Dexmedetomidine Attenuates Lung Injury in Toxic Shock Rats by Inhibiting Inflammation and Autophagy.

OBJECTIVE: To explore the mechanisms whereby dexmedetomidine reversed lung injury in rats with toxic shock via inhibiting inflammation and autophagy. METHODS: Thirty-six specific pathogen-free male Sprague Dawley rats with were screened and randomly divided into three groups. Toxic shock was induced by intestinal leakage. The control group received no cecal ligation and the treatment group received dexmedetomidine hydrochloride. Lung tissue morphology was studied by hematoxylin-eosin staining. The expression levels of inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). The expression levels of beclin l and LC3 were measured, and the expression levels of apoptosis gene Bax and Bcl-2 were determined. The autophagosomes in lung cells were observed by transmission electron microscopy. Extracellular signal-regulated kinase (ERK) 1/2 expression was determined by Western blotting assays. RESULTS: The results showed that the W/D, total protein and myeloperoxidase (MPO) index in the toxic shock group were 5.45 ± 0.35, 3.21 ± 0.47 and 4.53 ± 0.36, respectively. The W/D (4.02 ± 0.67), total protein (2.01 ± 0.35) and MPO index (2.31 ± 0.59) were significantly lower in the dexmedetomidine group (p <0.05). Similarly, compared with the toxic shock group, the expression of p-ERK1/2 protein in the dexmedetomidine treatment group was significantly decreased (p <0.05). The expression levels of autophagy proteins beclin1 and LC3 in the dexmedetomidine treatment group were not significantly different from those of the control group (p >0.05). Transmission electron microscopy showed that the number of autophagic bodies in lung cells decreased. After induction with dexmedetomidine hydrochloride, the proapoptotic gene Bax was significantly downregulated in the cells. Bax expression levels in each group were 0.36 ± 0.12, 0.67 ± 0.06, and 0.32 ± 0.12, respectively. Compared with the control group, Bax expression in lung tissue significantly increased in the toxic shock group (p <0.05). CONCLUSION: Dexmedetomidine attenuates lung injury in toxic shock rats by inhibiting inflammation and autophagy.

Associations of body weight and weight change with cardiovascular events and mortality in patients with coronary heart disease.

BACKGROUND AND AIMS: It is recommended that patients with coronary heart disease (CHD) pursue a normal body weight, while the effects of body weight and weight change on prognosis are still controversial. The present study was to assess these effects using a large-scale population with CHD in China. METHODS: A total of 5276 patients with CHD were included from Jan 2000 to Dec 2014. Baseline and endpoint weights were measured. Outcomes including mortality and cardiovascular events were obtained. RESULTS: Relative to patients with normal weight, risks for adverse outcomes were lowest in overweight patients and similar in obese patients. Hazard ratios (HRs) and 95% confidence interval (95% CI) for all-cause death were 1.42 (1.06, 1.91) if overweight turned into normal weight and were 2.01 (1.28, 3.16) or 5.33 (2.81, 10.1) if obese turned into overweight or normal weight. Death risk increased with the extent of weight loss and moderate or large weight gain (p<0.05 for all). Similar results were found when risks for cardiovascular mortality and events were considered. Furthermore, these results remained significant when the patients were stratified by several covariates and even when several definitions of weight change were considered. CONCLUSIONS: Obesity did not increase adverse outcome risks in patients with CHD. Both weight loss and weight gain increased adverse outcome risks regardless of baseline body weight. The findings suggest that maintaining a stable weight may be a better strategy for the reduction of risks for cardiovascular outcomes and all-cause death in patients with CHD.

Inhibition of microRNA-34a protects against propofol anesthesia-induced neurotoxicity and cognitive dysfunction via the MAPK/ERK signaling pathway.

