SNP interactions of Helicobacter pylori-related host genes PGC,PTPN11, IL1B,and TLR4 in susceptibility to gastric carcinogenesis

A series of host genes that respond to Helicobacter pylori (H. pylori) infection are involved in the process of gastric carcinogenesis. This study sought to examine interactions among polymorphisms of H. pylori-related genes PGC, PTPN11, TLR4, and IL1B and assess whether their interaction effects were modified by H. pylori infection. Thirteen polymorphisms of the aforementioned genes were genotyped by the Sequenom MassARRAY platform in 714 gastric cancer patients, 907 atrophic gastritis cases and 1276 healthy control subjects. When we considered the host genetic effects alone, gene–gene interactions consistently decreased the risks of gastric cancer and/or atrophic gastritis, including three two-way interactions: PGC rs6912200-PTPN11 rs12229892, PGC rs4711690-IL1B rs1143623 and PTPN11 rs12229892-IL1B rs1143623 and a three-way interaction: PGC rs4711690-PGC rs6912200-PTPN11 rs12229892. When the effect modification of H. pylori infection was evaluated, the cumulative effects of the aforementioned three-way interaction on atrophic gastritis susceptibility switched from being beneficial to being risky by the status of H. pylori infection. These data showed that SNP interactions among H. pylori-related genes PGC, PTPN11, and IL1B, are associated with susceptibility to gastric carcinogenesis. Moreover, we provided important hints of an effect modification by H. pylori infection on the cumulative effect of PGC and PTPN11 polymorphisms. Functional experiments and further independent large-scale studies especially in other ethnic populations are still needed to confirm our results.     

激励式护理对围术期士兵病人焦虑和睡眠状态的影响

战士长期处在封闭、严肃、紧张有序的军营环境中,一旦罹患疾病,失去常态的生活秩序,进入医院这个特殊环境必然感到盲然无措,严肃的纪律要求又使他们远离亲朋好友,信息采集受到制约以及病痛的折磨等因素都会对战士伤病员身心产生强烈的负性刺激,引发焦虑、抑郁、失眠等精神症状,从而对治疗的依从性和治疗效果产生影响.适当的心理干预可增强病人信心,减轻病人紧张、焦虑的情绪[1].现对围术期战士病人进行持续激励式护理,观察其焦虑状态及睡眠状况的改变.     

MiR-634 sensitizes nasopharyngeal carcinoma cells to paclitaxel and inhibits cell growth both in vitro and in vivo

Resistance to chemotherapy is one of the key causal factors in cancer death and increasing evidence has revealed that microRNAs (miRNAs) are involved in chemoresistance in many kinds of human cancers. Paclitaxel has been used for treatment of advanced nasopharyngeal carcinoma (NPC); however, treatment failure often occurs due to development of acquired paclitaxel resistance. In this study, based on miRNA microarray screening and qRT-PCR validation, we found six differentially expressed miRNAs in our induced paclitaxel-resistant NPC CNE-1/Taxol cells. Furthermore, we clarified the role of miR-634, most significantly downregulated in the paclitaxel-resistant CNE-1/Taxol, in regulating the paclitaxel sensitivity in NPC cells. We restored miR-634 expression in the CNE-1/Taxol cells by lentivirus infection, and found restoration of miR-634 re-sensitized the CNE-1/Taxol cells to paclitaxel in vitro by MTT assay and colony formation assay. In xenograft mouse model, we found that miR-634 inhibited tumor growth and enhanced paclitaxel sensitivity. Thus, our findings provide important information for the development of targeted gene therapy for reversing paclitaxel resistance in NPC.     

