MiR-15a expression analysis in non-small cell lung cancer A549 cells under local hypoxia microenvironment.

OBJECTIVE: Lung cancer is a common tumor in the clinic. Hypoxia is an important biological characteristic in the solid malignant tumor. MiRNA participates in cell proliferation, differentiation, and apoptosis. This study tested hypoxia-inducible factor 1-α (HIF-1α) in lung cancer patients and analyzed the microRNA-15a (miR-15a) expression in A549 cells under different local hypoxia microenvironments. PATIENTS AND METHODS: A total of 40 non-small cell lung cancer (NSCLC) patients in First Affiliated Hospital of Zhengzhou University between Jan 2015 and Jan 2016 were involved in this study. The serum and tissue samples of lung cancer were collected. Serum HIF-1α level was tested by enzyme-linked immunosorbent assay (ELISA) assay. HIF-1α expression in tissue was evaluated by using the immunohistochemistry. A549 cells were cultured under normoxic, hypoxic, and anaerobic environment, respectively. HIF-1α mRNA and miR-15a levels were determined by RT-PCR. RESULTS: HIF-1α levels were up-regulated in serum and tissue (p<0.05). HIF-1α mRNA increased, while miR-15a down-regulated in A549 from hypoxia and anaerobic groups compared with control (p<0.05). HIF-1α shRNA transfection significantly reduced HIF-1α and elevated miR-15a level (p<0.05). MiR-15a shRNA transfection exhibited no statistical impact on HIF-1α expression (p>0.05). CONCLUSIONS: HIF-1α highly expressed in lung cancer patients. MiR-15a levels were down-regulated in A549 cells under hypoxia and anaerobic conditions.

Effect of intra-operative autonomic nerve stimulation on pelvic nerve preservation during radical laparoscopic proctectomy.

AIM: This study assessed the effect of intra-operative electrical nerve stimulation (INS) on pelvic autonomic nerve preservation (PANP) during laparoscopic resection for rectal cancer. METHOD: A total of 189 consecutive cases of radical laparoscopic proctectomy were included. PANP was assessed visually or with INS. Urinary function was evaluated by residual urine volume (RUV), International Prostatic Symptom Score (IPSS) and recatheterization rate. Erectile function was evaluated using the International Index of Erectile Function (IIEF-5) scale. RESULTS: INS successfully confirmed PANP in 65 (91.5%) patients, while direct vision confirmed PANP in only 72 (61.0%) patients. Compared with the successfully confirmed patients, failed patients in the INS group exhibited higher postoperative RUV (100.0 ± 34.6 vs 25.2 ± 13.6 ml, P = 0.003), higher IPSS (7 days, 20.0 ± 8.6 vs 6.5 ± 2.4, P = 0.012; 1 month, 13.5 ± 6.0 vs 5.3 ± 1.9, P = 0.020; 6 months, 11.7 ± 5.1 vs 4.5 ± 1.7, P = 0.018), a greater number of incidences of a micturition disorder (66.7% vs 1.5%, P = 0.000), higher recatheterization rates (33.3% vs 1.5%, P = 0.017) and a lower IIEF score at 3 months (8.25 ± 0.96 vs 10.93 ± 1.99, P = 0.012) and 6 months (12.50 ± 1.29 vs 15.63 ± 1.65, P = 0.001) postoperatively. Compared with the vision group, the INS group had less deterioration in postoperative RUV (31.5 ± 26.4 vs 54.0 ± 46.7 ml, P = 0.000), lower IPSS (7 days, 7.7 ± 5.0 vs 11.0 ± 6.6, P = 0.000; 1 month, 6.0 ± 3.3 vs 7.6 ± 5.4, P = 0.012) and higher IIEF score (3 months, 10.69 ± 2.07 vs 9.42 ± 2.05, P = 0.001; 6 months, 15.36 ± 1.85 vs 13.64 ± 2.00, P = 0.000) as well as a lower incidence of urination disorders (7.0% vs 17.8%, P = 0.038). CONCLUSION: INS is effective for the accurate evaluation of PANP during radical laparoscopic proctectomy. Combined with INS, laparoscopic proctectomy is more effective in urogenital function protection.

Relationships Between Pharmacovigilance, Molecular, Structural, and Pathway Data: Revealing Mechanisms for Immune-Mediated Drug-Induced Liver Injury.

