Combined 3D-QSAR and Docking Modelling Study on Indolocarbazole Series Compounds as Tie-2 Inhibitors

Tie-2, a kind of endothelial cell tyrosine kinase receptor, is required for embryonic blood vessel development and tumor angiogenesis. Several compounds that showed potent activity toward this attractive anticancer drug target in the assay have been reported. In order to investigate the structure-activity correlation of indolocarbazole series compounds and modify them to improve their selectivity and activity, 3D-QSAR models were built using CoMFA and CoMSIA methods and molecular docking was used to check the results. Based on the common sketch align, two good QSAR models with high predictabilities (CoMFA model: q2 = 0.823, r2 = 0.979; CoMSIA model: q2 = 0.804, r2 = 0.967) were obtained and the contour maps obtained from both models were applied to identify the influence on the biological activity. Molecular docking was then used to confirm the results. Combined with the molecular docking results, the detail binding mode between the ligands and Tie-2 was elucidated, which enabled us to interpret the structure-activity relationship. These satisf actory results not only offered help to comprehend the action mechanism of indolocarbazole series compounds, but also provide new information for the design of new potent inhibitors

Pain Clinic in Tibet, China: A Single-Center Retrospective Study

Pain disease is a worldwide problem.The prevalence of chronic pain in developed and developing countries has been reported in some published research. However, little knowledge of situation of pain clinic in Tibet is known. Tibet Autonomous Region People’s Hospital established the first pain clinic in Tibet. This study collected and analyzed the data of medical records of pain clinic in Tibet Autonomous Region People’s Hospital from September 2017 to August 2018. The results showed that the total amounts of patients visiting pain clinic were very small, the most common pain diseases were postherpetic neuralgia and sciatica, and more female patients visited the pain clinic than male patients. All these results indicate that the hospital and government need to pay more attention to the development and promotion of pain medicine in Tibet to make Tibetans being accessed to high-quality pain clinic service

Ginsenoside metabolite compound K induces apoptosis and autophagy in non-small cell lung cancer cells via AMPK/mTOR and JNK pathways

Compound K (C-K, 20-O-(β-D-glucopyranosyl)-20(S)-protopanaxadiol), as a metabolite of ginsenoside, has been verified to have antitumor effects in various cancers, including non-small cell lung cancer (NSCLC). However, the detailed mechanisms of C-K in NSCLC remain largely unknown. In this study, we aimed to evaluate the effect of C-K on apoptosis and autophagy in NSCLC cells as well as its related mechanisms. According to the results, C-K suppressed the proliferation, led to G1 phase arrest and apoptosis in A549 and H1975 cells. Subsequently, C-K promoted autophagy as confirmed by enhanced rate of positive acridine orange staining cells, increased LC3II and Beclin-1 levels, while decreased p62 level in A549 and H1975 cells. Moreover, 3-Methyladenine (3-MA, an inhibitor of autophagy) effectively suppressed proliferation inhibition and apoptosis induced by C-K. Finally, C-K treatment promoted the activation of AMPK/mTOR and JNK signaling pathways. Treatment with compound C (AMPK inhibitor) or SP600125 (JNK inhibitor) significantly restrained C-K-induced proliferation inhibition, apoptosis and autophagy in A549 and H1975 cells. In conclusion, this study demonstrates that C-K promotes autophagy-mediated apoptosis in NSCLC via AMPK/mTOR and JNK signaling pathways.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Comparison of combined general-epidural anesthesia with general anesthesia effects on survival and cancer recurrence: a meta-analysis of retrospective and prospective studies.

Animals underwent combined general-epidural anesthesia (EGA) is reported to have better long-time outcome than general anesthesia (GA). This study aimed to make overall evaluation of the association between these two anesthetic techniques and prognosis of cancer patients undergoing surgery.Related databases such as PubMed and EMbase were searched for eligible studies that evaluated the influence of EGA and GA on the prognosis of cancer patients undergoing surgery. Selected studies were evaluated according to the inclusion criteria by two reviewers respectively, followed by data extraction and quality assessment. The odds ratio (OR) with their 95% confidence intervals (CIs) were calculated to assess the influence strength of EGA and GA on prognosis of cancer patients.A total of ten studies involving 3254 patients were included. The overall results demonstrated that there was no significant difference between EGA and GA group (OR = 0.88, 95% CI 0.73 to 1.06, P = 0.187) concerning postoperative recurrence and metastasis rate. In regard to the following two factors: cancer category and time of follow-up, subgroup analysis identified significant differences between EGA and GA in the group of patients with prostate cancer and the group with follow-up less than or equal to two years (OR = 0.66, 95% CI 0.46 to 0.95, P = 0.027; OR = 0.70, 95% CI 0.51 to 0.98, P = 0.035; respectively) concerning postoperative recurrence and metastasis rate. However, no significant difference was found in the group of patients with colorectal cancer (OR = 1.06, 95% CI 0.84-1.33, P = 0.62).This meta-analysis showed that EGA might be associated with improvement in prognosis of patients with operable prostate cancer and the cancer patients with follow-up less than or equal to two years. However, no obvious relationship between the improvement in prognosis of colorectal cancer and EGA were detected, comparing to GA. Furthermore, all the results should be interpreted cautiously, as heterogeneous data were used for analyzing

