Exosomal MEF2C's Association With the Progression of CRC in Regulating CD36 Transcription.

Context: Exosomes are biologically active, extracellular vesicles that are involved in tumor-related processes, including activating tumors, facilitating tumor growth, and promoting inflammation. Objective: The study intended to investigate microRNAs (miRNAs) in exosomes that are associated with colorectal cancer (CRC). Design: The research team performed bioinformatics analysis, extracting RNA-sequencing (RNA-seq) datasets from the Cancer Genome Atlas (TCGA); ExoRBase, a database of different types of RNA information that scientists have extracted from human exosomes; and the Gene Expression Omnibus (GEO) databases, and analyzed the data. Setting: The study took place at the Department of Colorectal Surgery at the Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, China. Participants: From October 2020 to March 2021, a total of 28 CRC patients who underwent curative resection at the National Cancer Center were enrolled. Tumor samples and tumor-adjacent normal sample were obtained from these CRC patients. Postoperative pathological characteristics all shown adenocarcinoma. The research team recruited participants from the hospitals connected with CAMS and PUMC and obtained written informed consent from them for publication of a case report and any accompanying images. The Ethics Committee of the Cancer Institute (Hospital), CAMS & PUMC has officially recognized the study (NCC 2017-YZ-026). Outcome Measures: The research team: (1) extracted RNA-seq datasets from the TCGA, exoRBase and GEO and analyzed the differentially expressed genes (DEGs); (2) performed a cluster analysis of variant genes using weighted gene co-expression network analysis (WGCNA);(3) verified expression of myocyte enhancer factor 2C-genecards (MEF2C) and cluster of differentiation 36 (CD36) in CRC tissues; (4) explored the biological function of the MEF2C by performing proliferation, migration, and invasion assays; and (5) used a chromatin immunoprecipitation (ChIP) experiment to analyze mechanisms to reveal CD36 transcription regulated by exosomal MEF2C. Results: A significant mean difference in exosomal MEF2C existed between normal and tumor tissues. By performing a correlation analysis, the research team found 609 potential target points of exosomal MEF2C (r > 0.5, P < .05). Weighted correlation network analysis (WGCNA) and protein-protein interaction (PPI) network analysis indicated that CD36 may be the target of exosomal MEF2C. Univariate, multivariate, and Kaplan-Meier analyses showed that CD36 was closely related to the overall survival (OS) of CRC patients. Obvious differences existed in the expression levels of MEF2C and CD36 in CRC and normal tissues according to qPCR and immunohistochemical assays. Functional-experiments analysis in vitro showed that exosomal-MEF2C could be considered as an antioncogene. Mechanistically, ChIP assays showed that MEF2C regulated the transcriptional level of CD 36; thus, the expression of CD36 increased significantly. Conclusion: MEF2C is a potential biomarker of a favorable prognosis in CRC and is related to the progression of CRC. Moreover, the MEF2C-CD36 pathway may reveal the tumor regulation mechanism in CRC. The exosomal MEF2C was the hub gene in exosomes, with CD36 was identified as the potential target. Exosomal MEF2C may be a promising molecular biomarker for predicting a good prognosis and may have potential as a medical target for CRC.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Young Patients With Peritoneal Metastasis of Colorectal Cancer-An Asian Experience.

INTRODUCTION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are accepted treatment options for patients with cancers associated with the abdominal region. Currently, there are insufficient data that evaluate the effectiveness of these therapeutic options in young patients who have peritoneal metastasis (PM) originating from colorectal cancer. METHODS: In this investigation, we evaluated perioperative data, clinicopathological manifestations, and survival consequences in 46 younger (≤50 y) patients who underwent CRS and HIPEC therapy between 2017 June and 2019 June and then compared these data with 94 older patients (aged >50 y). RESULTS: Compared with older patients, younger patients had a higher synchronous PM incidence (78.3% versus 51.1%, P < 0.001) and were more likely to exhibit signet ring histology and mucinous (29.8% versus 60.9%; P < 0.001). The cancer-specific survival rates after CRS and HIPEC treatment were similar in both age sets. Multivariate Cox regression revealed that mucinous/signet adenocarcinoma (hazard ratio 2.20, 95% confidence interval 1.02-4.74; P = 0.044) and rectal origin (hazard ratio 2.51, 95% confidence interval 1.11-5.67; P = 0.027) were independent risk factors for a lower cancer-specific survival rate. CONCLUSIONS: Younger (age ≤50 y) patients who have PM of colorectal cancer origin often present synchronous PM, which is less commonly observed in older patients. Tumors in younger patients are more aggressive; however, post-CRS and HIPEC treatment, the benefits are similar to those observed in older cohorts.

An efficient high-speed counter-current chromatography method for the preparative separation of potential antioxidants from Paeonia lactiflora Pall. combination of in vitro evaluation and molecular docking.

