Circular RNA circ-ERBB2 promotes HER2-positive breast cancer progression and metastasis via sponging miR-136-5p and miR-198.

BACKGROUND: Circular RNAs (circRNAs) are pivotal regulators of various human cancers and circ-ERBB2 is abnormally expressed in breast cancer cells. However, the role and mechanism of circ-ERBB2 in HER2-positive breast cancer are still unknown. METHODS: The circ-ERBB2 expressions in the tumor tissues of HER2-positive breast cancer patients were tested using quantitative real-time PCR. The circ-ERBB2 function was investigated by cell counting kit 8 assay, Transwell, flow cytometry and Western blot. Mechanistically, fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull-down and dual-luciferase reporter gene assays were conducted to confirm the interaction between circ-ERBB2 and miR-136-5p or miR-198 in HER2-positive breast cancer cells. RESULTS: Circ-ERBB2 was elevated in the tumor tissues of HER2-positive breast cancer patients. Functionally, the interference with circ-ERBB2 repressed HER2-positive breast cancer cell proliferation, migration, invasion and accelerated cell apoptosis. Furthermore, the mechanistic analysis corroborated that circ-ERBB2 acted as a competing endogenous RNA for miR-136-5p or miR-198 to relieve the repressive influence of miR-136-5p or miR-198 on its target transcription factor activator protein 2C (TFAP2C). Meanwhile, in vivo assays further corroborated the oncogenic function of circ-ERBB2 in HER2-positive breast cancer. CONCLUSIONS: Circ-ERBB2 accelerated HER2-positive breast cancer progression through the circ-ERBB2/miR-136-5p/TFAP2C axis or the circ-ERBB2/miR-198/TFAP2C axis.

Sensory block level prediction of spinal anaesthesia with 0.5% hyperbaric bupivacaine: a retrospective study.

There is still no consensus on how to determine the dose of spinal anaesthesia with adequate sensory block for a planned surgery. This retrospective study aimed to explore the associations of miscellaneous factors with peak sensory block level after spinal anaesthesia with hyperbaric bupivacaine, and to construct a predictive model for single-shot spinal anaesthesia. We collected the records of 401 non-pregnant adults who underwent spinal anaesthesia with 0.5% hyperbaric bupivacaine at the L3-4 or L4-5 intervertebral space for lower body surgeries. Multiple linear regression analysis was used to investigate predictors of the block level and build up the predictive model. Five variables were identified as independent predictors of the peak sensory block level, including bupivacaine dose, height, weight, gender and age. The predictive model for peak block level after spinal anaesthesia could be expressed as a formula with these five variables and the estimated predictive power was 0.72. Based on this model, it is possible to determine a reasonable dose of hyperbaric bupivacaine for spinal anaesthesia, which gives adequate sensory block required for diverse surgical procedures in various patients and could be considered as a dose reference for sensory block height in spinal anaesthesia.

Predicting the Best Fit: A Comparison of Response Surface Models for Midazolam and Alfentanil Sedation in Procedures With Varying Stimulation.

BACKGROUND: Selecting an effective dose of sedative drugs in combined upper and lower gastrointestinal endoscopy is complicated by varying degrees of pain stimulation. We tested the ability of 5 response surface models to predict depth of sedation after administration of midazolam and alfentanil in this complex model. The procedure was divided into 3 phases: esophagogastroduodenoscopy (EGD), colonoscopy, and the time interval between the 2 (intersession). METHODS: The depth of sedation in 33 adult patients was monitored by Observer Assessment of Alertness/Scores. A total of 218 combinations of midazolam and alfentanil effect-site concentrations derived from pharmacokinetic models were used to test 5 response surface models in each of the 3 phases of endoscopy. Model fit was evaluated with objective function value, corrected Akaike Information Criterion (AICc), and Spearman ranked correlation. A model was arbitrarily defined as accurate if the predicted probability is <0.5 from the observed response. RESULTS: The effect-site concentrations tested ranged from 1 to 76 ng/mL and from 5 to 80 ng/mL for midazolam and alfentanil, respectively. Midazolam and alfentanil had synergistic effects in colonoscopy and EGD, but additivity was observed in the intersession group. Adequate prediction rates were 84% to 85% in the intersession group, 84% to 88% during colonoscopy, and 82% to 87% during EGD. The reduced Greco and Fixed alfentanil concentration required for 50% of the patients to achieve targeted response Hierarchy models performed better with comparable predictive strength. The reduced Greco model had the lowest AICc with strong correlation in all 3 phases of endoscopy. Dynamic, rather than fixed, γ and γalf in the Hierarchy model improved model fit. CONCLUSIONS: The reduced Greco model had the lowest objective function value and AICc and thus the best fit. This model was reliable with acceptable predictive ability based on adequate clinical correlation. We suggest that this model has practical clinical value for patients undergoing procedures with varying degrees of stimulation.

Functional identification of an outwardly rectifying pH- and anesthetic-sensitive leak K(+) conductance in hippocampal astrocytes.

