Restructuring multi-phase interfaces from Cu-based metal-organic frameworks for selective electroreduction of CO2 to C2H4.

Multi-phase interfaces are promising for surmounting the energy barriers of electrochemical CO2 reduction involving multiple electron transfer steps, but challenges still remain in constructing interfacial micro-structures and unraveling their dynamic changes and working mechanism. Herein, highly active Ag/Cu/Cu2O heterostructures are in situ electrochemically restructured from Ag-incorporating HKUST-1, a Cu-based metal-organic framework (MOF), and accomplish efficient CO2-to-C2H4 conversion with a high faradaic efficiency (57.2% at -1.3 V vs. RHE) and satisfactory stability in flow cells, performing among the best of recently reported MOFs and their derivatives. The combination of in/ex situ characterizations and theoretical calculations reveals that Ag plays a crucial role in stabilizing Cu(i) and increasing the CO surface coverage, while the active Cu/Cu2O interfaces significantly reduce the energy barrier of C-C coupling toward the boosted ethylene production. This work not only proves MOFs as feasible precursors to derive efficient electrocatalysts on site, but also provides in-depth understanding on the working interfaces at an atomic level.

Behavioral carry-over effect and power consideration in crossover trials.

A crossover trial is an efficient trial design when there is no carry-over effect. To reduce the impact of the biological carry-over effect, a washout period is often designed. However, the carry-over effect remains an outstanding concern when a washout period is unethical or cannot sufficiently diminish the impact of the carry-over effect. The latter can occur in comparative effectiveness research, where the carry-over effect is often non-biological but behavioral. In this paper, we investigate the crossover design under a potential outcomes framework with and without the carry-over effect. We find that when the carry-over effect exists and satisfies a sign condition, the basic estimator underestimates the treatment effect, which does not inflate the type I error of one-sided tests but negatively impacts the power. This leads to a power trade-off between the crossover design and the parallel-group design, and we derive the condition under which the crossover design does not lead to type I error inflation and is still more powerful than the parallel-group design. We also develop covariate adjustment methods for crossover trials. We evaluate the performance of cross-over design and covariate adjustment using data from the MTN-034/REACH study.

Association between hemoglobin A1c and abdominal aortic calcification: results from the National Health and Nutrition Examination Survey 2013-2014.

BACKGROUND: Hemoglobin A1c (HbA1c), a "gold standard" for the assessment of glycemic control, was associated with an increased risk of cardiovascular disease and coronary artery calcification. However, its effects on abdominal aortic calcification (AAC) are uncertain. The present study comprehensively investigated the association between HbA1c and AAC in the 2013-2014 National Health and Nutrition Examinations Surveys. METHODS: Among 1,799 participants ≥ 40 years, dual-energy X-ray absorptiometry-derived AAC was quantified using the Kauppila score (AAC-24). Severe AAC was defined as a total AAC-24 > 6. Weighted linear regression models and logistic regression models were used to determine the effects of HbA1c on AAC. The restricted cubic spline model was used for the dose-response analysis. RESULTS: The mean AAC-24 of participants was 1.3, and 6.7% of them suffered from severe AAC. Both AAC-24 and the prevalence of severe AAC increased with the higher tertile of HbA1c (P < 0.001). Elevated HbA1c levels would increase the AAC-24 (ß = 0.73, 95% CI: 0.30-1.16) and the risk of severe AAC (OR = 1.63, 95% CI: 1.29-2.06), resulting in nearly linear dose-response relationships in all participants. However, this positive correlation were not statistically significant when participants with diabetes were excluded. Furthermore, subgroup analysis showed significant interactions effect between HbA1c and hypertension on severe AAC with the OR (95% CI) of 2.35 (1.62-3.40) for normotensives and 1.39 (1.09-1.79) for hypertensives (P for interaction = 0.022). CONCLUSION: Controlling HbA1c could reduce AAC scores and the risk of severe AAC. Glycemic management might be a component of strategies for preventing AAC among all participants, especially normotensives.

Safety profile of methotrexate used off-label in ectopic pregnancy: an active monitoring study based on a Chinese hospital pharmacovigilance system.