AIM: To investigate the protective effect of microRNA-34a (miR-34a) on propofol-induced neurotoxicity and cognitive dysfunction. METHODS: After SH-SY5Y cells were treated with propofol to induce neurotoxicity, microRNA-34a mimics and inhibitors were transfected into the cells. The expression of apoptosis-related genes and the proteins were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. Sprague-Dawley (SD) rats received intraperitoneal injections of propofol, and were treated with microRNA-34a mimics and lentivirus-mediated microRNA-34a inhibitors. The Morris water maze (MWM) test was used to detect changes in motor function. RESULTS: Propofol anesthesia had an adverse effect on cell survival due to the increased expression of apoptosis-related genes such as cleaved caspase-3/8 and Bax, which was accompanied by reduced expression of ERK1/2, pERK1/2, and phosphorylated NF-kappaB p65 both in vivo and in vitro. Unexpectedly, microRNA-34a was upregulated after propofol treatment, and the inhibitors protected the SH-SY5Y cells from propofol-induced apoptosis. The microRNA-34a inhibitor suppressed the apoptosis-induced effects of propofol. This protection may have been partly diminished by PD98059, a MAPK kinase inhibitor. MicroRNA-34a inhibited or reverted the reduced expression of ERK1/2 and upregulated the expression of p-CREB significantly and specifically. Additionally, the microRNA inhibitors improved the learning and memory functions of animals suffering from neurologic impairment due to propofol treatment and reduced cell apoptosis in the hippocampus. CONCLUSION: microRNA-34a could improve anesthesia-induced cognitive dysfunction by suppressing cell apoptosis and recovering the expression of genes associated with the MAPK/ERK signaling pathway.

Effects of body mass index and weight change on mortality in older men with impaired glucose regulation.

OBJECTIVES: To assess the effect of baseline body mass index (BMI) status and weight change on mortality in older men with impaired glucose regulation (IGR). METHODS: Eight hundred eighty-five men with IGR aged 60 to 90 were included. Baseline and endpoint weight were measured. All-cause and cardiovascular mortality were observed during a median follow-up period of 10years. Multivariate Cox regressions were used to estimate associations between BMI, weight change and mortality. RESULTS: Relative to normal weight, overweight was associated with lower all-cause mortality (hazard ratios, HRs [95% confidence interval, 95% CI]: 0.57 [0.41, 0.78]) and cardiovascular mortality (0.52 [0.29, 0.93]), whereas obesity did not significantly decrease or increase the mortality risk. Furthermore, compared to weight stability, all types of weight change led to increased mortality risk, except small weight gain. Specifically, after adjustment for covariates and the initial weight, the HRs (95% CI) of large weight loss were 1.64 (1.15, 2.34) for all-cause mortality and 1.85 (1.10, 3.14) for cardiovascular mortality, and the HRs (95% CI) of large weight gain were 1.55 (1.01, 2.40) for all-cause mortality and 2.11 (1.04, 4.30) for cardiovascular mortality. Similar associations were observed when weight change was redefined in sensitivity analyses. CONCLUSIONS: Both BMI at baseline and weight change have independent U-shaped associations with all-cause and cardiovascular mortality among older men with IGR. The present study suggests that older men with IGR may ensure their best survival by being overweight at baseline or by maintaining their weight regardless of their baseline weight status.

[Influencing factors of glycemic variability in elderly patients with type 2 diabetes].

OBJECTIVE: To explore the influencing factors of glycemic variability in elderly patients with type 2 diabetes. METHODS: A total of 337 elderly patients received continuous glucose monitoring (CGM) from January 2007 to January 2011. The evaluation variables of glycemic variability included standard deviation of blood glucose (SDBG), mean amplitude of glycemic excursion (MAGE), absolute means of daily differences (MODD) and postprandial glucose excursion (PPGE). The normal reference value of glycemic variability was defined according to the diagnostic criteria of Chinese Diabetes Society guideline. RESULTS: The difference of glycemic variability was compared by gender, age and diabetic duration. The values of SDBG, MAGE, MODD and PPGE in females were all higher than those in males (P < 0.05) and no difference existed between various age groups. The level of glycemic variability increased gradually with the extension of diabetic duration (P < 0.01). Logistic regression analysis showed that gender (MAGE: OR = 0.44, P = 0.023; SDBG: OR = 0.39, P = 0.023), diabetic duration (MAGE: OR = 1.58, P = 0.006; SDBG: OR = 2.42, P < 0.001) and HbA1c (MAGE: OR = 2.44, P < 0.001; SDBG: OR = 2.68, P < 0.001) were significant influencing factors of glycemic variability (MAGE/SDBG) in elderly patients with type 2 diabetes (P < 0.05), but not age, body mass index (BMI) or diabetic neuropathy. CONCLUSION: Gender, diabetic duration and HbA1c are significant influencing factors of glycemic variability while age, BMI or diabetic neuropathy has no association with glycemic variability in elderly patients with type 2 diabetes.

