[Clinical research in cell therapy of liver diseases: progress and challenges].

The high incidence of chronic liver disease is a serious threat to public health, and the current comprehensive internal medicine treatment is ineffective. Liver transplantation is limited by the shortage of liver source and post-transplant rejection, and thus unmet the clinical needs. More importantly, cell therapy shows great promise for the treatment of chronic liver disease. Over recent years, domestic and foreign scholars have carried out a variety of cell therapy preclinical and clinical trials for critical liver disease, and achieved certain results, providing new methods for the treatment of chronic liver diseases. This review discusses the cell therapy research status and application progress, various existing problems and challenges, and key issues of mesenchymal stem cells in the treatment of chronic liver diseases.

[Serum exosomal miRNAs profiling and functional study in patients with non-alcoholic fatty liver disease].

Objective: Differential expression of serum exosomal miRNAs were detected for NAFLD patients and healthy controls, thereby determining the role of serum exosomal miRNAs in the pathogenesis, diagnosis, and treatment of NAFLD. Methods: Four patients with S2-3 NAFLD who shared similar demographic features and personal histories, and matched healthy controls were recruited for high-throughput sequencing of serum exosomal miRNAs. Four miRNAs with the most significant differential expression were verified by qRT-PCR in three groups (S1, S2-3, and control groups) with 20 cases in each group. Target gene prediction was performed for these differentially-expressed miRNAs, along with GO and KEGG enrichment analyses for the target genes. T-test or ANOVA were used for normally distributed data. Wilcoxon rank sum test was used for ranked data and non-normally distributed data. The count data used Pearson chi-square test or Fisher's exact test. Results: There were 19 serum exosomal miRNAs with significantly different levels of expression (P < 0.05) and a fold-change > 2. The expression of hsa-miR-122-5p, hsa-miR-146b-5p, and hsa-miR-197-3P was highest in the S2-3 group, followed by the S1 and control groups (in order); hsa-miR-483-3p expression was higher in the NAFLD group (S1 or S2-3) than the control group. There were 84 pathways significantly enriched in target genes. From 20 pathways closely related to NAFLD, at least 5 target genes which were simultaneously correlated to all 10 pathways were screened (PIK3R2, AKT2, AKT3, MAPK1, and NFKB1). Conclusion: Differential expression of serum exosomal miRNAs was detected in NAFLD patients and healthy controls. Four miRNAs with the greatest fold-changes were assessed to judge the severity of fatty degeneration of the liver. The research findings provide reference for non-invasive identification of new biomarkers and specific targets for NAFLD treatment.

Efficacy of triamcinolone-soaked polyglycolic acid sheet plus fully covered metal stent for preventing stricture formation after large esophageal endoscopic submucosal dissection.

Esophageal stricture is a major problem for patients with large superficial esophageal squamous cell neoplasms (SESCNs) after endoscopic submucosal dissection (ESD). Although many measures could be used as prophylaxis for post-ESD strictures, a well-accepted method has not yet been established. We propose using a triamcinolone-soaked polyglycolic acid sheet plus fully covered metal stent (TS-PGA+FCMS) as a novel method to prevent stricture formation after large esophageal ESD. From June 2016 to May 2017, nine patients with SESCNs (≥3/4 of the esophageal circumference) who underwent TS-PGA+FCMS placement immediately after ESD and did not require additional surgical resection were enrolled in this case series. All stents were removed 4-6 weeks post-ESD. The sizes of mucosal defects in 9 patients were 3/4 (n = 1), 4/5 (n = 2), 1/1 (n = 6). The average size of resection was 90.0 mm (range: 60-140 mm). The incidence of stricture was 33.3% (3/9) of patients. No stricture occurred in 3 patients with noncircumferential resection, while stricture occurred in 50% (3/6) patients with circumferential resection. The median number of EBD sessions was 4 (range: 3-4 sessions). No adverse events or recurrences were observed during the median follow-up period of 15.2 months (range: 12-22 months). The TS-PGA+FCMS method is safe and may decrease the incidence of esophageal stricture and the number of EBD sessions after large esophageal ESD.

Long interspersed nucleotide acid element-1 ORF-1 protein promotes proliferation and invasion of human colorectal cancer LoVo cells through enhancing ETS-1 activity.

The human proto-oncogene long interspersed nucleotide acid element-1 (LINE-1) open reading frame-1 protein (ORF-1p) is involved in the progress of several cancers. The transcription factor ETS-1 can mediate the transcription of some downstream genes that play specific roles in the regulation of cancerous cell invasion and metastasis. In this study, the effects of LINE-1 ORF-1p on ETS-1 activity and on the proliferation and invasion of human colorectal cancer LoVo cells were investigated. Results showed that the overexpression of LINE-1 ORF-1p enhanced the transcription of ETS-1 downstream genes and increased their protein levels, and downregulation of the LINE-1 ORF-1p level by small interfering RNA (siRNA) reduced the transcriptional activation of ETS-1. In addition, overexpression of LINE-1 ORF-1p promoted LoVo cell proliferation and anchor-independent growth, and a knockdown of the LINE-1 protein level by siRNA reduced the proliferation and anchor-independent growth ability of LoVo cells. In vivo data revealed that LINE-1 ORF-1p overexpression increased LoVo tumor growth in nude mice, whereas the siRNA knockdown of endogenous LINE-1 ORF-1p expression decreased LoVo cell growth in nude mice. Therefore, LINE- 1 ORF-1p could promote LoVo cell proliferation and invasion both in vitro and in vivo, indicating that it might be a useful molecular target for the treatment of human colorectal cancer.

Endoscopic submucosal tunnel dissection for large esophageal neoplastic lesions.

Endoscopic submucosal dissection (ESD) has been widely used for resection of esophageal neoplastic lesions, but there are still technical challenges in treating large ones. Based on the development of tunneling technique, we report the first series in which the new technique of endoscopic submucosal tunnel dissection (ESTD) was used to remove large lesions in the esophagus. ESTD was attempted in five consecutive patients with esophageal lesions for which resection was indicated. In the operation, once the margin of the lesions had been marked, a submucosal tunnel was created by submucosal dissection from the oral incision to the anal incision. Bilateral resection was then performed to remove the lesion completely. The average length of the five lesions was 5.7 cm, and their extent as a proportion of the whole circumference of the lumen ranged from one third to four fifths. Operative time ranged from 50 minutes to 120 minutes (mean, 77 minutes). En bloc resection with negative lateral and basal margins was achieved in all lesions without complications.