The study was designed to investigate the effect of estradiol on the excitatory effect of oxytocin (OT) on colon motility. Female Wistar rats were used, and some of them were ovariectomized (OVX) and treated with vehicle or estradiol (E2). A plastic balloon made of condom was inserted into colon to monitor the change of colonic pressure in vivo. Longitudinal muscle strips of distal colon were prepared to monitor the spontaneous contraction of colon in vitro. Expression of OT receptor (OTR) was investigated by Western blot analysis. Expression of OTR mRNA was detected by RT-PCR. Immunohistochemistry was used to locate OTR. In OVX rats, pretreatment of E2 (4 -100 g/kg sc) dose-dependently increased the excitatory effect of OT on colon motility both in vivo and in vitro and increased the expression of OTR and OTR mRNA in colon. Systemic administration of OT excited the colon motility in vivo in rats at perioda of proestrus and estrus but did not influence it at diestrus period, when the concentration of plasma E2 was lowest in the estrous cycle. Pretreatment of atosiban, the specific OTR antagonist, and TTX, the blocker of voltage-dependent sodium channel on nerve fiber, attenuated the excitatory effect of OT on colon motility. OTR was located in myenteric plexus of colon. These results suggested that E2 increased the excitatory effect of OT on colon motility by upregulating the expression of OTR in myenteric plexus.colon; motility OXYTOCIN (OT) has been traditionally regarded as a hormone that is involved in parturition and milk ejection. In recent years, more evidence has indicated that OT may play a role in regulation of the gastrointestinal (GI) functions such as motility, sensation (13, 18), and immune response to inflammation (4, 10). Exogenous OT influences the GI motility, although the reports are diverse because of the differences of species, methods, and area of the gut (18, 24). It has been suggested that the effect of OT on GI motility might be physiological. OT is released in response to a fatty meal in women (16). Systemic administration of atosiban, the antagonist of OT receptor (OTR), inhibited the spontaneous contraction of gallbladder in rabbits (12) and gastric emptying in humans (16). It has been well established that mRNA for OT and its receptor can be found throughout the human GI tract (15), but the cell types that express OTR were undetectable in human gut by indirect immunofluorescence (19).In women, colonic dysmotility is very common, and bowel function changes during the reproductive cycle. Although the fluctuation of steroid hormones, especially estradiol (E 2 ) and progesterone, were believed to be the major reason, the mechanism has not been clearly illustrated. Steroid hormones regulate the activity of OTR via both genomic and nongenomic pathways (26). E 2 induced the mRNA expression of the OTR and increased the OTR density on the membranes of the uterine smooth muscle and central nervous system (8, 21). The recent study of our group also indicated that the pretreatment of E 2 increas...

Background and Objectives: Evidence for associations between alcohol consumption with breast cancer survival are conflicting, so we conducted the present meta-analysis. Methods: Comprehensive searches were conducted to find cohort studies that evaluated the relationship between alcohol consumption with breast cancer survival. Data were analyzed with meta-analysis software. Results: We included 25 cohort studies. The meta-analysis results showed that alcohol consumption was not associated with increased breast cancer mortality and recurrence after pooling all data from highest versus lowest comparisons. Subgroup analyses showed that pre-diagnostic or post-diagnostic consumpotion, and ER status did not affect the relationship with breast cancer mortality and recurrence. Although the relationships of different alcohol consumption with breast cancer mortality and recurrence were not significant, there seemed to be a dose-response relationship of alcohol consumption with breast cancer mortality and recurrence. Only alcohol consumption of >20 g/d was associated with increased breast cancer mortality, but not with increased breast cancer recurrence. Conclusion: Although our meta-analysis showed alcohol drinking was not associated with increased breast cancer mortality and recurrence, there seemed to be a dose-response relationship of alcohol consumption with breast cancer mortality and recurrence and alcohol consumption of >20 g/d was associated with increased breast cancer mortality.

