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1Alteration of the esophageal microbiota in Barrett's esophagus and esophageal adenocarcinoma显示文摘The incidence of esophageal adenocarcinoma(EAC) has increased in recent decades, and its 5-year survival rate is less than 20%. As a well-established precursor, patients with Barrett's esophagus(BE) have a persistent risk of progression to EAC. Many researchers have already identified some factors that may contribute to the development of BE and EAC, and the identified risks include gastroesophageal reflux(GER), male sex, older age, central obesity,tobacco smoking, Helicobacter pylori(H. pylori) eradication, and the administration of proton pump inhibitors(PPIs) and antibiotics. The human gut harbors trillions of microorganisms, the majority of which are bacteria. These microorganisms benefit the human host in many ways, such as helping in digestion, assisting in the synthesis of certain vitamins, promoting the development of the gastrointestinal immune system, regulating metabolism and preventing invasion by specific pathogens. In contrast, microbial dysbiosis may play important roles in various diseases, such as inflammation and cancers. The composition of the microbiota located in the normal esophagus is relatively conserved without distinct microbial preferences in the upper, middle and lower esophagus. Six major phyla constitute the esophageal microbiota, including Firmicutes,Bacteroides, Actinobacteria, Proteobacteria, Fusobacteria and TM7, similar to the oral microbiota. Streptococcus dominates the esophageal microbiota. However, the microbiota varies in different esophageal diseases compared to that in the healthy esophagus. The type Ⅰ microbiota, which is primarily composed of gram-positive bacteria, is closely associated with the normal esophagus, while type Ⅱ microbiota has enriched gram-negative bacteria and is mainly associated with the abnormal esophagus. These increased gram-negative anaerobes/microaerophiles include Veillonella, Prevotella, Haemophilus, Neisseria, Granulicatella and Fusobacterium, many of which are associated with BE. The microbial diversity in the esophagus is decreased in EAC patients, and Lactobacillus fermentum is enriched compared to that in controls and BE patients. Furthermore, the microbiota may be associated with BE and EAC by interacting with their risk factors, including central obesity, GER, H. pylori, administration of PPIs and antibiotics. Therefore, a large gap in research must be bridged to elucidate the associations among these factors. Some studies have already proposed several potential mechanisms by which the microbiota participates in human carcinogenesis by complicated interactions with the human host immune system and signaling pathways. The activation of the LPS-TLR4-NF-κB pathway may contribute to inflammation and malignant transformation. This exciting field of gastrointestinal microbiota allows us to unravel the mystery of carcinogenesis from another perspective. Further studies are needed to explore whether the microbiota changes before or after disease onset, to improve our understanding of the pathogenesis, and to find novel targets for prevention, diagnosis and therapy, which could offer more cost-effective and relatively safe choices.Jing Lv Lei Guo Ji-Jun Liu He-Ping Zhao Jun Zhang Ji-Han Wang 2019World Journal of Gastroenterology2019,25,18:27
2Manganese is critical for antitumor immune responses via cGAS-STING and improves the efficacy of clinical immunotherapy显示文摘CD8^+T cell-mediated cancer clearance is often suppressed by the interaction between inhibitory molecules like PD-1 and PD-L1,an interaction acts like brakes to prevent T cell overreaction under normal conditions but is exploited by tumor cells to escape the immune surveillance.Immune checkpoint inhibitors have revolutionized cancer therapeutics by removing such brakes.Unfortunately,only a minority of cancer patients respond to immunotherapies presumably due to inadequate immunity.Antitumor immunity depends on the activation of the cGAS-STING pathway,as STING-deficient mice fail to stimulate tumor-infiltrating dendritic cells(DCs)to activate CD8^+T cells.STING agonists also enhance natural killer(NK)cells to mediate the clearance of CD8^+T cell-resistant tumors.Therefore STING agonists have been intensively sought