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| 1 | Clinical epidemiology and disease burden of nonalcoholic fatty liver disease显示文摘Nonalcoholic fatty liver disease(NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis(NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma(HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type Ⅱ diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear toexperience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis. | Brandon J Perumpail Muhammad Ali Khan Eric R Yoo George Cholankeril Donghee Kim Aijaz Ahmed | 2017 | World Journal of Gastroenterology2017，23，47： | 70 |
| 2 | 帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。 | 陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh | 2021 | 中华肿瘤防治杂志2021，28，24： | 49 |
| 3 | Portal vein thrombosis, mortality and hepatic decompensation in patients with cirrhosis: A meta-analysis显示文摘AIM: To determine the clinical impact of portal vein thrombosis in terms of both mortality and hepatic decompensations(variceal hemorrhage, ascites, portosystemic encephalopathy) in adult patients with cirrhosis.METHODS: We identified original articles reported through February 2015 in MEDLINE, Scopus, Science Citation Index, AMED, the Cochrane Library, and relevant examples available in the grey literature. Two independent reviewers screened all citations for inclusion criteria and extracted summary data. Random effects odds ratios were calculated to obtain aggregate estimates of effect size across included studies, with 95%CI.RESULTS: A total of 226 citations were identified and reviewed, and 3 studies with 2436 participants were included in the meta-analysis of summary effect. Patients with portal vein thrombosis had an increased risk of mortality(OR = 1.62, 95%CI: 1.11-2.36, P = 0.01). Portal vein thrombosis was associated with an increased risk of ascites(OR = 2.52, 95%CI: 1.63-3.89, P < 0.001). There was insufficient data available to determine the pooled effect on other markers of decompensation including gastroesophageal variceal bleeding or hepatic encephalopathy. CONCLUSION: Portal vein thrombosis appears to increase mortality and ascites, however, the relatively small number of included studies limits more generalizable conclusions. More trials with a direct comparison group are needed. | Jonathan G Stine Puja M Shah Scott L Cornella Sean R Rudnick Marwan S Ghabril George J Stukenborg Patrick G Northup | 2015 | World Journal of Hepatology2015，7，27： | 42 |
| 4 | Bone mineral density and disorders of mineral metabolism in chronic liver disease显示文摘AIM:To estimate the prevalence and identify the risk factors for metabolic bone disease in patients with cirrhosis.METHODS:The study was performed on 72 Indian patients with cirrhosis(63 male, 9 female;aged < 50 years).Etiology of cirrhosis was alcoholism(n = 37), hepatitis B(n = 25) and hepatitis C(n = 10).Twenty-three patients belonged to Child class A, while 39 were in class B and 10 in class C.Secondary causes for metabolic bone disease and osteoporosis were ruled out.Sunlight exposure, physical activity and dietary constituents were calculated.Complete metabolic profiles were derived, and bone mineral density(BMD) was measured using dual energy X ray absorptiometry.Low BMD was defined as a Z score below-2.RESULTS:Low BMD was found in 68% of patients.Lumbar spine was the most frequently and severely affected site.Risk factors for low BMD included low physical activity, decreased sunlight exposure, and low lean body mass.Calcium intake was adequate, with unfavorable calcium:protein ratio and calcium:phosphorus ratio.Vitamin D deficiency was highly prevalent(92%).There was a high incidence of hypogonadism(41%).Serum estradiol level was elevated significantly in patients with normal BMD.Insulin-like growth factor(IGF) 1 and IGF binding protein 3 levels were below the age-related normal range in both groups.IGF-1 was signiflcantly lower in patients with low BMD.Serum osteocalcin level was low(68%) and urinary deoxypyridinoline to creatinine ratio was high(79%), which demonstrated low bone formation with high resorption.CONCLUSION:Patients with cirrhosis have low BMD.Contributory factors are reduced physical activity, low lean body mass, vitamin D def iciency and hypogonadism and low IGF-1 level. | Joe George Hosahithlu K Ganesh Shrikrishna Acharya Tushar R Bandgar Vyankatesh Shivane Anjana Karvat Shobna J Bhatia Samir Shah Padmavathy S Menon Nalini Shah | 2009 | World Journal of Gastroenterology2009，15，28： | 15 |