OBJECTIVE: Methotrexate (MTX) is characterized as first-line therapy although its indication of ectopic pregnancy is off-label use. We aimed to conduct a retrospective cohort study to investigate the incidence, characteristics of adverse drug reactions (ADRs) of MTX, provide valuable insights for medical workers. METHODS: Basing on China Hospital Pharmacovigilance System (CHPS), a retrospective analysis was performed to evaluate the safety of MTX (n = 672). An active monitoring model was set to detect ADR signals from the hospital information system. Frequency, Common Terminology Criteria for Adverse Events (CTCAE) grade proportion and association of dose exposure with ADRs were presented as outcomes. RESULTS: The total incidence of ADRs was 54.0%. Anaemia (37.6%) was the most frequent ADR, followed by hepatic function abnormal (11.3%), hyperuricemia (6.1%), neutropenia (4.6%), leukopenia (4.0%), and dyslipidaemia (2.5%). For the composition of all ADRs, CTCAE grade one, two and three dominated for 86.3%, 12.1% and 1.6%, respectively. The severity of hepatic function abnormal was more serious in the two-dose exposed group (p = .021), while other types of ADRs had no statistical or clinical differences. Logistic regression analysis showed the incidence of any ADRs (OR 1.87 [1.31-2.64]; p = .001), hepatic function abnormal (OR 2.75 [1.69-4.48]; p < .001), dyslipidaemia (OR 5.15 [1.87-14.13]; p = .001) were significantly higher in the two-dose exposed group. After adjusted, the positive associations were still maintained. CONCLUSIONS: MTX is quite safe in ectopic pregnancy, despite its mild to moderate hematotoxicity, hepatotoxicity and nephrotoxicity. Taking CHPS can present the accurate denominator of the incidence of adverse drug reactions into account, our study advocates that it may have great potential to be used as an active monitoring tool for off-label drug use risk management.

Association between the occurrence of buccally displaced canine and palatal and craniofacial morphology in adolescents.

The main objective of the present research study is to evaluate the association between the occurrence of buccally displaced canine (BDC) and the palatal as well as the craniofacial morphology in adolescents in accordance at the early permanent dentition. As the experimental group, 100 adolescents of Chinese ethnicity (mean age 13.05 years) with crowding and buccally displaced canine (BDC-c) were selected in comparison with the same number of candidates (mean age 12.59 years) without BDC and crowding as control group. Digital dental casts and cephalograms were collected for three dimensional (3D) and cephalometric measurements. An independent sample T-test was used to compare the cephalometric values between the two groups. Logistic regression as commonly statistical methods used in empirical study including categorical dependent variables was used to identify the joint effects of the dental variables' 3D measurements. When comparing the groups with above analysis, patients with BDC showed a statistically significant narrower and higher palatal vault. For the cephalometric variables, the anterior cranial base length, sagittal position of the maxilla (SNA), sagittal position of the mandible (SNB), and skeletal relationship between maxilla and mandible (ANB) appeared to be smaller, whilst palatal plane angle (SN-PP), Frankfort-mandibular plane angle (FMA), anterior facial height, and lower facial height were larger in BDC-c control group (p < 0.05). A smaller inter-first premolar width was significant in the prediction model (p = 0.002). This study highlights that BDC-c participants in early permanent dentition exhibited a narrower dental arch and higher palatal vault, of which a smaller inter-first premolar width would significantly increase the occurrence of BDC.

Chlorine-mediated electrodeposition of hierarchical and hydrophobic copper electrocatalysts for efficient CO2 electroreduction to ethylene.

Hierarchical Cu dendrites fabricated via Cl-mediated electrodeposition afford high C2H4 efficiency (58% faradaic efficiency at -0.9 V vs. RHE) for CO2 electroreduction thanks to not only the optimal hydrophobicity/aerophilicity, but also the dominant distribution of active (100) and (110) facets.

Preparation of Bi/BiOBr sensitized titania nanorod arrays via a one-pot solvothermal method and construction of kanamycin photoelectrochemical aptasensors.

