BackgroundHepatocellular carcinoma (HCC) is a lethal disease, while the precise underlying molecular mechanisms of HCC pathogenesis remain to be defined. MicroRNA (miRNA), a class of non-coding small RNAs, can post-transcriptionally regulate gene expression. Altered miRNA expression has been reported in HCCs. This study assessed expression and the oncogenic activity of miRNA-10b (miR-10b) in HCC.MethodsForty-five paired human HCC and adjacent non-tumor tissues were collected for qRT-PCR and immunohistochemistry analysis of miR-10b and CUB and Sushi multiple domains 1 (CSMD1), respectively. We analyzed the clinicopathological data from these patients to further determine if there was an association between miR-10b and CSMD1. HCC cell lines were used to assess the effects of miR-10b mimics or inhibitors on cell viability, migration, invasion, cell cycle distribution, and colony formation. Luciferase assay was used to assess miR-10b binding to the 3’-untranslated region (3’-UTR) of CSMD1.ResultsmiR-10b was highly expressed in HCC tissues compared to normal tissues. In vitro, overexpression of miR-10b enhanced HCC cell viability, migration, and invasion; whereas, downregulation of miR-10b expression suppressed these properties in HCC cells. Injection of miR-10b mimics into tumor cell xenografts also promoted xenograft growth in nude mice. Bioinformatics and luciferase reporter assay demonstrated that CSMD1 was the target gene of miR-10b. Immunocytochemical, immunohistochemical, and qRT-PCR data indicated that miR-10b decreased CSMD1 expression in HCC cells.ConclusionsWe showed that miR-10b is overexpressed in HCC tissues and miR-10b mimics promoted HCC cell viability and invasion via targeting CSMD1 expression. Our findings suggest that miR-10b acts as an oncogene by targeting the tumor suppressor gene, CSMD1, in HCC.

BackgroundThe purpose of the study was to investigate the effects of the pregnane X receptor (PXR)*1B polymorphisms on CYP3A4 enzyme activity and postoperative fentanyl consumption in Chinese patients undergoing gynecological surgery.MethodsA total of 287 females of Han ethnicity, aged 20 to 50 years old, ASA I or II, scheduled to abdominal total hysterectomy or myomectomy under general anesthesia were enrolled. The analgesic model used was fentanyl consumption via patient-controlled intravenous analgesia (PCIA) in the post-operative period. Additionally, pain was assessed using a visual analog score (VAS). Pain scores, occurrence of adverse reactions and consumption of fentanyl were recorded during the 24 h postoperative period. The enzyme activity of CYP3A4 was evaluated by measuring the plasma ratio of 1′-hydroxymidazolam to midazolam 1 h after intravenous administration of 0.1 mg/kg midazolam. PXR genotyping was performed by direct DNA sequencing and the PXR*1B haplotype was analyzed via PHASE V.2.1 software.ResultsThe polymorphism frequency of PXR11156A > C/11193 T > C and 8055C > T were 49.6 and 49.3%, and the rate of PXR*1B haplotype was 48.8% in our study. None of the pain scores, consumption of fentanyl 24 h post-operatively or enzyme activity of CYP3A4, showed differences among different genotypes.ConclusionsPXR11156A > C, PXR11193T > C, PXR8055C > T or the PXR*1B haplotype do not appear to be important factors contributing to CYP3A4 activity and interindividual variations in postoperative fentanyl consumption in Han female patients undergoing gynecological surgery.Trial registrationThe DNA samples were obtained since 2007 to 2010 year in our hospital, there was no registration at that time. So this section is not applicable to our research.

