Direct insertion of an ultra‐slim upper endoscope for cholangioscopy in patients undergoing choledochoduodenostomy

Direct peroral cholangioscopy (POC) using an ultra‐slim upper endoscope is one modality of POC for intraductal endoscopic evaluation and treatment of the bile duct. Choledochoduodenostomy (CDS) is one modality of biliary bypass surgery that provides a new route to the bile duct. We carried out direct POC using an ultra‐slim upper endoscope without the use of accessories in 10 patients (four sump syndromes, three bile duct strictures and three intrahepatic duct stones) previously undergoing surgical CDS. Direct POC was successful in all patients. The use of an intraductal balloon catheter was required in one patient for advancement of the endoscope into the bile duct. Distal bile ducts with sump syndromes were cleared using baskets and water irrigation under direct POC. Cholangiocarcinoma was diagnosed in one patient with hilar bile duct stricture after cholangioscopic evaluation and a targeting forceps biopsy under direct POC. Intrahepatic duct stones were successfully extracted after intraductal fragmentation under direct POC. Oozing bleeding occurred during intraductal lithotripsy but stopped spontaneously. Direct POC using an ultra‐slim upper endoscope without the assistance of accessories can easily be carried out in patients undergoing CDS.     

Exosomes from miRNA‐126‐modified endothelial progenitor cells alleviate brain injury and promote functional recovery after stroke

AimsWe previously showed that the protective effects of endothelial progenitor cells (EPCs)‐released exosomes (EPC‐EXs) on endothelium in diabetes. However, whether EPC‐EXs are protective in diabetic ischemic stroke is unknown. Here, we investigated the effects of EPC‐EXs on diabetic stroke mice and tested whether miR‐126 enriched EPC‐EXs (EPC‐EXs^miR126) have enhanced efficacy.MethodsThe db/db mice subjected to ischemic stroke were intravenously administrated with EPC‐EXs 2 hours after ischemic stroke. The infarct volume, cerebral microvascular density (MVD), cerebral blood flow (CBF), neurological function, angiogenesis and neurogenesis, and levels of cleaved caspase‐3, miR‐126, and VEGFR2 were measured on day 2 and 14.ResultsWe found that (a) injected EPC‐EXs merged with brain endothelial cells, neurons, astrocytes, and microglia in the peri‐infarct area; (b) EPC‐EXs^miR126 were more effective than EPC‐EXs in decreasing infarct size and increasing CBF and MVD, and in promoting angiogenesis and neurogenesis as well as neurological functional recovery; (c) These effects were accompanied with downregulated cleaved caspase‐3 on day 2 and vascular endothelial growth factor receptor 2 (VEGFR2) upregulation till day 14.ConclusionOur results indicate that enrichment of miR126 enhanced the therapeutic efficacy of EPC‐EXs on diabetic ischemic stroke by attenuating acute injury and promoting neurological function recovery.     

国际内镜疝学会腹壁疝和切口疝腹腔镜治疗指南更新解读（六）

<正>第5章术前辅助措施在腹疝修补术中的作用通过Medline、PubMed、Cochrane Library以及相关期刊和参考文献进行了系统的文献检索,证据结论:(1)在腹壁疝修补术之前使用A型肉毒素(botulinum toxin type A,BTA)与阿片类镇痛的使用显著减少疼痛。证据级别:3级。(2)(1)应用BTA可使腹壁疝直径减小,腹壁外侧肌厚度显著减少,腹壁外侧肌显著延长。在大多数腹疝患者中,单独     

Comparison Between Phenylephrine and Dopamine in Maintaining Cerebral Oxygen Saturation in Thoracic Surgery: A Randomized Controlled Trial

Fluid is usually restricted during thoracic surgery, and vasoactive agents are often administered to maintain blood pressure. One-lung ventilation (OLV) decreases arterial oxygenation; thus oxygen delivery to the brain can be decreased. In this study, we compared phenylephrine and dopamine with respect to maintaining cerebral oxygenation during OLV in major thoracic surgery.Sixty-three patients undergoing lobectomies were randomly assigned to the dopamine (D) or phenylephrine (P) group. The patients’ mean arterial pressure was maintained within 20% of baseline by a continuous infusion of dopamine or phenylephrine. Maintenance fluid was kept at 5 mL/kg/h. The depth of anesthesia was maintained with desflurane 1MAC and remifentanil infusion under bispectral index guidance. Regional cerebral oxygen saturation (rScO₂) and hemodynamic variables were recorded using near-infrared spectroscopy and esophageal cardiac Doppler.The rScO₂ was higher in the D group than the P group during OLV (OLV 60 min: 71 ± 6% vs 63 ± 12%; P = 0.03). The number of patients whose rScO₂ dropped more than 20% from baseline was 0 and 6 in the D and P groups, respectively (P = 0.02). The D group showed higher cardiac output, but lower mean arterial pressure than the P group (4.7 ± 1.0 vs 3.9 ± 1.2 L/min; 76.7 ± 8.1 vs 84.5 ± 7.5 mm Hg; P = 0.02, P = 0.02). Among the variables, age, hemoglobin concentration, and cardiac output were associated with rScO₂ by correlation analysis.Dopamine was superior to phenylephrine in maintaining cerebral oxygenation during OLV in thoracic surgery.     

Protein kinase Cδ mediates trimethyltin-induced neurotoxicity in mice in vivo via inhibition of glutathione defense mechanism

We investigated whether protein kinase C (PKC) is involved in trimethyltin (TMT)-induced neurotoxicity. TMT treatment (2.8 mg/kg, i.p.) significantly increased PKCδ expression out of PKC isozymes (i.e., α, βI, βII, δ, and ?) in the hippocampus of wild-type (WT) mice. Consistently, treatment with TMT resulted in significant increases in cleaved PKCδ expression. Genetic or pharmacological inhibition (PKCδ knockout or rottlerin) was less susceptible to TMT-induced seizures than WT mice. TMT treatment increased glutathione oxidation, lipid peroxidation, protein oxidation, and levels of reactive oxygen species. These effects were more pronounced in the WT mice than in PKCδ knockout mice. In addition, the ability of TMT to induce nuclear translocation of Nrf2, Nrf2 DNA-binding activity, and upregulation of γ-glutamylcysteine ligase was significantly increased in the PKCδ knockout mice and rottlerin (10 or 20 mg/kg, p.o. × 6)-treated WT mice. Furthermore, neuronal degeneration (as shown by nuclear chromatin clumping and TUNEL staining) in WT mice was most pronounced 2 days after TMT. At the same time, TMT-induced inhibition of phosphoinositol 3-kinase (PI3K)/Akt signaling was evident, thereby decreasing phospho-Bad, expression of Bcl-xL and Bcl-2, and the interaction between phospho-Bad and 14-3-3 protein, and increasing Bax expression and caspase-3 cleavage were observed. Rottlerin or PKCδ knockout significantly protected these changes in anti- and pro-apoptotic factors. Importantly, treatment of the PI3K inhibitor LY294002 (0.8 or 1.6 µg, i.c.v.) 4 h before TMT counteracted protective effects (i.e., Nrf-2-dependent glutathione induction and pro-survival phenomenon) of rottlerin. Therefore, our results suggest that down-regulation of PKCδ and up-regulations of Nrf2-dependent glutathione defense mechanism and PI3K/Akt signaling are critical for attenuating TMT neurotoxicity.