after.We previously discovered that manganese(Mn)is indispensable for the host defense against cytosolic dsDNA by activating cGAS-STING.Here we report that Mn is also essential in innate immune sensing of tumors and enhances adaptive immune responses against tumors.Mn-insufficient mice had significantly enhanced tumor growth and metastasis,with greatly reduced tumor-infiltrating CD8^+T cells.Mechanically,Mn^2+promoted DC and macrophage maturation and tumor-specific antigen presentation,augmented CD8^+T cell differentiation,activation and NK cell activation,and increased memory CD8^+T cells.Combining Mn^2+with immune checkpoint inhibition synergistically boosted antitumor efficacies and reduced the anti-PD-1 antibody dosage required in mice.Importantly,a completed phase 1 clinical trial with the combined regimen of Mn^2+and anti-PD-1 antibody showed promising efficacy,exhibiting type I IFN induction,manageable safety and revived responses to immunotherapy in most patients with advanced metastatic solid tumors.We propose that this combination strategy warrants further clinical translation.Mengze Lv Meixia Chen Rui Zhang Wen Zhang Chenguang Wang Yan Zhang Xiaoming Wei Yukun Guan Jiejie Liu Kaichao Feng Miao Jing Xurui Wang Yun-Cai Liu Qian Mei Weidong Han Zhengfan Jiang 2020Cell Research2020,30,11:27
3Nonalcoholic fatty liver disease and microvascular complications in type 2 diabetes显示文摘AIM:To evaluate the correlation between nonalcoholic fatty liver disease(NAFLD) and microvascular complications in type 2 diabetes mellitus(T2DM).METHODS:Data were obtained from 1217 inpatients with T2DM(757 females,460 males;aged 63.39 ± 12.28 years).NAFLD was diagnosed by hepatic ultrasonography.Diabetic nephropathy(DN),diabetic peripheral neuropathy(DPN),and diabetic retinopathy(DR) were diagnosed according to their respective criteria.The prevalence of NAFLD and the independent correlations of clinical characteristics with NAFLD were determined by cross-tabulation and logistic regression,respectively.RESULTS:Approximately 61% of inpatients with T2DM in Qingdao,China had NAFLD,which decreased significantly with increase in age and prolonged course of diabetes.The prevalence of NAFLD in patients presenting with DN,DPN and DR was 49.4%,57.2% and 54.9%,respectively.These rates were significantly lower than those of patients without DN,DPN and DR(65.9%,65.6% and 66.1%,respectively,P < 0.05).Participants with NAFLD had greater body weight,waist circumference(WC),body mass index(BMI),fasting blood glucose(FBG),hemoglobin A1c,alanine aminotransferase,aspartate aminotransferase,γ-glutamyltransferase,blood pressure,as well as triglyceride(TG) levels and lower high-density lipoprotein(HDL) concentration than those without NAFLD(P < 0.05).NAFLD was positively correlated with BMI,WC,TG,FBG,diastolic blood pressure,and systolic blood pressure but negatively correlated with the duration of diabetes,DR,DPN,DN,and HDL.CONCLUSION:Despite the benign nature of NAFLD,efforts should be directed toward early diagnosis,intensive blood glucose and blood pressure control,and effective dyslipidemia correction.Wen-Shan Lv Rui-Xia Sun Yan-Yan Gao Jun-Ping Wen Rong-Fang Pan Li Li Jing Wang Yu-Xin Xian Cai-Xia Cao Ming Zheng 2013World Journal of Gastroenterology2013,19,20:26
4Age-related rhesus macaque models of COVID-19显示文摘Background:Since December 2019,an outbreak of the Corona Virus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)in Wuhan,China,has become a public health emergency of international concern.The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.Methods:Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2,and then analyzed by clinical signs,viral replication,chest X-ray,histopathological changes and immune response.Results:Viral replication of nasopharyngeal swabs,anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge.Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema,notably,old monkeys exhibited diffuse severe interstitial pneumonia.Viral antigens were detected mainly in alveolar epithelial cells and macrophages.Conclusion:SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys.Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.Pin Yu Feifei Qi Yanfeng Xu Fengdi Li Peipei Liu Jiayi Liu Linlin Bao Wei Deng Hong Gao Zhiguang Xiang Chong Xiao Qi Lv Shuran Gong Jiangning Liu Zhiqi Song Yajin Qu Jing Xue Qiang Wei Mingya Liu Guanpeng Wang Shunyi Wang Haisheng Yu Xing Liu Baoying Huang Wenling Wang Li Zhao Huijuan Wang Fei Ye Weimin Zhou Wei Zhen Jun Han Guizhen Wu Qi Jin Jianwei Wang Wenjie Tan Chuan Qin 2020Animal Models and Experimental Medicine2020,3,1:22
