC) analysis. Subsequently, a series of bioinformatics analyses such as expression estimation, survival assessment, and correlation analysis were implemented to dig out the possible upstream noncoding RNAs (ncRNAs) for TSPAN9 in HCC. In this way, the relevance within TSPAN9 and tumor immunity was then explored. We found that the TSPAN9 was downregulated in HCC tissues and had a correlation with HCC prognosis. Furthermore, we identified that the AL139383.1-hsa-miR-9-5p axis was the upstream ncRNA-related pathway most associated with TSPAN9 in HCC. Besides that, expression of TSPAN9 held a significantly negative correlation with tumor immunocyte infiltration as well as immune checkpoint CTLA4. TSPAN9-related immunomodulators were mainly enriched in T cell activation, leukocyte cell-cell adhesion, regulation of T cell activation, and regulation of leukocyte cell-cell adhesion signaling pathway. In conclusion, our results indicated that hsa-miR-9-5p-mediated downregulation of TSPAN9 was associated with poor HCC prognosis, immune-related signaling pathway, and tumor immune infiltration.

Serum microcystin-LR levels and risk of gestational diabetes mellitus: A Chinese nested case-control study.

Background: Previous experimental studies have reported an association between microcystin-LR (MC-LR) and glucose homeostasis, but whether exposure to MC-LR is a risk factor for the pathogenesis of gestational diabetes mellitus (GDM) requires further epidemiological study. This study aims to explore the effects of MC-LR on GDM. Methods: A prospective nested case-control study was performed in the Hunan Provincial Maternal and Child Health Hospital (HPMCHH) in South China. A total of 119 patients with GDM and 238 controls were enrolled in the study. The two independent samples t-test, or chi-square test was used to compare the difference between the GDM group and the non-GDM group. Binary logistic regression was used to obtain odds ratios (ORs) by controlling for confounders. Results: The cumulative incidence of GDM in our sample was 13.7%. The detection rate of MC-LR in the GDM group were significantly higher than those in the control group (44.2% vs. 29.4%; p=0.007). Our results show that an elevated serum MC-LR level in the first trimester of pregnancy was related to an increased risk of GDM (OR: 1.924; 95% CI: 1.092-3.391; p<0.05). When stratified by age, educational level, parity, and passive smoking, significantly relationships were observed among those aged >30 years, lower income, higher education, none passive smoking, and more likely to be multiparous. Conclusions: Our data reveals that serum MC-LR level in the first trimester is independently associated with GDM.

Determinants of Urinary Incontinence and Subtypes Among the Elderly in Nursing Homes.

Urinary incontinence (UI) is a common problem among older adults. This study investigated the prevalence of UI in nursing home residents aged ≥75 years in China and examined potential risk factors associated with UI and its subtypes. Data were collected during face-to-face interviews using a general questionnaire, the International Consultation Incontinence Questionnaire Short-Form, and the Barthel Index. A total of 551 participants aged ≥75 years residing in Changsha city were enrolled from June to December 2018. The UI prevalence rate among nursing home residents aged ≥75 years was 24.3%. The most frequent subtype was mixed (M) UI (38.1%), followed by urge (U) UI (35.1%), stress (S) UI (11.9%), and other types (14.9%). In terms of severity, 57.5% had moderate UI, while 35.1% had mild and 7.5% had severe UI. Constipation, immobility, wheelchair use, cardiovascular disease (CVD), and pelvic or spinal surgery were significant risk factors for UI. Participants with a history of surgery had higher risks of SUI (odds ratio [OR] = 4.87, 95% confidence interval [CI]: 1.55-15.30) and UUI (OR = 1.97, 95% CI: 1.05-3.71), those who were immobile or used a wheelchair had higher rates of MUI (OR = 11.07, 95% CI: 4.19-29.28; OR = 3.36, 95% CI: 1.16-9.78) and other UI types (OR = 7.89, 95% CI: 1.99-31.30; OR = 14.90, 95% CI: 4.88-45.50), those with CVD had a higher rate of UUI (OR = 2.25, 95% CI: 1.17-4.34), and those with diabetes had a higher risk of UUI (OR = 2.250, 95% CI: 1.14-4.44). Use of oral antithrombotic agents increased UUI risk (OR = 4.98, 95% CI: 2.10-11.85) whereas sedative hypnotic drug use was associated with a higher risk of MUI (OR = 3.62, 95% CI: 1.25-10.45). Each UI subtype has distinct risk factors, and elderly residents of nursing homes with a history of CVD and pelvic or spinal surgery who experience constipation should be closely monitored. Reducing time spent in bed and engaging in active rehabilitation including walking and muscle strengthening may aid in UI prevention and treatment.

