Peripheral blood monocyte count is an easily assessable parameter of systemic inflammatory response. The aim of this study was to determine whether monocyte count was prognostic in hepatocellular carcinoma (HCC) following hepatic resection. We retrospectively reviewed 351 patients with HCC treated with hepatic resection from 2006 to 2009. Preoperative absolute peripheral monocyte count, demographics, and clinical and pathological data were analyzed. On univariate and multivariate analysis, elevated monocyte counts (≥545/mm3), tumor size ≥5 cm, non-capsulation, and multiple tumors were associated with poor disease-free survival (DFS) and overall survival (OS). The 1-, 3- and 5-year DFS rates were 58%, 41% and 35%, respectively, for patients with monocyte counts <545/mm3, and 36%, 23% and 21% for patients with monocyte counts ≥545/mm3. Correspondingly, the 1-, 3- and 5-year OS rates were 79%, 53% and 46% for monocyte counts <545/mm3, and 64%, 36% and 29% for monocyte counts ≥545/mm3. Subgroup analysis indicated that DFS after hepatic resection in hepatitis B virus (HBV)-infected patients was significantly better in those with a peripheral blood monocyte counts <545/mm3, but it did not differ between patients without HBV infection. In addition, DFS was significantly better for patients with a peripheral blood monocyte count <545/mm3, whether or not cirrhosis was present. Patients with elevated monocyte counts tended to have larger tumors. Elevated preoperative monocyte count is an independent predictor of worse prognosis for patients with HCC after hepatic resection, especially for those with HBV infection. Postoperative adjuvant treatment might be considered for patients with elevated preoperative monocyte counts.
Background Opioid analgesics play an important role in clinical settings.However,they also have some side effects,such as nausea,vomiting,pruritus,respiratory depression and so on,which could limit their wide use.Recently,lots of preclinical arid clinical studies have demonstrated that cotreatments with extremely small dose of opioid receptor antagonists can markedly enhance the efficacy of opioid analgesics and simultaneously reduce side effects induced by opioids including tolerance and dependence. Objective This article intends to review the progress in the study of the clinical application of opioid analgesics combined with ultra-low-dose naloxone in order to inspire some new research ideas. Content This article is a review of the progress in the preclinical and clinical studies of combining opioid analgesics and ultra-low-dose naloxone.In the mean time,we set out the probable mechanisms that could account for the enhancement of opioids' analgesic potency and attenuation of side effects,tolerance and dependence,which induced by opioids,during cotreatment with opioids and naloxone. Trend Recently,directions of the research are not limited to observation of the effectiveness in combining ultra -low -dose naloxone and morphine as well as in company with other opioids.More and more researchers are eager to concern about the mechanism of this eotreatment.
Key words:
Opioid analgesics; Morphin; Ultra-low-dose naloxone; Tolerance/dependence attenuation; Mechanisms; AC/cAMP/PKA; Go/Gi-opioid receptor; Gs-opioid receptor; Filamin A
Endothelial injury related to oxidative stress is a key event in cardiovascular diseases, such as hypertension and atherosclerosis. The activation of the redox-sensitive Kv1.5 potassium channel mediates mitochondrial reactive oxygen species (ROS)-induced apoptosis in vascular smooth muscle cells and some cancer cells. Kv1.5 channel is therefore taken as a new potential therapeutic target for pulmonary hypertension and cancers. Although Kv1.5 is abundantly expressed in vascular endothelium, there is little knowledge of its role in endothelial injury related to oxidative stress. We found that DPO-1, a specific inhibitor of Kv1.5, attenuated H2O2-evoked endothelial cell apoptosis in an in vivo rat carotid arterial model. In human umbilical vein endothelial cells (HUVECs) and human pulmonary arterial endothelial cells (HPAECs), angiotensin II and oxLDL time- or concentration-dependently enhanced Kv1.5 protein expression in parallel with the production of intracellular ROS and endothelial cell injury. Moreover, siRNA-mediated knockdown of Kv1.5 attenuated, whereas adenovirus-mediated Kv1.5 cDNA overexpression enhanced oxLDL–induced cellular damage, NADPH oxidase and mitochondria-derived ROS production and restored the decrease in protein expression of mitochondria uncoupling protein 2 (UCP2). Collectively, these data suggest that Kv1.5 may play an important role in oxidative vascular endothelial injury.
Abstract Background Although mid-thoracic epidural analgesia benefits patients undergoing major surgery, technical difficulties often discourage its use. Improvements in technology are warranted to improve the success rate on first pass and patient comfort. The previously reported ultrasound-assisted technique using a generic needle insertion site failed to demonstrate superiority over conventional landmark techniques. A stratified needle insertion site based on sonoanatomic features may improve the technique. Methods Patients who presented for elective abdominal or thoracic surgery requesting thoracic epidural analgesia for postoperative pain control were included in this observational study. A modified ultrasound-assisted technique using a stratified needle insertion site based on ultrasound images was adopted. The number of needle passes, needle skin punctures, procedure time, overall success rate, and incidence of procedure complications were recorded. Results One hundred and twenty-eight subjects were included. The first-pass success and overall success rates were 75% (96/128) and 98% (126/128), respectively. In 95% (122/128) of patients, only one needle skin puncture was needed to access the epidural space. The median [IQR] time needed from needle insertion to access the epidural space was 59 [47–122] seconds. No complications were observed during the procedure. Conclusions This modified ultrasound-assisted mid-thoracic epidural technique has the potential to improve success rates and reduce the needling time. The data shown in our study may be a feasible basis for a prospective study comparing our ultrasound-assisted epidural placements to conventional landmark-based techniques.