Background Traumatic cervical spinal cord injury (CSCI) is a common disease that has high complication, disability, and mortality rates and a poor prognosis. Tracheostomy is an important supportive therapy for patients with CSCI. However, a consensus on the predictive factors for tracheostomy after CSCI has not been reached. Objective This meta-analysis study assessed the influencing factors for tracheostomy after CSCI. Methods We searched for relevant studies on the influencing factors for tracheostomy after CSCI. The extracted data were analyzed using RevMan 5.3 software. We calculated the odds ratio (OR) or mean difference (MD) and 95% confidence intervals (CIs). Results Sixteen eligible studies containing 9697 patients with CSCI were selected. The pooled OR (MD) and 95% CI of the influencing factors were as follows: age (mean ± SD): -0.98 (-4.00 to 2.03), advanced age: 1.93 (0.80 to 4.63), sex (male): 1.29 (1.12 to 1.49), American Spinal Injury Association Impairment Scale (AIS) A grade: 7.79 (5.28 to 11.50), AIS B grade: 1.15 (1.13 to 2.02), AIS C grade: 0.28 (0.20 to 0.41), AIS D grade: 0.04 (0.02 to 0.09), neurological level of injury (upper CSCI): 2.36 (1.51 to 3.68), injury severity score (ISS): 8.97 (8.11 to 9.82), Glasgow Coma Scale (GCS) score ≤8: 6.03 (2.19 to 16.61), thoracic injury: 1.78 (1.55 to 2.04), brain injury: 0.96 (0.55 to 1.69), respiratory complications: 5.97 (4.03 to 8.86), smoking history: 1.45 (0.99 to 2.13), traffic accident injury: 1.27 (0.92 to 1.74), and fall injury: 0.72 (0.52 to 1.01). Conclusions The current evidence shows that male sex, AIS A grade, AIS B grade, neurological level of injury (upper CSCI), high ISS, GCS≤8, thoracic injury, and respiratory complications are risk factors for tracheostomy after CSCI, and AIS C grade and AIS D grade are protective factors. This study will allow us to use these factors for tracheostomy decisions and ultimately optimize airway management in patients with CSCI.

The aim of the present study was to investigate the effect of ethanol on colon motility in rats and to test the possibility that nitric oxide (NO) mediates this effect. Proximal colon longitudinal muscle strips (LM) (8 x 3 mm) cut parallel to the longitudinal muscle fibres of the colon were isolated and mounted in an organ bath. Ethanol (0.57, 0.87 and 1.30 mmol L(-1)) dose-dependently inhibited the motility of LM. Longitudinal muscle strips from female rats were more sensitive to the inhibitory effect of ethanol than that from male rats. L-NAME (N-nitro-L-arginine methyl ester) (100 micromol L(-1)), AG (aminoguanidine) (10 micromol L(-1)), ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one) (10 micromol L(-1)) and PTIO (2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide) (200 micromol L(-1)) partly blocked the inhibitory effect of ethanol on LM. Pretreatment with L-NAME, AG, ODQ and PTIO abolished the sex difference of the inhibitory effect of ethanol on LM. Tetrodotoxin (TTX) (10 micromol L(-1)) partly blocked the inhibitory effect but did not influence the sex difference. The relaxation of LM induced by SNP (sodium nitroprusside) (0.1-10 micromol L(-1)) in female rats was greater than that in male rats. In conclusion, ethanol inhibited the colon motility in vitro. This inhibitory effect on LM was mediated by NO through the iNOS - NO - cGMP pathway.

Vascular smooth muscle cell (VSMC) phenotypic switching plays a critical role in the formation of abdominal aortic aneurysms (AAAs). FoxO3a is a key suppressor of VSMC homeostasis. We found that in human and animal AAA tissues, FoxO3a was upregulated, SM22α and α-smooth muscle actin (α-SMA) proteins were downregulated and synthetic phenotypic markers were upregulated, indicating that VSMC phenotypic switching occurred in these diseased tissues. In addition, in cultured VSMCs, significant enhancement of FoxO3a expression was found during angiotensin II (Ang II)-induced VSMC phenotypic switching. In vivo, FoxO3a overexpression in C57BL/6J mice treated with Ang II increased the formation of AAAs, whereas FoxO3a knockdown exerted an inhibitory effect on AAA formation in ApoE−/− mice infused with Ang II. Mechanistically, FoxO3a overexpression significantly inhibited the expression of differentiated smooth muscle cell (SMC) markers, activated autophagy, the essential repressor of VSMC homeostasis, and promoted AAA formation. Our study revealed that FoxO3a promotes VSMC phenotypic switching to accelerate AAA formation through the P62/LC3BII autophagy signaling pathway and that therapeutic approaches that decrease FoxO3a expression may prevent AAA formation.