Genetic mutation and tumor microbiota determine heterogenicity of tumor immune signature: Evidence from gastric and colorectal synchronous cancers.

Both colorectal and gastric cancer are lethal solid-tumor malignancies, leading to the majority of cancer-associated deaths worldwide. Although colorectal cancer (CRC) and gastric cancer (GC) share many similarities, the prognosis and drug response of CRC and GC are different. However, determinants for such differences have not been elucidated. To avoid genetic background variance, we performed multi-omics analysis, including single-cell RNA sequencing, whole-exome sequencing, and microbiome sequencing, to dissect the tumor immune signature of synchronous primary tumors of GC and CRC. We found that cellular components of juxta-tumoral sites were quite similar, while tumoral cellular components were specific to the tumoral sites. In addition, the mutational landscape and microbiome contributed to the distinct TME cellular components. Overall, we found that different prognoses and drug responses of GC and CRC were mainly due to the distinct TME determined by mutational landscape and microbiome components.

A novel surgical predictive model for Chinese Crohn's disease patients.

Due to the complexity of Crohn's disease (CD), it is difficult to predict disease course with a single stratification factor or biomarker. A logistic regression (LR) model has been proposed by Guizzetti et al to stratify patients with CD-related surgical risk, which could help decision-making on disease treatment. However, there are no reports on relevant studies on Chinese population. The aim of the study is to present and validate a novel surgical predictive model to facilitate therapeutic decision-making for Chinese CD patients. Data was extracted from retrospective full-mode electronic medical records, which contained 239 CD patients and 1524 instances. Two sub-datasets were generated according to different attribute selection strategies, both of which were split into training and testing sets randomly. The imbalanced data in the training sets was addressed by synthetic minority over-sampling technique (SMOTE) algorithm before model development. Seven predictive models were employed using 5 popular machine learning algorithms: random forest (RF), LR, support vector machine (SVM), decision tree (DT) and artificial neural networks (ANN). The performance of each model was evaluated by accuracy, precision, F1-score, true negative (TN) rate, and the area under the receiver operating characteristic curve (AuROC). The result revealed that RF outperformed all other baseline models on both sub-datasets. The 10 leading risk factors for CD-related surgery returned from RF for attribute ranking were changes of radiology, presence of a fistula, presence of an abscess, no infliximab use, enteroscopy findings, C-reactive protein, abdominal pain, white blood cells, erythrocyte sedimentation rate and platelet count. The proposed machine learning model can accurately predict the risk of surgical intervention in Chinese CD patients, which could be used to tailor and modify the treatment strategies for CD patients in clinical practice.

Long Noncoding RNA Antisense Noncoding RNA in the INK4 Locus Correlates With Risk, Severity, Inflammation and Infliximab Efficacy in Crohn's Disease.

BACKGROUND: The aim of this study was to investigate the association of intestinal mucosa long noncoding RNA (lncRNA) antisense noncoding RNA in the INK4 locus (ANRIL) expression with disease risk, activity and inflammatory cytokines levels of Crohn's disease (CD). METHODS: Forty-two patients with active CD (A-CD), 59 patients with CD in remission (R-CD) and 67 controls were consecutively recruited. Intestinal mucosa samples were collected from all participants at baseline and from A-CD patients at 3-months after infliximab treatment. LncRNA ANRIL level, mRNA expression of tumor necrosis factor-α, interleukin (IL)-10, IL-17, IL-23 and interferon gamma were assessed by quantitative polymerase chain reaction. C-reactive protein, erythrocyte sedimentation rate and Crohn's disease activity index were used to evaluate the disease activity of CD. RESULTS: LncRNA ANRIL expression was decreased in patients with A-CD compared with patients with R-CD (P < 0.001) and controls (P < 0.001) and was also reduced in patients with R-CD compared with controls (P < 0.001). Receiver operating characteristic curves showed that lncRNA ANRIL expression distinguished CD, A-CD and R-CD from controls, as well as A-CD from R-CD. Additionally, lncRNA ANRIL expression was negatively associated with Crohn's disease activity index (P = 0.002), C-reactive protein (P < 0.001) and erythrocyte sedimentation rate (P = 0.001), and associated with tumor necrosis factor-α (P < 0.001), IL-17 (P < 0.001) and interferon gamma messenger RNA levels (P = 0.004) but positively associated with IL-10 messenger RNA level (P = 0.002). Furthermore, IncRNA ANRIL expression was increased after infliximab treatment compared with baseline in patients with A-CD that responded to treatment (P < 0.001) but remained stable in patients with A-CD that did not respond (P = 0.897). CONCLUSIONS: lncRNA ANRIL downregulation in intestinal mucosa correlates with increased disease risk, higher disease activity and elevated proinflammatory cytokines levels, and its change associates with infliximab treatment response in patients with CD.

