Randomised controlled trial: effect of metformin add-on therapy on functional cure in entecavir-treated patients with chronic hepatitis B.

INTRODUCTION AND OBJECTIVES: Hepatitis B surface antigen (HBsAg) clearance, indicating functional cure or resolved chronic hepatitis B (CHB), remains difficult to achieve via nucleos(t)ide analogue monotherapy. We investigated whether metformin add-on therapy could help achieve this goal in entecavir-treated patients with hepatitis B e antigen (HBeAg)-negative CHB. PATIENTS AND METHODS: Patients with HBeAg-negative CHB who met eligibility criteria (entecavir treatment for > 12 months, HBsAg < 1000 IU/mL) were randomly assigned (1:1) to receive 24 weeks of either metformin (1000 mg, oral, once a day) or placebo (oral, once a day) add-on therapy. The group allocation was blinded for both patients and investigators. Efficacy and safety analyses were based on the intention-to-treat set. The primary outcome, serum HBsAg level (IU/mL) at weeks 24 and 36, was analysed using mixed models. RESULTS: Sixty eligible patients were randomly assigned to the metformin (n = 29) and placebo (n = 31) groups. There was no substantial between-group difference in the HBsAg level at week 24 (adjusted mean difference 0.05, 95% confidence interval -0.04 to 0.13, p = 0.278) or week 36 (0.06, -0.03 to 0.15, p = 0.187), and no significant effect of group-by-time interaction on the HBsAg level throughout the trial (p = 0.814). The occurrence of total adverse events between the two groups was comparable (9 [31.0%] of 29 vs. 5 [16.1%] of 31, p = 0.227) and no patient experienced serious adverse events during the study. CONCLUSION: Although it was safe, metformin add-on therapy did not accelerate HBsAg clearance in entecavir-treated patients with HBeAg-negative CHB.

Effects of Nogo-A and its receptor on the repair of sciatic nerve injury in rats.

Regeneration of injured peripheral nerves is an extremely complex process. Nogo-A (neurite outgrowth inhibitor-A) inhibits axonal regeneration by interacting with Nogo receptor in the myelin sheath of the central nervous system (CNS). The aim of this study was to investigate the effects of Nogo-A and its receptor on the repair of sciatic nerve injury in rats. Sprague-Dawley rats (n=96) were randomly divided into 4 groups: control group (control), sciatic nerve transection group (model), immediate repair group (immediate repair), and delayed repair group (delayed repair). The rats were euthanized 1 week and 6 weeks after operation. The injured end tissues of the spinal cord and sciatic nerve were obtained. The protein expressions of Nogo-A and Nogo-66 receptor (NgR) were detected by immunohistochemistry. The protein expressions of Nogo-A, NgR, and Ras homolog family member A (RhoA) were detected by western blot. At 1 week after operation, the pathological changes in the immediate repaired group were less, and the protein expressions of Nogo-A, NgR, and RhoA in the spinal cord and sciatic nerve tissues were decreased (P<0.05) compared with the model group. After 6 weeks, the pathological changes in the immediate repair group and the delayed repair group were alleviated and the protein expressions decreased (P<0.05). The situation of the immediate repair group was better than that of the delayed repair group. Our data suggest that the expression of Nogo-A and its receptor increased after sciatic nerve injury, indicating that Nogo-A and its receptor play an inhibitory role in the repair process of sciatic nerve injury in rats.