5Gegen Qinlian decoction enhances immunity and protects intestinal barrier function in colorectal cancer patients via gut microbiota显示文摘BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD)-1 inhibitors to treat microsatellite stable(MSS)tumor-bearing mice.However,the effect of GQD on patients with colorectal cancer(CRC)is not clear.AIM To determine the therapeutic mechanism of GQD in improving immune function,reducing inflammation and protecting intestinal barrier function.METHODS Seventy patients with CRC were included in this study:37 in the control group and 33 in the treatment group.The proportions of CD4+T,CD8+T,natural killer(NK),NKT and T regulatory cells were measured by flow cytometry.Levels of the cytokines tumor necrosis factor(TNF)-α,interferon(IFN)-γ,interleukin(IL)-2,IL-6,IL-10 and serotonin(5-hydroxytryptamine;5-HT)in serum were assessed by enzyme-linked immunosorbent assay(ELISA).The expression of zonula occludens(ZO)-1,occludin,nuclear factor(NF)-κB and TNF-αin tumor and normal tissues was measured by immunohistochemistry.The composition of gut microbiota from patients in the treatment group was assessed using 16S rDNA analysis.RESULTS There were no adverse events in the treatment group.The proportion of CD4+T cells and NKT cells in the post-treatment group was significantly higher than that in the pre-treatment and control groups(P<0.05).The level of TNF-αin the posttreatment group was significantly lower than that in the pre-treatment and control groups(P<0.05).The concentration of 5-HT in the post-treatment group was significantly lower than that in the pre-treatment group(P<0.05).The expression of ZO-1 and occludin in tumor tissues in the treatment group was significantly higher than that in the control group(P<0.05).The expression of ZO-1 in normal tissues of the treatment group was significantly higher than that in the control group(P=0.010).Compared with the control group,expression of NF-κB and TNF-αin tumor tissues of the treatment group was significantly decreased(P<0.05).Compared with the pre-treatment group,GQD decreased the relative abundance of Megamonas and Veillonella.In addition,GQD increased the relative abundance of Bacteroides,Akkermansia and Prevotella.CONCLUSION GQD enhances immunity and protects intestinal barrier function in patients with CRC by regulating the composition of gut microbiota.Yang Li Zhong-Xin Li Chen-Yang Xie Jing Fan Ji Lv Xin-Jian Xu Jian Lv Wen-Tao Kuai Yi-Tao Jia 2020World Journal of Gastroenterology2020,26,48:23
6Review of the characteristics and graded utilisation of coal gasification slag显示文摘The characteristics of the energy structure of rich coal,less oil and less gas,coupling with a high external dependence on oil and natural gas and the emphasis on the efficient and clean utilisation of coal,have brought opportunities for coal chemical industry.However,with the large-scale popularisation of coal gasification technology,the production and resulting storage of coal gasification slag continue to increase,which not only result in serious environmental pollution and a waste of terrestrial resources,but also seriously affect the sustainable development of coal chemical enterprises.Hence,the treatment of coal gasification slag is extremely important.In this paper,the production,composition,morphology,particle size structure and water holding characteristics of coal gasification slag are introduced,and the methods of carbon ash separation of gasification slag,both domestically and abroad,are summarised.In addition,the paper also summarises the research progress on gasification slag in building materials,ecological restoration,residual carbon utilisation and other high-value utilisation,and ultimately puts forward the idea of the comprehensive utilisation of gasification slag.For large-scale consumption to solve the environmental problems of enterprises and achieve high-value utilisation to increase the economic benefits of enterprises,it is urgent to zealously design a reasonable and comprehensive utilisation technologies with simple operational processes,strong adaptability and economic benefits.Xiaodong Liu Zhengwei Jin Yunhuan Jing Panpan Fan Zhili Qi Weiren Bao Jiancheng Wang Xiaohui Yan Peng Lv Lianping Dong 2021Chinese Journal of Chemical Engineering2021,34,7:21