Spousal Concordance of Cardiovascular Risk Factors in Newly Married Couples in China.

Importance: Several studies have shown that older married couples share a propensity for accruing the same cardiovascular risk factors such as hypertension and dyslipidemia. However, it remains unclear if these spousal associations reflect their shared home environment and lifestyle or the tendency to choose a partner with a similar perspective on lifestyle choices and behaviors (assortative mating). Evaluating these associations in young, newly married couples may help to differentiate between these 2 possibilities. Objective: To evaluate the spousal concordance of cardiovascular risk factors in young, newly married couples. Design, Setting, and Participants: This prospective cohort study recruited 831 couples around the time of marriage registration in Liuyang, China, from February 1, 2009, to November 4, 2015. Statistical analysis was performed from April to May 2021. Main Outcomes and Measures: Spousal concordance of cardiovascular risk factors. Both partners underwent systematic assessment of cardiovascular risk factors, including evaluation of anthropometrics, blood pressure, and fasting lipids. Results: Among the 831 participating couples, mean (SD) age was 24 (3) years in the women and 26 (4) years in the men. There were significant correlations between spouses in systolic blood pressure (r = 0.43; P < .001), diastolic blood pressure (r = 0.36; P < .001), total cholesterol (r = 0.13; P < .001), low-density lipoprotein cholesterol (r = 0.11; P = .003), high-density lipoprotein (HDL) cholesterol (r = 0.22, P < .001), and triglycerides (r = 0.13; P = .001). After adjustment for covariates (age, household income, education level, smoking, and either body mass index or waist circumference), significant correlations persisted between spouses in their systolic blood pressure (r = 0.42; P < .001), diastolic blood pressure (r = 0.34; P < .001), HDL cholesterol (r = 0.17; P < .001), and triglycerides (r = 0.10; P = .04). Conclusions and Relevance: This cohort study found spousal concordance of cardiovascular risk factors among young newly married couples. Assortative mating based on these concordant risk factors at the time of marriage may partially explain the shared vascular risk profile of older marital partners and raises the possibility of couple-based care.

Paternal weight prior to conception and infant birthweight: a prospective cohort study.

BACKGROUND/OBJECTIVE: Previous studies have consistently demonstrated that maternal weight status both before and during pregnancy is associated with infant birthweight. However, a fundamental limitation across this literature remains that previous studies have not evaluated the concomitant impact of paternal weight at conception, owing to the paucity of studies in which fathers were assessed prior to pregnancy. Thus, we established a cohort of preconception couples to prospectively evaluate the associations of maternal and paternal weight prior to pregnancy with infant birthweight at delivery. METHODS: In this prospective observational cohort study, 1292 newly-married women and their partners in Liuyang, China, were assessed at median of 23.3 weeks before a singleton pregnancy, thereby enabling concomitant assessment of preconception maternal and paternal body mass index (BMI) in relation to infant birthweight. RESULTS: Mean birthweight was 3294 ± 450 g with 147 neonates (11.4%) born large-for-gestational-age (LGA) and 94 (7.3%) small-for-gestational-age (SGA). After adjustment for maternal and paternal factors prior to conception (age, education, smoking, BMI, household income), length of gestation, total gestational weight gain, gestational diabetes, preeclampsia, and infant sex, it was noted that infant birthweight increased by 42.2 g (95% CI 29.5-54.8; p < 0.0001) per unit increase in maternal pregravid BMI and 10.7 g (95% CI 0.5-20.9; p = 0.04) per unit increase in paternal pregravid BMI. Maternal pregravid BMI explained 6.2% of the variance in birthweight whereas paternal BMI explained only 0.7%. Independent predictors of LGA delivery were maternal pregravid BMI (aOR = 1.91, 95% CI 1.50-2.44), maternal age (aOR = 1.48, 95% CI 1.09-2.00), and gestational weight gain (aOR = 1.80, 95% CI 1.40-2.30). Paternal pregravid BMI was not independently associated with LGA or SGA. CONCLUSION: Paternal BMI prior to conception is associated with infant birthweight but only modestly so, in contrast to the dominant impact of maternal weight.