Astrocytes function as spatial K(+) buffers by expressing a rich repertoire of K(+) channels. Earlier studies suggest that acid-sensitive tandem-pore K(+) channels, mainly TWIK-related acid-sensitive K(+) (TASK) channels, mediate part of the passive astroglial membrane conductance. Here, using a combination of electrophysiology and pharmacology, we investigated the presence of TASK-like conductance in hippocampal astrocytes of rat brain slices. Extracellular pH shifts to below 7.4 (or above 7.4) induced a prominent inward (or outward) current in astrocytes in the presence of tetrodotoxin, a Na(+) channel blocker, and 4,4'-diisothiocyanatostilbene-2,2'-disulfonate, a co-transporter blocker. The pH-sensitive current was insensitive to quinine, a potent blocker of tandem-pore K(+) channels including TWIK-1 and TREK-1 channels. Voltage-clamp analysis revealed that the pH-sensitive current exhibited weak outward rectification with a reversal potential of -112 mV, close to the Nernst equilibrium potential for K(+) . Furthermore, the current-voltage relationship was well fitted with the Goldman-Hodgkin-Katz current equation for the classical open-rectifier 'leak' K(+) channel. The pH-sensitive K(+) current was potentiated by TASK channel modulators such as the volatile anesthetic isoflurane but depressed by the local anesthetic bupivacaine. However, unlike TASK channels, the pH-sensitive current was insensitive to Ba(2+) and quinine. Thus, the molecular identity of the pH-sensitive leak K(+) channel is unlikely to be attributable to TASK channels. Taken together, our results suggest a novel yet unknown leak K(+) channel underlying the pH- and anesthetic-sensitive background conductance in hippocampal astrocytes.

Paradoxical carbon dioxide embolism during pneumoperitoneum in laparoscopic surgery for a huge renal angiomyolipoma.

We present a case of paradoxical gas embolism during CO2 insufflation in laparoscopic nephrectomy for a huge renal angiomyolipoma. Paradoxical CO2 embolism in the left heart chambers without demonstrable intracardiac right-to-left shunt was detected by transesophageal echocardiography (TEE). The surgical procedure was stopped immediately, but the patient recovered with mild neurologic deficit. We speculate that rapid pneumoperitoneum introduction pushed CO2 into the abnormal vasculature of the angiomyolipoma, which communicates with the systemic vascular system, causing pseudoaneurysm formation. Follow-up abdominal computed tomography showed a new pseudoaneurysm inside the tumor. If intracardiac right-to-left shunt is excluded for the reason of paradoxical gas existence, there remains extracardiac right-to-left shunt, with transpulmonary passage of the venous emboli being the most likely mechanism. In fact, the cause of paradoxical gas embolism in this case remains unknown. Therefore, laparoscopic surgery for huge angiomyolipoma should be performed with extreme caution; an open procedure may be considered as an alternative.

Desipramine activated Bcl-2 expression and inhibited lipopolysaccharide-induced apoptosis in hippocampus-derived adult neural stem cells.

Desipramine (DP) is a tricyclic antidepressant used for treating depression and numerous other psychiatric disorders. Recent studies have shown that DP can promote neurogenesis and improve the survival rate of hippocampal neurons. However, whether DP induces neuroprotection or promotes the differentiation of neural stem cells (NSCs) needs to be elucidated. In this study, we cultured NSCs derived from the hippocampal tissues of adult rats as an in vitro model to evaluate the modulation effect of DP on NSCs. First, we demonstrated that the expression of Bcl-2 mRNA and nestin in 2 microM DP-treated NSCs were up-regulated and detected by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The results of Western blotting and immunofluorescent study confirmed that Bcl-2 protein expression was significantly increased in Day 3 DP-treated NSCs. Using the Bcl-2 small interfering RNA (siRNA) method, our results further showed that DP protects the lipopolysaccharide (LPS)-induced apoptosis in NSCs, in part by activating the expression of Bcl-2. Furthermore, DP treatment significantly inhibited the induction of proinflammatory factor interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha in the culture medium of LPS-treated NSCs mediated by Bcl-2 modulation. The results of high performance liquid chromatography coupled to electrochemical detection further confirmed that DP significantly increased the functional production of serotonin (26+/-3.5 microM, DP-treated 96 h) and noradrenaline (50+/-8.9 microM, DP-treated 96 h) in NSCs through activation of the MAPK/ERK pathway and partially mediated by Bcl-2. In conclusion, the present results indicate that DP can increase neuroprotection ability by inhibiting the LPS-induced inflammatory process in NSCs via the modulation of Bcl-2 expression, as confirmed by the siRNA method.

Conscious sedation in gastrointestinal endoscopy.

In recent years, the incidences of stomach and colon cancers have ranked within the top fives of all malignancies in Taiwan. To say healthwise, regular gastrointestinal (GI) endoscopic examinations are recommended, as they are the best way for early detection. However, unpleasantness of and terrible experience from the examination greatly discourage the acceptance of many people even of the suspected groups. Now, the administration of sedative or analgesic to achieve the so called "conscious sedation" during GI endoscopy which brings about better tolerability and improves general acceptance offers a more satisfactory service. In this article, the related issues about preprocedure evaluation, preparation, medications and complications of conscious sedation in GI endoscopy are discussed after review.

General anesthesia for patient with homocystinuria--a case report.

Homocystinuria is an autosomal recessive disease with multiple systemic disorders. Here we report a 15-year-old lad suffering from homocystinuria who required an ocular surgery including lentectomy and implant of plastic lens, OS and anterior retinal cryotherapy, OD under general anesthesia because of lens subluxation and lattice degeneration. It is the elective ocular procedure most commonly performed for homocystinuric children. Proper precautions should be taken during anesthetic management since this condition inspires some particular anesthetic complications that could be prevented by careful consideration and understanding of its pathophysiology. Providentially our patient stood the operation well and was discharged without subsequent thromboembolism or other complication as an aftermath.