BackgroundAlthough laparoscopic surgery has been recommended as an optional therapy for patients with early gastric cancer, whether patients with locally advanced gastric cancer (AGC) could benefit from laparoscopy-assisted distal gastrectomy (LADG) with D2 lymphadenectomy remains elusive due to a lack of comprehensive clinical data. To evaluate the efficacy of LADG, we conducted a multi-institutional randomized controlled trial to compare laparoscopy-assisted versus open distal gastrectomy (ODG) for AGC in North China.MethodsIn this RCT, after patients were enrolled according to the eligibility criteria, they were preoperatively assigned to LADG or ODG arm randomly with a 1:1 allocation ratio. The primary endpoint was the morbidity and mortality within 30 postoperative days to evaluate the surgical safety of LADG. The secondary endpoint was 3-year disease-free survival. This trial was registered at ClinicalTrial.gov as NCT02464215.ResultsBetween March 2014 and August 2017, a total of 446 patients with cT2-4aN0-3M0 (AJCC 7th staging system) were enrolled. Of these, 222 patients underwent LADG and 220 patients underwent ODG were included in the modified intention-to-treat analysis. The compliance rate of D2 lymph node dissection was identical between the LADG and ODG arms (99.5%, P = 1.000). No significant difference was observed regarding the overall postoperative complication rate in two groups (LADG 13.1%, ODG 17.7%, P = 0.174). No operation-related death occurred in both arms.ConclusionsThis trial confirmed that LADG performed by credentialed surgeons was safe and feasible for patients with AGC compared with conventional ODG.

Laparoscopic surgery is an acceptable alternative to open surgery in colorectal cancer treatment. However, in gastric cancer, there is not much scientific evidence. Here, we proposed a prospective randomized clinical trial to evaluate the radicalness and safety of laparoscopic D2 dissection for gastric cancer. From October 2010 to September 2012, 300 patients with gastric cancer were randomized to undergo either laparoscopy-assisted gastrectomy (LAG) or conventional open gastrectomy (OG) with D2 dissection. Clinicopathological parameters, recovery and complications were compared between these two groups. Thirty cases were excluded because of refusing to be involved in the trial, having peritoneal seeding metastasis or LAG conversed to OG, and finally 270 cases were analyzed (128 in LAG and 142 in OG). No significant differences were observed in gender, age, body mass index, stages and types of radical resection [radical proximal gastrectomy (PG + D2), radical distal gastrectomy (DG + D2) and radical total gastrectomy (TG + D2)] (P > 0.05). The number of harvested lymph nodes (HLNs) was similar (29.3 ± 11.8 in LAG vs. 30.1 ± 11.4 in OG, P = 0.574). And in the same type of radical resection, no significant difference was found in the number of HLNs between the two groups (PG + D2, P = 0.770; DG + D2, P = 0.500; TG + D2, P = 0.993). The morbidity of the LAG group (21.8 %) was also comparable to the OG group (19.0 %, P = 0.560). However, the LAG group had significantly less blood loss and faster recovery, and a longer operation time (P < 0.05). Laparoscopic D2 dissection is feasible, safe and capable of fulfilling oncologic criteria for the treatment of gastric cancer.

EZH2 is a critical epigenetic regulator that is deregulated in various types of cancers including multiple myeloma (MM). In the present study, we hypothesized that targeting EZH2 might induce apoptosis in myeloma cells including stem cell-like cells (CSCs). We investigated the effect of EZH2 inhibition on MM cells using a potent inhibitor (GSK126). The results showed that GSK126 effectively abrogated the methylated histone 3 (H3K27me3) level in MM.1S and LP1 cells, and inhibited the number of live cells and colony formation in soft agar of six MM cell lines. GSK126 induced massive apoptosis in MM.1S, LP1 and RPMI8226 cells. Progressive release of mitochondrial cytochrome c and AIF into the cytosol was detected in GSK126-treated MM cells. GSK126 treatment elicited caspase-3-dependent MCL-1 cleavage with accumulation of proapoptotic truncated MCL-1. These results suggested that GSK126 triggers the intrinsic mitochondrial apoptosis pathway. Enhanced apoptosis was observed in the combination of GSK126 with bortezomib. Using ALDH and side population (SP) assays to characterize CSCs, we found that GSK126 eliminated the stem-like myeloma cells by blocking the Wnt/β-catenin pathway. The in vivo anti-tumor effect of GSK126 was confirmed by using RPMI8226 cells in a xenograft mouse model. In conclusion, our findings suggest that EZH2 inactivation by GSK126 is effective in killing MM cells and CSCs as a single agent or in combination with bortezomib. Clinical trial of GSK126 in patients with MM may be warranted.