7Effects of Short-Term Forest Bathing on Human Health in a Broad-Leaved Evergreen Forest in Zhejiang Province,China显示文摘Objective To investigate the effects of short-term forest bathing on human health.Methods Twenty healthy male university students participated as subjects and were randomly divided into two groups of 10.One group was sent on a two-night trip to a broad-leaved evergreen forest,and the other was sent to a city area.Serum cytokine levels reflecting inflammatory and stress response,indicators reflecting oxidative stress,the distribution of leukocyte subsets,and plasma endothelin-1 (ET-1) concentrations were measured before and after the experiment to evaluate the positive health effects of forest environments.A profile of mood states (POMS) evaluation was used to assess changes in mood states.Results No significant differences in the baseline values of the indicators were observed between the two groups before the experiment.Subjects exposed to the forest environment showed reduced oxidative stress and pro-inflammatory level,as evidenced by decreased malondialdehyde,interleukin-6,and tumor necrosis factor α levels compared with the urban group.Serum cortisol levels were also lower than in the urban group.Notably,the concentration of plasma ET-1 was much lower in subjects exposed to the forest environment.The POMS evaluation showed that after exposure to the forest environment,subjects had lower scores in the negative subscales,and the score for vigor was increased.Conclusion Forest bathing is beneficial to human health,perhaps through preventive effects related to several pathological factors.MAO Gen Xiang LAN Xiao Guang CAO Yong Bao CHEN Zhuo Mei HE Zhi Huat LV Yuan Dong WANG Ya Zhen HU Xi Lian WANG Guo Fu YAN Jing 2012Biomedical and Environmental Sciences2012,25,3:20
8Surveillance-based evidence:elimination of schistosomiasis as a public health problem in the Peoples’Republic of China显示文摘Background:A steady progress on schistosomiasis control in the Peoples’Republic of China(P.R.China)was achieved and broadened into the twelve-year medium and long term national plan(MLNP)which marled the implementation of an integrated control strategy across all endemic areas in P.R.China in 2004.To understand the endemic trends of schistosomiasis to assess the effectiveness of an integrated strategy,we conducted an analysis of schistosomiasis surveillance data spanned from 2005 to 2015.Methods:The schistosomiasis sentinel surveillance data from sentinel sites were collected and analyzed from 2005 to 2015.In these sentinel sites,residents aged 6 years or above were screened annually by indirect hemagglutination assay(IHA),while only antibody positives were followed by stool examination either Kato-katz method(KK)and/or hatching technique(HT).Domestic animals raised in sentinel sites were examined by HT for confirming the infection of schistosomes.Snail investigation was conducted each year through systematic sampling method combined with environmental sampling method.The snails collected from field were tested by microscopic dissection method.The infection rates of schistosomes in residents,domestic animals and snails,as well as the indicators reflecting the snails’distribution were calculated and analyzed.ANOVA analysis was used to examine the changes of the number of eggs per gram feces in population and Chi-square test was used to examine any change in proportions among groups.Results:A total of 148902 residents from sentinel sites attended this study and 631676 blood samples were examined by IHA test during the 11 covered years.The annual average antibody positive rates presented a significant decrease trends,from 17.48%(95%CI:17.20–17.75%)in 2005 to 5.93%(95%CI:5.71–6.15%)(χ2=8890.47,P<0.001)in 2015.During 2005–2015,the average infection rate of schistosomes in residents declined from 2.07%(95%CI:1.96–2.17%)to 0.13%(95%CI:0.09–0.16%),accompanied by significant decrease of infection intensity in population.In 2015,the stool positives were only found in farmers,fishermen and boatmen with infection rate of 0.16%(95%CI:0.11–0.20%),0.17%(95%CI:0–0.50%)respectively.The