Association between ELABELA Serum Concentrations in First Trimester and Pregnancy-Induced Hypertension.

ELABELA (ELA) is considered to be implicated in the pathophysiology of preeclampsia (PE), since ELA-deficient mice exhibited PE-like symptoms and infusion of exogenous ELA normalized the gestational hypertension (GH) and proteinuria. However, no evidence show that circulating ELA is deficient in early placental development among women who destined to develop GH/PE. This nested case-control study was conducted to investigate the association between serum ELA concentration in early pregnancy and the risk of later GH/PE. Participants were recruited and sampled in 10-14+6 weeks of gestation. Definite GH/PE cases were matched 1 : 3 to controls with respect to age and gestational age. Serum concentration of ELA was measured using enzyme immunoassay. Women with later GH (N = 28) had a slightly lower median concentration of ELA (46.72 ng/mL versus 53.54 ng/mL), while those with later PE (N = 16) had a slightly higher median concentration of ELA (74.8 ng/mL versus 66.30 ng/mL) compared to the controls. Yet, both the increments did not reach statistically significant difference (GH: P = 0.380, PE: P = 0.799). ELA serum concentrations were unchanged in first trimester in women with GH/PE. Further studies are still needed to identify the dynamic changes in serum ELA concentrations during the whole pregnancy, especially in those with pregnancy-induced hypertensive disorders.

SOX1 Promoter Hypermethylation as a Potential Biomarker for High-Grade Squamous Intraepithelial Neoplasia Lesion and Cervical Carcinoma: A Meta-Analysis With Trial Sequential Analysis.

Background: DNA methylation has been widely assessed as a potential biomarker for the early detection of cervical cancer (CC). Herein, we assessed the associations of SOX1 promoter hypermethylation with squamous intraepithelial lesion and CC. Methods: Published studies and genome-wide methylation datasets were searched from electronic databases (up to April 2019). The associations of SOX1 hypermethylation with high-grade squamous intraepithelial lesion (HSIL) and CC risks were evaluated by odds ratios (ORs) and 95% confidence intervals (CIs). The summary receiver operator characteristic test was used to assess the diagnostic value of the SOX1 promoter hypermethylation of CC and intraepithelial neoplasia type III or worse (CIN3+). Trial sequential analysis (TSA) was performed to evaluate the stability of results and estimate the required information size (RIS). Results: In this meta-analysis of 17 published studies, the SOX1 methylation rates increased among low-grade SIL (LSIL, 27.27%), HSIL (40.75%), and CC (84.56%) specimens. Compared with control specimens, SOX1 promoter hypermethylation progressively increased the risk of HSIL by 4.20-fold (p < 0.001) and CC by 41.26-fold (p < 0.001). The pooled sensitivity of SOX1 methylation was estimated to be 0.85 (95% CI: 0.81-0.88) in differentiating patients with CC, corresponding to a specificity of 0.72 (95% CI: 0.69-0.75) and an area under the curve (AUC) of 0.93. Furthermore, the pooled sensitivity of SOX1 methylation was estimated to be 0.75 (95% CI: 0.72-0.78) in differentiating patients with CIN3+, corresponding to a specificity of 0.71 (95% CI: 0.69-0.73) and an AUC of 0.84. The pooled results of TCGA and GEO datasets showed that all CpG sites in SOX1 were associated with CC and 16 of 19 CpG sites were associated with HSIL. The results of TSA illustrated that the size was sufficient and significant associations were observed. Conclusion: This meta-analysis indicated that SOX1 promoter hypermethylation might have a potential value in the clinical diagnosis of CC and CIN3+.

Down-Regulated CMTM2 Promotes Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma.

BACKGROUND: Our recent study identified that human chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing family member 2 (CMTM2) was deregulated in hepatocellular carcinoma (HCC) tissues and posed as a potential tumor suppressor. However, the mechanism of CMTM2 in HCC occurrence and development has not been well elaborated. MATERIALS AND METHODS: The expression of CMTM2 was knocked-down by RNA interruption in Huh-7 and SMMC7721 cells. Cell proliferation ability was detected by CCK8 test and colony formation assay. The cell invasion and migration were measured by wound healing and Transwell assay. RESULTS: We found that the cell proliferation was significantly increased by interruption of CMTM2 expression, both in Huh-7 and SMMC7721 cells. Moreover, down-regulated CMTM2 could promote the invasion and migration ability of HCC cells through inducing the epithelial-mesenchymal transition (EMT) process. We further discovered that both the expression of CMTM2 and the EMT-associated marker E-cadherin were decreased in the same thirty cases of HCC tissues compared with the corresponding adjacent non-tumor tissues. Pearson correlation test showed that there was a significantly positive correlation between CMTM2 and E-cadherin in HCC tissues (P<0.05). CONCLUSION: Based on the results of cell model and HCC tissues, our study suggests that down-regulated CMTM2 promotes HCC metastasis through inducing the EMT process.