BackgroundHepatocellular carcinoma (HCC) is a lethal disease, while the precise underlying molecular mechanisms of HCC pathogenesis remain to be defined. MicroRNA (miRNA), a class of non-coding small RNAs, can post-transcriptionally regulate gene expression. Altered miRNA expression has been reported in HCCs. This study assessed expression and the oncogenic activity of miRNA-10b (miR-10b) in HCC.MethodsForty-five paired human HCC and adjacent non-tumor tissues were collected for qRT-PCR and immunohistochemistry analysis of miR-10b and CUB and Sushi multiple domains 1 (CSMD1), respectively. We analyzed the clinicopathological data from these patients to further determine if there was an association between miR-10b and CSMD1. HCC cell lines were used to assess the effects of miR-10b mimics or inhibitors on cell viability, migration, invasion, cell cycle distribution, and colony formation. Luciferase assay was used to assess miR-10b binding to the 3’-untranslated region (3’-UTR) of CSMD1.ResultsmiR-10b was highly expressed in HCC tissues compared to normal tissues. In vitro, overexpression of miR-10b enhanced HCC cell viability, migration, and invasion; whereas, downregulation of miR-10b expression suppressed these properties in HCC cells. Injection of miR-10b mimics into tumor cell xenografts also promoted xenograft growth in nude mice. Bioinformatics and luciferase reporter assay demonstrated that CSMD1 was the target gene of miR-10b. Immunocytochemical, immunohistochemical, and qRT-PCR data indicated that miR-10b decreased CSMD1 expression in HCC cells.ConclusionsWe showed that miR-10b is overexpressed in HCC tissues and miR-10b mimics promoted HCC cell viability and invasion via targeting CSMD1 expression. Our findings suggest that miR-10b acts as an oncogene by targeting the tumor suppressor gene, CSMD1, in HCC.

BackgroundBoth multimorbidity and activities of daily living (ADL) disability and instrument activities of daily living (IADL) disability are common among elderly individuals. ADL/IADL disability may reduce individuals’ capacities for independent living and quality of life. This study aimed to examine the association between multimorbidity and ADL/IADL disability.MethodsA multi-stage cluster sample of 2058 residents aged 80 or older was investigated in Shanghai, China. Multimorbidity was defined as the simultaneous presence of two or more chronic diseases with ten common chronic conditions under consideration. Subjects who responded that they “need partial or full assistance” to any ADL/IADL items were defined as having ADL/IADL disability. We examined the association of multimorbidity with ADL/IADL disability, adjusted for socio-demographic characteristics by using logistic regression.ResultsOf respondents, 23.23 % had ADL disability, 37.90 % had IADL disability, and 49.17 % had multimorbidity. After adjusted socio-demographic characteristics, a graded association was showed between ADL disability and the quantity of chronic conditions: odds ratio (OR) for 1 condition, 1.53(95 % confidence interval [CI], 1.04-2.24); OR for 2 conditions, 2.06(95 % CI, 1.43-2.96); OR for 3 conditions, 3.23(95 % CI, 2.14-4.86); OR for 4 or more conditions, 5.61(95 % CI, 3.26-9.66). Similar associations were also observed between the quantity of chronic conditions and IADL disability.ConclusionsThe quantity of chronic conditions had relatively strong association with both ADL and IADL disability. Initiating prevention of additional chronic conditions and interventions on clusters of diseases may decrease the potential risk of ADL/IADL disability. Additionally, more attention should been given to the older low-income women living with relatives/non-relatives with multimorbidity.

BackgroundThe nonparametric trend test (NPT) is well suitable for identifying the genetic variants associated with quantitative traits when the trait values do not satisfy the normal distribution assumption. If the genetic model, defined according to the mode of inheritance, is known, the NPT derived under the given genetic model is optimal. However, in practice, the genetic model is often unknown beforehand. The NPT derived from an uncorrected model might result in loss of power. When the underlying genetic model is unknown, a robust test is preferred to maintain satisfactory power.ResultsWe propose a two-phase procedure to handle the uncertainty of the genetic model for non-normal quantitative trait genetic association study. First, a model selection procedure is employed to help choose the genetic model. Then the optimal test derived under the selected model is constructed to test for possible association. To control the type I error rate, we derive the joint distribution of the test statistics developed in the two phases and obtain the proper size.ConclusionsThe proposed method is more robust than existing methods through the simulation results and application to gene DNAH9 from the Genetic Analysis Workshop 16 for associated with Anti-cyclic citrullinated peptide antibody further demonstrate its performance.