infection rate of schistosomes in domestic animals dropped from 9.42%(538/5711,95%CI:8.66–10.18%)to 0.08%(2/2360,95%CI:0–0.20%)from 2005 to 2015.Infections were found in eight species of domestic animals at the beginning of surveillance while only two cattle were infected in 2015.Totally 98 ha of new snail habitats were found,while 94.90%(93/98)distributed in lake and marshland regions.The percentage of frames with snails decreased from 16.96%(56884/335391,95%CI:16.83–17.09%)in 2005 to 4.28%(18121/423755,95%CI:4.22–4.34%)in 2014,with a slightly increase in 2015.Meanwhile,the infection rate of schistosomes in snails was decreased from 0.26%(663/256531,95%CI:0.24–0.28%)to zero during 2005–2015.Conclusions:The infection rate of schistosomes declined significantly,providing evidence that the goal of the MLNP was achieved.Elimination of schistosomiasis as a public health problem defined as WHO was also reached in P.R.China nationwide.Surveillance-response system should be improved and strengthened to realize the final goal of schistosomiasis elimination.Jing Xu Shi-Zhu Li Li-Juan Zhang Robert Bergquist Hui Dang Qiang Wang Shan Lv Tian-Ping Wang Dan-Dan Lin Jian-Bing Liu Guang-Hui Ren Kun Yang Yang Liu Yi Dong Shi-Qing Zhang Xiao-Nong Zhou 2020Infectious Diseases of Poverty2020,9,3:20
9L-3-n-butylphthalide protects against vascular dementia via activation of the Akt kinase pathway显示文摘As a neuroprotective drug for the treatment of ischemic stroke, 3-n-butylphthalide, a celery seed extract, has been approved by the State Food and Drug Administration of China as a clinical therapeutic drug for ischemic stroke patients. L-3-n-butylphthalide possesses significant efficacy in the treatment of acute ischemic stroke. The activated Akt kinase pathway can prevent the death of nerve cells and exhibit neuroprotective effects in the brain after stroke. This study provides the hypothesis that l-3-n-butylphthalide has a certain therapeutic effect on vascular dementia, and its mechanism depends on the activation of the Akt kinase pathway. A vascular dementia mouse model was established by cerebral repetitive ischemia/reperfusion, and intragastrically administered l-3-n-butylphthalide daily for 28 consecutive days after ischemia/reperfusion, or 7 consecutive days before ischemia/reperfusion. The Morris water maze test showed significant impairment of spatial learning and memory at 4 weeks after operation, but intragastric administration of l-3-n-butylphthalide, especially pretreatment with l-3-n-butylphthalide, significantly reversed these changes. Thionine staining and western blot analylsis showed that preventive and therapeutic application of l-3-n-butylphthalide can reduce loss of pyramidal neurons in the hippocampal CA1 region and alleviate nerve damage in mice with vascular demen-tia. In addition, phosphorylated Akt expression in hippocampal tissue increased significantly after l-3-n-butylphthalide treatment. Experimental findings demonstrate that l-3-n-butylphthalide has preventive and therapeutic effects on vascular dementia, and its mechanism may be mediated by upregulation of phosphorylated Akt in the hippocampus.Yaping Huai Yanhong Dong Jing Xu Nan Meng Chunfeng Song Wenbin Li Peiyuan Lv 2013Neural Regeneration Research2013,8,19:17
10Baseline Naive CD4+ T-cell Level Predicting Immune Reconstitution in Treated HIV-infected Late Presenters显示文摘Fu-Ping Guo Yi-Jia Li Zhi-Feng Qiu Wei Lv Yang Han Jing Xie Yan-Ling Li Xiao-Jing Song Shan-Shan Du Vikram Mehraj Tai-Sheng Li Jean-Pierre Routy 2016Chinese Medical Journal2016,,22:16
11MicroRNA-15a/b are up-regulated in response to myocardial ischemia/reperfusion injury显示文摘ObjectiveSeveral 研究显示了 miR-15a, miR-15b 和 miR-16 可以是 apoptosis 的重要管理者。后来稀释 apoptosis 能保护心肌层和还原剂梗塞尺寸,现在的学习被瞄准发现是否这些 miRNAs 参予调整心肌的局部缺血灌注( I/R )在受到 I/R 的老鼠心的 injury.MethodsApoptosis 被 TUNEL 试金在 vivo 检测,当流动 cytometry 分析由 Annexin V/PI 列在后面时,在 vitro 的两倍污点被用来在受到 hypoxia/reoxygenation ( H/R )的有教养的 cardiomyocytes 检测 apoptosis 。Taqman 即时量的 PCR 被用来证实 miR-15a/15b/16 是否涉及心脏的 I/R 的规定,控制, I/R 或 H/R 的到那些的 H/R.ResultsCompared 导致了 cardiomyocytes 的 apoptosis 显著地在 vivo 两个都被增加(24.4%±9.4% 对 2.2%±1.9% , P <0.01, n = 5 ) 并且在 vitro (14.12%±0.92% 对 2.22%±0.08%) 。 miR-15a 和 miR-15b 的表达式,然而并非 miR-16 ,在鼠标 I/R 模型,和结果被增加在 H/R model.ConclusionsOur 数据是一致的显示因此, miR-15 和 miR-15b 响应心脏的 I/R 损害是起来调整的 miR-15a/b 的下面规定可以是有希望的策略减少心脏的 I/R 损害导致的心肌的 apoptosis 。Li-Feng Liu Zhuo Liang Zhen-Rong Lv Xiu-Hua Liu Jing Bai Jie Chen Chen Chen Yu Wang 2012Journal of Geriatric Cardiology2012,9,1:15