Associations of MGMT promoter hypermethylation with squamous intraepithelial lesion and cervical carcinoma: A meta-analysis.

BACKGROUND: In this research, an meta-analysis was performed for assessment of the associations between O6-methyguanine-DNA methyltransferase (MGMT) promoter hypermethylation possessing low-grade intraepithelial lesion (LSIL), high-grade intraepithelial lesion (HSIL), cervical cancer (CC), and clinicopathological characters of CC. METHODS: Literature selection were conducted through searching PubMed, Web of science, EMBASE, China National Knowledge Infrastructure and Wanfang databases (up to November 2018). An assessment of associations between MGMT methylation and LSIL, HSIL, CC risk and clinicopathological characteristics was performed through pooled odds ratios (ORs) with relevant 95% confidence intervals (CIs). Subgroup analyses, meta-regressions and Galbraith plots were conducted to conduct an exploration on the possible sources of heterogeneity. The genome-wide DNA methylation array studies were extracted from Gene Expression Omnibus (GEO) databases for validation of these outcomes. RESULTS: In this meta-analysis of 25 published articles, MGMT hypermethylation gradually elevated the rates among control group (12.16%), LSIL (20.92%), HSIL (36.33%) and CC (41.50%) specimens. MGMT promoter methylation was significant associated with the increased risk of LSIL by 1.74-fold (P<0.001), HSIL by 3.71-fold (P<0.001) and CC by 7.08-fold (P<0.001) compared with control. A significant association between MGMT promoter methylation with FIGO stage was also found (OR = 2.81, 95% CI: 1.79-4.41, p<0.001). The results of GEO datasets showed that 5 CpG sites in MGMT with a great diagnostic value for the screening of cervical cancer. CONCLUSION: The meta-analysis indicated the association between MGMT promoter hypermethylation and squamous intraepithelial lesion and cervical cancer. MGMT methylation detection might have a potential value to be an epigenetic marker for the clinical diagnosis of cervical cancer.

Prevalence of metabolic syndrome and its risk factors among 10,348 police officers in a large city of China: A cross-sectional study.

The aim of this study was to assess the prevalence of metabolic syndrome (MS) and its risk factors among the police officers in a large city of China.A cross-sectional study was conducted in 10,348 police officers in 2017 in Changsha, a provincial capital located in central-south China. All participants underwent a physical examination to measure the compotents of MS and completed a questionnaire to collect data on potential risk factors. According to the current guidelines of China, MS was defined as the presence of any 3 of the following five traits: abdominal obesity, defined as a waist circumference ≥90 cm in men and ≥85 cm in women; fasting serum triglycerides ≥1.70 mmol/L, or drug treatment for elevated triglycerides; fasting serum high-density lipoprotein cholesterol <1.03 mmol/L, or drug treatment for low high-density lipoprotein cholesterol; blood pressure ≥130/85 mmHg, or drug treatment for elevated blood pressure; fasting plasma glucose ≥6.1 mmol/L, or 2-hour plasma glucose ≥7.8 mmol/L after a 75-g oral glucose load, or drug treatment for elevated blood glucose.The prevalence of MS was 23.2% (95% confidence interval [CI]: 22.2%-24.2%). The main risk factors associated with MS were older age (odds ratio [OR] 1.546, 95% CI 1.431-1.670), being male (OR 11.256, 95%CI 7.147-17.726), alcohol consumption (OR 1.250, 95% CI 1.070-1.461), and tobacco use (OR 1.398, 95% CI 1.232-1.586). Exercise was associated with decreased risk of MS (OR 0.865, 95% CI 0.755-0.991).The prevalence of MS was low in the study population. Its risk factors were similar to those identified in the general population of China. Lifestyle intervention is warranted in policemen to reduce the risk of MS and prevent diabetes and cardiovascular disease.

Rare RNF213 variants and the risk of intracranial artery stenosis/occlusion disease in Chinese population: a case-control study.