In this work, a photoelectrochemical (PEC) aptasensor for detecting kanamycin (KAN) was designed based on an aptamer modified Bi/BiOBr/titania nanorod array (TiO2 NRA). Bi/BiOBr was loaded onto the TiO2 NRA via a one-pot solvothermal method using glucose as a reductant. The p-n heterojunction structure constructed from chrysanthemums like BiOBr and the TiO2 NRA improves the electron transfer rate. Combined with metal Bi with the surface plasmon resonance (SPR) effect, it further increases the absorption range of visible light and enhances the light response performance of the PEC aptasensor. The KAN aptamer is fixed to the Bi/BiOBr/TiO2 NRA photoelectric material through the CN structure. Once the aptamer precisely captures KAN molecules, photocurrent changes are generated to realize the detection of KAN. The designed PEC aptasensor shows good detection performance in the linear response range of 1 pM-200 nM, and the detection limit is 0.7 pM (S/N = 3). The aptasensor was applied to the determination of KAN in milk with satisfactory results.

The effects of cortical bone thickness and miniscrew implant root proximity on the success rate of miniscrew implant: A retrospective study.

OBJECTIVE: To investigate the effects of cortical bone thickness (CBT), miniscrew implant root proximity (MRP) and other related factors on the success rate of miniscrew implant (MSI). MATERIALS AND METHODS: Four hundred and five MSIs placed in 171 patients were analysed in this retrospective study. The primary predictor variables were CBT and MRP at MSI insertion sites. The predictor variables also included patient, location, MSI design and procedure related factors. The outcome variable was the survival of MSI. The differences in measurement data between success group and failed group were evaluated by the analysis of variance and independent samples t tests. Patient, location, MSI design and procedure related factors associated with the MSI prognosis were analysed by survival analysis with Cox proportional hazard regression model. The P value was set at .05. And the survival curves of independent factors were plotted. RESULTS: The overall success rate of MSI was 82.7%. The age of MSI host, CBT, interdental root distance (IRD) and MRP at MSI sites showed no significant differences between failed group and success group. CBT and insertion jaws were independent prognosis factors screened out by Cox proportional hazard regression model. Failure risk (hazard ratio) of MSI with CBT <1 mm was 4.72. The failure risk in the mandible was 3.80 times as high as that in the maxilla. CONCLUSION: Inadequate CBT (<1 mm) contributed to the failure of MSI. MSI placed in the maxilla showed better prognosis compared to the mandible. MRP had no significant effect on the prognosis.

Machine learning algorithms to predict early pregnancy loss after in vitro fertilization-embryo transfer with fetal heart rate as a strong predictor.

BACKGROUND AND OBJECTIVE: According to previous studies, after in vitro fertilization-embryo transfer (IVF-ET) there exist a high early pregnancy loss (EPL) rate. The objectives of this study were to construct a prediction model of embryonic development by using machine learning algorithms based on historical case data, in this way doctors can make more accurate suggestions on the number of patient follow-ups, and provide decision support for doctors who are relatively inexperienced in clinical practice. METHODS: We analyzed the significance of the same type of features between ongoing pregnancy samples and EPL samples. At the same time, by analyzing the correlation between days after embryo transfer (ETD) and fetal heart rate (FHR) of those normal embryo samples, a regression model between the two was established to obtain FHR model of normal development, and the residual analysis was used to further clarify the importance of FHR in predicting pregnancy outcome. Finally we applied six representative machine learning algorithms including Logistic Regression (LR), Support Vector Machine (SVM), Decision Tree (DT), Back Propagation Neural Network (BNN), XGBoost and Random Forest (RF) to build prediction models. Sensitivity was selected to evaluate prediction results, and accuracy of what each algorithm above predicted under both the conditions with and without FHR was compared as well. RESULTS: There were statically significant differences in the same type of features between ongoing pregnancy samples and EPL samples, which could serve as predictors. FHR, of which the normal development showed a strong correlation with ETD, had great predictive value for embryonic development. Among the six predictive models the one predicted with the highest accuracy was Random Forest, of which recall ratio and F1 could reach 97%, and AUC could reach 0.97, FHR taken into account as a feature. In addition, Random Forest had a higher prediction accuracy rate for samples with longer ETD-its accuracy rate could reach 99% when predicting those at 10 weeks after embryo transfer. CONCLUSION: In this study, we established and compared six classification models to accurately predict EPL after the appearance of embryonic cardiac activity undergoing IVF-ET. Finally, Random Forest model outperformed the others. The implementation of Random Forest model in clinical environment can assist doctors to make clinical decisions.

