Abstract Background PTEN is one of the most frequently mutated genes in human cancer. Although the roles of canonical PTEN protein and PTEN isoforms have been extensively explored, the current understanding of PTEN family members cannot fully illustrate the diversity of their roles in biological processes and tumor development. Notably, the function of noncoding RNAs arising from PTEN has been less elucidated. Methods We searched circBase and circInteractome to analyze the potential of PTEN for generating circRNAs. Then, Sanger sequencing, RNase R and Actinomycin D assays were used to verify the ring structure of circPTEN1. In situ hybridization and qRT-PCR were used to determine the level of circPTEN1 in peritumor and tumor tissues of colorectal cancer (CRC). Furthermore, functional experiments, including Transwell assay, 3D multicellular tumor spheroid invasion assay and metastasis models, were performed using circPTEN1 knockdown and overexpression cell lines in vitro and in vivo to investigate the effects of circPTEN1 on tumor metastasis in CRC. Mechanistically, luciferase reporter assay, fluorescence in situ hybridization, electrophoretic mobility shift assay, RNA immunoprecipitation, RNA pull-down and mass spectrometry were executed. Results We identified a circular RNA generated from the PTEN gene, designated circPTEN1, that is frequently downregulated in colorectal cancer, and decreased expression of circPTEN1 predicts poor survival. Low expression of circPTEN1 promotes metastasis in PDX models in vivo and accelerates cancer cell invasion in vitro, whereas overexpression of circPTEN1 reveals opposite roles. Mechanically, we found that circPTEN1 is capable of binding the MH2 domain of Smad4 to disrupt its physical interaction with Smad2/3, which reduces the formation and subsequent nucleus translocation of Smad complexes and consequently suppresses the expression of its downstream genes associated with epithelial-mesenchymal transition upon TGF-β stimulation. Furthermore, we found that eIF4A3 suppresses the cyclization of circPTEN1 by directly binding to the circPTEN1 flanking region. Conclusions Our study uncovered a novel PTEN gene-generated circRNA with a tumor suppression function, and further revealed the mechanism of circPTEN1 in CRC metastasis mediated by TGF-β. The identification of circPTEN1 provides a new direction for PTEN investigation, and elucidation of circPTEN1/TGF-β/Smad signaling may pave the way for the development of a potential therapeutic strategy for the suppression of cancer progression.
There is controversy about the outcomes of prophylactic ileostomy via the specimen extraction site (SES) after laparoscopic rectal cancer surgery (LRCS). We, therefore, performed a meta-analysis to determine the efficacy and safety of stoma through the SES versus new site (NS).All relevant studies from 1997 to 2022 were searched in the PubMed, EMBASE, Cochrane Library, CNKI, VIP databases. This meta-analysis was performed using RevMan software 5.3 for statistical analysis.7 studies with 1736 patients were included. The present meta-analysis noted that prophylactic ileostomy via SES was associated with a higher risk of overall stoma-related complications, especially parastomal hernia (OR, 2.39, 95% CI 1.43-4.00; p=0.0008). No statistical difference was found in terms of wound infection, ileus, stoma edema, stoma prolapse, stoma necrosis, stoma infection, stoma bleeding, stoma stenosis, skin inflammation around the stoma, stoma retraction and postoperative pain score on postoperative day 1 and 3 between SES group and NS group. However, prophylactic ileostomy via SES was associated with lesser blood loss (MD = -0.38, 95% CI: -0.62 - -0.13; p=0.003), shorter operation time(MD = -0.43, 95% CI: -0.54 - -0.32 min; p<0.00001), shorter post-operative hospital stay (MD = -0.26, 95% CI: -0.43 - -0.08; p=0.004), shorter time to first flatus(MD = -0.23, 95% CI: -0.39 - -0.08; p=0.003) and lower postoperative pain score on postoperative day 2.Prophylactic ileostomy via SES after LRCS reduces new incision, decreases operative time, promotes postoperative recovery, and improves cosmetic outcomes, but may increase the incidence of parastomal hernias. The vast majority of parastomal hernias can be repaired by closing the ileostomy, therefore SES remain an option for temporary ileostomy after LRCS.
Abstract Background The persistence and spread of the COVID-19 pandemic adversely affected the efficiency of hospitals with different ownership. This article aims to compare the differences and changes in technical efficiency of public and private hospitals before and after the pandemic. Methods We collected institutional and operational data for all 519 general hospitals (including 243 public and 356 private hospitals) in Hubei province China from 2019 to 2021. Using the slacks-based measure model (SBM), we measured and compared technical efficiency. The effect of the pandemic on hospital efficiency was examined with a two-way fixed effect model and a lasso regression model. PSM, Tobit regression was used for robustness testing. Results Public hospitals were much more efficient than private hospitals both before and after the epidemic in Hubei. The mean efficiency score of public and private hospitals was 0.52 and 0.26 in 2019, 0.37 and 0.22 in 2020, 0.44 and 0.24 in 2021. The difference in efficiency between public and private hospitals was significant in 2019 and 2021(p<0.001). Public hospital efficiency showed a faster recovery in the face of the epidemic. Conclusions Public hospitals run by the administrative system have shown greater efficiency and played a major role in the fight against the pandemic. The country's public health protection network should be fortified and efforts should be made to promote the high-quality development of public hospitals. The widening of the overall gap between public and private hospitals appeared. In the post-epidemic era, private hospitals need to prioritize finding the right positioning and offering highly specific medical services in China.
Objective To study the changes of serum proteomic spectra in patients with colorectal cancer before and after surgical operation in order to detect the specific protein markers.Methods Proteomic spectra of 64 serum samples from patients with colorectal cancer before and after operation and 40 from normal individuals were generated by IMAC Cu proteinchip array and SELDI TOF mass spectroscopy.Results Nineteen differentially expressed proteins in serum were screened by analysis of protemic spectra of preoperative patients and normal individuals.We obtained 5 proteins (5 908.55 Da and so on) making up markers pattern which was able to class the patient team and normal team.Corresponding correct ratio was 97.5% (56/64) and 80.0% (32/40) respectively.The proteins that overexprssed in serum of preoperative patients were obviously down regulated.These markers pattern yieded 96.8% sensitivity and 92.5% specificity respectively.Conclusion Clssification system will provide a highly accurate and innovative approach for the early diagnosis of colorectal cancer and judgment of prognosis.SELDI TOF mass spectrometry is a useful tool for the detection and idenification of new protein markers in serum.
As a rational and effective management system bureaucracy caters both to the needs of capitalist development and to the requirements of era of industrial society.Bureaucracy has rationalness and defect whichfails to meet the newrequirements of the post-industrial societies of present-day western world. As China's general idea of administrative reform, we should further strengthen the base of rational spiritand legal principle authority of bureaucracy and continuously sublate and improve bureaucracy in China's administrative practices.
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