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A facile Pd-catalyzed cascade of intramolecular Heck cyclization/alkylpalladium activated dearomatization of aryl alkyne-tethered indole is described. In this single step two nonadjacent all-carbon quaternary centers, two nitrogen-containing heterocycles, and three C(sp

A convenient and straightforward approach for the construction of indole alkaloid scaffolds from indole-containing alkene-tethered aryl halides and alkynes through a sequential C-H activation, five-membered palladacycle formation, and alkyne insertion process has been described. The approach provides a series of indole alkaloid compounds in moderate to excellent yields with good functional tolerance.

Opioids like morphine have negative side effects such analgesia tolerance and morphine induced hyperalgesia (MIH), which is why their usage is restricted. Raising the dosage of morphine counteracts analgesic tolerance and MIH. Here, we discover that YTHDF1 and TNF receptor-associated factor 6 (TRAF6) expression, which are crucial for morphine analgesic tolerance and MIH. The m6A reader YTHDF1 positively controls the translation of TRAF6 mRNA, and chronic morphine treatments can enhance the m6A modification of TRAF6 mRNA. TRAF6 protein is drastically reduced by YTHDF1 knockdown, although TRAF6 mRNA level is unaffected. By reducing inflammatory markers such TNFα, IL-6, IL-1β and NF-κB, targeted reduction of YTHDF1 or suppression of TRAF6 activity in ventrolateral periaqueductal gray (vlPAG) slows the development of morphine analgesia tolerance and MIH. Our findings provide new insights into the mechanism by which YTHDF1 participates in morphine analgesia tolerance and MIH by regulating the inflammatory response involved in the expression of TRAF6 protein.

Background A substantial number of patients with esophageal squamous cell carcinoma (ESCC) do not achieve complete remission after definitive concurrent chemoradiotherapy (dCRT). We performed this retrospective study to evaluate the efficacy and safety of apatinib combined with S-1/capecitabine as the oral maintenance therapy for these patients. Methods Thirty-nine ESCC patients with residual disease after dCRT were included. Patients were treated with apatinib combined with S-1 /capecitabine after dCRT. Efficacy, toxicity, and survival were analyzed. Results Of the 39 patients, 5 (12.8%) achieved a partial response and 29 (74.4%) achieved stable disease, yielding a disease control rate of 87.2%. The median progression-free survival (PFS) and overall survival (OS) were 27.5 (95%CI: 14.9 - 40.1) and 38.1 (95%CI: 31.3 - 44.8) months. Most frequent adverse events were of grade 1 to 2. Multivariate analysis revealed the occurrence of any adverse events (HR = 0.274, 95%[CI] = 0.119 - 0.630) correlated to better PFS and occurrence of proteinuria (HR = 0.108, 95%[CI] = 0.025 - 0.456) predicted better OS. Conclusion The oral combination therapy consisting of apatinib and S-1/capecitabine showed a tolerable toxicity profile and achieved satisfactory disease control in ESCC patients with residual disease after dCRT.

Background Postoperative pain is a common problem that occurs in pediatric patients following neurosurgery which may lead to severe complications. Dexmedetomidine is a commonly used adjuvant medicine in craniotomy owing to its sedative, amnestic, analgesic, and neuroprotective properties. Besides, studies suggest that lidocaine has similar effects on sedation, analgesia, and neuroprotection. Both two adjuvants can reduce postoperative pain after neurosurgery in adults. However, it is still unknown whether dexmedetomidine or lidocaine can reduce postoperative pain in children undergoing craniotomy, and if yes, which is a better medicine choice. Therefore, we aimed to compare the effect of dexmedetomidine vs. lidocaine on postoperative pain in pediatric patients after craniotomy. Methods/design We will perform a randomized (1:1:1), double-blind, placebo-controlled, single-center trial. Children aged 1–12 years scheduled for craniotomy will be eligible for inclusion. The 255 recruited participants will be stratified by age in two strata (1–6 years and 7–12 years), and then each stratum will be equally randomized to three groups: group D (infusion of dexmedetomidine [intervention group]), group L (infusion of lidocaine [intervention group]), and group C (infusion of normal saline [control group]). Patients will be followed up at 1 h, 2 h, 4 h, 24 h, and 48 h after surgery. The primary outcome will be total sufentanil consumption within 24 h after surgery. Discussion In this clinical trial, we expect to clarify and compare the postoperative analgesic effect of dexmedetomidine vs. lidocaine infusion on pediatric patients undergoing craniotomy. We believe that the results of this trial will provide more choices for postoperative analgesia for the pediatric population. Trial registration Chinese ClinicalTrials.gov ChiCTR1800019411. Registered on 10 November 2018