Because influenza is a contagious respiratory illness that seriously threatens public health, accurate real-time prediction of influenza outbreaks may help save lives. In this paper, we use the Twitter data set and the United States Centers for Disease Control’s influenza-like illness (ILI) data set to predict a nearly real-time regional unweighted percentage ILI in the United States by use of an artificial neural network optimized by the improved artificial tree algorithm. The results show that the proposed method is an efficient approach to real-time prediction.

BackgroundGolgi phosphoprotein 3 (GOLPH3) has been validated as a potent oncogene involved in the progression of many types of solid tumors, and its overexpression is associated with poor clinical outcome in many cancers. However, it is still unknown the association of GOLPH3 expression with the prognosis of colorectal cancer (CRC) patients who received 5-fluorouracil (5-FU)-based adjuvant chemotherapy.MethodsThe expression of GOLPH3 was determined by qRT-PCR and immunohistochemistry in colorectal tissues from CRC patients treated with 5-FU based adjuvant chemotherapy after surgery. The association of GOLPH3 with clinicopathologic features and prognosis was analysed. The effects of GOLPH3 on 5-FU sensitivity were examined in CRC cell lines.ResultsGOLPH3 expression was elevated in CRC tissues compared with matched adjacent noncancerous tissues. Kaplan-Meier survival curves indicated that high GOLPH3 expression was significantly associated with prolonged disease-free survival (DFS, P = 0.002) and overall survival (OS, P = 0.011) in patients who received 5-FU-based adjuvant chemotherapy. Moreover, multivariate analysis showed that GOLPH3 expression was an independent prognostic factor for DFS in CRC patients treated with 5-FU-based chemotherapy (HR, 0.468; 95%CI, 0.222-0.987; P = 0.046). In vitro, overexpression of GOLPH3 facilitated the 5-FU chemosensitivity in CRC cells; while siRNA-mediated knockdown of GOLPH3 reduced the sensitivity of CRC cells to 5-FU-induced apoptosis.ConclusionsOur results suggest that GOLPH3 is associated with prognosis in CRC patients treated with postoperative 5-FU-based adjuvant chemotherapy, and may serve as a potential indicator to predict 5-FU chemosensitivity.

Abstract. During infectious disease outbreaks, people may reduce their contact numbers or take other precautions to prevent transmission. The change in their behavior can be directly or indirectly triggered by the density of infected individuals in the population. In this paper, we investigate an SIS (susceptible-infected-susceptible) model where the transmission rate is a decreasing function of the prevalence of the disease (determined by a reduction function h), with the assumption that such a change in the transmission rate occurs with some time delay. We prove that if the basic reproduction number R 0 is less than one, then the disease-free equilibrium is globally asymptotically stable, while for R 0 > 1 a unique endemic equilibrium exists and the disease uniformly persists, regardless of the delay or the specific form of h. However, characterized by the shape of the response function h, various dynamics are possible if R 0 > 1. Roughly speaking, if h is decreasing slowly (weak response), then the endemic equilibrium is absolutely globally asymptotically stable. When the slope of h is larger (strong response), then the endemic equilibrium loses its stability and periodic orbits appear via Hopf bifurcation as R 0 increases. Further increasing R 0 , the endemic equilibrium regains its stability, forming an interesting structure in the bifurcation diagram that we call an endemic bubble.

We investigate epidemic models with spatial structure based on the cellular automata method. The construction of the cellular automata is from the study by Weimar and Boon about the reactiondiffusion equations [Phys. Rev. E 49, 1749]. Our results show that the spatial epidemic models exhibits spontaneous formation of irregular spiral waves at large scales within the domain of chaos. Moreover the irregular spiral waves grow stably. The system also shows spatial period-2 structure at one dimension outside the domain of chaos. It is interesting that the spatial period-2 structure will break and transform to spatial synchronous configuration in the domain of chaos. Our results confirm that populations embed and disperse more stably in space than they do in non-spatial counterparts.

The MSKCC nomogram for colon cancer provides more accurate survival predictions than the AJCC staging system when applied to an external Chinese cohort. The MSKCC nomogram improved individualized prediction of survival and may aid in more accurate patient counseling, selection of various treatment options, and follow-up scheduling.