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Background Patients with gastric cancer often suffer from generalized and progressive reduction of skeletal muscle mass and strength, which negatively affects the quality of life (QOL). In this study, we explored the impact of sarcopenia on QOL and overall survival (OS). Methods From December 2015 to June 2017, 135 patients underwent radical gastrectomy at the First Affiliated Hospital of Wenzhou Medical University. Based on the diagnostic criteria of the Asian Working Group for Sarcopenia (AWGS), data including handgrip strength, 6-m gait speed and muscle mass were collected and analyzed. EORTC QLQ-C30 and EORTC QLQ-STO22 were used to evaluate the QOL before surgery, 1, 3 and 6 months after surgery. Results A total of 27 out of the 135 patients (20.00%) were diagnosed with sarcopenia. Compared with non-sarcopenia group, patients in sarcopenia group had a higher incidence of postoperative complications (14.80% vs. 40.70%, p = 0.003), and more hospitalization costs (p = 0.029). The scores of eating restriction (p = 0.026), anxiety (p = 0.045) and body image (p = 0.046) were significantly higher in sarcopenia group at postoperative 6 months. Besides, sarcopenia was an independent risk factor for global health status at 6 months after operation (OR: 2.881, 95% CI: 1.110–7.475, p = 0.030) and OS (HR: 3.140, 95% CI: 1.255–7.855, p = 0.014). Other factors, including tumor stage III and the postoperative complications, had negative influences on OS. Conclusion Sarcopenia is a predictive factor of poor QOL and prognosis in patients with gastric cancer.

Summary Background In 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) reached a consensus on sarcopenia (EWGSOP1). In 2018, the EWGSOP met again (EWGSOP2) to update original definition of sarcopenia. This study aimed to investigate the association of sarcopenia and survival and compare the prognostic effects of sarcopenia as defined by EWGSOP1 and EWGSOP2 after gastrectomy. Methods We conducted a prospective study including patients who underwent curative gastrectomy for gastric cancer from August 2014 to February 2018. The sarcopenia elements, including skeletal muscle index, muscle attenuation, handgrip strength, and gait speed were measured before surgery. Patients were followed up after gastrectomy to gain the actual clinical outcomes. Results The prevalence of sarcopenia was 17.0% and 18.9% according to the EWGSOP1 and EWGSOP2 respectively. Sarcopenia was independent risk factor for postoperative complications. Compared with EWGSOP1-sarcopenia, EWGSOP2-sarcopenia and had a higher odds ratio (OR) (2.453 vs. 1.550) in multivariate model. Area under the ROC curve of model including EWGSOP2-sarcopenia was larger than that of the model including EWGSOP1-sarcopenia (AUC 0.653 vs. 0.634, P = 0.021). For both of EWGSOP1 and EWGSOP2, sarcopenia was an independent risk factor for overall survival (OS) and disease-free survival (DFS), but EWGSOP2-sarcopenia seemed to have a higher hazard ratio (OS, 1.667 vs. 1.449; DFS, 1.603 vs. 1.563). In addition, severe sarcopenia, as defined by either EWGSOP2 or EWGSOP1, had a strong predictive power (OR 4.909 vs. 3.827) for postoperative complications. Both versions of severe sarcopenia were significantly predictive of OS and DFS in Cox analysis. Conclusion Sarcopenia at uniform diagnosis standard was an independent risk factor for survival in patients undergoing radical gastrectomy for gastric cancer. Sarcopenia defined by EWGSOP2 criteria better predicts clinical outcomes than that defined by EWGSOP1 criteria in patients with gastric cancer after gastrectomy.

