Correlations of MC4R and MSH2 expression with obesity in colon cancer patients.

OBJECTIVE: To investigate the correlations of MC4R and MSH2 with adult obesity, a total of 46 patients with early-stage colon cancer were treated in our hospital between February 2008 and February 2009 and were enrolled. PATIENTS AND METHODS: Venous blood was regularly drawn from subjects of the observation group and 48 healthy subjects for 6 years. Expression levels of MC4R and MSH2 genes were tested using quantitative polymerase chain reaction analyses, and the ensuing proteins were determined using enzyme-linked immunosorbent assays and Western blotting and immunohistochemical analyses. Finally, correlations with body mass index (BMI) and the presence of colon cancer were identified using multivariate analyses. RESULTS: Compared with the control group, MSH2 mRNA and protein expression increased significantly over time (p < 0.05) in patients with colon cancer. Moreover, MSH2 expression was correlated with colon cancer progression, and MC4R mRNA and protein expression increase concurrently in comparison with the control group (p < 0.05). Also, the mean BMI among patients with colon cancer was 30.8, whereas that among control subjects was only 21.4. These data indicate a relationship between BMI and colon cancer. CONCLUSIONS: Expression of MSH2 in patients with colon cancer may promote the expression of the obesity gene MC4R, potentially contributing to body weight gains.

Cerebrospinal fluid-contacting nucleus mediates nociception via release of fractalkine

Increasing evidence suggests that the cerebrospinal fluid-contacting nucleus (CSF-contacting nucleus) mediates the transduction and regulation of pain signals. However, the precise molecular mechanisms remain unclear. Studies show that release of fractalkine (FKN) from neurons plays a critical role in nerve injury-related pain. We tested the hypothesis that release of FKN from the CSF-contacting nucleus regulates neuropathic pain, in a chronic constriction injury rat model. The results show that FKN is expressed by neurons, via expression of its only receptor CX3CR1 in the microglia. The levels of soluble FKN (sFKN) were markedly upregulated along with the increase in FKN mRNA level in rats subjected to chronic constriction injury. In addition, injection of FKN-neutralizing antibody into the lateral ventricle alleviated neuropathic pain-related behavior followed by reduction in microglial activation in the CSF-contacting nucleus. The results indicate that inhibition of FKN release by the CSF-contacting nucleus may ameliorate neuropathic pain clinically.

Efficacy and safety of pregabalin for treating painful diabetic peripheral neuropathy: a meta-analysis.

BACKGROUND: Pregabalin is considered to be an effective treatment for painful diabetic peripheral neuropathy (DPN), but controversy exists about its efficacy and safety. We performed a meta-analysis to systematically assess the efficacy and safety of pregabalin for managing pain associated with DPN. METHODS: Medline, EMBASE, and the Cochrane Central Register were searched in July 2014 for randomized, double-blind, placebo-controlled trials published in English on the use of pregabalin to treat DPN-associated pain. Principal outcomes were mean pain score after pregabalin treatment and the proportions of patients showing a pain reduction of at least 50%. RESULTS: Nine trials involving a total of 2056 participants were identified. Pooled analysis showed that pregabalin was significantly superior to placebo for improving mean pain scores [mean difference (MD) = -0.79, P < 0.001]. Pregabalin reduced pain below baseline by at least 50% in a significantly greater proportion of patients than placebo did [relative risk = 1.54, P < 0.001]. Patients were more likely to self-report their status as 'improved' after taking pregabalin than placebo (relative risk = 1.38, P < 0.001). Pregabalin also improved sleep quality more than placebo (MD = -0.88, P < 0.001). On the other hand, patients receiving pregabalin were more likely to experience mild side effects than were patients receiving placebo. CONCLUSIONS: Our meta-analysis indicates that pregabalin is more effective than placebo for managing DPN-associated pain and other symptoms that reduce quality of life. The drug is also reasonably well tolerated.

2D speckle tracking imaging to assess sepsis induced early systolic myocardial dysfunction and its underlying mechanisms.

OBJECTIVE: The aim of this study was to apply speckle tracking imaging (STI) to evaluate rabbit sepsis induced myocardial injury. MATERIALS AND METHODS: Rabbits were injected with the endotoxin lipopolysaccharide (LPS). before and 2h, 4h, 6h, 8h, 12h after the injection of LPS, conventional echocardiography and STI were performed to measure left ventricular end diastolic diameter (LVDd), end-systolic diameter (LVDs), cardiac output (CO), left ventricular ejection fraction (EF), fractional shortening (FS), left ventricular global longitudinal strain (GLS)/GLS rate (GLSr), global circumferential strain/strain rate (GCS/GCSr), and the global radial strain/strain rate (GRS/GRSr). We also observed the injury with optical microscopy. Serum troponin cTnT and TUNEL assays determining myocardial apoptosis were also carried out to determine the induced injury levels. RESULTS: None of the indicators measured are statistically different in the two groups before the LPS treatment (p > 0.05). 2h after LPS injection, in LPS treated group, only GLS/GLSr, GCS/GCSr significantly reduced compared to the control group (p < 0.05). 6h, 8h, 12h after LPS injection, EF and FS were lower (p < 0.05), LVDd and LVDs were higher (p < 0.05), and GLS/GLSr, GCS/GCSr, GRS/GRSr were significantly lower (p < 0.05). LPS significantly elevated serum cTnT level in the experimental group (p < 0.05). In the LPS treated group, we found pathological changes of the myocardium. CONCLUSIONS: STI is more sensitive than the conventional echocardiography for the early detection of abnormal myocardial contractility. It is a noninvasive, accurate and timely detection of myocardial dysfunction in sepsis.