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Shi-Bin Jiang,1,2,* Xu-Jun He,1,3,* Ying-Jie Xia,1,3 Wei-Jian Hu,2 Jun-Gang Luo,1,2 Jun Zhang,2,3 Hou-Quan Tao1–31Department of Surgery, Zhejiang Provincial People’s Hospital, Hangzhou, 2Wenzhou Medical University, Wenzhou, 3Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally tothis workAbstract: MicroRNA (miR)-145-5p has been reported to function as a suppressor of cancer and plays an important role in cancer invasiveness. Epithelial–mesenchymal transition (EMT) is an important process in cancer invasion and migration. However, the involvement of miR-145-5p in EMT in human gastric cancer (GC) remains unclear. In this study, we aimed to investigate the molecular mechanisms by which miR-145-5p regulates EMT in GC invasiveness. We used quantitative real-time polymerase chain reaction to investigate the miR-145-5p expression level in GC and matched normal tissues. The effects of miR-145-5p on GC cell invasion and migration abilities were evaluated using Transwell models. The relationships among miR-145-5p and zinc-finger E-box binding homeobox 2 (ZEB2), E-cadherin, and N-cadherin were analyzed by quantitative real-time polymerase chain reaction and Western blot analyses. miR-145-5p levels in primary GC tissues obtained from 60 patients were significantly downregulated, compared to those in paired normal tissues. Lauren classification, depth of tumor invasion, lymph node metastasis, lymphatic invasion, and tumor–node–metastasis stage were associated with miR-145-5p expression. miR-145-5p inhibits the expression of the candidate target gene ZEB2 to delay the invasion and migration of GC cells. ZEB2 acts as transcriptional repressor of E-cadherin, while miR-145-5p is known to suppress N-cadherin directly to regulate EMT. Therefore, we concluded that miR-145-5p may target N-cadherin and ZEB2 directly to influence EMT.Keywords: miR-145-5p, zinc-finger E-box binding homeobox 2 (ZEB2), epithelial–mesenchymal transition (EMT), gastric cancer

Xiaofen Chen,1 Weiting Chen,1 Weijie Hu,2 Kui Huang,3 Jing Huang,4 Yu Zhou5 1Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 2People Hospital of Tiantai, Taizhou, 3Department of Orthodontics, Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 4The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, 5Department of Orthodontics, Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People’s Republic of China Background: Continuous positive airway pressure (CPAP) is widely recommended for the treatment of sleep apnea/hypopnea syndrome (SAHS), but its usage by patients is very low. The aim of this study was to assess intensive educational programs and nursing support for the improvement of CPAP use and outcomes in SAHS patients.Methods: Eighty new SAHS patients were randomized to receive nurse-led intensive interventions or usual support at hospital and home. The main outcome measure was CPAP use; changes in sleeping, symptoms, mood, and quality of life were also assessed after 12 months of treatment.Results: All outcome measures were improved after treatment in both groups. However, patients receiving intensive support with significantly higher CPAP use (higher daily CPAP usage by 2.2 hours/day) had greater improvements in SAHS symptoms and mood (P

The aim of this study was to explore the genetic polymorphism, genotype, and haplotype characteristics of the KIR locus in the Xinjiang Han population in order to establish a foundation for future analysis of the relationship between KIR genes and disease. KIR genes were detected by sequence-specific primer-polymerase chain reaction in 184 randomly selected, healthy individuals from the Han population in Xinjiang, China. Standard genotype and haplotype analyses were conducted using Hsu's standards classified for analysis. Sixteen KIR genes were detected: 3DL3, 2DL4, 3DL2, and 3DL2 (100%); 2DL1 and 2DP1 (99.46%); 2DL3 (98.91%); and so on. The 2DS2 gene frequency was the lowest at 21.74%. Twenty-one genotypes were detected: AJ (2, 2) was relatively common (42.39%), followed by AH (5, 2), AE (2, 8) and H (2, 4), with frequencies of 17.39, 11.96, and 8.15%, respectively. In addition, six novel genotypes were identified in 11 Han individuals as well as in other populations in China, which could not be classified for analysis. These results indicated that the Xinjiang Han population shares KIR gene, genotype, and haplotype frequency distributions with the Chinese Han population, but also has unique genotypes and haplotypes.

We investigate the spin-$\frac{1}{2}$ Heisenberg model on the triangular lattice in the presence of nearest-neighbor $J_1$ and next-nearest-neighbor $J_2$ antiferromagnetic couplings. Motivated by recent findings from density-matrix renormalization group (DMRG) claiming the existence of a gapped spin liquid with signatures of spontaneously broken lattice point group symmetry [Zhu and White, Phys. Rev. B 92, 041105 (2015); Hu, Gong, Zhu, and Sheng, Phys. Rev. B 92, 140403 (2015)], we employ the variational Monte Carlo (VMC) approach to analyze the model from an alternative perspective that considers both magnetically ordered and paramagnetic trial states. We find a quantum paramagnet in the regime $0.08\lesssim J_2/J_1\lesssim 0.16$, framed by $120^{\circ}$ coplanar (stripe collinear) antiferromagnetic order for smaller (larger) $J_2/J_1$. By considering the optimization of spin-liquid wave functions of a different gauge group and lattice point group content as derived from Abrikosov mean-field theory, we obtain the gapless $U(1)$ Dirac spin liquid as the energetically most preferable state in comparison to all symmetric or nematic gapped $\mathbb{Z}_{2}$ spin liquids so far advocated by DMRG. Moreover, by the application of few Lanczos iterations, we find the energy to be the same as the DMRG result within error-bars. To further resolve the intriguing disagreement between VMC and DMRG, we complement our methodological approach by the pseudofermion functional renormalization group (PFFRG) to compare the spin structure factors for the paramagnetic regime calculated by VMC, DMRG, and PFFRG. This model promises to be an ideal test-bed for future numerical refinements in tracking the long-range correlations in frustrated magnets., Comment: Editors' Suggestion. 16 pages, 13 figures, 4 tables