Genetic variant in miR-21 binding sites is associated with colorectal cancer risk.

Single nucleotide polymorphisms (SNPs) within binding sites of microRNAs (miRNAs) could modify cancer susceptibility by changing the binding affinity of miRNAs on their target mRNA 3'-untranslated regions (UTRs). MicroRNA-21 (miR-21) is involved in the development of colorectal cancer. However, the relationship between SNPs within the binding sites of miR-21 and colorectal cancer risk has not been widely investigated. A case-control study including 1147 patients and 1203 controls was performed to evaluate the association of SNPs in miR-21 binding sites and colorectal cancer risk. Dual-luciferase reporter assays and functional assays were performed to evaluate the effects of miR-21. The SNP rs6504593 C allele conferred an increased risk of colorectal cancer compared with the T allele in an additive model (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36, P = 0.011). Dual-luciferase reporter assays demonstrated that the rs6504593 T allele negatively post-transcriptionally regulated IGF2BP1 by altering the binding affinity of miR-21. Additionally, colorectal cancer cells transiently transfected with miR-21 mimics promoted cell proliferation and suppressed apoptosis, whereas inhibition of miR-21 decreased cell growth. These data suggest that the miR-21 binding site SNP rs6504593 in the IGF2BP1 3'-UTR may alter IGF2BP1 expression and contribute to colorectal cancer risk.

MiR-183-5p Alleviates Chronic Constriction Injury-Induced Neuropathic Pain Through Inhibition of TREK-1.

MicroRNAs have been implicated in nerve injury and neuropathic pain. In the previous study we had shown that miR-96 can attenuate neuropathic pain through inhibition of Nav1.3. In this study, we investigated the role of miR-183, a same cluster member of microRNA with miR-96, in neuropathic pain and its potential mechanisms. We found that the expression level of miR-183-5p in dorsal root ganglion was decreased with the development of neuropathic pain induced by chronic constriction sciatic nerve injury (CCI). By contrast, the TREK-1, a K+ channel, was increased. Further investigation identified that intrathecal injection of miR-183-5p mimic efficiently ameliorated neuropathic pain and inhibited the expression of TREK-1, a predicted target gene of miR-183-5p. Luciferase assays confirmed the binding of miR-183-5p and TREK-1. In addition, over-expression of TREK-1 blocked the roles of miR-183-5p in neuropathic pain. Our findings suggested that miR-183-5P participated in the regulation of CCI-induced neuropathic pain through inhibiting the expression of TREK-1.

Celecoxib alleviates oxaliplatin-induced hyperalgesia through inhibition of spinal ERK1/2 signaling.

Numerous pieces of evidence have revealed that oxaliplatin (OXA) evokes mechanical and cold hypersensitivity. However, the mechanism underlying these bothersome side effects needs to be further investigated. It is well known that cyclooxygenase-2 (COX-2) and extracellular signal-regulated kinases (ERK1/2) signaling play crucial roles in several pain states. Our previous data showed that Akt2 in the dorsal root ganglion (DRG) participated in the regulation of OXA-induced neuropathic pain. But it is still unclear whether spinal ERK1/2 signaling is involved in the regulation of OXA-induced hyperalgesia, and the linkage between COX-2 and ERK1/2 signaling in mediating OXA-induced hyperalgesia also remains unclear. In this research, we investigated the possible mechanism of celecoxib, a COX-2 inhibitor, in OXA-induced neuropathic pain. Our results show that single dose of OXA (12 mg/kg) significantly attenuated both the tail withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) at days 4 after the OXA treatment. Administration of celecoxib (30 mg/kg/day) for 4 and 6 days inhibited the decrease in TWL and MWT, and each was significantly higher than that of the OXA+vehicle group and was equivalent to that of the vehicles group. OXA increased the expression of cyclooxygenase-2 (COX-2) mRNA and phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) protein in the lumbar 4-5 (L4-5) spinal cord dorsal horn neurons. Administration of celecoxib for 7 days suppressed the increase in expression of COX-2 and pERK1/2 induced by OXA. Our findings suggested that COX-2 and ERK1/2 signaling in spinal cord contributed to the OXA-induced neuropathic pain.