12p38 MAPK inhibition alleviates experimental acute pancreatitis in mice显示文摘BACKGROUND: The mitogen-activated protein kinases (MAPKs) signaling pathway is involved in inflammatory process. However,the mechanism is not clear. The present study was to investigate the role of p38 MAPK in acute pancreatitis in mice.METHODS: Mice were divided into 4 groups: saline control; acute pancreatitis induced with repeated injections of cerulein; control plus p38 MAPK inhibitor SB203580; and acute pancreatitis plus SB203580. The pancreatic histology, pancreatic enzymes, cytokines, myeloperoxidase activity, p38 MAPK and heat shock protein (HSP) 60 and 70 were evaluated.RESULTS: Repeated injections of cerulein resulted in acute pancreatitis in mice, accompanying with the activation of p38 MAPK and overexpression of HSP60 and HSP70 in the pancreatic tissues. Treatment with SB203580 significantly inhibited the activation of p38 MAPK, and furthermore, inhibited the expression of HSP60 and HSP70 in the pancreas, the inflammatory cytokines in the serum, and myeloperoxidase activity in the lung.CONCLUSION: The p38 MAPK signaling pathway is involved in the regulation of inflammatory response and the expression of HSP60 and HSP70 in acute pancreatitis.Ming-Hua Cao Jing Xu Hai-Dong Cai Zhong-Wei Lv Ya-Jing Feng Kun Li Chun-Qiu Chen Yong-Yu Li 2015Hepatobiliary & Pancreatic Diseases International2015,14,1:15
13Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation显示文摘用 Yamanaka 因素产生的导致的 pluripotent 茎(iPS ) 细胞在自体同源的细胞治疗为使用有大潜力。然而, genomic 畸形充分在人的 iPS 房间,和房间不是的大多数老鼠 iPS 存在 pluripotent 由 tetraploid 互补试金评估了 TCA ) ;这很可能与 DNA 损坏反应(DDR ) 被联系在 Yamanaka 因素导致的早 reprogramming 发生了。相反,原子转移忠实地装改编体的房间进胚胎的茎(ES ) 满足 TCA 的房间。我们因此假设了涉及导致卵母细胞的 reprogramming 的因素可以在 reprogramming 期间稳定体的染色体,并且改进结果的 iPS 房间的质量。测试这个假设,我们在 iPS 期间为能减少的因素屏蔽了 DDR 信号房间正式就职。我们决定了那 Zscan4,在有 Yamanaka 因素的联合,不是仅仅显著地减少了 DDR 而且显著地支持了 iPS 房间产生的效率。Zscan4 的包括稳定了 genomic DNA,导致 p53 downregulation。而且, Zscan4 也提高了象通过 telomere 感染以后的 3 天一样早变长的 telomere 基于再结合的机制。作为结果,与 Zscan4 的增加产生的 iPS 房间比古典 iPS 房间展出了更长的 telomeres。惊人地,超过 50% iPS 房间线(11/19 ) 经由这生产了 “ Zscan4 protocol”产生了由 TCA 决定了的实时熊的 all-iPS 房间老鼠,与为用古典 Yamanaka 因素生产的线的 1/12 相比。我们的调查结果提供在 reprogramming 期间维持 genomic 稳定性支持的第一示范高质量的 iPS 房间的产生。Jing Jiang Wenjian Lv Xiaoying Ye Lingbo Wang Man Zhang Hui Yang Maja Okuka Chikai Zhou Xuan Zhang Lin Liu Jinsong Li 2013Cell Research2013,23,1:14
14A novel approach of testability modeling and analysis for PHM systems based on failure evolution mechanism显示文摘Prognostics and health management (PHM) significantly improves system availability and reliability, and reduces the cost of system operations. Design for testability (DFT) developed concurrently with system design is an important way to improve PHM capability. Testability modeling and analysis are the foundation of DFT. This paper proposes a novel approach of testability modeling and analysis based on failure evolution mechanisms. At the component level, the fault progression-related information of each unit under test (UUT) in a system is obtained by means of failure modes, evolution mechanisms, effects and criticality analysis (FMEMECA), and then the failure-symptom dependency can be generated. At the system level, the dynamic attributes of UUTs are assigned by using the bond graph methodology, and then the symptom-test dependency can be obtained by means of the functional flow method. Based on the failure-symptom and symptom-test dependencies, testability analysis for PHM systems can be realized. A shunt motor is used to verify the application of the approach proposed in this paper. Experimental results show that this approach is able to be applied to testability modeling and analysis for PHM systems very well, and the analysis results can provide a guide for engineers to design for testability in order to improve PHM performance.Tan Xiaodong Qiu Jing Liu Guanjun Lv Kehong Yang Shuming Wang Chao 2013Chinese Journal of Aeronautics2013,26,3:14
15Involvement of endoplasmic reticulum stress in angiotensin Ⅱ-induced NLRP3 inflammasome activation in human renal proximal tubular cells in vitro显示文摘目的: NLRP3 inflammasome 在肾的损害起一个重要作用并且可以是在有进步的长期的肾疾病的病人的治疗的一个治疗学的目标。在我们调查了血管收缩素 II (Ang II ) 是否导致了 NLRP3 inflammasome 的这研究,激活在 vitro 在人的肾的近似管状的房间被连接到 endoplasmic 蜂窝胃应力(ERS ) 。Jing WANG Yi WEN Lin-li LV Hong LIU Ri-ning TANG Kun-ling MA Bi-cheng LIU 2015Acta Pharmacologica Sinica2015,36,7:13