Chemotherapy drugs, including 5-fluorouracil (5-FU), oxaliplatin and docetaxel, are commonly used in the treatment of gastric cancer (GC). Apoptosis-relevant genes may be associated with drug resistance. In the present study, the messenger RNA (mRNA) expression levels of B-cell lymphoma 2 interacting mediator of cell death (BIM), astrocyte elevated gene-1 (AEG-1) and AXL receptor tyrosine kinase (AXL) were investigated in 131 advanced GC samples, and the expression levels of these genes were correlated with patients' overall survival (OS). All 131 patients received first-line FOLFOX combination chemotherapy with folinic acid and 5-FU, in which 56 patients were further treated with second-line docetaxel-based chemotherapy. A correlation between the mRNA expression levels of BIM and AEG-1 was observed (r(s)=0.30; P=0.002). There was no association between the mRNA expression levels of any of the individual genes analyzed and OS in patients only receiving first-line FOLFOX chemotherapy. In a subgroup of patients receiving docetaxel-based second-line chemotherapy, those with high or intermediate levels of BIM exhibited a median OS of 18.2 months [95% confidence interval (CI), 12.8-23.6], compared with 9.6 months (95% CI, 8.9-10.3) in patients with low BIM levels (P=0.008). However, there was no correlation between the mRNA expression levels of AEG-1 or AXL and OS. The risk of mortality was higher in patients with low BIM mRNA levels than in those with high or intermediate BIM mRNA levels (hazard ratio, 2.61; 95% CI, 1.21-5.62; P=0.010). Therefore, BIM may be considered as a biomarker to identify whether patients could benefit from docetaxel-based second-line chemotherapy in GC.

Fang-bo Cui,1,* Qin Liu,1,* Ru-Tian Li,1 Jie Shen,1 Pu-yuan Wu,1 Li-Xia Yu,1 Wen-jing Hu,1 Feng-lei Wu,2 Chun-Ping Jiang,1 Guo-feng Yue,2 Xiao-Ping Qian,1 Xi-Qun Jiang,3 Bao-Rui Liu11The Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, 2Nanjing Medical University, 3Laboratory of Mesoscopic Chemistry and Department of Polymer Science and Engineering, College of Chemistry and Chemical Engineering, Nanjing University, Nanjing, People's Republic of China*These authors contributed equally to this workAbstract: Radiotherapy is the main locoregional control modality for many types of unresectable tumors, including gastric cancer. However, many patients fail radiotherapy due to intrinsic radioresistance of cancer cells, which has been found to be strongly associated with cancer stem cell (CSC)-like properties. In this study, we developed a nanoparticle formulation to deliver miR-200c, which is reported to inhibit CSC-like properties, and then evaluated its potential activity as a radiosensitizer. miR-200c nanoparticles significantly augmented radiosensitivity in three gastric cancer cell lines (sensitization enhancement ratio 1.13–1.25), but only slightly in GES-1 cells (1.06). In addition to radioenhancement, miR-200c nanoparticles reduced the expression of CD44, a putative CSC marker, and the percentage of CD44+ BGC823 cells. Meanwhile, other CSC-like properties, including invasiveness and resistance to apoptosis, could be suppressed by miR-200c nanoparticles. CSC-associated radioresistance mechanisms, involving reactive oxygen species levels and DNA repair capacity, were also attenuated. We have demonstrated that miR-200c nanoparticles are an effective radiosensitizer in gastric cancer cells and induce little radiosensitization in normal cells, which suggests that they are as a promising candidate for further preclinical and clinical evaluation.Keywords: radiosensitizer, miR-200c, gelatinase-stimuli nanoparticles, cancer stem cell-like properties, gastric cancer

We investigate the extended Heisenberg model on the Kagome lattice by using Gutzwiller projected fermionic states and the variational Monte Carlo technique. In particular, when both second- and third-neighbor super-exchanges are considered, we find that a gapped spin liquid described by non-trivial magnetic fluxes and long-range chiral-chiral correlations is energetically favored compared to the gapless U(1) Dirac state. Furthermore, the topological Chern number, obtained by integrating the Berry curvature, and the degeneracy of the ground state, by constructing linearly independent states, lead us to identify this flux state as the chiral spin liquid with $C=1/2$ fractionalized Chern number., 9 pages, 7 figures

By using the variational Monte Carlo technique, we study the spin-$1/2$ XXZ antiferromagnetic model (with easy-plane anisotropy) on the kagome lattice. A class of Gutzwiller projected fermionic states with a spin Jastrow factor is considered to describe either spin liquids (with $U(1)$ or $Z_2$ symmetry) or magnetically ordered phases (with ${\bf q}=(0,0)$ or ${\bf q}=(4\pi/3,0)$). We find that the magnetic states are not stable in the thermodynamic limit. Moreover, there is no energy gain to break the gauge symmetry from $U(1)$ to $Z_2$ within the spin-liquid states, as previously found in the Heisenberg model. The best variational wave function is therefore the $U(1)$ Dirac state, supplemented by the spin Jastrow factor. Furthermore, a vanishing $S=2$ spin gap is obtained at the variational level, in the whole regime from the $XY$ to the Heisenberg model., Comment: 7 pages, 7 figures