SERPINA5 inhibits tumor cell migration by modulating the fibronectin–integrin β1 signaling pathway in hepatocellular carcinoma

In our previous study, we identified 1241 loci with somatic copy number alterations in human hepatocellular carcinoma (HCC) using Affymetrix SNP 6.0 arrays, and a putative cancer gene SERPINA5 was uncovered in a novel chromosomal region with recurrent copy number loss at 14q31.1–32.13. The SERPINA5 was reported to be deregulated in renal, breast, prostate and ovarian cancers. However, the roles of SERPINA5 in cancer remain greatly elusive. In this study, we found that the DNA dosage and expression level of the SERPINA5 gene were significantly decreased in HCC by quantitative real-time PCR. Notably, the expression levels of SERPINA5 negatively correlated with malignant progression of HCC. The SERPINA5 gene was further observed to reduce in vitro and in vivo metastatic potential of HCC cells. Moreover, secreted SERPINA5 protein also could inhibit the metastatic ability of HCC cells. Finally, we discovered that one of the mechanisms explaining SERPINA5 inhibition of HCC metastasis is through direct interaction with fibronectin and disruption of the fibronectin–integrin signaling pathway. These findings highlight an important role of SERPINA5 in the regulation of migratory and metastatic potentials of HCC and suggest a potential application of SERPINA5 in cancer treatment.     

Is failure to awaken and wean malpractice?

BackgroundRespiratory failure is among the most common primary causes of or complications of critical illness, and although mechanical ventilation can be lifesaving, it also engenders substantial risk of morbidity and mortality to patients. Three decades of research suggests that the duration of invasive mechanical ventilation can be reduced substantially, reducing morbidity and mortality. Mean duration of ventilation reported in recent international studies suggests a quality chasm in management of this common critical illness.MethodsThis is a selective review of the literature and synthesis with precepts of medical professionalism and ethics.ConclusionsTo the extent that daily wake-up-and-breathe reduces morbidity, mortality, and length of stay, failure to deploy this strategy is, by definition, malpractice (ie, poor practice). Practical measures are offered to close this quality chasm.     

Elimination plus Transformation——Chinese and Western Medicine Integration Brings Hope to Protracted War on Cancer

正Modern medicine has been fighting the battle with cancer for near 200 years,achieved substantial progresses but yet to claim the final victory.Author believes that the battle strategy has the profound impact to the result.Since Virchow discovered the cellular origin of cancer in 1863,cancers are being seeing as a localized disease resulting from foreign invasions whereas eradication therapies     

Pre-treatment waking cortisol response and vulnerability to interferon α induced depression

Depressive disorder is a common consequence of interferon α treatment. An understanding of the aetiological processes involved is evolving. HPA axis abnormalities are clearly described in community depressive disorder and represent vulnerability to depression development. We explored whether pre-treatment HPA axis abnormalities influence depression emergence during interferon α treatment. We examined waking HPA axis response via salivary cortisol sampling in 44 non-depressed, chronic hepatitis C infected patients due to commence standard interferon α treatment. Hamilton depression scales and the structured clinical interview for DSM-IV major depressive disorder status were administered monthly during treatment. Major depressive disorder developed in 26 of 44 subjects during interferon-α treatment. The pre-treatment waking cortisol response over 1 h was significantly greater in the subsequent switch to depression group (F=4.23, p=0.046). The waking cortisol response pre-treatment with interferon α appears greater in those subsequently switching to depressive disorder during treatment. This waking response may join other vulnerability factors for depression emergence in this group. This model could prove a valuable tool in understanding non-iatrogenic depressive disorder in the general population and notably the role of cytokines.     

Gamma-glutamyl transferase and risk of type II diabetes: an updated systematic review and dose-response meta-analysis

PurposeWe assessed the nature of the dose-response relationship between gamma-glutamyl transferase (GGT) levels and risk of incident type II diabetes mellitus (T2DM) in the general population.MethodsSystematic review and dose-response meta-analysis of published prospective studies. Relevant studies were identified in a literature search of MEDLINE, EMBASE, and Web of Science databases up to June 2014. We examined a potential nonlinear relationship using restricted cubic splines.ResultsOf the 300 titles reviewed, we included 24 cohort studies with data on 177,307 participants and 11,155 T2DM cases. In pooled analysis of 16 studies with relevant data, there was evidence of a nonlinear association between GGT and T2DM risk in both males (P for nonlinearity = .02) and females (P for nonlinearity = .0005). In a comparison of extreme thirds of baseline levels of GGT, relative risk for T2DM in pooled analysis of all 24 studies was 1.34 (95% confidence interval, 1.27–1.42). There was heterogeneity among the studies (P < .001), which was to a large part explained by blood sample used, study size, degree of confounder adjustment, and quality of studies.ConclusionsCirculating level of GGT contributes to an increased risk of T2DM in the general population in a nonlinear dose-response pattern.     

Diagnostic performance and factors influencing the accuracy of EUS-FNA of pancreatic neuroendocrine neoplasms

Journal of Gastroenterology -