OBIA: An Open Biomedical Imaging Archive

With the development of artificial intelligence (AI) technologies, biomedical imaging data play an important role in scientific research and clinical application, but the available resources are limited. Here we present Open Biomedical Imaging Archive (OBIA), a repository for archiving biomedical imaging and related clinical data. OBIA adopts five data objects (Collection, Individual, Study, Series, and Image) for data organization, and accepts the submission of biomedical images of multiple modalities, organs, and diseases. In order to protect personal privacy, OBIA has formulated a unified de-identification and quality control process. In addition, OBIA provides friendly and intuitive web interfaces for data submission, browsing, and retrieval, as well as image retrieval. As of September 2023, OBIA has housed data for a total of 937 individuals, 4136 studies, 24,701 series, and 1,938,309 images covering 9 modalities and 30 anatomical sites. Collectively, OBIA provides a reliable platform for biomedical imaging data management and offers free open access to all publicly available data to support research activities throughout the world. OBIA can be accessed at https://ngdc.cncb.ac.cn/obia

Basic characteristics of included studies (Number of events).

<p>Events: cancer recurrence or metastasis.</p><p>Basic characteristics of included studies (Number of events).</p

Ultrasound-Assisted Thoracic Paravertebral Block Reduces Intraoperative Opioid Requirement and Improves Analgesia after Breast Cancer Surgery: A Randomized, Controlled, Single-Center Trial

<div><p>Objectives</p><p>The contribution of ultrasound-assisted thoracic paravertebral block to postoperative analgesia remains unclear. We compared the effect of a combination of ultrasound assisted-thoracic paravertebral block and propofol general anesthesia with opioid and sevoflurane general anesthesia on volatile anesthetic, propofol and opioid consumption, and postoperative pain in patients having breast cancer surgery.</p><p>Methods</p><p>Patients undergoing breast cancer surgery were randomly assigned to ultrasound-assisted paravertebral block with propofol general anesthesia (PPA group, n = 121) or fentanyl with sevoflurane general anesthesia (GA group, n = 126). Volatile anesthetic, propofol and opioid consumption, and postoperative pain intensity were compared between the groups using noninferiority and superiority tests.</p><p>Results</p><p>Patients in the PPA group required less sevoflurane than those in the GA group (median [interquartile range] of 0 [0, 0] vs. 0.4 [0.3, 0.6] minimum alveolar concentration [MAC]-hours), less intraoperative fentanyl requirements (100 [50, 100] vs. 250 [200, 300]μg,), less intense postoperative pain (median visual analog scale score 2 [1, 3.5] vs. 3 [2, 4.5]), but more propofol (median 529 [424, 672] vs. 100 [100, 130] mg). Noninferiority was detected for all four outcomes; one-tailed superiority tests for each outcome were highly significant at P<0.001 in the expected directions.</p><p>Conclusions</p><p>The combination of propofol anesthesia with ultrasound-assisted paravertebral block reduces intraoperative volatile anesthetic and opioid requirements, and results in less post operative pain in patients undergoing breast cancer surgery.</p><p>Trial Registration</p><p>ClinicalTrial.gov <a href="https://clinicaltrials.gov/ct2/show/NCT00418457" target="_blank">NCT00418457</a></p></div

Basic characteristics of included studies.

<p>*evaluated by the 9-star Newcastle-Ottawa Scale; EGA: epidural anesthesia combined with general anesthesia; GA: general anesthesia.</p><p>Basic characteristics of included studies.</p

Flowchart of included and excluded studies.

<p>Flowchart of included and excluded studies.</p

Superiority plots showing the ratios of mean ranks (98.75% confidence intervals, CIs) between the regional and general groups for each primary outcome.

<p>Parentheses indicate two-sided 98.75% CIs estimated using bootstrap resampling. Joint hypothesis testing of the four primary outcomes indicated effectiveness of paravertebral analgesia over general anesthesia, as all four CIs lie within the superiority regions: less pain, less intraoperative fentanyl use, less volatile anesthetic use, and increased propofol use.</p