Microfluidic printed 3D bioactive scaffolds for postoperative treatment of gastric cancer.

Tumor recurrence and tissue regeneration are two major challenges in the postoperative treatment of cancer. Current research hotspots are focusing on developing novel scaffold materials that can simultaneously suppress tumor recurrence and promote tissue repair. Here, we propose a microfluidic 3D-printed methacrylate fish gelatin (F-GelMA@BBR) scaffold loaded with berberine (BBR) for the postoperative treatment of gastric cancer. The F-GelMA@BBR scaffold displayed a significant killing effect on gastric cancer MKN-45 cells in vitro and demonstrated excellent anti-recurrence efficiency in gastric cancer postoperative models. In vitro experiments have shown that F-GelMA@BBR exhibits significant cytotoxicity on gastric cancer cells while maintaining the cell viability of normal cells. The results of in vivo experiments show that F-GelMA@BBR can significantly suppress the tumor volume to 49.7 % of the control group. In addition, the scaffold has an ordered porous structure and good biocompatibility, which could support the attachment and proliferation of normal cells to promote tissue repair at the tumor resection site. These features indicated that such scaffold material is a promising candidate for postoperative tumor treatment in the practical application.

Predicting the prognosis of operable gastric cancer patients by dynamic changes in platelets before and after surgery: a retrospective cohort study.

PURPOSE: Since the relationship between postoperative platelet count and prognosis is still unclear, we designed a standardized index of platelet count to predict the prognosis of gastric cancer (GC). METHODS: We designed a development validation cohort for the pre/post platelet ratio. We determined the ability of PPR to predict mortality in gastric cancer patients and validated them by a separate cohort. Survival was assessed by Kaplan-Meier analysis and associations explored by multivariate and multivariate analyses. The usefulness of the prediction was estimated by measuring the time-dependent ROC. Decision-curve analysis was used to validate the net clinical benefit. RESULTS: The sample distribution was similar in the two cohorts, and the 1-, 3-, and 5-year OS evaluation of the postoperative/preoperative platelet ratio was the largest for AUC in the two cohorts. Meanwhile, PPR has a good predictive value and a net clinical benefit. CONCLUSIONS: PPR has been identified and validated to be independently concerned about OS of patients with GC and was a reliable and economic indicator to evaluate the prognosis.

lncRNA MCF2L-AS1/miR-105/ IL-1ß Axis Regulates Colorectal Cancer Cell Oxaliplatin Resistance.

BACKGROUND: Interactions between non-coding RNAs and mRNAs have been shown to play key roles in colorectal cancer (CRC) resistance to chemotherapeutic drugs, but the regulatory network of these ncRNA/mRNA interactions in the context of CRC cell resistance to oxaliplatin has yet to be fully defined. METHODS: MCF2L-AS1, miR-105, and IL-1ß expression levels were measured in cells and serum samples via qPCR, while ELISAs were additionally used to quantify IL-1ß levels in these samples. Interactions between MCF2L-AS1, miR-105, and IL-1ß were detected through pull-down, RNA immunoprecipitation, and luciferase reporter assays. Cellular viability and OXA IC50 values were established through MTT assays, while in vivo OXA resistance was assessed using a tumor xenograft model system. RESULTS: MCF2L-AS1 levels were significantly elevated in CRC patients that did not respond to chemotherapy and in CRC/OXA cells relative to responders and chemosensitive CRC cells. From a mechanistic perspective, miR-105 was identified as a MCF2L-AS1 target, with this miRNA, in turn, suppressing the expression of IL-1ß. Knocking down MCF2L-AS1 or overexpressing miR-105 was sufficient to alleviate CRC/OXA cell chemoresistance, while overexpressing IL-1ß reversed this effect. CONCLUSION: The MCF2L-AS1/miR-105/IL-1ß regulatory axis regulates the resistance of CRC cells to OXA treatment.

A pilot study on clinicopathological features and intestinal microflora changes in colorectal cancer patients born over a nine-year period encompassing three years before and after the Great Chinese famine.

BACKGROUND: Exposure to energy restriction during childhood is associated with a lower risk of developing colorectal cancer (CRC). To date, the association between this critical period of growth and prognosis of CRC has rarely been investigated. Changes in microbiota and epigenetic dysregulation may be key underlying mechanisms. METHODOLOGY: Tissues collected from patients born between 1956 and 1964 were grouped based on time-period. The differences in overall survival among patients from the three time-periods were examined via univariate analysis. The 16S rRNA gene sequencing approach was to determine differences in microbiota among the groups. Samples were randomly selected to detect BRAF mutations, microsatellite instability (MSI) and promoter CpG island methylator phenotype (CIMP) status. The chi-square test was to assess the relationship between alterations in these molecules and microbiota differences. RESULTS: Patients from the three groups differed in terms of location of CRC (P = 0.034) and carcinoembryonic antigen (CEA) level (P = 0.036). A survival advantage was observed in the famine group compared with the other two groups. Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were more abundant in the two comparing groups. Abundance of B. fragilis was associated with BRAF mutations, microsatellite instability (MSI) and abundance of E. coli. Moreover, the incidence of CIMP and MSI was higher in patients with greater abundance of F. nucleatum. CONCLUSIONS: Limitation of energy intake during childhood may affect the composition of gut microbiota, resulting in persistent epigenetic changes that subsequently influence the prognosis of patients with CRC.