16Electroacupuncture at Dazhui(GV14) and Mingmen(GV4) protects against spinal cord injury:the role of the Wnt/β-catenin signaling pathway显示文摘Electroacupuncture at Dazhui(GV14) and Mingmen(GV4) on the Governor Vessel has been shown to exhibit curative effects on spinal cord injury; however, the underlying mechanism remains poorly understood. In this study, we established rat models of spinal cord injury using a modified Allen's weight-drop method. Ninety-nine male Sprague-Dawley rats were randomly divided into three equal groups: sham(only laminectomy), SCI(induction of spinal cord injury at T10), and EA(induction of spinal cord injury at T10 and electroacupuncture intervention at GV14 and GV4 for 20 minutes once a day). Rats in the SCI and EA groups were further randomly divided into the following subgroups: 1-day(n = 11), 7-day(n = 11), and 14-day(n = 11). At 1, 7, and 14 days after electroacupuncture treatment, the Basso, Beattie and Bresnahan locomotor rating scale showed obvious improvement in rat hind limb locomotor function, hematoxylin-eosin staining showed that the histological change of injured spinal cord tissue was obviously alleviated, and immunohistochemistry and western blot analysis showed that Wnt1, Wnt3 a, β-catenin immunoreactivity and protein expression in the injured spinal cord tissue were greatly increased compared with the sham and SCI groups. These findings suggest that electroacupuncture at GV14 and GV4 upregulates Wnt1, Wnt3 a, and β-catenin expression in the Wnt/β-catenin signaling pathway, exhibiting neuroprotective effects against spinal cord injury.Xin Wang Su-hua Shi Hai-jiang Yao Quan-kai Jing Yu-ping Mo Wei Lv Liang-yu Song Xiao-chen Yuan Zhi-gang Li Li-na Qin 2016Neural Regeneration Research2016,11,12:13
17A Randomised Controlled PhaseⅡTrial of the Combination of XELOX with Thalidomide for the First-line Treatment of Metastatic Colorectal Cancer显示文摘Objective To evaluate the efficacy and safety of the combination of XELOX regimen(oxaliplatin plus capecitabine) with thalidomide for the first-line treatment of metastatic colorectal cancer(MCRC). Methods All of the 89 patients with MCRC who fulfilled eligibility criteria were randomly assigned to treatment group(n=44) and control group(n=45).The treatment group received a combination of XELOX with thalidomide and the control group received XELOX alone.Each patient received at least 2 cycles of treatment(1 cycle=21 d).The primary endpoint was progression-free survival(PFS) and the secondary endpoints were objective response rate(ORR) as well as disease control rate(DCR).Drug safety and quality of life were also assessed. Results The median PFS of the treatment and control groups were 5.6 and 5.2 months,respectively.The difference did not have a statistical significance(P=0.307).The ORRs of the two groups also had no statistical difference(34.1%vs.26.7%,P=0.446).The addition of thalidomide to XELOX significantly improved the DCR(63.6%vs.42.2%,P=0.043).Among 24 patients with hepatic metastasis in the treatment group,2 patients satisfied the surgical criteria after treatment but none of 23 patients in the control group did.Grade 3 or 4 constipation in patients treated with thalidomide was significantly increased(20.5%) vs.4.4%,P=0.022) but didn’t result in treatment interruption.The rate of lethargy was increased but the difference between the two groups had no statistical significance(13.6%vs. 4.4%,P=0.130).The quality of life had no statistical difference between the two groups. Conclusions The combination of XELOX with thalidomide for the first-line treatment of MCRC was well tolerated.Statistically significant improvement was achieved for the DCR but not for PFS.Jing Lv Ning Liu Ke-wei Liu Ai-ping Ding Hao Wang Wen-sheng Qiu 2012Clinical oncology and cancer resexreh2012,9,2:12