Distinctive Origin and Spread Route of Pyrimethamine-Resistant Plasmodium falciparum in Southern China

Southeast Asia (the Thailand-Cambodia border) has been considered the primal epicenter for most antimalarial drug resistance; however, numerous molecular epidemiological studies have successively reported multiple independent origins of sulfadoxine-pyrimethamine (SP) resistance-associated Plasmodium falciparum dhfr (pfdhfr) and pfdhps alleles in other areas. To better understand the origin and evolutionary pathway of the SP resistance in Southeast Asia, a total of 374 P. falciparum field isolates from the Yunnan-Burma border and Hainan Island in southern China have been collected for comprehensive investigations on the mutation patterns of the pfdhfr/pfdhps genes as well as their microsatellite haplotypes. By comparative analysis of single-nucleotide polymorphism (SNP) genotyping and flanking microsatellite haplotypes, we reveal a unique origin of pyrimethamine-resistant mutations in Pfdhfr gene in Hainan Island and an oriented spread route of the pyrimethamine resistance from the Thailand-Cambodia border into the Hainan area, which reflects the geographical traits and SP administration histories in the two geographically independent areas. Moreover, genetic linkages between the high-level SP resistance-conferring pfdhfr/pfdhps alleles have been established in the isolates from the Yunnan-Burma border, raising the concern of a genetic basis in adopting combination chemotherapies against falciparum malaria.     

TCR-T细胞免疫疗法治疗肝细胞癌的研究现状及策略

肝细胞癌是原发性肝癌的主要病理类型,目前的临床治疗方法难以达到理想的效果,迫切需要探索新的、有效的治疗方法。T细胞受体基因工程改造T细胞(TCR-T)疗法因在实体瘤中的成功应用,被认为是最有前景的免疫治疗方式之一。本文主要从TCR-T治疗在肝细胞癌中的研究进展进行综述,并针对性提出一些解决策略,包括优化TCR亲和力、降低毒性反应、减少外源性和内源性TCR双链错配、改善肿瘤微环境、促进TCR-T细胞扩增。     

Catalase-Negative Staphylococcus lugdunensis Strain with a Novel Point Mutation in the Catalase Gene Isolated from a Patient with Chronic Suppurative Otitis Media

This report describes the results of the sequence analysis of a methicillin-susceptible strain of catalase-negative Staphylococcus lugdunensis. Molecular characterization of the deduced sequence revealed a novel point mutation in the catalase gene. To our knowledge, this is the first report of a catalase-negative S. lugdunensis strain, although catalase-negative isolates of Staphylococcus aureus and Staphylococcus epidermidis have been previously reported.     

Impact of Margin Status on Survival in Patients with Pancreatic Ductal Adenocarcinoma Receiving Neoadjuvant Chemotherapy

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Melatonin mediates protective effects on inflammatory response induced by interleukin‐1 beta in human mesenchymal stem cells

Joint diseases like osteoarthritis usually are accompanied with inflammatory processes, in which pro‐inflammatory cytokines mediate the generation of intracellular reactive oxygen species (ROS) and compromise survival of subchondral osteoblasts. Melatonin is capable of manipulating bone formation and osteogenic differentiation of mesenchymal stem cells (MSCs). The aim of this work was to investigate the anti‐inflammatory effect of melatonin on MSC proliferation and osteogenic differentiation in the absence or presence of interleukin‐1 beta (IL‐1β), which was used to induce inflammation. Our data showed that melatonin improved cell viability and reduced ROS generation in MSCs in a dose‐dependent manner. When exposed to 10 ng/mL IL‐1β, various concentrations of melatonin resulted in significant reduction of ROS by 34.9% averagely. Luzindole as a melatonin receptor antagonist reversed the anti‐oxidant effect of melatonin in MSCs with co‐exposure to IL‐1β. Real‐time RT‐PCR data suggested that melatonin treatment up‐regulated the expression of CuZnSOD and MnSOD, while down‐regulated the expression of Bax. To investigate the effect of melatonin on osteogenesis, MSCs were cultured in osteogenic differentiation medium supplemented with IL‐1β, melatonin, or luzindole. After exposed to IL‐1β for 21 days, 1 μm melatonin treatment significantly increased the levels of type I collagen, ALP, and osteocalcin, and 100 μm melatonin treatment yielded the highest level of osteopontin. Our study demonstrated that melatonin maintained MSC survival and promoted osteogenic differentiation in inflammatory environment induced by IL‐1β, suggesting melatonin treatment could be a promising method for bone regenerative engineering in future studies.