Circulating miR-497 and miR-663b in plasma are potential novel biomarkers for bladder cancer.

MicroRNAs (miRNAs), abundant and highly stable in the plasma, have been widely reported. This greatly pursued us to investigate whether plasma miRNAs could be considered as powerful biomarkers for diagnosing bladder cancer (BC). We performed a plasma miRNAs profile with the TaqMan Low Density Array, and a two-phase validation to detect the candidate miRNAs expression by quantitative PCR. The receiver operating characteristic curve (ROC) and the area under curve (AUC) were used to evaluate diagnostic accuracy. A total of eight plasma miRNAs abnormally expressed between BC patients and healthy controls in microarray analysis (i.e., elevated miRNAs for miR-505, miR-363 and miR-663b, and decreased for miR-99a, miR-194, miR-100, miR-497 and miR-1 in BC plasma). In further independent cohorts, miR-497 and miR-663b with significantly differential expression were confirmed. Moreover, the AUC, sensitivity and specificity were raised to 0.711 (95% CI = 0.641-0.780), 69.7% and 69.6%, respectively, when miR-497 and miR-663b were integrated. This is the first study systematically exploring the existence of specific plasma miRNAs as early diagnostic biomarkers for BC in Chinese population; and these findings supported that plasma miR-497 and miR-663b could be promising novel circulating biomarkers in clinical detection of BC.

Identification of novel piRNAs in bladder cancer.

PIWI-interacting RNAs (piRNAs) are a newly identified class of small non-coding RNAs that can play important roles in germline development and carcinogenesis. In this study, piRNA microarrays were used to investigate global piRNA expression in three bladder cancer tissues and their adjacent normal tissues. Using the 3' untranslated region (UTR) sequence complementarily method, we predicted the target gene of piRNA. Our results showed that the expression levels of 106 piRNAs were up-regulated and 91 were down-regulated in bladder cancer tissues, among which the fold-change of down-regulated piRNA DQ594040 associated with bladder cancer (piRABC) was the highest piRNA. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to confirm piRABC expression in paired bladder cancer tissues and their adjacent normal tissues (n = 25). Over-expression of piRABC can inhibit bladder cancer cell proliferation, colony formation, and promote cell apoptosis (all P < 0.05). Luciferase reporter gene assays indicated that piRABC could increase the luciferase activity of TNFSF4. Western blotting analyses and ELISA assays also confirmed that the expression of TNFSF4 protein was up-regulated in control subjects compared with bladder cancer subjects. In conclusion, piRABC plays a crucial role in the development of bladder cancer.

The prognostic value of long-term visit-to-visit blood pressure variability on stroke in real-world practice: a dynamic cohort study in a large representative sample of Chinese hypertensive population.

BACKGROUND: The prognostic significance of long-term visit-to-visit blood pressure variability (BPV) has not yet been validated in "real world" hypertensive patients. The aim of the current study is to explore the prognostic value of BPV on stroke in hypertensive patients. METHODS: This was a dynamic prospective cohort study based on electronic medical records in Shanghai, China. Hypertensive patients (N=122,636) without history of stroke at baseline, were followed up from 2005 to 2011. The cohort comprised of 4522 stroke patients and 118,114 non-stroke patients during a mean follow-up duration of 48 months. BPV was measured by standard deviation (SD) and the coefficient of variation (CV) of blood pressure. RESULTS: The visit-to-visit variability of both systolic blood pressure (SBP) and diastolic blood pressure (DBP) was independently associated with the occurrence of stroke [SD: the hazard ratios (95% confidence intervals) of SBP and DBP were 1.042 (1.021 to 1.064) and 1.052 (1.040 to 1.065); CV: the hazard ratios (95% confidence intervals) of SBP and DBP were 1.183 (1.010 to 1.356) and 1.151 (1.005 to 1.317), respectively]. The hazard ratio values increased along with an increase of the BPV levels of SBP and DBP. The increment effect remained significant after controlling the blood pressure control status of subjects. CONCLUSIONS: Increased BPV of both SBP and DBP, independent of the average blood pressure, is a predictor of stroke among community hypertensive patients in real-world clinical practice. The risk of stroke increased along with increased BPV. Stabilizing BPV might be a therapeutic target in hypertension.