A palladium-catalyzed cascade allylative dicarbofunctionalization of aryl phenol-tethered alkynes with allyl iodides is described. A series of polysubstituted spirocyclo-containing skipped dienes with an all-carbon tetrasubstituted alkene unit are synthesized through this convenient process. The cascade reaction proceeds selectively through dearomative C-allylation instead of O-allylation of aryl phenols.

2613 Background: Proton pump inhibitors (PPIs) were revealed to regulate gut microbiome alterations and further impact the response to immune checkpoint inhibitors (ICIs). Contradictory impacts on survival were observed in ICI-treated patients when concomitantly use PPI or not. We performed this systematic review and meta-analysis to analyze the association of PPI use with survival outcomes in ICI-treated cancer patients. Methods: EMBASE, MEDLINE/PubMed, Cochrane Library databases and major oncology conferences proceedings were comprehensively searched. Studies comparing overall survival (OS) and progression-free survival (PFS) between PPI use and PPI non-use in ICI-treated cancer patients were included. Data regarding the characteristics, ICI and PPI treatments and survival outcomes for patients were extracted. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effect models. Subgroup meta-analyses and meta-regressions were performed to explore possible factors of heterogeneity among study results. Results: A total of 20 studies were included, comprising 2812 ICI- and PPI-treated patients and 3990 ICI-treated and PPI-free patients. The pooled HR is 1.30 (95% CI, 1.17-1.45; P

// Haidan Lan 1,* , Leng Zhou 1,* , Dongmei Chi 1 , Qinghua Zhou 2 , XiaoJun Tang 2 , Daxing Zhu 2 , Jianmin Yue 1 and Bin Liu 1 1 Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, Sichuan, China 2 The lung cancer center, West China Hospital of Sichuan University, Chengdu, Sichuan, China * These authors have contributed equally to this work Correspondence to: Bin Liu, email: // Keywords : non small cell lung cancer; platelet to lymphocyte ratio; neutrophil to lymphocyte ratio; postoperative pulmonary complications; overall survival Received : September 02, 2016 Accepted : October 28, 2016 Published : November 11, 2016 Abstract Background: The aim of this study was to assess the prognostic value for NSCLC patients who were scheduled to receive lung cancer radical resection. Methods: In this cohort study (Dec.2014-Feb.2016), patients with non-small cell lung cancer (NSCLC) who underwent radical lung cancer thoracotomy were enrolled and accessed at postoperative complications, one-year overall survival (OS) and relapse-free survival (RFS). The preoperative PLR and NLR of all patients were calculated based on preoperative complete blood counts. Univariate and multivariate Cox regression analyses were performed to determine the associations of PLR and NLR with OS and RFS. Results. A total of 174 NSCLC patients were studied. The results indicated that both high PLR (>148.6) and NLR (>2.9) were related to a high rate of postoperative pulmonary complications significantly (49.3%vs.29.1%, P = 0.007; 50.7% vs . 28.6%, P = 0.003). Moreover, NSCLC patients with a high PLR level (> 148.6) was significantly associated with a lower one-year OS (90.3% vs . 77.5%, P = 0.034). Conclusions. Preoperative PLR and NLR were good prognostic factors for postoperative pulmonary complications and OS in NSCLC patients undergoing radical lung cancer surgery. Thus, blood PLR and NLR would be helpful as a prognostic tool before radical lung cancer surgery.

Supplemental Digital Content is available in the text, Background: Since postoperative pulmonary complications are one of the main causes of morbidity and mortality in patients undergoing lung resection surgery, we performed a meta-analysis to compare the incidence of postoperative pulmonary complications and hospital death, and the length of hospital stay in patients who received nonintubated or intubated anesthesia during thoracoscopic surgery for lung resection and further explore the tricks in nonintubated anesthesia. Methods: PubMed, Embase, and Cochrane Library were searched from inception to September 2017. We included eligible research comparing nonintubated anesthesia with intubated anesthesia in thoracoscopic surgery for lung resection. The primary outcomes involved postoperative pulmonary complications, hospital death, and hospital stay. The rates and causes of conversion from nonintubated anesthesia to intubated anesthesia were also analyzed. Results: After screening through 754 potentially relevant articles, we included 3 randomized controlled trials and 7 observational studies with 1138 patients. There was no perioperative mortality in 2 groups. The nonintubated group revealed comparable postoperative pulmonary complications (OR = 0.57; P = .07; P for heterogeneity = .49, I2 = 0%) and shorter hospital stay (WMD = −1.10; P