BACKGROUND: RNF213 rare variant-p.R4810K (rs112735431) was significantly associated with intracranial artery stenosis/occlusion disease (ICASO) in Japan and Korea and to a lesser degree in China. Considering the allelic heterogeneity, we performed target exome sequencing of RNF213 with the aim to identify the rare variants spectrum and their association with ICASO in a Chinese population and further to explore whether the rare variants carrier patients present specific clinical phenotype. METHODS: Target exome sequencing of RNF213 was performed in 250 ICASO patients using FastTarget sequencing technology. Various filtering process were used to select the candidate variants. Control individuals were obtain from 1000 Genome Project (208 Chinese samples) and GeneSky in-house database (1007 samples). Gene-based association analyses were conducted to identify the association between RNF213 rare variants and ICASO. The clinical characteristics of rare variant carriers and non-carriers were compared using Chi-squared test or Fisher's exact test. RESULTS: After filtration, 18 rare variants were identified in 39 patients. Gene-based association test showed that rare variants of RNF213 were significantly associated with ICASO (Minor allele frequency < 0.05, WSS p = 4.88 × 10- 10; SKAT p = 9.68 × 10- 6; SKAT-O p = 3.42 × 10- 9). There were no significant clinical characteristic differences other than the diagnosis age which was older in the carriers than the non-carriers (60.5 ± 6.2 vs 57.3 ± 8.9 years old, p = 0.028). CONCLUSION: Rare variants of RNF213 are associated with ICASO in Chinese. However, there are limited genetic diagnosis values of the gene due to no specific phenotypic presentation in the carriers and non carrier patients.

Abnormal octadeca-carbon fatty acids distribution in erythrocyte membrane phospholipids of patients with gastrointestinal tumor.

Fatty acid (FA) composition is closely associated with tumorigenesis and neoplasm metastasis. This study was designed to investigate the differences of phospholipid FA (PLFA) composition in erythrocyte and platelet cell membranes in both gastrointestinal (GI) tumor patients and healthy controls.In this prospective study, 50 GI tumor patients and 33 healthy volunteers were recruited between the years 2013 and 2015. Blood samples were collected from healthy volunteers and patients, and FA composition was assessed using gas chromatography-mass spectrometer (GC-MS), and data were analyzed by multifactor regression analysis.Compared with healthy controls, the percentages of C18:0 (stearic acid, SA), C22:6 (docosahexaenoic acid, DHA), and n-3 polyunsaturated FAs (n-3 PUFA) were significantly increased, while C18:1 (oleic acid, OA), C18:2 (linoleic acid, LA), and monounsaturated FAs (MUFA) decreased in erythrocyte membranes of GI tumor patients. Also, patient's platelets revealed higher levels of C20:4 (arachidonic acid, AA) and DHA, and lower levels of OA and MUFA.Our study displayed a remarkable change in the FA composition of erythrocyte and platelet membranes in GI tumor patients as compared with healthy controls. The octadeca-carbon FAs (SA, OA, and LA) in erythrocyte membranes could serve as a potential indicator for GI tumor detection.

Meta-analysis of studies using metformin as a reducer for liver cancer risk in diabetic patients.

Metformin has garnered more interest as a chemo-preventive agent given the increased liver cancer risk in diabetic patients. This work was undertaken to better understand the effect of metformin use on liver cancer risk in diabetic patients.A comprehensive literature search was performed in PubMed, Embase, BIOSIS Previews, Web of Science, and Cochrane Library through July 30, 2016. Meta-analyses were performed using Stata version 12.0, with odds ratio (ORs) and 95% confidence intervals (CIs) as effect measures.Twenty-three studies were included. Meta-analysis of 19 studies involving 550,882 diabetic subjects suggested that metformin use reduced the ratio of liver cancer by 48% (OR = 0.52; 95% CI, 0.40-0.68) compared with nonusers. The protective effect was validated in all the exploratory subgroup analyses, except that pooled result of post hoc analyses of 2 randomized controlled trials found no significant difference between subjects with metformin and those without, with OR being 0.84 (95% CI, 0.10-6.83). After adjusting for hepatitis B/C virus infection, cirrhosis, obesity, behavioral factors, and time-related bias, the association was stable, pooled OR ranged from 0.42 to 0.75.A protective effect for liver cancer was found in diabetic metformin users. However, more randomized clinical evidence is still needed to verify the results.