A tumour-promoting role of Th9 cells in hepatocellular carcinoma through CCL20 and STAT3 pathways.

Hepatocellular carcinoma (HCC) is a common and aggressive human malignancy. An imperative demand is present for a better understanding of the functions and regulations of the immune system and how they affect HCC pathogenesis. Recently, a group of interleukin 9 (IL-9)-producing CD4+ T cells, termed Th9 cells, has been described in mice and humans with both tumour-inhibiting as well as tumour-promoting effects. The specific roles of Th9 cells in human HCC are not entirely understood. Here, we examined the frequencies and functions of IL-9-producing Th9 cells in HCC patients. We found that the frequencies of circulating IL-9-producing Th9 cells were significantly higher in HCC patients compared to in healthy individuals. In HCC patients, the frequencies of IL-9-producing Th9 cells were significantly higher in peritumour and tumour tissues than in unaffected liver tissues. Interestingly, HCC patients with higher tumour-infiltrating Th9 frequency had significantly shorter disease-free survival period after resection. Previously, high expression of CCL20 was associated with poor prognosis in HCC. CCL20 also induced epithelial-mesenchymal transition-like changes in HCC cells. We found that incubation of primary HCC cells with autologous Th9 significantly elevated the CCL20 production from tumour cells, which could be partially inhibited by suppressing STAT3. Together, this study suggested a tumour-promoting role of Th9 cells in HCC.

The Dynamics and Optimal Control of a Hand-Foot-Mouth Disease Model.

We build and study the transmission dynamics of a hand-foot-mouth disease model with vaccination. The reproduction number is given, the existence of equilibria is obtained, and the global stability of disease-free equilibrium is proved by constructing the Lyapunov function. We also apply optimal control theory to the hand-foot-mouth disease model. The treatment and vaccination interventions are considered in the hand-foot-mouth disease model, and the optimal control strategies based on minimizing the cost of intervention and minimizing the number of the infected people are given. Numerical results show the usefulness of the optimization strategies.

The efficacy of gabapentin in reducing pain intensity and postoperative nausea and vomiting following laparoscopic cholecystectomy: A meta-analysis.

BACKGROUND: It is unknown whether gabapentin is effective in reducing acute pain following laparoscopic cholecystectomy. The purpose of the current meta-analysis was to evaluate the efficacy of gabapentin in reducing pain intensity and postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy. METHODS: All randomized controlled trials (RCTs) evaluating the efficacy of gabapentin in reducing pain intensity and PONV after laparoscopic cholecystectomy were searched on the following databases: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), the Google database, the Chinese Wanfang database, and the China National Knowledge Infrastructure (CNKI). The most recent literature search was conducted on March 21, 2017. Outcomes including visual analog scale (VAS) at 12 and 24 hours, total morphine consumption, and the occurrence of PONV. Continuous outcomes were expressed as the weighted mean difference (WMD) and 95% confidence interval (CI), and the one discontinuous outcome was expressed as risk ratio (RR) and 95% CI. Stata 12.0 software was used for meta-analysis. RESULTS: A total of 9 studies involving 966 patients were identified. In total, there were 484 gabapentin subjects and 482 controls. Compared with the control group, gabapentin was associated with lower VAS at 12 hours (WMD = -10.18, 95% CI: -17.36 to -2.80, P = .007) and 24 hours (WMD = -6.33, 95% CI: -8.41 to -4.25, P = .000), which was equivalent on a 110-point VAS scale to 10.18 points at 12 hours and 6.33 points at 24 hours. Compared with the control group, gabapentin was associated with less total morphine consumption by approximately 110.83 mg (WMD = -110.83, 95% CI: -183.25 to -38.42, P = .003). In addition, the occurrence of nausea and vomiting in gabapentin was decreased (25.2% vs 47.6, RR = 0.53, 95% CI: 0.44-0.63, P = .000). CONCLUSION: Gabapentin was efficacious in reducing postoperative pain, total morphine consumption, and morphine-related complications following laparoscopic cholecystectomy. In addition, there was a negative correlation between the gabapentin dosage and the occurrence of nausea and vomiting. The number of included studies is limited, and more studies are needed to verify the effects of gabapentin in laparoscopic cholecystectomy patients.

miR141 expression is downregulated and negatively correlated with STAT5 expression in esophageal squamous cell carcinoma.

The aim of the present study was to investigate the association between microRNA-141 (miR141) and signal transducer and activator of transcription 5 (STAT5) expression levels in human esophageal squamous cell carcinoma (ESCC) and to investigate the effects of miR141 on ESCC cells. A total of 45 consecutive patients with ESCC were enrolled in the study. The expression of miR141 in ESCC tissue samples was detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The expression of STAT5 in the ESCC tissues was detected using immunohistochemical staining and western blotting. In addition, Eca109 cells were transfected with miR141 mimic, and the levels of STAT5 were detected using western blotting. The effects of miR141 on the proliferation, invasion and migration of the cells were also detected using MTT, scratch and Transwell invasion assays, respectively. The miR141 expression level in the ESCC tissue samples was significantly decreased compared with that in the adjacent normal tissues (P<0.05). The expression of miR141 in the tissues from patients with lymph node metastasis was significantly decreased compared with that in the tissues of patients without such metastasis (P<0.05). The expression levels of STAT were significantly increased in the ESCC tissues compared with those in the adjacent normal tissues (P<0.05). Furthermore, the levels of STAT5 were significantly increased in the tissues from patients with lymph node metastasis compared with those without such metastasis (P<0.05); however, no statistically significant differences in miR141 expression were observed according to gender, age, tumor size, lesion location, differentiation and invasion (P>0.05). The results suggest that the miR141 mimic significantly inhibited the proliferation, migration and invasion of Eca109 cells in vitro. miR141 and STAT5 expression levels exhibited a negative association in the ESCC tissues, and were both closely associated with the progression of ESCC. Therefore, it appears that miR141 plays an important role in the development, invasion and metastasis of ESCC by regulating the expression of STAT5.

Overrepresentation of IL-10-Expressing B Cells Suppresses Cytotoxic CD4+ T Cell Activity in HBV-Induced Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis and low five-year survival rate. A strong and effective CD4+ T cell-mediated cytotoxicity was associated with better survival and low recurrence rate in HCC, but the regulatory mechanism that controls CD4+ T cell cytotoxicity in HCC patients is not fully examined. Given that IL-10-expressing B cells could suppress the inflammation of cytotoxic CD8+ T cells, T helper 1 (Th1) cells and Th17 cells, while promoting regulatory T (Treg) cell differentiation, we examined the role of IL-10-expressing B cells in HBV-related HCC patients. We found that compared to healthy controls, HCC patients exhibited significantly higher frequencies of IL-10-expressing B cells, which were negatively correlated with the frequencies of granzyme A, granzyme B, and perforin expressing CD4+ T cells. Surface molecule Tim-1 was preferentially expressed on IL-10-expressing B cells. Therefore, we separated total B cells into Tim-1+ and Tim-1- B cells. CD4+ T cells incubated with Tim-1+ B cells exhibited significantly reduced levels of granzyme A, granzyme B and perforin expression, compared to the CD4+ T cells incubated with Tim-1- B cells. Antagonizing IL-10 in culture rescued CD4+ T cell cytotoxicity. Compared to that in peripheral blood, the level of IL-10-expressing B cells were further upregulated in resected tumor, while the level of CD4+ cytotoxic T cells was downregulated. The negative correlations between IL-10-expressing B cells and CD4+ cytotoxic T cells were also observed in tumor-infiltrating cells. Together, our data revealed an additional antitumor mechanism mediated by IL-10-expressing B cells.