18Garcinol inhibits esophageal cancer metastasis by suppressing the p300 and TGF-β1 signaling pathways显示文摘Metastasis causes the main lethality in esophageal cancer patient.Garcinol,a natural compound extracted from Gambogic genera,is a histone acetyltransferase(HAT)inhibitor that has shown anticancer activities such as cell cycle arrest and apoptosis induction.In this study,we investigated the effects of garcinol on the metastasis of esophageal cancer in vitro and in vivo.We found that garcinol(5-15μM)dose-dependently inhibited the migration and invasion of human esophageal cancer cell lines KYSE150 and KYSE450 in wound healing,transwell migration,and Matrigel invasion assays.Furthermore,garcinol treatment dose-dependently decreased the protein levels of p300/CBP(transcriptional cofactors and HATs)and p-Smad2/3 expression in the nucleus,thus impeding tumor cell proliferation and metastasis.Knockdown of p300 could inhibit cell metastasis,but CBP knockdown did not affect the cell mobility.It has been reported that TGF-β1 stimulated the phosphorylation of Smad2/3,which directly interact with p300/CBP in the nucleus,and upregulating HAT activity of p300.We showed that garcinol treatment dose-dependently suppressed TGF-β1-activated Smad and non-Smad pathway,inhibiting esophageal cancer cell metastasis.In a tail vein injection pulmonary metastasis mouse model,intraperitoneal administration of garcinol(20 mg/kg)or 5-FU(20 mg/kg)significantly decreased the number of lung tumor nodules and the expression levels of Ki-67,p300,and p-Smad2/3 in lung tissues.In conclusion,our study demonstrates that garcinol inhibits esophageal cancer metastasis in vitro and in vivo,which might be related to the suppression of p300 and TGF-β1 signaling pathways,suggesting the therapeutic potential of Garcinol for metastatic tumors.Jing Wang Man Wu Dan Zheng Hong Zhang Yue Lv Li Zhang Hong-sheng Tan Hua Zhou Yuan-zhi Lao Hong-xi Xu 2020Acta Pharmacologica Sinica2020,41,1:12
19Science Letters:IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis with its expression associated with DNA hypomethylation of exon 1显示文摘Insulin-like growth factor binding-protein-7 (IGFBP7) was obtained from our previous colonic adenocarcinoma (CRC) and normal mucosa suppression subtraction hybridization (SSH) cDNA libraries. By RT-PCR and immunohistochemistry, we found that IGFBP7 was overexpressed in CRC tissue compared to normal tissue. However, our in vitro experiments performed in 10 CRC cell lines showed that IGFBP7 expressed only in SW480 and Caco2 cell lines, which implied an underlying reversible regulatory mechanism. Using methylation-specific PCR (MSP) and bisulfite sodium PCR (BSP), we found that its expression was associated with DNA hypomethylation of exon1. This was further supported by the in vitro study which showed restored IGFBP7 expression after demethylation agent 5-aza-2’-deoxycytidine treatment. Correlation analysis between IGFBP7 expression and prognosis indicated that overexpression of IGFBP7 in CRC tissue correlated with favourable survival. Investigation of the func-tional role of IGFBP7 through transfection studies showed that IGFBP7 protein could inhibit growth rate, decrease colony for-mation activity, and induce apoptosis in RKO and SW620 cells, suggesting it a potential tumor suppressor protein in colorectal carcinogenesis. In conclusion, our study clearly demonstrated that IGFBP7 plays a potential tumor suppressor role against colo-rectal carcinogenesis and its expression is associated with DNA hypomethylation of exon 1.RUAN Wen-jing LIN Jie XU En-ping XU Fang-ying MA Yu DENG Hong HUANG Qiong LV Bing-jian HU Hu CUI Jing DI Mei-juan DONG Jian-kang LAI Mao-de 2006Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)2006,7,11:11
20Isatin hybrids and their anti-tuberculosis activity显示文摘Tuberculosis(TB) is one of the most common and even fatal infectious diseases known to mankind.Millions of new cases are reported every year over the world,and one-third of the world's population is potentially infected with mycobacteria tuberculosis(MTB).Research to develop novel anti-TB drugs led to the identification of several isatin-based antimycobacterial agents,among which a number of potential candidates displayed excellent antimycobacterial activity and were found to be free of cytotoxicity.This review outlines the advances in the application of isatin hybrids as antimycobacterial agents and the critical aspects of design and structure-activity relationship of these derivatives.Zhi Xu Shu Zhang Chuan Gao Jing Fan Feng Zhao Zao-Sheng Lv Lian-Shun Feng 2017Chinese Chemical Letters2017,28,2:10
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