Paeonia lactiflora Pall., one of the most famous classical herbal medicine, has been used to treat diseases for over 1200 years. In this research, the functional ingredients were purified by online-switch two-dimensional high-speed counter-current chromatography combined with inner-recycling and continuous injection mode. The antioxidant activity was evaluated by investigating the 2,2'-azobis (2-amidinopropane) dihydrochloride-induced oxidant damage in vitro and confirmed through molecular docking. n-Butanol/ethyl acetate/water (2:3:5, v/v) solvent system was used for the first-dimensional separation and optimized the sample loading. Two pure compounds and a polyphenol-enriched fraction were separated. The polyphenol-enriched fraction was separated with a solvent system n-hexane/ethyl acetate/methanol/water (2:8:4:6, v/v) with continuous injection mode. Five compounds were successfully separated, including gallic acid (1), methyl gallate (2), albiflorin (3), paeoniflorin (4), and ethyl gallate (5). Their structures were identified by mass spectrometry and NMR spectroscopy. The results from the antioxidant effect showed that albiflorin had stronger antioxidant activity. Molecular docking results indicated that the affinity energy of the identified compounds ranged from -3.79 to -8.22 kcal/mol and albiflorin showed the lowest affinity energy. Overall, all those findings suggested that the strong antioxidant capacity of albiflorin can be potentially used for the treatment of diseases caused by oxidation.

Neoadjuvant chemotherapy followed by hyperthermic intraperitoneal chemotherapy for patients with colorectal peritoneal metastasis: a retrospective study of its safety and efficacy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are effective routine treatments for colorectal peritoneal metastasis (PM). However, the safety and efficacy of neoadjuvant chemotherapy (NAC) before CRS+HIPEC are poorly understood. Therefore, this study aimed to assess the perioperative safety and long-term efficacy of NAC prior to CRS+HIPEC for patients with synchronous colorectal PM. METHODS: Patients with synchronous colorectal PM who received NAC prior to CRS+HIPEC were systematically reviewed at the China National Cancer Center and Huanxing Cancer Hospital from June 2017 to June 2019. The clinicopathologic characteristics, perioperative parameters, and survival rates of patients who underwent CRS+HIPEC with NAC (NAC group) and patients who underwent CRS+HIPEC without NAC (non-NAC group) were compared. RESULTS: The study enrolled 52 patients, with 20 patients in the NAC group and 32 in the non-NAC group. In the NAC group, the proportion of patients with a peritoneal carcinomatosis index (PCI) score < 12 was significantly higher than that in the non-NAC group (80.0% vs 50.0%, P = 0.031), and more patients achieved complete cytoreduction (80.0% vs 46.9%, P = 0.018). The two groups had comparable grade III/IV complications and similar reoperation and mortality rates (P > 0.05). However, patients who received NAC had lower platelet counts (151.9 vs 197.7 × 109/L, P = 0.036) and neutrophil counts (4.7 vs 7.2 × 109/L, P = 0.030) on postoperative day 1. More patients survived for 2 years in the NAC group than in the non-NAC group (67.4% vs 32.2%, respectively, P = 0.044). However, the completeness of cytoreduction score (HR, 2.99; 95% CI, 1.14-7.84; P = 0.026), rather than NAC, was independently associated with overall survival (OS) in the multivariate analysis after controlling for confounding factors. CONCLUSION: NAC administration before CRS+HIPEC can be regarded as safe and feasible for patients with colorectal PM with comparably low mortality rates and acceptable morbidity rates. Nevertheless, large-sample randomized controlled studies are needed to confirm whether the administration of NAC before CRS+HIPEC confers a survival benefit to patients.

[Clinical study of post-stroke speech apraxia treated with scalp electric acupuncture under anatomic orientation and rehabilitation training].

OBJECTIVE: To compare the differences in the clinical efficacy on post-stroke speech disorder between scalp electric acupuncture (EA) under anatomic orientation combined with rehabilitation training and simple rehabilitation training. METHODS: Sixty patients of post-stroke speech apraxia were randomized into an observation group and a control group, 30 cases in each one. In the observation group, under anatomic orientation, the scalp EA was adopted to the dominant hemisphere Broca area on the left cerebrum. Additionally, the speech rehabilitation training was combined. In the control group, the speech rehabilitation training was simply,used. The treatment lasted for 4 weeks totally. The speech movement program module in the psychological language assessment and treatment system of Chinese aphasia was used for the evident of efficacy assessment. The scores of counting, singing scale, repeating phonetic alphabet, repeating monosyllable and repeating disyllable were observed in the patients of the two groups. The assessment was done separately on the day of grouping and 4 weeks after treatment. RESULTS: In 4 weeks of treatment, the scores of counting, singing scale, repeating phonetic alphabet, repeating monosyllable and repeating disyllable were all improved as compared with those before treatment in the two groups (all P<0. 001). The results in the observation group were better than those in the control group (all P< 0. 05). The total effective rate was 100. 0% (30/30) in the observation group, superior apparently to 53. 3% (16/30) in the control group (P<0. 001). CONCLUSION: The scalp EA under anatomic orientation combined with' speech rehabilitation training obviously improves speech apraxia in stroke patients so that the speech disorder cani be relieved. The efficacy is better than that in simple rehabilitation training.