Immune-mediated drug-induced liver injury (IMDILI) can be devastating, irreversible, and fatal in the absence of successful transplantation surgery. We present a novel approach that combines the methods of pharmacoepidemiology with in silico molecular modeling to identify specific features in toxic ligands that are associated with clinical features of IMDILI. Specifically, from pharmacovigilance data multivariate logistic regression identified 18 drugs associated with IMDILI (P < 0.00015). Eleven of these drugs, along with their known and proposed metabolites, constituted a training set used to develop a four-point pharmacophore model (sensitivity 75%; specificity 85%). Subsequently, this information was combined with information from immune-pathway reviews and genetic-association studies and complemented with ligand-protein docking simulations to support a hypothesis implicating two putative targets within separate, possibly interacting, immune-system pathways: the major histocompatibility complex within the adaptive immune system and Toll-like receptors (TLRs), in particular TLR-7, which represent pattern recognition receptors of the innate immune system.

A retrospective study of psychotropic drug use among individuals with mental illness issued a community treatment order.

BACKGROUND: Community treatment orders (CTOs) are legal orders which require individuals with mental illness to accept treatment in the community. Previous studies report that long-acting injectable (LAI) antipsychotics are associated with CTOs, however, little is known about the specific treatment plans prescribed in CTOs. The objective of this study was to describe the patterns of psychotropic drugs prescribed to individuals issued a CTO, focusing on LAI antipsychotics, antipsychotic polypharmacy and high-dose antipsychotics. METHODS: This was a retrospective cross-sectional study of 378 individuals randomly selected from a sample of 1317 individuals with a CTO expiry date up to and including 30 April 2010, taken from all 2856 individuals issued a CTO by the New South Wales Mental Health Review Tribunal, Australia, in 2009. De-identified information relating to individuals' treatment plans, demographic and clinical details were systematically extracted. RESULTS: A total of 377 (99.7%) individuals were prescribed at least one antipsychotic. Of these, 310 (82%) were prescribed a LAI antipsychotic, either alone (45%), or in combination with, an oral antipsychotic (37%). Risperidone was the most prevalent antipsychotic, prescribed to 164 (43%) individuals. Antipsychotic polypharmacy was prescribed to 121 (32%) individuals and between 20% and 27% of individuals were prescribed high-dose antipsychotics. Antipsychotic polypharmacy accounted for 74-80% of individuals prescribed high-dose antipsychotics. CONCLUSIONS: The results from this study confirm that LAI antipsychotics are commonly prescribed in CTOs. Antipsychotic polypharmacy was also common, and accounted for the majority of individuals prescribed high-dose antipsychotics. Further research is needed to determine the potential outcomes and implications of the patterns observed.

Inhibitory mechanisms of kinetin, a plant growth-promoting hormone, in platelet aggregation.

Kinetin has been shown to have anti-aging effects on several different systems including plants and human cells. The aim of this study was to examine the detailed inhibitory mechanisms of kinetin in platelet aggregation. In this study, kinetin concentration-dependently (50-150 microM) inhibited platelet aggregation in human platelets stimulated by agonists. Kinetin (70 and 150 microM) also concentration-dependently inhibited intracellular Ca2+ mobilization and phosphoinositide breakdown in platelets stimulated by collagen (1 microg/ml). Kinetin (70 and 150 microM) significantly inhibited thromboxane A2 formation stimulated by collagen (1 microg/ml) and arachidonic acid (60 microM) in human platelets. In addition, kinetin (70 and 150 microM) significantly increased the formation of cyclic AMP. Intracellular pH values were measured spectrofluorometrically using the fluorescent probe BCECF-AM in platelets. The thrombin-evoked increase in pHi was markedly inhibited in the presence of kinetin (70 and 150 microM). Rapid phosphorylation of a platelet protein of molecular weight (Mr) 47000 (P47), a marker of protein kinase C activation, was triggered by collagen (1 microg/ml). This phosphorylation was inhibited by kinetin (70 and 150 microM). In conclusion, these results indicate that the anti-platelet activity of kinetin may be involved in the following pathways: kinetin's effects may initially be due to inhibition of the activation of phospholipase C and the Na+/H+ exchanger. This leads to lower intracellular Ca2+ mobilization, followed by inhibition of TxA2 formation and then increased cyclic AMP formation, followed by a further inhibition of the Na+/H+ exchanger, ultimately resulting in markedly decreased intracellular Ca2+ mobilization and phosphorylation of P47. These results suggest that kinetin has an effective anti-platelet effect and that it may be a potential therapeutic agent for arterial thrombosis.

