TFE3 Regulates the Function of the Autophagy-Lysosome Pathway to Drive the Invasion and Metastasis of Papillary Thyroid Carcinoma.

BACKGROUND: Accumulating evidence shows that autophagy plays a vital role in tumor occurrence, development, and metastasis and even determines tumor prognosis. However, little is known about its role in papillary thyroid carcinoma (PTC) or the potentially oncogenic role of TFE3 in regulating the autophagy-lysosome system. METHODS: Immunohistochemistry and quantitative real-time PCR (qRT-PCR) were used to examine the expression of TFE3, P62/SQSTM1, and LC3 in PTC and paracancerous tissues. TFE3, P62/SQSTM1, LC3, cathepsin L (CTSL), and cathepsin B (CTSB) were evaluated using Western blot analysis. After inducing TFE3 overexpression by plasmid or TFE3 downregulation by small interfering RNA (siRNA) transfection, MTT, wound healing, and cell migration and invasion assays were used to verify the effects on invasion, migration, and the levels of autophagy-lysosome system-related proteins such as P62/SQSTM1, LC3, CTSL, and CTSB. RESULTS: TFE3 was overexpressed in PTC tissues compared with paracancerous tissues. Analysis of the clinicopathological characteristics of PTC patients showed that high TFE3 expression was significantly correlated with lymph node metastasis. TFE3 overexpression in the PTC cell lines KTC-1 and BCPAP promoted proliferation, invasion, and migration, while TFE3 knockdown had the opposite effects. Furthermore, we identified a positive relationship among the expression levels of TFE3, P62/SQSTM1, LC3, CTSL, and CTSB. We found that silencing TFE3 inhibited the expression of P62/SQSTM1, LC3, CTSL, and CTSB in PTC cells. However, TFE3 overexpression had the opposite effects. CONCLUSIONS: The present study provided evidence for the underlying mechanisms by which TFE3 induces autophagy-lysosome system activity in PTC.

[Lineage polymorphism of TCR Vα CDR3 in peripheral blood of uveitis patients].

OBJECTIVE: To study the lineage polymorphism of TCR Vα complementarity determining region 3 (CDR3) in the peripheral blood of uveitis patients. METHODS: Thirty-four subfamilies of TCR Vα CDR3 in the peripheral blood mononuclear cells (PBMC) of uveitis patients were amplified by RT-PCR, and then TCR Vα CDR3 lineage polymorphism was analyzed by immunoscope spectratyping. RESULTS: Most spectral type of the 34 subfamilies in 5 normal controls showed Gauss distribution. TCR Vα CDR3 scanning spectrum of 4 uveitis patients showed abnormal distribution peak, including monoclonal, oligoclonal/oligoclonal trend, skewing peak and irregular abnormal peak. The frequencies of abnormal peak type varied in the 34 TCR Vα subfamilies. A higher frequency of abnormal peak type was found in Vα13 and Vα17 subfamilies, while no abnormal peak type was found in Vα1.1, Vα10, Vα20 and Vα28 subfamilies. Abnormal peak was shown in Vα7 subfamily in the HLA-B27-negative patient (U2) , but no abnormal peak was shown in Vα7 subfamily in the 3 HLA-B27-positive patients (U1, U3, U4); Conversely, abnormal peak type of TCR Vα13 was found in all the 3 HLA-B27-positive patients, but normal in HLA-B27-negative patients. CONCLUSION: TCR Vα CDR3 lineage has significant characteristic polymorphism in the peripheral blood of uveitis patients. Monoclonal/oligoclonal expansion of T cells may be autoreactive T cells in nature and they may be involved in pathogenesis of uveitis.

Association between TaqIB polymorphism of cholesteryl ester transfer protein and coronary artery disease in the Chinese population.

OBJECTIVE: To assess whether the TaqIB polymorphism of cholesteryl ester transfer protein (CETP) is associated with coronary artery disease (CAD) in Chinese population, we performed a meta-analysis in this paper. METHODS: We searched PubMed, Embase, the Science Citation Index (SCI), the China Biological Medicine database (CBM), the China National Knowledge Infrastructure (CNKI), and the Wanfang database for relevant articles. Data were extracted, and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: The literature search yielded 448 studies, in which 10 case-control studies including 1694 cases and 1456 controls matched the selection criteria. The combined B1 and B2 allele frequencies were 0.587 and 0.413, respectively. The pooled OR was 1.10 (95% CI, 0.89-1.34) for comparing the B1B1 or B1B2 carriers with B2B2 carriers, and was 1.27 (95% CI, 1.09-1.49) in the B1B1 carriers versus B2B2 or B1B2 carriers. CONCLUSIONS: In the present study, the TaqIB polymorphism of CETP was found to be associated with CAD in the Chinese population.

Interferon plus Chinese herbs are associated with higher sustained virological response than interferon alone in chronic Hepatitis C: a meta-analysis of randomised trials.