Clinical potential role of circulating microRNAs in early diagnosis of colorectal cancer patients.

Current procedures for diagnosis and biomarker examination of colorectal cancer (CRC) are invasive and unpleasant. There is a great need to identify sensitive and specific biomarkers for early diagnosis of CRC. Circulating microRNAs (miRNAs) are promising molecular markers for CRC prediction. We performed a comprehensive meta-analysis to integrate an evaluation index for diagnostic accuracy of circulating miRNAs in diagnosing CRC patients. Furthermore, we conducted an independent validation set of 49 CRC patients and 49 healthy controls. In our meta-analysis, we found that miR-21 yielded a pooled area under ROC curve (AUC) of 0.867 (sensitivity: 76%, specificity: 82%) in discriminating CRC from controls, and miR-92a yielded a summary AUC of 0.803 (sensitivity: 77%, specificity: 68%); miR-21 had a higher diagnostic efficiency than miR-92a. In the further validation, plasma miR-21 levels in CRC patients were significantly higher than levels observed in healthy subjects. A ROC curve analysis showed a consistent result. However, this phenotype was not present in miR-92a. Moreover, the expression trend of miR-21 in plasma samples was in line with that of tissue samples, along with the cellular level. Current evidences suggest that plasma miR-21 could be a reliable and non-invasive biomarker for CRC diagnosis. Studies with larger cohorts that include the diagnostic value of plasma miR-21 for CRC are warranted.

Hsa-miR-196a2 polymorphism increases the risk of acute lymphoblastic leukemia in Chinese children.

Acute lymphoblastic leukemia (ALL) is a major cause of mortality and morbidity in childhood, and the causes of ALL are not completely understood. microRNAs (miRNAs) regulate various biological processes including organ development, cell growth regulation, cell differentiation, apoptosis, and tumorigenesis. We performed a case-control study with 570 childhood ALL cases and 673 cancer-free controls to investigate the association between hsa-miR-196a2 rs11614913 T>C polymorphism and ALL risk. The bioinformatics was used to estimate the potential target of hsa-miR-196a2. In the present study, the hsa-miR-196a2 variant TC heterozygote, and CC/TC genotypes were found to be associated with a significantly increased childhood ALL risk, compared with the TT wild-type homozygote (adjusted OR=1.50, 95% CI=1.15-1.95 for TC and OR=1.40, 95% CI=1.09-1.79 for CC/TC). Further, the difference was pronounced in younger (≤6) subjects or parental non-drinker. The significance of the increased risk is more obvious than the higher treatment branch. Additionally, we found that the rs11614913 TC genotype can increase B-phenotype ALL risk (OR=1.37, 95% CI=1.07-1.76). Finally, combination of three bioinformatics approaches revealed that HOXC8 may be the target gene of hsa-miR-196a2. Taken together, our finding suggested that hsa-miR-196a2 rs11614913 T>C may increase the risk of childhood ALL. Large studies with the function of hsa-miR-196a2 are needed in the further study.

Genetic variation in DROSHA 3'UTR regulated by hsa-miR-27b is associated with bladder cancer risk.