Involvement of nuclear factor-kappaB in lipoteichoic acid-induced cyclooxygenase-2 expression in RAW 264.7 macrophages.

We have investigated the role of protein kinase C (PKC) and nuclear factor-kappaB (NF-kappaB) in cyclooxygenase-2 (COX-2) expression caused by Staphylococcus aureus lipoteichoic acid in RAW 264.7 macrophages. A phosphatidylcholine-phospholipase C (PC-PLC) inhibitor (D-609) and a phosphatidylinositol-phospholipase C (PI-PLC) inhibitor (U-73122) attenuated lipoteichoic acid-induced COX-2 expression, while a phosphatidate phosphohydrolase inhibitor (propranolol) had no effect. Two PKC inhibitors (Go 6976 and Ro 31-8220) and the NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), also attenuated lipoteichoic acid-induced COX-2 expression. Lipoteichoic acid resulted in a decrease in PKC activity in the cytosol and an increase in PKC activity in membranes. The lipoteichoic acid-induced translocation of p65 NF-kappaB from the cytosol to the nucleus was inhibited by D-609, U-73122, Go 6976, Ro 31-8220, and PDTC, but not by propranolol. The results suggested that lipoteichoic acid might have activated PC-PLC and PI-PLC to induce PKC activation, which in turn initiated NF-kappaB activation, and finally induced COX-2 expression in RAW 264.7 macrophages.

[Treatment of nasofacial hemangioma with interventional embolization and pingyungmycin injection].

OBJECTIVE: To investigate a new method with interventional embolization and pingyugmycin injection for treating nasofacial Hemangioma. METHOD: The fillets and coil were used for interventional embolization facial artery, internal maxillary artery, temporal superficial artery, and pingyungmycin injected for 4 patients. RESULT: The tumor and vascular beat in this series of 4 patients were disappeared by follow up of one year. There are not nasal obstruction and epistaxis. CONCLUSION: Treatment with interventional embolization and pingyungmycin injection is a safe and effective method for nasofacial hemangioma.

Intermuscular bupivacaine infusion for control of pain after renal surgery: a preliminary report.

OBJECTIVE: To assess the value of continuous bupivacaine wound infusion for post-operative pain relief after renal surgery. PATIENTS AND METHODS: The analgesic efficacy of continuous intermuscular wound infusion with 0.25% bupivacaine was studied in 10 patients (four men, six women), with a mean age of 47.5 years (range 25-71) and a mean weight of 71.2 kg (range 44-99), after renal surgery in a single-blind randomized trial. The results were compared with those of an age- and weight-matched control group of 10 patients (five men, five women) with a mean age of 47.7 years (range 27-73) and a mean weight of 67.3 kg (range 51-85). Post-operative pain was studied objectively by assessing individual patient's morphine requirements administered via a patient controlled analgesia system, and subjectively with pain scores. Patient mobility was assessed by ward nursing staff using mobility score charts. RESULTS: There was a lower demand for post-operative analgesia in the bupivacaine group compared with the control. Although there was no significant difference in the pain scores between the two groups, the bupivacaine group was significantly more mobile than the control group after surgery. There was no significant difference in the mean post-operative hospital stay between the two groups. CONCLUSION: Continuous intermuscular bupivacaine wound infusion is a simple and safe procedure which lowers the patients' post-operative analgesic requirements, allows for earlier mobility and may promote more rapid discharge from hospital.

Inhibition in the human urinary bladder by gamma-amino-butyric acid.

OBJECTIVE: To investigate the effects of gamma-amino-butyric acid (GABA) on detrusor activity in man to determine whether it has any inhibitory effect on detrusor contraction. The inhibitory neurotransmitter GABA has been found in mammalian urinary bladders and the effects of GABA on detrusor activity in the rabbit bladder has previously been described [1]. MATERIALS AND METHODS: Human detrusor muscle strips, obtained at cystectomy, were made to contract by electrical stimulation of their autonomic nerves or by the addition of carbachol in a superfusion apparatus. GABA and its analogues were added to the superfusion chamber and any changes in the responses were measured. RESULTS: The electrically evoked nerve-mediated contractions in human bladder muscle were exclusively cholinergic. GABA inhibited nerve-mediated contractions in human detrusor muscle-strips by the activation of the GABAB receptor, since baclofen (a GABAB receptor agonist) produced similar inhibition and muscimol (a GABAA receptor agonist) did not. There was no inhibition of carbachol-mediated contractions by GABA. CONCLUSION: This in vitro study shows that GABA has a peripherally mediated inhibitory effect on excitatory neurotransmission in human detrusor muscle. The site of action is on the post-ganglionic nerves and appears to be mediated via the GABAB receptor.