Elucidation of the post-transcriptional modification has led to novel strategies to treat intractable tumors, especially glioblastoma (GBM). The ubiquitin-proteasome system (UPS) mediates a reversible, stringent and stepwise post-translational modification which is closely associated with malignant processes of GBM. To this end, developing novel therapeutic approaches to target the UPS may contribute to the treatment of this disease. This study aimed to screen the vital and aberrantly regulated component of the UPS in GBM. Based on the molecular identification, functional characterization, and mechanism investigation, we sought to elaborate a novel therapeutic strategy to target this vital factor to combat GBM.We combined glioma datasets and human patient samples to screen and identify aberrantly regulated E3 ubiquitin ligase. Multidimensional database analysis and molecular and functional experiments in vivo and in vitro were used to evaluate the roles of HECT, UBA and WWE domain-containing E3 ubiquitin ligase 1 (HUWE1) in GBM. dCas9 synergistic activation mediator system and recombinant adeno-associated virus (rAAV) were used to endogenously overexpress full-length HUWE1 in vitro and in glioma orthotopic xenografts.Low expression of HUWE1 was closely associated with worse prognosis of GBM patients. The ubiquitination and subsequent degradation of N-Myc mediated by HUWE1, leading to the inactivation of downstream Delta-like 1 (DLL1)-NOTCH1 signaling pathways, inhibited the proliferation, invasion, and migration of GBM cells in vitro and in vivo. A rAAV dual-vector system for packaging and delivery of dCas9-VP64 was used to augment endogenous HUWE1 expression in vivo and showed an antitumor activity in glioma orthotopic xenografts.The E3 ubiquitin ligase HUWE1 acts through the N-Myc-DLL1-NOTCH1 signaling axis to suppress GBM progression. Antitumor activity of rAAV dual-vector delivering dCas9-HUWE1 system uncovers a promising therapeutic strategy for GBM.

Few studies have comprehensively analyzed the correlations among body composition parameters, muscle strength, and physical performance, as well as the influence of these factors on the postoperative complications and survival after radical gastrectomy for gastric cancer.A prospective study was conducted including patients who underwent radical gastrectomy for gastric cancer from August 2014 to June 2019. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral fat area (VFA), subcutaneous fat area (SFA) was obtained by measurement of preoperative computed tomography (CT) images. Grip strength and 6-m gait speed were measured to assess muscle strength and physical performance before surgery.There was a positive correlation between SMI and SMD, as well as between SFA and VFA. SMD negatively correlated with SFA and VFA. SMI had a positive correlation with VFA, but showed minimal correlation with SFA and visceral to subcutaneous fat ratio (VSR). Grip strength and gait speed were both positively correlated with SMI and SMD, but showed minimal correlation with SFA, VFA and VSR. SMI and grip strength independently predicted postoperative complications, rather than SMD or gait speed. Whereas SMD and gait speed had independent predictive value for overall survival (OS) and/or disease-free survival (DFS), rather than SMI or grip strength. VSR independently predicted postoperative complications, rather than VFA or SFA alone. Low SFA was an independent risk factor for OS and DFS. High VFA was associated with worse survival in overweight patients (body mass index, BMI ≥25), but was associated with better survival in non-overweight patients (BMI25). High SFA did not significantly influence survival in overweight patients, but was associated with better survival in non-overweight patients.There is an extensive and complex correlation among body composition parameters, grip strength, and gait speed in patients with operable gastric cancer. A comprehensive analysis of these parameters has significant predictive value for postoperative complications and survival.

The aim of this study was to determine the feasibility of substituting handgrip strength (HGS) for muscle mass as a constituent in the Global Leadership Initiative on Malnutrition (GLIM) to diagnose malnourished patients with gastrointestinal (GI) cancer.The study included 2209 patients diagnosed with GI cancer from two centers. All patients were evaluated for nutritional risk using Nutritional Risk Screening 2002 within 24 h of admission. The GLIM consensus was then used to diagnose malnourished patients. The evaluation of muscle mass as one of the constituents contained in the GLIM consensus was measured by computed tomography presented as skeletal muscle mass index (SMI) and HGS, respectively. Consistency test was carried out to evaluate the diagnostic value of SMI and HGS.There were 1042 (47.2%) cases of gastric cancer and 1167 (52.8%) cases of colorectal cancer. Among these cases were 768 patients (34.8%) at nutritional risk. Furthermore, 603 (27.3%) and 593 patients (26.8%) were diagnosed with malnutrition in the GLIM (SMI) group and the GLIM (HGS) group, respectively, and 544 (24.6%) patients in the two groups overlapped. The consistency test results showed that the κ value in the GLIM (HGS) group compared with the GLIM (SMI) group was 0.881 (P0.001) in patients with gastric cancer and 0.872 (P0.001) in those with colorectal cancer.HGS can be a substitute for muscle mass as a constituent in the diagnostic criteria of GLIM in patients with GI cancer.