BACKGROUND/AIMS: Traditional Chinese herbal therapies are widely used for the treatment of chronic hepatitis C (CHC) in Asia. The aim of this study was to perform a meta-analysis of randomised controlled trials (RCTs) comparing interferon therapies with Chinese herbal therapies and/or interferon plus Chinese herb therapies for the treatment of CHC. METHODS: The Cochrane Central Register of Controlled Trials, Medline, Science Citation Index, EMBASE, China National Knowledge Infrastructure, Wanfang Database and China Biomedical Database were searched to identify RCTs that evaluated the virological response to interferon therapies, Chinese herbal therapies and interferon plus Chinese herb therapies in CHC patients. We statistically combined data using a random-effect meta-analysis according to the intention-to-treat principle. RESULTS: The literature search yielded 770 studies, and 26 RCTs comprising 1905 patients matched the selection criteria. Overall, the sustained virological response (SVR) was significantly higher in patients treated with interferon plus Chinese herbs than in patients treated with interferon alone (49% vs 33%, relative risk, 1.52; 95% confidence interval: 1.23-1.89; p<0.05). Combined therapies of interferon plus Chinese herb therapies were also superior to interferon therapies alone in achieving the end-of-treatment viral response (ETVR), and resulted in fewer relapses, fewer adverse events and more rapid alanine transaminase normalisation. Interferon therapies achieved higher ETVR than Chinese herbal therapies, but they yielded a similar SVR. CONCLUSIONS: The current evidence suggests that combined therapies of interferon plus Chinese herbs yielded a higher SVR, and resulted in fewer relapses and fewer adverse events than interferon therapies.

A comparison of peginterferon α-2a and α-2b for treatment-naive patients with chronic hepatitis C virus: A meta-analysis of randomized trials.

BACKGROUND: The standard treatments for chronic infection with the hepatitis C virus (HCV) are peginterferon α-2a or α-2b plus ribavirin, but it remains unclear if one has a better efficacy and safety profile. OBJECTIVE: The aim of this study was to perform a meta-analysis of randomized controlled trials (RCTs) comparing peginterferon α-2a and α-2b (in combination with ribavirin) treatments for chronic HCV. METHODS: The Cochrane Central Register of Controlled Trials, MEDLINE, Science Citation Index, and EMBASE were searched (1966-April 2010) to identify RCTs that evaluated the sustained virologic response (SVR) to peginterferon α-2a and peginterferon α-2b in patients with chronic HCV. The inclusion criteria were: RCT studies designed to compare the therapeutic effects of peginterferon α-2a (180 µg/wk) and peginterferon α-2b (1.5 µg/kg/wk) for treatment-naive patients with chronic HCV; patients treated for ≥24 weeks if infected with HCV genotypes 2 or 3 and for ≥48 weeks if infected with genotypes 1 or 4, with 24-week follow-ups; and publications written in any language. Reports of duplicated studies were excluded by examining the author list, parent institution, sample size, and results. The primary outcome was the SVR, and the other measures included the liver-related morbidity, all-cause mortality, and adverse events leading to treatment discontinuation. RESULTS: The literature search yielded 5580 studies, and 7 RCTs comprising 3212 patients matched the inclusion/exclusion criteria. Overall, the SVR rate was significantly higher in patients treated with peginterferon α-2a than in patients treated with peginterferon α-2b (50% vs 46%, respectively; relative risk [RR] = 1.11; 95% CI, 1.02-1.20; P < 0.05) and varying levels of ribavirin treatment. The subgroup analysis found that, in patients with genotypes 1 or 4, the difference between SVR rate in patients treated with peginterferon α-2a and patients treated with peginterferon α-2b was not statistically significant (43% vs 39%; RR = 1.25; 95% CI, 0.99-1.57). A significantly higher SVR rate was achieved in the HCV patients with genotypes 2 or 3 treated with peginterferon α-2a compared with the patients treated with peginterferon α-2b (86% vs 77%; RR = 1.11; 95% CI, 1.02-1.22; P = 0.02). The meta-analysis of adverse events leading to treatment discontinuation revealed no significant differences between the 2 treatments. CONCLUSIONS: The evidence reviewed in this meta-analysis suggests that peginterferon α-2a treatment was associated with a higher SVR rate than peginterferon α-2b treatment in patients with chronic HCV also treated with ribavirin. However, the available evidence on adverse events was insufficient to make recommendations.

[Meta analysis on acupuncture treatment of aphasia].

OBJECTIVE: To evaluate the therapeutic effect of acupuncture for the aphasia. METHODS: The publications of acupuncture for the treatment of aphasia are comprehensively searched from relevant domestic medical literature databases, China National Knowledge Infrastructure and Chinese BioMedical Literature Database. Meta analysis was conducted by using the publications. RESULTS: Twenty six trials of 338 matched the selection criteria and their data were suitable for Meta analysis. The total aphasia patients were 1749. The total odds ratio (OR) of the improvement with acupuncture plus language training and drugs compared with language training plus drug intervention was 3.66 (95% confidence interval, 2.81, 4.76), and the funnel plot was approximately symmetry. It is indicated that the curative effect of the acupuncture group is better than that of the control group (Z = 9.60, P < 0.001). CONCLUSION: The effect of acupuncture with language training plus drugs for the treatment of aphasia is better than that of language training plus drugs only.