Effects of Nogo-A and its receptor on the repair of sciatic nerve injury in rats

Regeneration of injured peripheral nerves is an extremely complex process. Nogo-A (neurite outgrowth inhibitor-A) inhibits axonal regeneration by interacting with Nogo receptor in the myelin sheath of the central nervous system (CNS). The aim of this study was to investigate the effects of Nogo-A and its receptor on the repair of sciatic nerve injury in rats. Sprague-Dawley rats (n=96) were randomly divided into 4 groups: control group (control), sciatic nerve transection group (model), immediate repair group (immediate repair), and delayed repair group (delayed repair). The rats were euthanized 1 week and 6 weeks after operation. The injured end tissues of the spinal cord and sciatic nerve were obtained. The protein expressions of Nogo-A and Nogo-66 receptor (NgR) were detected by immunohistochemistry. The protein expressions of Nogo-A, NgR, and Ras homolog family member A (RhoA) were detected by western blot. At 1 week after operation, the pathological changes in the immediate repaired group were less, and the protein expressions of Nogo-A, NgR, and RhoA in the spinal cord and sciatic nerve tissues were decreased (P<0.05) compared with the model group. After 6 weeks, the pathological changes in the immediate repair group and the delayed repair group were alleviated and the protein expressions decreased (P<0.05). The situation of the immediate repair group was better than that of the delayed repair group. Our data suggest that the expression of Nogo-A and its receptor increased after sciatic nerve injury, indicating that Nogo-A and its receptor play an inhibitory role in the repair process of sciatic nerve injury in rats.

Expression of long noncoding RNA NBAT1 is associated with the outcome of patients with non-small cell lung cancer.

OBJECTIVE Long noncoding RNA neuroblastoma-associated transcript 1 (NBAT1) has been reported to be involved in cancer progression. However, the clinical significance of NBAT1 in non-small cell lung cancer (NSCLC) is still unclear. Our present research aimed to explore whether NBAT1 serves as a biomarker for NSCLC prognosis. METHODS The expression of NBAT1 was examined by RT-PCR in tissue samples of 162 NSCLC patients and was compared with the adjacent non-tumor lung specimens. Then the association between NBAT1 expression and clinical-pathological parameters was further evaluated. Survival analysis was performed using the Kaplan-Meier method. The prognostic significance of NBAT1 expression in NSCLC patients was explored by the use of univariate and multivariate analyses. RESULTS NBAT1 expression was prominently decreased in NSCLC tissues compared with matched normal lung specimens (p < 0.01). Moreover, survival analyses indicated that patients with low expression displayed dramatically decreased 5-year overall survival (p = 0.008). CONCLUSIONS NBAT1 expression might contribute to tumor progression and poor prognosis of NSCLC and might be a new therapeutic target in NSCLC.

Expression of long noncoding RNA NBAT1 is associated with the outcome of patients with non-small cell lung cancer

SUMMARY OBJECTIVE Long noncoding RNA neuroblastoma-associated transcript 1 (NBAT1) has been reported to be involved in cancer progression. However, the clinical significance of NBAT1 in non-small cell lung cancer (NSCLC) is still unclear. Our present research aimed to explore whether NBAT1 serves as a biomarker for NSCLC prognosis. METHODS The expression of NBAT1 was examined by RT-PCR in tissue samples of 162 NSCLC patients and was compared with the adjacent non-tumor lung specimens. Then the association between NBAT1 expression and clinical-pathological parameters was further evaluated. Survival analysis was performed using the Kaplan-Meier method. The prognostic significance of NBAT1 expression in NSCLC patients was explored by the use of univariate and multivariate analyses. RESULTS NBAT1 expression was prominently decreased in NSCLC tissues compared with matched normal lung specimens (p < 0.01). Moreover, survival analyses indicated that patients with low expression displayed dramatically decreased 5-year overall survival (p = 0.008). CONCLUSIONS NBAT1 expression might contribute to tumor progression and poor prognosis of NSCLC and might be a new therapeutic target in NSCLC.

