Langhoffbateman3491

A series of 3-nitro-naphthalimides 1(1a-1h) were designed and synthesized as antitumor agents. MTT assay results showed that all these compounds exhibited obvious antiproliferative activity against SKOV3, HepG2, A549, T-24 and SMMC-7721 cancer cell lines, while compound 1a displayed the best antiproliferative activity against HepG2 and T-24 cell lines in comparison with mitonafide, with IC50 of 9.2 ± 1.8 and 4.133 ± 0.9 μM, respectively. In vivo antiproliferative activity assay results showed that compound 1a exhibited good antiproliferative activity in the HepG2 and T-24 models, compared with mitonafide. Action mechanism results showed that compound 1a could induced the damage of DNA and the inhibition topo I, accompanying by inducing the G2-stage arresting and the apoptosis of T-24 cancer cells through up-regulating expression levels of cyclin B1, cdc 2-pTy, Wee1, γH2AX, p21, Bax and cytochrome c and down-regulating expression of Bcl-2. One achiral tetra-aryl cyclobutane [rheundulin A (1)] and three stilbene glycosides [rheundulins B-D (2-4)] were isolated from the methanol extract of Rheum undulatum L., along with eight known compounds (5-12). Structural determination of the new compounds (1-4) was accomplished using comprehensive spectroscopic methods. Compound 1 represents the first example of a dimeric stilbene linked via a cyclobutane ring from the Rheum genus. All isolates were screened for their inhibition against α-glucosidase. Among them, stilbene derivatives (5 and 6) showed strong inhibitory effects on α-glucosidase with IC50 values of 0.5 and 15.4 µM, respectively, which were significantly higher than that of the positive control, acarbose (IC50 = 126.8 µM). Rheundulin A (1) showed moderate α-glucosidase inhibition with an IC50 value of 80.1 µM. see more In addition, kinetic analysis and molecular docking simulation of the most active compound (5) with α-glucosidase were performed for the first time. Kinetic studies revealed that compound 5 competitively inhibited the active site of α-glucosidase (Ki = 0.40 µM), while 6 had a mixed-type inhibitory effect against α-glucosidase (Ki = 15.34 µM). Molecular docking simulations of 5 and 6 demonstrated negative-binding energies, indicating high proximity to the active site and tight binding to α-glucosidase enzyme. BACKGROUND Current practice patterns and opinions regarding subspecialization within pediatric surgery are not well known. We aimed to characterize the prevalence of and attitudes surrounding subspecialization within pediatric surgery. METHODS An anonymous survey regarding subspecialization was distributed to all nonresident members of the American Pediatric Surgical Association. RESULTS Of 1118 surveys, we received 458 responses (41%). A majority of respondents labeled themselves 'general pediatric surgeons' (63%), while 34% considered themselves general surgeons with a specific clinical focus, and 3% reported practicing solely within a specific niche. Subspecialists commonly serve as consultants for relevant cases (52%). Common niches included oncology (10%) and anorectal malformations (9%). Subspecialists felt to be necessary included transplant (79%) and fetal (78%) surgeons. Opinions about subspecialization were variable 41% felt subspecialization improves patient care while 39% believe it is detrimental to surgeon well-roundedness. Only 10% felt subspecialists should practice solely within their subspecialty. Practicing at an academic hospital or fellowship program correlated with subspecialization, while length of time in practice did not. CONCLUSION While pediatric surgeons report that subspecialization may benefit patient care, concerns exist regarding the unfavorable effect it may have on the individual surgeon. A better understanding of how subspecialization affects quality and outcomes would help clarify its utility. TYPE OF STUDY Review article. LEVEL OF EVIDENCE Level V. BACKGROUND Eighty percent of caustic ingestions occur in children and esophageal neoplasms may develop as a late complication of such injury. The identification of biomarkers is a promising strategy to improve early diagnosis of esophageal cancer or caustic lesions that are at an increased risk of progression. STUDY DESIGN/AIMS This study aimed at identifying global microRNA (miRNA) expression changes in esophageal mucosa from children with caustic stenosis. The study included 27 biopsy samples from 15 patients. Samples were divided into two groups, according to the time elapsed after injury (N = 15 in Group A, with less than five years of follow-up and N = 12 in Group B, with more than five years of follow-up). miRNA expression profiles were determined in each lesion, compared with normal esophageal tissues from control group. We used the TaqMan Human MicroRNA Arrays (Thermo Fisher) platform. Furthermore, bioinformatic algorithms were used to identify miRNA target genes and biological pathways including miRNAs and their target genes potentially associated with esophageal disease. RESULTS Thirteen miRNAs were significantly deregulated (9 over- and 4 underexpressed) in patients from Group A. In patients from Group B, two miRNAs were over- and two were underexpressed. Of note, miR-374 and miR-574 were deregulated in Group B patients and have been linked to esophageal tumorigenesis. We identified signal transduction and transcription factor networks with genes strongly related to development and progression of esophageal cancer. CONCLUSION miRNAs identified here contribute to a better understanding of pathways associated with malignant transformation from caustic stenosis to neoplastic lesions. This study may serve as a basis for validation of miRNAs, including miR-374 and miR-574, as potential biomarkers of early cancer detection. OBJECTIVE Del Nido cardioplegia solution offers prolonged cardiac protection with single-dose administration; this is particularly interesting for aortic root surgery. However, there is a scarcity of data supporting its safety in adults undergoing complex