Extracellular vesicles (EVs) have stimulated considerable scientific and clinical interest, yet protein profiling and sizing of individual EVs remains challenging due to their small particle size, low abundance of proteins, and overall heterogeneity. Building upon a laboratory-built high-sensitivity flow cytometer (HSFCM), we report here a rapid approach for quantitative multiparameter analysis of single EVs down to 40 nm with an analysis rate up to 10 000 particles per minute. Statistically robust particle size distribution was acquired in minutes with a resolution and profile well matched with those of cryo-TEM measurements. Subpopulations of EVs expressing CD9, CD63, and/or CD81 were quantified upon immunofluorescent staining. When HSFCM was used to analyze blood samples, a significantly elevated level of CD147-positive EVs was identified in colorectal cancer patients compared to healthy controls (P < 0.001). HSFCM provides a sensitive and rapid platform for surface protein profiling and sizing of individual EVs, which could greatly aid the understanding of EV-mediated intercellular communication and the development of advanced diagnostic and therapeutic strategies.

BackgroundThe ideal level of ligation of the inferior mesenteric artery (IMA) during curative resection of sigmoid colon and rectal cancer is still controversial. The aim of this meta-analysis was to examine the impact of high ligation and low ligation of the IMA on anastomotic leakage, overall morbidity, postoperative mortality, and oncological outcomes in patients undergoing surgery for sigmoid colon and rectal cancer.MethodsPubMed, EMBASE, Web of Science, and BioMed Central databases were searched to identify relevant articles published from May 1953 to March 2018. A total of 18 articles (14 non-randomized studies and 4 randomized clinical trials) were identified. Review Manager 5.3 software was used for analysis of data. The pooled odds ratio (OR) and weighted mean difference (WMD), with 95% CI, were calculated using either the fixed effects model or random effects model.ResultsOf the 5917 patients included in this meta-analysis, 3652 patients underwent low ligation of the IMA and 2265 patients underwent high ligation of the IMA. Anastomotic leakage rate was 9.8% in high ligation patients vs. 7.0% in low ligation patients; the risk of anastomotic leakage was significantly higher in high ligation patients (OR = 1.33; 95% CI 1.10–1.62; P = 0.004). What is more, overall morbidity was also significantly higher in high ligation patients (OR = 1.39; 95% CI, 1.05–1.68; P = 0.05). Postoperative mortality, number of harvested lymph nodes, overall recurrence rate, and 5-year survival rate did not differ significantly between the two groups.ConclusionLow ligation of the IMA during curative resection of sigmoid colon and rectal cancer appears to be associated with lower risk of anastomotic leakage and overall morbidity. However, there was no significant advantage of low ligation over high ligation of IMA in terms of postoperative mortality, the number of harvested lymph nodes, overall recurrence rate, or 5-year survival rate.

The abbreviations used are: JMJD1A, jumonji domain containing 1A; CRC, colorectal cancer; PCNA, proliferating cell nuclear antigen; MMP9, matrix metallopeptidase 9; IP, immunoprecipitation; ChIP, chromatin immunoprecipitation; H3K9, histone-3 lysine-9; GEO, Gene Expression Omnibus. Key words: histone demethylase; JMJD1A; epigenetics; colorectal cancer; proliferation; metastasis; Wnt/β-catenin signaling ABSTRACTThe histone demethylase Jumonji domain containing 1A (JMJD1A) is overexpressed in multiple tumors and promotes cancer progression. JMJD1A has been shown to promote colorectal cancer (CRC) progression, but its molecular role in CRC is unclear. Here, we report that JMJD1A is overexpressed in CRC specimens and that its expression is positively correlated with that of proliferating cell nuclear antigen (PCNA). JMJD1A knockdown decreased the expression of proliferative genes such as c-Myc, cyclin D1, and PCNA, suppressed CRC cell proliferation, arrested cell cycle progression, and reduced xenograft tumorigenesis. Furthermore, JMJD1A knockdown inhibited CRC cell migration, invasion, and lung metastasis by decreasing matrix metallopeptidase 9 (MMP9) expression and enzymatic activity. Moreover, bioinformatics analysis of GEO profile datasets revealed that JMJD1A expression in human CRC specimens is positively correlated with the expression of Wnt/β-catenin target genes, including c-Myc, cyclin D1, and MMP9. Mechanistically, JMJD1A enhanced Wnt/β-catenin signaling by promoting β-catenin expression and interacting with β-catenin to enhance its transactivation. JMJD1A removed the methyl groups of the H3K9me2 at the promoters of c-Myc and MMP9 genes. In contrast, the JMJD1A H1120Y variant, which lacked demethylase activity, did not demethylate H3K9me2 at these promoters, failed to assist β-catenin to induce the expression of Wnt/β-catenin target genes, and failed to promote CRC progression. These findings suggest that JMJD1A's demethylase activity is required for Wnt/β-catenin activation. Of note, high JMJD1A levels in CRC specimens predicted poor cancer outcomes. In summary, JMJD1A promotes CRC progression by enhancing Wnt/β-catenin signaling, implicating JMJD1A as a potential molecular target for CRC management.Colorectal cancer (CRC) is the third most commonly diagnosed cancers in males and the second in females, with an established 1.4 million new cases and 693,900 deaths occurring in the worldwide in 2012(1). In China, colorectal cancer is the fifth most commonly diagnosed cancers in males and the forth in females, and is the fifth leading causes of cancer death in 2015(2). The high incidence and mortality of CRC urge us to figure out the molecular mechanism of CRC progression and develop effective therapeutics. However, the potential mechanism which triggers CRC development is not clearly identified.Aberrant activation of Wnt/β-catenin signaling pathway, mostly caused by the mutations of the tumor suppressor APC or oncogene β-catenin, is found in 90% of human CRC specimens and plays an essential role in CRC prog...