RESUMO OBJETIVO Há relatos de que o NBAT1 está associado à progressão do câncer. Contudo, o significado clínico do NBAT1 no câncer de pulmão de células não pequenas (NSCLC) ainda não está claro. O objetivo da nossa pesquisa foi explorar se NBAT1 serve como biomarcador para o prognóstico de NSCLC. MÉTODOS A expressão de NBAT1 foi examinada por RT-PCR em amostras de tecido de 162 pacientes com NSCLC e comparada a amostras adjacentes não tumorais de pulmão. Em seguida, a associação entre a expressão do NBAT1 e os parâmetros clínico-patológicos foi avaliada. A análise de sobrevivência foi realizada utilizando o método Kaplan-Meier. A significância prognóstica da expressão do NBAT1 em pacientes com NSCLC foi explorada através de análises univariadas e multivariadas. RESULTADOS A expressão do NBAT1 foi claramente diminuída nos tecidos de NSCLC em comparação aos espécimes normais dos pulmões (p<0,01). Além disso, as análises de sobrevivência indicaram que pacientes com baixa expressão apresentavam uma diminuição drástica da sobrevivência global em cinco anos (p=0,008). CONCLUSÃO A expressão do NBAT1 pode contribuir para a progressão tumoral e um prognóstico negativo do NSCLC e pode ser um novo alvo de terapia no NSCLC.

The measurement of dorsal radial tilt by x-ray and computed tomography.

OBJECTIVE: We conducted this study to define and measure the dorsal radial tilt, and to guide the reduction of distal radius fractures and the pre-bending of steel plates used in surgery. METHODS: The dorsal radial tilt was measured using both computed tomography (CT) and x-ray from both left and right side. The differences and correlations of the data measured by those two methods and from two sides were analyzed. RESULTS: The tilts measured by x-ray were significantly bigger than those measured by CT from the left side (t=55.51, p < 0.01) and from the right side (t=49.81, p < 0.01). The tilts measured by those two methods from the left and right sides were correlated (r=0.85, p < 0.01; r=0.81, p < 0.01). The dorsal radial tilts measured from the left side were not significantly different from those measured from the right side by CT (t=1.49, p > 0.05) and by x-ray (t=1.51, p > 0.05). The dorsal radial tilts measured from the left side by CT were significantly different from those measured from the right side by x-ray (t=43.07, p < 0.01), and these two sets of data were correlated (r=0.71, p < 0.01). The dorsal radial tilts measured from the left side by x-ray was significantly different from that measured from right side by CT (t=40.43, p < 0.01), and those two sets of data were also correlated (r=0.75, p < 0.01). CONCLUSIONS: The dorsal radial tilts measured from one side by one method can be used to estimate the tilts measured from the other side / the same side by the same method / the other method.

The measurement of dorsal radial tilt by x-ray and computed tomography

SUMMARY OBJECTIVE: We conducted this study to define and measure the dorsal radial tilt, and to guide the reduction of distal radius fractures and the pre-bending of steel plates used in surgery. METHODS: The dorsal radial tilt was measured using both computed tomography (CT) and x-ray from both left and right side. The differences and correlations of the data measured by those two methods and from two sides were analyzed. RESULTS: The tilts measured by x-ray were significantly bigger than those measured by CT from the left side (t=55.51, p < 0.01) and from the right side (t=49.81, p < 0.01). The tilts measured by those two methods from the left and right sides were correlated (r=0.85, p < 0.01; r=0.81, p < 0.01). The dorsal radial tilts measured from the left side were not significantly different from those measured from the right side by CT (t=1.49, p > 0.05) and by x-ray (t=1.51, p > 0.05). The dorsal radial tilts measured from the left side by CT were significantly different from those measured from the right side by x-ray (t=43.07, p < 0.01), and these two sets of data were correlated (r=0.71, p < 0.01). The dorsal radial tilts measured from the left side by x-ray was significantly different from that measured from right side by CT (t=40.43, p < 0.01), and those two sets of data were also correlated (r=0.75, p < 0.01). Conclusions: The dorsal radial tilts measured from one side by one method can be used to estimate the tilts measured from the other side / the same side by the same method / the other method.