PURPOSE: miRNAs can regulate the biological processes, including differentiation, proliferation and apoptosis. DICER and DROSHA are two members of RNase III family, playing pivotal roles in the pathway of miRNAs biogenesis. In this study, we hypothesized that genetic variations of the DICER and DROSHA genes were associated with the bladder cancer risk. EXPERIMENTAL DESIGN: We performed a case-control study of 685 bladder cancer cases and 730 controls to investigate the association between the seven functional SNPs of DICER and DROSHA genes and bladder cancer risk. We then evaluated the functionality of the important SNPs. RESULTS: We found that rs10719T>C polymorphism located in 3' untranslated region (UTR) of DROSHA gene was associated with the increased risk of bladder cancer. Stratified analysis suggested that rs10719TC/CC genotype can increase risk of bladder cancer among male patients (Adjusted OR = 1.34, 95% CI = 1.05-1.70, P = 0.018), and ever smokers (1.56, 1.14-2.14, 0.006), compared with TT genotype. Furthermore, DROSHA rs10719T>C polymorphism was predicted to regulate the binding activity of hsa-miR-27a/b. Luciferase reported gene assay confirmed that rs10719 T to G substitution disrupted the binding site for hsa-miR-27b, resulting the increased levels of DROSHA protein. CONCLUSIONS: Taken together, these findings suggested that DROSHA rs10719T>C polymorphism may be associated with bladder cancer risk in a Chinese population, and hsa-miR-27b can influence the expression of DROSHA protein by binding with 3'UTR.

AdipoQ polymorphisms are associated with type 2 diabetes mellitus: a meta-analysis study.

OBJECTIVE: Adiponectin (AdipoQ) plays an important role in the pathogenesis of diabetes mellitus and is considered as an important candidate gene for type 2 diabetes mellitus (T2DM). So far, there have been many studies to investigate the association between the adiponectin polymorphisms and T2DM risk. However, the results are conflicting. To derive a more precise estimation, we performed a meta-analysis to assess the association between five AdipoQ polymorphisms [-11426A > G (rs16861194), -11391G > A (rs17300539), -11377C > G (rs266729), +45T > G (rs2241766) and +276G > T (rs1501299)], and T2DM risk. METHODS: The fixed and random-effects model should be used to assess the summary odds ratios (ORs) of each study. ORs with 95% confidence intervals (CIs) were used to evaluate the strength of association. On the basis of the included criteria, we selected 39 papers, among which eight for -11426A > G, 14 for -11391G > A, 21 for -11377C > G, 28 for +45 T > G and 24 for +276G > T. Sensitivity analyses were conducted to assess the stability of the results. Both Begg's funnel plots and Egger's test are commonly used to evaluate publication bias. RESULTS: Overall, we found that individuals with the -11426G allele had a 0.15-fold significantly increased T2DM risk (additive model: 1.15, 1.04-1.27, 0.222). In the stratified analyses, we found that the -11426A > G, -11391G > A and -11377C > G polymorphisms could increase T2DM risk in European populations in the additive model. For Asian populations, we found that the -11377C > G polymorphism also could elevate T2DM risk. CONCLUSIONS: Our results suggested that the adiponectin -11426A > G polymorphism could contribute to the T2DM risk.

EGFR 3'UTR 774T>C polymorphism contributes to bladder cancer risk.

Much evidence show that over-expression of epidermal growth factor receptor (EGFR) plays an important role in regulating carcinogenesis. Genetic variations in 3' untranslated region (3'UTR) of gene have been reported to affect gene expression by interfering with microRNAs (miRNAs), which are thought to function as either tumour suppressors or oncogenes by binding to their target mRNA. In this study, we investigated the association between the EGFR 3'UTR 774T>C polymorphism and bladder cancer risk. We used the TaqMan technology to genotype this genetic variant in a hospital-based case-control study of 908 bladder cancer patients and 1239 controls in a Chinese population. We found that the 774CC genotype was associated with a statistically significantly increased risk of bladder cancer [adjusted odds ratio = 1.29, 95% confidence interval = 1.05-1.58], compared with the 774TT/TC genotype, and this increased risk was more pronounced among subgroups of age > 65 years, non-smokers and patients' tumour invasive stage. Furthermore, luciferase assays in T24 cell showed that EGFR 3'UTR 774 T to C substitution could increase the expression of EGFR, which was consistent with the association study finding. Additionally, we also provide evidence that 774T>C polymorphism increasing EGFR expression was not regulated by hsa-miR-214 binding. These findings suggested that EGFR 3'UTR 774T>C polymorphism may contribute to susceptibility to bladder cancer.