Newly discovered molecules associated with trimetazidine on improvement of skeletal muscle function in aging: evidence from myoblasts and mice.

Poor muscle function is increasingly obvious with aging and needs effective and safe medicine for treatment. Trimetazidine (TMZ) has potential benefits for the condition but has not yet been fully recognized. In the randomized-control pilot study part, fifty-three old patients were assigned to the TMZ group or control group. For the TMZ group, a dose of 35 mg of oral TMZ was administered with a meal twice a day for 3 months. Only conventional treatments were administrated in the control group. Muscle strength, gait speed, muscle endurance, and balance maintenance were measured during the visits. In the experiments part, thirty mice were screened and randomly assigned to three groups: model group received a D-gal (500 mg/kg) intraperitoneal injection every two days for six weeks, the control group received saline at the same condition, and the intervention group received 5 mg/kg TMZ solution every two days by gavage for two weeks. Swimming tests and forelimb grip strength measurements were also performed. Furthermore, significantly clustered profiles from differentially expressed genes were found by RNA-seq and verified by qRT-PCR and WB. Myofiber analyses were done by H&E staining. Here, we found the improvement of skeletal performance in aged individuals and aged mouse. The dominant handgrip strength (HS) was increased by 24.4% and dominant pinch strength (PS) by 12.4% in participants with TMZ modified-release tablets consumption. Exhaustive time was increased by 23.6% and upper limb grip strength by 44.1% in aged mouse with TMZ-treated. Besides, we also identified some newly discovered molecules associated with TMZ on muscle function improvement during aging. To aged C2C12 cells and aged mouse muscle, TMZ-treated was related to a statistically significant decrease in the expressions of NOS3 and MMP-9, but a statistically significant increase in the expressions of OMD and MyoG. In summary, TMZ modified-release tablets can improve the muscle strength of elderly patients. Besides, the improvement of skeletal muscle function affected by TMZ was associated with reducing NOS3 expression in senescent myoblasts.

Comparison of endoscopic submucosal dissection and surgery for the treatment of gastric submucosal tumors originating from the muscularis propria layer: a single-center study (with video).

INTRODUCTION: Endoscopic submucosal dissection (ESD) has been used for the treatment of gastric submucosal tumors (SMTs). This study aims to compare clinical outcomes of ESD versus laparoscopic wedge resection (LWR) for gastric SMTs. METHODS: This is a retrospective cohort study. Patients with SMTs who underwent ESD or LWR were enrolled in this study at a university-affiliated hospital from January 2010 to October 2015. Preoperative endoscopic ultrasound and computed tomography were performed to determine origin of layer and growth pattern. Clinical outcomes including baseline demographics, tumor size, operation time, blood loss, hospital stay, cost, pathology and postoperative complications were compared. RESULTS: From January 2010 to October 2015, 68 patients with SMTs received ESD and 47 patients with SMTs received LWR. There was no difference in age, gender, body mass index, origin of layer and proportion with symptoms between ESD group and LWR group. However, tumor size was significantly larger in the LWR group (37.1 mm) than in the ESD group (25.8 mm, P = 0.041). For patients with tumors smaller than 20 mm, ESD was associated with shorter mean operation time (89.7 ± 23.5 vs 117.6 ± 23.7 min, P = 0.043), less blood loss (4.9 ± 1.7 vs 72.3 ± 23.3 ml, P < 0.001), shorter length of hospital stay (3.6 ± 1.9 vs 6.9 ± 3.7 days, P = 0.024) and lower cost (2471 ± 573 vs 4498 ± 1257 dollars, P = 0.031) when compared with LWR. For patients with tumors between 20 mm and 50 mm, ESD was associated with shorter mean operation time (99.3 ± 27.8 vs 125.2 ± 31.5 min, P = 0.039), less blood loss (10.1 ± 5.3 vs 87.6 ± 31.3 ml, P < 0.001), shorter length of hospital stay (4.0 ± 1.7 vs 7.3 ± 4.5 days, P = 0.027) and lower cost (2783 ± 601 vs 4798 ± 1343 dollars, P = 0.033) when compared with LWR. There were no significant differences in terms of rates of en bloc resection, complete resection and complication and histological diagnosis regardless of tumor size. CONCLUSIONS: ESD can achieve similar oncological outcomes when compared with surgery for treatment of gastric SMT smaller than 50 mm.

Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers therapy and colorectal cancer: a systematic review and meta-analysis.

PURPOSE: We aim to investigate the association between angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) therapy and colorectal cancer (CRC) by conducting a systematic review with meta-analysis. METHODS: Literature was searched on PubMed, Scopus, and the Cochrane library to identify relevant studies evaluating ACEIs/ARBs therapy and risk of CRC incidence or survival of CRC patients. Pooled risk ratio (RR) with 95% confidence intervals was calculated for the association between ACEIs/ARBs and CRC risk and mortality. RESULTS: Eleven observational studies were included in the systematic review. A meta-analysis of six studies totaling 113,048 individuals indicated a 6% decreased risk of CRC in ACEIs/ARBs users compared to non-users (95% CI 0.89-0.98). In the four case-control studies, individuals using ACEIs/ARBs were associated with a 6% decreased risk of CRC (95% CI 0.90-0.99). The meta-analysis of three studies investigating the relationship between ACEIs/ARBs and survival of CRC did not show a significantly decreased mortality in ACEIs/ARBs users (RR 0.81, 95% CI 0.60-1.09). Seven studies evaluated the dose-response relationship between ACEIs/ARBs therapy and CRC, and two of them showed that the association was related to longer duration and higher dose. CONCLUSIONS: CEIs/ARBs therapy might be associated with a reduce risk of CRC development, but whether use of these medications improves the outcomes of CRC remains unknown. Large-scale and more robust studies are needed to further explore this association.