cardiac surgery, such as aortic root repair. We hypothesized that del Nido cardioplegia solution and blood cardioplegia solution provide equivalent safety during aortic root surgery. METHODS Between January 2015 and June 2018, 283 consecutive patients undergoing the Ross procedure (204) and valve-sparing operation (79) with del Nido cardioplegia solution or blood cardioplegia solution were 11 propensity matched (110 aortic root surgery), and outcomes were compared. Clinical patient characteristics and data were extracted from our local database for valve-sparing operations and for Ross procedures. RESULTS Preoperative characteristics were similar between del Nido cardioplegia solution and blood cardioplegia solution after propensity matching (mean age, 48.6 gent use (P = .8). Postoperative left ventricle ejection fraction was similar (0.54 ± 0.09 vs 0.55 ± 0.08 for del Nido cardioplegia solution and blood cardioplegia solution, respectively; P = .4). There was no difference between groups for perioperative mortality and postoperative complications. CONCLUSIONS Del Nido cardioplegia solution can be used as an alternative to blood cardioplegia solution in adults undergoing complex aortic root surgery, providing comparable clinical outcomes and improved surgical workflow. However, del Nido cardioplegia solution seems to be associated with increased myocardial injury, especially with extended myocardial ischemic times, but this finding did not translate into adverse clinical events. Caution is warranted in adopting this cardioplegic solution in aortic interventions requiring long ischemic times, and further study is required to establish its exact role in complex cardiac surgery. OBJECTIVE Various methods for cardiothoracic, cardiovascular, and cardiac surgical training exist across the globe, with the common goal of producing safe, independent surgeons. A comparative analysis of international training paradigms has not been undertaken, and our goal in doing so was to offer insights into how to best prepare future trainees and ensure the health of our specialty. METHODS We performed a comparative analysis of available publications offering detailed descriptions of various cardiothoracic, cardiovascular, and cardiac surgical training paradigms. Corresponding authors from previous publications and other international collaborators were also reached directly for further data acquisition. RESULTS We report various approaches to common challenges surrounding (1) selection of trainees and plans for the future surgical workforce; (2) trainee assessments and certification of competency before independent practice; and (3) challenges related to a changing practice landscape. CONCLUSIONS Cardiothoracic surgery remains a dynamic and rewarding specialty. Current and future trainees face several challenges that transcend national borders. To foster collaboration and adoption of best practices, we highlight international strengths and weaknesses of various nations in terms of workforce selection, trainee operative experience and assessment, board certification, and preparation for future changes anticipated in cardiothoracic surgery. OBJECTIVE We aim to evaluate the survival outcomes of primary cardiac sarcoma in a US nationwide cancer database. METHODS The Surveillance, Epidemiology, and End Results database was queried to identify patients with primary cardiac sarcoma from 1973 to 2015. Kaplan-Meier analysis and log-rank tests were performed to compare overall survival for subpopulations, stratified on year at diagnosis (dichotomized into 2 periods 1973-2005 and 2006-2015), pathological types, whether patients were treated with surgery or not, and surgery and chemotherapy combinations. Multivariable Cox regression was performed to estimate the adjusted hazard ratios and 95% confidence intervals of potentially clinically important factors. RESULTS A total of 442 patients (mean age, 47.2 ± 18.7 years; male 52.0%) were identified. Most patients were white (78.1%) and diagnosed at age 20 to 60 years (70.2%). Angiosarcoma (43.2%) was the most common histologic type. Overall, the median survival was 7 months, and the 1-, 3-, and 5-year survivals were 40.7%, 15.6%, and 9.8%, respectively. Patients who were diagnosed within the recent decade (2006-2015) did not achieve a better overall survival (P = .13). Surgery (adjusted hazard ratio, 0.49; 95% confidence interval, 0.37-0.64; P  less then  .001) and chemotherapy (adjusted hazard ratio, 0.70; 95% confidence interval, 0.54-0.92; P = .009) were independently associated with improved overall survival. Increasing age (adjusted hazard ratio of 5-year increment, 1.07; 95% confidence interval, 1.04-1.11; P  less then  .001) was independently associated with worse survival. CONCLUSIONS At the population level, primary cardiac sarcoma has a poor prognosis. Both surgery and chemotherapy are associated with improved survival, whereas increasing age at diagnosis was associated with worse survival. OBJECTIVE Thoracoscopic anatomic single or combined basal segmentectomy is technically challenging because of the variation and deep location of vessels and bronchi in the parenchyma. This study aimed to describe thoracoscopic segmentectomy of basal segments using a single-direction method. METHODS This retrospective study included 137 patients who underwent single or combined thoracoscopic basal segmentectomy between April 2015 and August 2019. All procedures were performed via the preferred inferior pulmonary ligament approach or an interlobar fissure approach following a single-direction strategy. RESULTS Ninety patients underwent single basal segmentectomy, and 47 patients underwent combined basal segmentectomy. Median operative time was 125 minutes (range, 52-237 minutes), and median blood loss was 30 mL (range, 5-250 mL). Median chest tube duration was 2 days (range, 1-22 days), and median postoperative hospital stay was 4 days (range, 2-24 days). The postoperative morbidity rate was 5.1% (7/137). No perioperative deaths were identified.