Influence of glycemic variability on the HbA1c level in elderly male patients with type 2 diabetes.

OBJECTIVE: To investigate the influence of glycemic variability on the HbA1c level in elderly male patients with type 2 diabetes (T2DM). METHODS: The 24-h glucose profiles were obtained using a continuous glucose monitoring system in 291 elderly male type 2 diabetic patients. The relationship between the glycemic variability and HbA1c level was assessed in these patients. RESULTS: The mean amplitude of glycemic excursions (MAGE) in patients with HbA1c ≥7.0% was significantly higher than in patients with HbA1c <7.0% (4.33±1.67 vs. 3.48±1.46 mmol/L, p<0.001). A simple (Pearson's) correlation analysis indicated that the MAGE was significantly correlated with the HbA1c (r=0.229, p<0.001). Compared with the lowest quartile, the highest quartile of the MAGE was associated with a significantly increased risk of having a HbA1c ≥7.0% after multiple adjustments (p (for trend) <0.001). CONCLUSION: The glycemic variability had a significant influence on the HbA1c level in elderly male patients with T2DM. The present data suggests that patients with higher glycemic variability might have higher HbA1c levels.

[Analysis of essential oil from the leaves and fruits of Eucalyptus tereticornis in Guangxi province by GC-MS].

OBJECTIVE: To Analyze the chemical composition and their relative contents of essential oil from the leaves and fruits of Eucalyptus tereticornis in Guangxi province. METHODS: The column temperature was controlled by a program with a capillary column HP-5 MS, and the MS analysis was performed with EI and quadrupole mass analyzer. The chemical compositions were identified by NIST98 searching and mass spectra comparing, and their relative contents were determined by using normalization method of chromatographic peak areas. RESULTS: 39 compounds constituting 96.69% of the oil of leaves were identified. The major components were eucalyptol (27.93%), 1R-alpha-pinene (22.60%), isopinocarveol (8.71%); 36 compounds constituting 93.50% of the oil of fruits were identified. The major components are 1R-alpha-pinene (32.88%), eucalyptol (13.64%), D-limonene (8.31%). CONCLUSION: The GC-MS is a simple, rapid and sensitive method.

[Renin-angiotensin system in mesenteric adipose tissues in rats with metabolic syndrome].

OBJECTIVE: To investigate the renin-angiotensin system (RAS) in mesenteric adipose tissues and effect of angiotensin II on adipocyte differentiation. METHODS: Thirty normal 8-week-old male Wistar rats were divided into groups on normal diet and high-fat diet. The rats on high-fat diet for 24 weeks developed the metabolic syndrome respectively. The mRNA and protein expression of mesenteric adipose tissue were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Lipid drop in 3T3-L1 preadipocytes and mature adipocytes were observed using oil-red O staining. The fluorescence microscope was used to detect cytosolic-free calcium in 3T3-L1 preadipocytes and mature adipocytes. RESULTS: The expressions of angiotensinogen, angiotensin converting enzyme, angiotensin II receptor type 1 in mesenteric adipose tissue were significantly increased in rats with metabolic syndrome compared with those in rats on normal diet (P <0. 05, P <0. 01). After administration of angiotensin II , no lipid droplet in 3T3 -L1 preadipocytes and adipocytes were observed, however, intensive lipid droplet in adipocyte was found after administration of captopril and candesartan. Angiotensin II increased the intracellular-free calcium concentration in preadipocytes (P < 0. 01 ) , which was blocked by captopril and candesartan; in contrast, angiotensin II effect was blunt in mature adipocyte. Captopril and candesartan partially recovered the angiotensin II -mediated increase of cytosolic-free calcium. CONCLUSION: RAS in the mesenteric adipose tissues is active in rats with metabolic syndrome, and antagonization of RAS can recover the lipogenesis of adipocyte.