The Potential Role of Cycloastragenol in Promoting Diabetic Wound Repair In Vitro.

BACKGROUND: Refractory wound healing is a severe complication of diabetes with a significant socioeconomic burden. Whereas current therapies are insufficient to accelerate repair, stem cell-based therapy is increasingly recognized as an alternative that improves healing outcomes. The aim of the present study is to explore the role of cycloastragenol (CAG), a naturally occurring compound in Astragali Radix, in ameliorating refractory cutaneous wound healing in vitro, which may provide a new insight into therapeutic strategy for diabetic wounds. METHODS: Human epidermal stem cells (EpSCs) obtained from nine patients were exposed to CAG, with or without DKK1 (a Wnt signaling inhibitor). A lentiviral short hairpin RNA (shRNA) system was used to establish the telomerase reverse transcriptase (TERT) and ß-catenin knockdown cell line. Cell counting kit-8, scratch wound healing, and transwell migration assay were used to determine the effects of CAG in cell growth and migration. The activation of TERT, ß-catenin, and c-Myc was determined using real-time qPCR and western blot analysis. Chromatin immunoprecipitation (ChIP) was performed to evaluate the associations among CAG, TERT, and Wnt/ß-catenin signals. RESULTS: CAG not only promoted the proliferation and migration ability of EpSCs but also increased the expression levels of TERT, ß-catenin, c-Myc. These effects of CAG were most pronounced at a dose of 0.3 µM. Notably, the CAG-promoted proliferative and migratory abilities of EpSCs were abrogated in TERT and ß-catenin-silenced cells. In addition, the ChIP results strongly suggested that CAG-modulated TERT was closely associated with the activation of Wnt/ß-catenin signaling. CONCLUSION: Our data indicate that CAG is a TERT activator of EpSCs and is associated with their proliferation and migration, a role it may play through the activation of Wnt/ß-catenin signaling.

A novel technique for the treatment of stages III to IV hemorrhoids: Homemade anal cushion suspension clamp combined with harmonic scalpel.

To compare the efficacy of homemade anal cushion suspension clamp combined with harmonic scalpel (ACS) and Milligan-Morgan hemorrhoidectomy combined with electric knife (MMH) in the treatment of stages III to IV hemorrhoids. We conducted a retrospective study of 99 patients with stages III to IV hemorrhoids hospitalized from January to December in 2013. Among them, 51 patients were treated with ACS, while 48 patients received MMH. Data from clinical recording and follow-up included operative time, intraoperative blood loss, hospitalization information, postoperative pain, and postoperative complications. Operative time, intraoperative blood loss and hospitalization time in ACS group were significantly less than those in MMH group (P < .05). Compared with MMH group, ACS group had a lower postoperative static pain score from days 1 to 14 (P < .01). The patients in ACS group exhibited less postoperative defecation pain scores from days 3 to 20 than those of MMH group (P < .05). The incidence of postoperative anal edema and delayed wound healing in ACS group was lower than that in MMH group (P < .05). Compared with MMH, our novel technique ACS was more effective and had fewer postoperative complications in the treatment of stages III to IV hemorrhoids.

Ligasure versus Ferguson hemorrhoidectomy in the treatment of hemorrhoids: a meta-analysis of randomized control trials.

AIM: To compare outcomes of Ligasure hemorrhoidectomy (LH) versus Ferguson hemorrhoidectomy (FH) by a meta-analysis of available randomized controlled trials. METHODS: Original studies in any language were searched from MEDLINE database, PubMed, Web of science and the Cochrane Library database, and Wangfang database. Randomizes control trials that compared LH with FH were identified. Data were extracted independently for each study and a meta-analysis was performed using fixed-effects and random-effects models. RESULTS: Five trials including 318 patients met the inclusion criteria. The urinary retention rate and early postoperative pain scores were higher in patients undergoing FH. Patients treated with Ligasure had a significantly shorter operative time and hospital stay than the patients submitted to Ferguson techniques. The blood loss during operation was less in Ligasure group than Ferguson group. No statistically significant differences were noted in postoperative bleeding, difficult defacating, anal fissure, anal stenosis, and incontinence. CONCLUSIONS: Our meta-analysis shows that LH is superior to FH in the short-term outcomes. Future studies addressing long-term outcomes are needed to prove these results.