The intricate molecular network shared between diabetes mellitus (DM) and cancer has been broadly understood. DM has been associated with several hormone-dependent malignancies, including breast, pancreatic, and colorectal cancer (CRC). Insulin resistance, hyperglycemia, and inflammation are the main pathophysiological mechanisms linking DM to cancer. Non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are widely appreciated as pervasive regulators of gene expression, governing the evolution of metabolic disorders, including DM and cancer. The ways ncRNAs affect the development of DM complicated with cancer have only started to be revealed in recent years. Insulin-like growth factor 1 receptor (IGF-1R) signaling is a master regulator of pathophysiological processes directing DM and cancer. In this review, we briefly summarize a number of well-known miRNAs and lncRNAs that regulate the IGF-1R in DM and cancer, respectively, and further discuss the potential underlying molecular pathogenesis of this disease association.

Supplemental Digital Content is available in the text, Background: Cardiopulmonary bypass (CPB) is necessary for most cardiac surgery, which may lead to postoperative lung injury. The objective of this paper is to systematically evaluate whether ventilation during CPB would benefit patients undergoing cardiac surgery. Methods: We searched randomized controlled trials (RCTs) through PubMed, Embase, and Cochrane Library from inception to October 2016. Eligible studies compared clinical outcomes of ventilation versus nonventilation during CPB in patients undergoing cardiac surgery. The primary outcome includes oxygenation index (PaO2/FiO2 ratio) or alveolar to arterial oxygen tension difference (AaDO2) immediately after weaning from bypass. The secondary outcomes include postoperative pulmonary complications (PPCs), shunt fraction (Qs/Qt), hospital stay, and AaDO2 4 hours after CPB. Results: Seventeen trials with 1162 patients were included in this meta-analysis. Ventilation during CPB significantly increased post-CPB PaO2/FiO2 ratio (mean difference [MD] = 21.84; 95% confidence interval [CI] = 1.30 to 42.37; P = 0.04; I2 = 75%) and reduced post-CPB AaDO2 (MD = –50.17; 95% CI = –71.36 to –28.99; P

Remote ischemic preconditioning (RIPC) may attenuate acute kidney injury (AKI). However, results of studies evaluating the effect of RIPC on AKI after cardiac surgery have been controversial and contradictory. The aim of this meta-analysis is to examine the association between RIPC and AKI after on-pump cardiac surgery. The authors searched relevant studies in PubMed, EMBASE, and the Cochrane Library through December 2015. We considered for inclusion all randomized controlled trials that the role of RIPC in reducing AKI and renal replacement therapy (RRT) among patients underwent on-pump cardiac surgical procedures. We collected the data on AKI, initiation of RRT, serum creatinine (sCr) levels, and in-hospital mortality. Random- and fixed-effect models were used for pooling data. Nineteen trials including 5100 patients were included. The results of this meta-analysis showed a significant benefit of RIPC for reducing the incidence of AKI after cardiac interventions (odds ratio [OR] = 0.84; 95% confidence interval [CI], 0.73–0.98; P = 0.02). No significant difference was found in the incidence of RRT between RIPC and control (OR, 0.76, 95% CI, 0.46–1.24; P = 0.36). In addition, compared with standard medical care, RIPC showed no significant difference in postoperative sCr (IV 0.07; 95% CI, −0.03 to 0.16; P = 0.20; postoperative day 1; IV 0.00; 95% CI, −0.08 to 0.09; P = 0.92; postoperative day 2; IV 0.04; 95% CI, −0.05 to 0.12; P = 0.39; postoperative day 3), and in-hospital mortality (OR, 1.21, 95% CI, 0.64–2.30; P = 0.56). According to the results from present meta-analysis, RIPC was associated with a significant reduction AKI after on-pump cardiac surgery but incidence of RRT, postoperative sCr, and in-hospital mortality. Further high-quality randomized controlled trials and experimental researches comparing RIPC are desirable.