Background In this systematic review and meta-analysis, we aimed to determine the risk factors associated with neck hematoma requiring surgical re-intervention after thyroidectomy. Methods We systematically searched all articles available in the literature published in PubMed and CNKI databases through May 30, 2017. The quality of these articles was assessed using the Newcastle-Ottawa Quality Assessment Scale, and data were extracted for classification and analysis by focusing on articles related with neck hematoma requiring surgical re-intervention after thyroidectomy. Our meta-analysis was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Results Of the 1028 screened articles, 26 met the inclusion criteria and were finally analyzed. The factors associated with a high risk of neck hematoma requiring surgical re-intervention after thyroidectomy included male gender (odds ratio [OR]: 1.86, 95% confidence interval [CI]: 1.60–2.17, P < 0.00001), age (MD: 4.92, 95% CI: 4.28–5.56, P < 0.00001), Graves disease (OR: 1.81, 95% CI: 1.60–2.05, P < 0.00001), hypertension (OR: 2.27, 95% CI: 1.43–3.60, P = 0.0005), antithrombotic drug use (OR: 1.92, 95% CI: 1.51–2.44, P < 0.00001), thyroid procedure in low-volume hospitals (OR: 1.32, 95% CI: 1.12–1.57, P = 0.001), prior thyroid surgery (OR: 1.93, 95% CI: 1.11–3.37, P = 0.02), bilateral thyroidectomy (OR: 1.19, 95% CI: 1.09–1.30, P < 0.0001), and neck dissection (OR: 1.55, 95% CI: 1.23–1.94, P = 0.0002). Smoking status (OR: 1.19, 95% CI: 0.99–1.42, P = 0.06), malignant tumors (OR: 1.00, 95% CI: 0.83–1.20, P = 0.97), and drainage used (OR: 2.02, 95% CI: 0.69–5.89, P = 0.20) were not significantly associated with postoperative neck hematoma. Conclusion: We identified certain risk factors for neck hematoma requiring surgical re-intervention after thyroidectomy, including male gender, age, Graves disease, hypertension, antithrombotic agent use, history of thyroid procedures in low-volume hospitals, previous thyroid surgery, bilateral thyroidectomy, and neck dissection. Appropriate intervention measures based on these risk factors may reduce the incidence of postoperative hematoma and yield greater benefits for the patients.

Aberrant activation of Notch signaling plays an essential role in colorectal cancer (CRC) progression. Amplified in breast cancer 1 (AIB1), also known as SRC-3 or NCOA3 is a transcriptional coactivator that promotes cancer cell proliferation and invasiveness. However AIB1 implication in CRC progression through enhancing Notch signaling is unknown. In this study we found that several CRC cell lines expressed high levels of AIB1, and knockdown of AIB1 decreased cell proliferation, colony formation and tumorigenesis of these CRC cells. Specifically, knockdown of AIB1 inhibited cell cycle progression at G1 phase by decreasing the mRNA levels of Cyclin A2, Cyclin B1, Cyclin E2 and Hes1. Furthermore, AIB1 interacted with Notch intracellular domain (NICD) and Mastermind-like 1 (MAMAL1) and was recruited to the Hes1 promoter to enhance Notch signaling. Downregulation of AIB1 also decreased CRC cell invasiveness in vitro and lung metastasis in vivo. Besides that, knockout of AIB1 in mice inhibited colon carcinogenesis induced by AOM/DSS treatment. The mRNA levels of Cyclin B1 and Hes5 were downregulated, but p27, ATOH1, and MUC2 were upregulated in the colon tumors from AIB1-deficient mice compared with those from wild-type mice. Thus our results signify the importance of AIB1 in CRC and demonstrate that AIB1 promotes CRC progression at least in part through enhancing Notch signaling, suggesting that AIB1 is a potential molecular target for CRC treatment.