| 5 | Acute upper gastrointestinal bleeding in octοgenarians:Clinical outcome and factors related to mortality显示文摘AIM: To evaluate the aetiology, clinical outcome and factors related to mortality of acute upper gastrointestinal bleeding (AUGIB) in octogenarians. METHODS: We reviewed the records of all patients over 65 years old who were hospitalised with AUGIB in two hospitals from January 2006 to December of 2006. Patients were divided into two groups: Group A (65-80 years old) and Group B (> 80 years old). RESULTS: Four hundred and sixteen patients over 65 years of age were hospitalized because of AUGIB. Group A included 269 patients and Group B 147 patients. Co-morbidity was more common in octogenarians (P = 0.04). The main cause of bleeding was peptic ulcer in both groups. Rebleeding and emergency surgery were uncommon in octogenarians and not different from those in younger patients. In-hospital complications were more common in octogenarians (P = 0.05) and more patients died in the group of octogenarians compared to the younger age group (P = 0.02). Inability to perform endoscopic examination (P = 0.002), presence of high risk for rebleeding stigmata (P = 0.004), urea on admission (P = 0.036), rebleeding (P = 0.004) and presenceof severe co-morbidity (P < 0.0001) were related to mortality. In multivariate analysis, only the presence of severe co-morbidity was independently related to mortality (P = 0.032). CONCLUSION: While rebleeding and emergency surgery rates are relatively low in octogenarians with AUGIB, the presence of severe co-morbidity is the main factor of adverse outcome. | George J Theocharis Vassiliki Arvaniti Stelios F Assimakopoulos Konstantinos C Thomopoulos Vassilis Xourgias Irini Mylonakou Vassiliki N Nikolopoulou | 2008 | World Journal of Gastroenterology2008，14，25： | 15 |
| 6 | miR-200 family expression is downregulated upon neoplastic progression of Barrett's esophagus显示文摘AIM: To investigate miR-200 family expression in Barrett's epithelium, gastric and duodenal epithelia, and esophageal adenocarcinoma. METHODS: Real-time reverse transcriptase-polymerase chain reaction was used to measure miR-200, ZEB1 and ZEB2 expression. Ingenuity Pathway Analysis of miR-200 targets was used to predict biological outcomes. RESULTS: Barrett's epithelium expressed lower levels of miR-141 and miR-200c than did gastric and duodenal epithelia (P < 0.001). In silico analysis indicated roles for the miR-200 family in molecular pathways that distinguish Barrett's epithelium from gastric and duodenalepithelia, and which control apoptosis and proliferation. All miR-200 members were downregulated in adenocarcinoma (P < 0.02), and miR-200c expression was also downregulated in non-invasive epithelium adjacent to adenocarcinoma (P < 0.02). The expression of all miR-200 members was lower in Barrett's epithelium derived high-grade dysplastic cell lines than in a cell line derived from benign Barrett's epithelium. We observed signif icant inverse correlations between miR-200 family expression and ZEB1 and ZEB2 expression in Barrett's epithelium and esophageal adenocarcinoma (P < 0.05). CONCLUSION: miR-200 expression might contribute to the anti-apoptotic and proliferative phenotype of Barrett's epithelium and regulate key neoplastic processes in this epithelium. | Cameron M Smith David I Watson Mary P Leong George C Mayne Michael Z Michael Bas PL Wijnhoven Damian J Hussey | 2011 | World Journal of Gastroenterology2011，17，8： | 13 |
| 7 | Severe scrub typhus infection: Clinical features, diagnostic challenges and management显示文摘Scrub typhus infection is an important cause of acute undifferentiated fever in South East Asia. The clinical picture is characterized by sudden onset fever with chills and non-specific symptoms that include headache, myalgia, sweating and vomiting. The presence of an eschar, in about half the patients with proven scrub typhus infection and usually seen in the axilla, groin or inguinal region, is characteristic of scrub typhus. Common laboratory findings are elevated liver transaminases, thrombocytopenia and leukocytosis. About a third of patients admitted to hospital with scrub typhus infection have evidence of organ dysfunction that may include respiratory failure, circulatory shock, mild renal or hepatic dysfunction, central nervous system involvement or hematological abnormalities. Since the symptoms and signs are non-specific and resemble other tropical infections like malaria, enteric fever, dengue or leptospirosis, appropriate laboratory tests are necessary to confirm diagnosis. Serological assays are the mainstay of diagnosis as they are easy to perform; the reference test is the indirect immunofluorescence assay(IFA) for the