The influence of neoadjuvant chemotherapy on gastric cancer patients' postoperative infectious complications: What is the negative role played by the intestinal barrier dysfunction?

Evidence has shown that neoadjuvant chemotherapy (NACT) is correlated with patients' overall postoperative complications. But investigations on relationship between NACT and postoperative infectious complications, which is closely linked to intestinal barrier damage, were scanty. Accordingly, 90 patients with advanced gastric cancer were included in this study. The differences in postoperative infectious complications were determined between NACT group in which patients received NACT before surgery and SURG group in which received surgical treatment immediately after diagnosis. The damage of mechanical structure of intestinal barrier was assessed by hematoxylin and eosin staining, transmission electron microscopy, and immunohistochemistry. Mucosal microbiota changes were determined by using a 16S rRNA gene sequencing approach. Results showed that the incidence of postoperative infectious complications were significantly higher in the NACT group. Tight junctions were disrupted, and claudin-1, ZO-1 and occludin were down-regulated in patients with infectious complications in overall compared with those without. And similarly, the patients in the NACT group also showed damaged intestinal barrier compared with those in SURG group. Besides, the total diversity of mucosal related bacteria was decreased and relative abundance of some probiotics, such as Bifidobacterium, Faecalibacterium and Ruminococcus, was reduced in the NACT group as well. In conclusion, our study identifies a higher incidence of postoperative infection in gastric cancer patients who underwent NACT treatment, and these changes might be caused by a significant damage in the intestinal barrier as well as reduced probiotics.

Could gut microbiota serve as prognostic biomarker associated with colorectal cancer patients' survival? A pilot study on relevant mechanism.

Evidences have shown that dysbiosis could promote the progression of colorectal cancer (CRC). However, the association of dysbiosis and prognosis of CRC is barely investigated. Therefore, we used 16S rRNA gene sequencing approach to determine differences in microbiota among tumor tissues of different prognosis and found that Fusobacterium nucleatum and Bacteroides fragilis were more abundant in worse prognosis groups, while Faecalibacterium prausnitzii displayed higher abundance in survival group. To further explore the prognostic value of the found bacteria, Kaplan-Meier and Cox proportional regression analyses were used and the results exhibited that high abundance of F. nucleatum and B. fragilis were independent indicators of poor patient's survival. Besides, the expression of major inflammatory mediator were analyzed using PCR and western blot methods, and it turned out that high abundance of F. nucleatum was associated with increased expression of TNF-α, ß-catenin and NF-κB, while COX-2, MMP-9 and NF-κB were positively related with high B. fragilis level, and high level of F. prausnitzii showed lower expression of ß-catenin, MMP-9 and NF-κB. Moreover, immunohistochemical analysis indicated that KRAS and BRAF expression were prominent in F. nucleatum and B. fragilis high abundance group, while MLH1 showed lower expression. In conclusion, F. nucleatum, B. fragilis and F. prausnitzii can be identified as useful prognostic biomarkers for CRC, and dysbiosis might worsen the patients' prognosis by up-regulating gut inflammation level.

Laparoscopic Versus Open Adhesiolysis for Small Bowel Obstruction: A Single-Center Retrospective Case-Control Study.

AIM: This study is to investigate the short-term outcomes of small bowel obstruction (SBO) patients undergoing laparoscopic versus open adhesiolysis. PATIENTS AND METHODS: A total of 202 patients with SBO were enrolled in this study. The patients underwent either laparoscopic (n=101) or open adhesiolysis (n=101). The primary end point was 30-day overall complications and secondary outcomes included major complications such as superficial and deep wound infections, mortality, postoperative length of stay, and operative time. RESULTS: There was no statistically significant difference in the demographic parameters between laparoscopic and open adhesiolysis populations. The mean operative time for laparoscopic adhesiolysis was significantly less than open adhesiolysis (70±34.2 vs. 101±50.2, P=0.01). Statistically significant differences in flatus day (3.5±1.2 vs. 4.5±1.8, P=0.035) and postoperative hospital stay (6.4±2.1 vs. 7.2±2.9, P=0.041) were identified in favor of laparoscopic group, whereas the medical expenses for both groups were not different (31012.0±3412.9 vs. 30029.0±3100.9, P>0.05). The overall complications for open and laparoscopic group were 19.8% and 9.9%, respectively (P=0.048). The important factors that led to a significantly lower overall complications rate in laparoscopic group might result from the lower wound (9.9% vs. 2.0%, P=0.017) and infectious (10.9% vs. 3.0%, P=0.027) complications. CONCLUSIONS: The laparoscopic approach for SBO is feasible because of its fewer complications and hospital stay.