CLG promotes mTOR/ULK1 pathway-mediated autophagy to inhibit OS development by inhibiting TRAF6-mediated FLT3 ubiquitination.

Corilagin (CLG) has antitumor activities in certain human malignant cancers. Herein, the effects and mechanisms of CLG on osteosarcoma (OS) were investigated. OS cell viability and proliferation were detected by MTT and colony formation assay. Cell cycle and apoptosis were examined using flow cytometry. The interaction between TRAF6 and FLT3 was investigated using a co-immunoprecipitation assay. Results demonstrated that CLG treatment inhibited OS cell viability and proliferation but promoted OS cell autophagy and apoptosis in a concentration-dependent manner. Mechanically, CLG inhibited TRAF6-mediated FLT3 ubiquitination degradation. TRAF6 overexpression abolished the effects of CLG on OS cell proliferation, autophagy, and apoptosis. Finally, CLG administration inhibited OS tumor growth in mice by inducing autophagy-dependent apoptosis. Taken together, CLG inhibited OS progression by facilitating mTOR/ULK1 pathway-mediated autophagy through inhibiting TRAF6-mediated FLT3 ubiquitination, which indicated that CLG was a promising candidate for the treatment of OS.

Blood biomarkers for sarcopenia: A systematic review and meta-analysis of diagnostic test accuracy studies.

Biomarkers are emerging as a potential tool for screening or diagnosing sarcopenia. We aimed to summarize the current evidence on the diagnostic test accuracy of biomarkers for sarcopenia. We comprehensively searched Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials up to January 2023 and only included diagnostic test accuracy studies. We identified 32 studies with 23,840 participants (women, 58.26%) that assessed a total of 30 biomarkers. The serum creatinine to cystatin C ratio (Cr/CysC) demonstrated a pooled sensitivity ranging from 51% (95% confidence interval [CI] 44-59%) to 86% (95% CI 70-95%) and a pooled specificity ranged from 55% (95% CI 38-70%) to 76% (95% CI 63-86%) for diagnosing sarcopenia defined by five different diagnostic criteria (11 studies, 7240 participants). The aspartate aminotransferase to alanine aminotransferase ratio demonstrated a pooled sensitivity of 62% (95% CI 56-67%) and a pooled specificity of 66% (95% CI 60-72%) (3 studies, 11,146 participants). The other 28 blood biomarkers exhibited low-to-moderate diagnostic accuracy for sarcopenia regardless of the reference standards. In conclusion, none of these biomarkers are optimal for screening or diagnosing sarcopenia. Well-designed studies are needed to explore and validate novel biomarkers for sarcopenia.

Nutritional Assessment in Patients with Chronic Diseases: Tools, Challenges, and Future Directions.

Chronic diseases, such as cardiovascular diseases, diabetes, cancer, and chronic respiratory diseases, are leading causes of morbidity and mortality worldwide [...].

Different computed tomography parameters for defining myosteatosis in patients with advanced non-small cell lung cancer.

BACKGROUND & AIMS: Myosteatosis, excess muscle fat infiltration, is a novel prognostic factor in cancer patients. To define myosteatosis, skeletal muscle radiodensity (SMD) is most commonly used, while intramuscular adipose tissue (IMAT) is newly introduced. We aimed to compare SMD-defined and IMAT-defined myosteatosis for predicting overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) and to explore whether patients with both low SMD and high IMAT had a shorter OS than patients with low SMD or high IMAT alone. METHODS: We consecutively and prospectively recruited adult patients with stage IIIB or IV NSCLC at a teaching hospital. The mean SMD of all skeletal muscle areas and the area of IMAT on the unenhanced chest computed tomography (CT) images at the 12th thoracic vertebral level were segmented using Mimics version 21.0. Myosteatosis was defined by either low SMD (SMD-defined myosteatosis) or high IMAT (IMAT-defined myosteatosis). The optimal cutoffs for low SMD and high IMAT were also determined using the maximally selected rank statistics method. We calculated hazard ratios (HRs) and the corresponding confidence intervals (CIs) to evaluate the associations of OS with low SMD, high IMAT, and a combination of them. RESULTS: We included 565 patients (345 men and 220 women; mean age 58.5 ± 9.0 years). Lower IMAT exhibited a tendency toward a favorable prognosis in men (p = 0.0015) and women (p < 0.0001); whereas higher SMD tended to have a favorable prognosis in men (p = 0.0006) and women (p < 0.0001). At baseline, 423 (74.9 %) participants had high IMAT, 432 (76.5 %) participants had low SMD and 370 (65.5 %) participants had both high IMAT and low SMD. Compared to those without either high IMAT or low SMD, the participants with either high IMAT or low SMD had a shorter OS, while the participants with both High IMAT and Low SMD had the shortest OS (log-rank p < 0.0001). After adjustment for the same confounders, high IMAT (HR, 1.44; 95 % CI, 1.10-1.87) and low SMD (HR, 1.92; 95 % CI, 1.36-2.43) were separately associated with poor prognosis. Moreover, the combination of high IMAT and low SMD indicated a higher risk of poor prognosis (HR, 2.43; 95 % CI, 1.62-3.66). CONCLUSIONS: Both SMD-defined and IMAT-defined myosteatosis are highly prevalent in patients with advanced NSCLC and may serve as independent prognostic factors for OS. The diagnosis of myosteatosis might consider a combination of low SMD and high IMAT because this would help identify patients at a higher risk of mortality.

[Risk Factors Associated with Intraoperative Blood Loss in Patients with Early Cervical Cancer].

OBJECTIVE: To determine risk factors associated with intraoperative blood loss in patients with early cervical cancer (stage ⅠB-ⅡA). METHODS: The medical records of 892 patients who underwent surgical treatments for early cervical cancer in the Second West China University Hospital of from Dec 2010 to Sep 2017 were retrospectively reviewed: 127 having ≥500 mL intraoperative blood loss patients compared with 765 less than 500 mL. Differences between the two groups in age, body mass index (BMI), gravidity, history of abdominal and pelvic operations, chronic pelvic inflammation disease, clinical stage, methods of operation, neoadjuvant chemotherapy (NACT) and post-NACT operative opportunity, preoperative and postoperative hemoglobin, and intraoperative transfusion volume were analyzed through univariate and multivariate statistical methods. RESULTS: The univariate analyses identified age, BMI, gravidity, history of abdominal and pelvic operation, chronic pelvic inflammation disease, clinical stage, methods of operation, NACT and post-NACT operative opportunity assignificant factors associated with intraoperative blood loss ( P<0.05). The multivariate logistic regression analysis confirmed that age ≥40 yr. [partial regression coefficient (B)=2.100)], BMI ≥24 kg/m2 (relative to 18.5-23.9 kg/m2)(B=1.842) , clinical stage ⅡA (relative to phase ⅠB, B=2.401) , trans-abdominal operative method (relative to laparoscopy, B=1.347), no NACT (B=1.540) and post-NACT operative opportunity <2 or >3 weeks (relative to within 2-3 weeks) (B=1.723) were independent predictors of higher intraoperative blood loss (≥500 mL). CONCLUSION: Clinical stage and age, etc. are risk factors associated with intraoperative blood loss in patients with early cervical cancer.