Rectal obstruction secondary to carcinoma of the prostate treated by transanal resection of the prostate.

Rectal obstruction caused by carcinoma of the prostate is uncommon. If the disease does not respond to either hormonal treatment or radiotherapy, the only surgical means of relieving the obstruction has been the formation of a colostomy. We present an alternative treatment, since many of these patients are elderly with a short life expectancy and they may have difficulty coping with a stoma. Seven transanal endoscopic resections of the prostate (TARP) have been performed on 5 patients. The procedure is not without complications, but it does offer simple surgical palliation of the rectal obstruction and obviates the need for a colostomy.

Epididymectomy for post-vasectomy pain: histological review.

Fifteen epididymectomies were performed on 10 patients with post-vasectomy pain and 12 specimens were available for histopathological review. The findings were compared with those in 2 groups in which epididymectomy was performed for chronic epididymo-orchitis and epididymal cysts. The results showed that 50% of the post-vasectomy group were cured by simple epididymectomy. Pathological findings revealed features of long-standing obstruction and interstitial and perineural fibrosis which may have accounted for the pain. It is important to recognise this late complication of vasectomy and, if surgery is to be performed, to include all of the distal vas and previous vasectomy site in the excision.

PIP: Epididymectomy was performed on 10 men with intractable post-vasectomy pain, on 7 with chronic epididymo-orchitis and 7 with epididymal cysts. The vasectomy patients had pain of mean 6 years duration, 6 months-20 years after surgery. In 9 the pain was a constant, dull ache. 5 had unilateral, and 5 bilateral epididymectomy. Only 5 were relieved of pain: 1 subsequently had orchidectomy with symptomatic improvement. The other 4 were offered orchidectomy. There was no obvious association of clinical findings with results. All 7 patients with epididymo-orchitis were relieved, although 1 required orchidectomy. 4 of the 7 with cysts had complained of pain, and all were asymptomatic after surgery. The most common pathological findings in the vasectomy patients were obstruction and dilatation of the efferent and epididymal ducts with interstitial fibrosis, and perineural inflammation and fibrosis around nerves, particularly in the tail of epididymis. So-called "late vasectomy syndrome" or unremitting pain is rare, and probable related to sperm granuloma.

Intraperitoneal rupture of an infected urachal cyst in an infant. Case report.

Peritonitis due to intraperitoneal rupture of an infected urachal cyst is a life-threatening condition, not previously reported in an infant. We report this condition in an 8-month-old infant. The child underwent complete excision of the urachal remnant and made an uneventful recovery; bacterial culture grew Staphylococcus aureus. Subsequent investigations did not reveal any other renal tract abnormalities.

Occult blood loss from small bowel tumours. Case report.

We report 4 patients who presented with occult blood loss, from a small bowel adenocarcinoma, in whom there was considerable delay in diagnosis. The difficulty in diagnosis and the role of CT scanning is discussed. We recommend a careful laparotomy when endoscopic and radiological investigations fail to reveal the source of blood loss.

Obstructing tracheal lipoma: management of a rare tumor.

Benign neoplasms of the trachea are rare. We describe a 46-year-old patient with a lipoma arising from the membranous trachea and causing severe respiratory obstruction. Investigation and management of this problem are discussed, and the literature is reviewed.

Endometriosis of the recto-vaginal septum treated by anterior resection.

Two young nulliparous females with severe symptomatic recto-vaginal endometriosis that had not responded to medical treatment were considered for surgery. Pre-operatively they were investigated by laparoscopy and Magnetic Resonance Imaging (M.R.I.) which demonstrated that the lesions were confined to the recto-vaginal septum with no intraperitoneal involvement. Both patients underwent resection of the middle third of the rectum and part of the posterior wall of the vagina with preservation of the ovaries, uterus and fallopian tubes. In one patient a J-colonic pouch with colo-anal anastomosis was fashioned and in the other patient a stapled colo-rectal anastomosis. Both patients are now asymptomatic with normal bowel function six months post-operatively. Radical surgery is indicated very rarely. We believe it should be considered in young nulliparous women who wish to conceive, in whom the diagnosis has been confirmed histologically and who have severe symptoms. M.R.I. is a useful pre-operative investigation to delineate the extent of the disease.