Polysaccharide of Ganoderma lucidum Ameliorates Cachectic Myopathy Induced by the Combination Cisplatin plus Docetaxel in Mice.

Cachexia is a lethal muscle-wasting syndrome associated with cancer and chemotherapy use. Mounting evidence suggests a correlation between cachexia and intestinal microbiota, but there is presently no effective treatment for cachexia. Whether the Ganoderma lucidum polysaccharide Liz-H exerts protective effects on cachexia and gut microbiota dysbiosis induced by the combination cisplatin plus docetaxel (cisplatin + docetaxel) was investigated. C57BL/6J mice were intraperitoneally injected with cisplatin + docetaxel, with or without oral administration of Liz-H. Body weight, food consumption, complete blood count, blood biochemistry, and muscle atrophy were measured. Next-generation sequencing was also performed to investigate changes to gut microbial ecology. Liz-H administration alleviated the cisplatin + docetaxel-induced weight loss, muscle atrophy, and neutropenia. Furthermore, upregulation of muscle protein degradation-related genes (MuRF-1 and Atrogin-1) and decline of myogenic factors (MyoD and myogenin) after treatment of cisplatin and docetaxel were prevented by Liz-H. Cisplatin and docetaxel treatment resulted in reducing comparative abundances of Ruminococcaceae and Bacteroides, but Liz-H treatment restored these to normal levels. This study indicates that Liz-H is a good chemoprotective reagent for cisplatin + docetaxel-induced cachexia. IMPORTANCE Cachexia is a multifactorial syndrome driven by metabolic dysregulation, anorexia, systemic inflammation, and insulin resistance. Approximately 80% of patients with advanced cancer have cachexia, and cachexia is the cause of death in 30% of cancer patients. Nutritional supplementation has not been shown to reverse cachexia progression. Thus, developing strategies to prevent and/or reverse cachexia is urgent. Polysaccharide is a major biologically active compound in the fungus Ganoderma lucidum. This study is the first to report that G. lucidum polysaccharides could alleviate chemotherapy-induced cachexia via reducing expression of genes that are known to drive muscle wasting, such as MuRF-1 and Atrogin-1. These results suggest that Liz-H is an effective treatment for cisplatin + docetaxel-induced cachexia.

Mitral valve repair versus replacement in patients with ischemic mitral regurgitation.

BACKGROUND: The optimal management of ischemic mitral regurgitation (IMR) is controversial. The aim of this study was to examine our eight years' experience of surgical treatment in patients with IMR, and to compare outcomes of mitral valve repair versus replacement with concomitant coronary artery bypass grafting (CABG). METHODS: A retrospective, observational, cohort study was undertaken to collect data on consecutive patients with IMR and coronary artery disease who received CABG and mitral valve surgery in our hospital between January 2008 and December 2015. Basic patient characteristics, operative data, and postoperative clinical outcomes were examined. RESULTS: The series included 22 consecutive patients (21 male; 1 female). The mean age was 62.1±11.4 years old. The mean preoperative left ventricular ejection fraction (LVEF) was 33.4%±15.4%. The mean cardiopulmonary bypass (CPB) time was 165.4±38.4 minutes, and the mean aortic cross clamp time was 113.8±33.6 minutes. Eighteen patients underwent CABG plus mitral valve repair, and four patients underwent CABG plus mitral valve replacement (MVR). There were three early in-hospital mortalities: two in the mitral valve repair group, and one in the replacement group. The follow-up was complete in all patients, with a mean follow-up duration of 3.1±2.3 years. The mean last LVEF was 35.3%±17.7%. There were 2 late mortalities. Both were from the repair group. The overall late survival rate was 81.6%, with 83.0% in the repair group and 75.0% in the replacement group. In patients with echocardiography follow-up of more than or equal to 1 year duration, the residual or recurrent mitral regurgitation rates were 0.0% in the replacement group and 57.1% in the repair group. One patient in the repair group later underwent MVR due to severe regurgitation postoperatively. CONCLUSIONS: Our preliminary findings showed that the surgical outcome of mitral valve repair might be comparable to that of MVR in terms of early mortality and long-term survival. However, mitral valve repair was associated with a higher residual or recurrent mitral regurgitation rate. According to the latest literature, the role of MVR can justifiably be indicated for severe IMR. As for moderate IMR, CABG alone without mitral valve intervention may provide similar clinical outcomes.

Integrated MicroRNA-mRNA Analysis Reveals miR-204 Inhibits Cell Proliferation in Gastric Cancer by Targeting CKS1B, CXCL1 and GPRC5A.

Gastric cancer (GC) is the second most frequent cause of cancer-related deaths worldwide. MicroRNAs are single-stranded RNA molecules of 21-23 nucleotides that regulate target gene expression through specific base-pairing interactions between miRNA and untranslated regions of targeted mRNAs. In this study, we generated a multistep approach for the integrated analysis of miRNA and mRNA expression. First, both miRNA and mRNA expression profiling datasets in gastric cancer from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) identified 79 and 1042 differentially expressed miRNAs and mRNAs, respectively, in gastric cancer. Second, inverse correlations between miRNA and mRNA expression levels identified 3206 miRNA-mRNA pairs combined with 79 dysregulated miRNAs and their 774 target mRNAs predicted by three prediction tools, miRanda, PITA, and RNAhybrid. Additionally, miR-204, which was found to be down-regulated in gastric cancer, was ectopically over-expressed in the AGS gastric cancer cell line and all down-regulated targets were identified by RNA sequencing (RNA-seq) analysis. Over-expression of miR-204 reduced the gastric cancer cell proliferation and suppressed the expression of three targets which were validated by qRT-PCR and luciferase assays. For the first time, we identified that CKS1B, CXCL1, and GPRC5A are putative targets of miR-204 and elucidated that miR-204 acted as potential tumor suppressor and, therefore, are useful as a promising therapeutic target for gastric cancer.

Cardiac surgery in patients with systemic lupus erythematosus.

Cardiac surgery was infrequently performed in patients with systemic lupus erythematosus (SLE), and its clinical outcome was reported only in small series. We sought to evaluate the clinical outcome of cardiac operation in patients with SLE. Between January 1996 and March 2005, 9 patients with SLE underwent cardiac surgery at the authors' hospital. Six patients underwent coronary artery bypass grafting (three conventional and three on-pump beating heart), two patients underwent valve replacement and 1 patient underwent simultaneous heart-kidney transplantation. All 6 patients with coronary artery bypass grafting had saphenous venous grafts and two of them had additional left internal mammary artery graft. The overall in-hospital mortality rate was 11% (1/9). Major postoperative complications occurred in 4 patients (44%) including profuse postoperative bleeding, ventricular tachycardia and early graft thrombosis. There were two late deaths including sudden cardiac death and sepsis. The median follow-up duration was 23 months (range, 1-110). In conclusion, although the postoperative complication was common, cardiac operation could be performed in patients with SLE.