RESUMO OBJETIVO: Realizamos este estudo para definir e medir a inclinação radial dorsal, e para orientar a redução das fraturas do raio distal e a pré-flexão das chapas de aço utilizadas na cirurgia. MÉTODOS: A inclinação radial dorsal foi medida usando tomografia computadorizada (TC) e raios X dos lados esquerdo e direito. As diferenças e correlações dos dados medidos por esses dois métodos e de dois lados foram analisadas. RESULTADOS: As inclinações medidas por raios X foram significativamente maiores que as medidas pela TC do lado esquerdo (t=55,51, p<0,01) e do lado direito (t=49,81, p<0,01). As inclinações medidas por esses dois métodos dos lados esquerdo e direito foram correlacionadas (r=0,85, p<0,01; r=0,81, p<0,01). As inclinações radiais dorsais medidas a partir do lado esquerdo não foram significativamente diferentes das medidas do lado direito por CT (t=1,49, p>0,05) e por raios X (t=1,51, p>0,05). As inclinações radiais dorsais medidas a partir do lado esquerdo por TC foram significativamente diferentes das medidas a partir do lado direito por raios X (t=43,07, p<0,01), e esses dois conjuntos de dados foram correlacionados (r=0,71, p<0,01). As inclinações radiais dorsais medidas a partir do lado esquerdo por raios X foram significativamente diferentes das medidas do lado direito por CT (t=40,43, p<0,01), e esses dois conjuntos de dados também foram correlacionados (r=0,75, p<0,01). CONCLUSÕES: As inclinações radiais dorsais medidas de um lado por um método podem ser usadas para estimar as inclinações medidas do outro lado/o mesmo lado pelo mesmo método/o outro método.

Clustering distributions with the marginalized nested Dirichlet process.

We introduce a marginal version of the nested Dirichlet process to cluster distributions or histograms. We apply the model to cluster genes by patterns of gene-gene interaction. The proposed approach is based on the nested partition that is implied in the original construction of the nested Dirichlet process. It allows simulation exact inference, as opposed to a truncated Dirichlet process approximation. More importantly, the construction highlights the nature of the nested Dirichlet process as a nested partition of experimental units. We apply the proposed model to inference on clustering genes related to DNA mismatch repair (DMR) by the distribution of gene-gene interactions with other genes. Gene-gene interactions are recorded as coefficients in an auto-logistic model for the co-expression of two genes, adjusting for copy number variation, methylation and protein activation. These coefficients are extracted from an online database, called Zodiac, computed based on The Cancer Genome Atlas (TCGA) data. We compare results with a variation of k-means clustering that is set up to cluster distributions, truncated NDP and a hierarchical clustering method. The proposed inference shows favorable performance, under simulated conditions and also in the real data sets.

A semiparametric Bayesian model for comparing DNA copy numbers.

We propose a two-step method for the analysis of copy number data. We first define the partitions of genome aberrations and conditional on the partitions we introduce a semiparametric Bayesian model for the analysis of multiple samples from patients with different subtypes of a disease. While the biological interest is to identify regions of differential copy numbers across disease subtypes, our model also includes sample-specific random effects that account for copy number alterations between different samples in the same disease subtype. We model the subtype and sample-specific effects using a random effects mixture model. The subtype's main effects are characterized by a mixture distribution whose components are assigned Dirichlet process priors. The performance of the proposed model is examined using simulated data as well as a breast cancer genomic data set.

A time-series DDP for functional proteomics profiles.

Using a new type of array technology, the reverse phase protein array (RPPA), we measure time-course protein expression for a set of selected markers that are known to coregulate biological functions in a pathway structure. To accommodate the complex dependent nature of the data, including temporal correlation and pathway dependence for the protein markers, we propose a mixed effects model with temporal and protein-specific components. We develop a sequence of random probability measures (RPM) to account for the dependence in time of the protein expression measurements. Marginally, for each RPM we assume a Dirichlet process model. The dependence is introduced by defining multivariate beta distributions for the unnormalized weights of the stick-breaking representation. We also acknowledge the pathway dependence among proteins via a conditionally autoregressive model. Applying our model to the RPPA data, we reveal a pathway-dependent functional profile for the set of proteins as well as marginal expression profiles over time for individual markers.