detection of Ig M antibodies. However in clinical practice, the enzyme-linked immuno-sorbent assay is done due to the ease of performing this test and a good sensitivity and sensitivity when compared with the IFA. Paired samples, obtained at least two weeks apart, demonstrating a ≥ 4 fold rise in titre, is necessary for confirmation of serologic diagnosis. The mainstay of treatment is the tetracycline group of antibiotics or chloramphenicol although macrolides are used alternatively. In mild cases, recovery is complete. In severe cases with multi-organ failure, mortality may be as high as 24%. | John Victor Peter Thomas I Sudarsan John Anthony J Prakash George M Varghese | 2015 | World Journal of Critical Care Medicine2015，4，3： | 13 |
| 8 | Delayed gastric emptying following pancreaticoduodenectomy:Incidence,risk factors,and healthcare utilization显示文摘AIM To characterize incidence and risk factors for delayed gastric emptying(DGE) following pancreaticoduodenectomy and examine its implications on healthcare utilization. METHODS A prospectively-maintained database was reviewed. DGE was classified using International Study Group of Pancreatic Surgery criteria. Patients who developed DGE and those who did not were compared. RESULTS Two hundred and seventy-six patients underwent pancreaticoduodenectomy(PD)(> 80% pyloruspreserving, antecolic-reconstruction). DGE developed in 49 patients(17.8%): 5.1% grade B, 3.6% grade C. Demographic, clinical, and operative variables were similar between patients with DGE and those without. DGE patients were more likely to present multiplecomplications(32.6% vs 4.4%, ≥ 3 complications, P < 0.001), including postoperative pancreatic fistula(POPF)(42.9% vs 18.9%, P = 0.001) and intra-abdominal abscess(IAA)(16.3% vs 4.0%, P = 0.012). Patients with DGE had longer hospital stay(median, 12 d vs 7 d, P < 0.001) and were more likely to require transitional care upon discharge(24.5% vs 6.6%, P < 0.001). On multivariate analysis, predictors for DGE included POPF [OR = 3.39(1.35-8.52), P = 0.009] and IAA [OR = 1.51(1.03-2.22), P = 0.035].CONCLUSION Although DGE occurred in < 20% of patients after PD, it was associated with increased healthcare utilization. Patients with POPF and IAA were at risk for DGE. Anticipating DGE can help individualize care and allocate resources to high-risk patients. | Somala Mohammed George Van Buren II Amy Mc Elhany Eric J Silberfein William E Fisher | 2017 | World Journal of Gastrointestinal Surgery2017，9，3： | 13 |
| 9 | Single nucleotide polymorphisms of OCTN1, OCTN2, and DLG5 genes in Greek patients with Crohn's disease显示文摘AIM: To validate novel single nucleotide polymorphisms (SNPs) in Greek patients with Crohn's disease (CD).METHODS: A total of 120 patients with CD, 85 patients with UC, and 100 unrelated healthy controls were genotyped. Genotyping was performed by allele-specific PCR or by PCR-RFLP analysis.RESULTS: Our results showed that the 1672T and -207C alleles were obviously over-represented in CD patients only (P<0.01 and P<0.05, respectively) compared to the control population. The G113A polymorphism was completely absent in our studied population. The odds ratio for the carriage of the TC haplotype was 2.21 for CD patients as compared with controls. Additionally, the frequency of the TC haplotype was increased in patients with ileocolitis or colitis, and was mainly associated with the fibrostenotic phenotype of the disease. Furthermore, when the TC haplotype was compared jointly with the carriage of at least one mutation of the NOD2/CARD15 gene, there was an increased risk for CD, but not for UC, compared to controls. Regarding the location of the disease, the concomitant presence of the TC haplotype and NOD2/CARD15 mutations was mainly associated with ileocolitis or ileitis. CONCLUSION: Collectively, our results suggest that the 1672T variant of the OCTN1 gene and the -207C variant of the OCTN2 gene represent risk factors for CD in the Greek population. | Maria Gazouli Gerassimos Mantzaris Athanassios J Archimandritis George Nasioulas Nicholas P Anagnou | 2005 | World Journal of Gastroenterology2005，11，47： | 12 |
| 10 | 半边旗提取物5F对非小细胞肺癌NCI-H460细胞生长的抑制作用显示文摘目的研究半边旗提取物5F对非小细胞肺癌NCI-H460细胞生长的抑制作用。方法MTT法检测5F对NCI-H460细胞的生长抑制作用;用PI-Hoechst荧光双染法和TUNEL法检测细胞凋亡;流式细胞仪检测5F对DNA含量的影响。结果5F抑制NCI-H460细胞的生长,其效果与5F的浓度和作用时间相关,24、48、72h的IC50分别为:21.40、4.52、1.02μg/ml;荧光双染色法显示经5F作用后细胞出现变形,染色质浓缩,产生凋亡小体;细胞被阻滞在G2/M期。结论5F在体外能有效地抑制NCI-H460细胞的生长,其作用可能是通过诱导其凋亡产生的。 | 刘义 吴科锋 李立 George G CHEN Michael KY HSIN Malcolm J UNDERWOOD 梁念慈 | 2009 | 肿瘤防治研究2009，36，1： | 9 |
| 11 | Current treatment indications and strategies in chronic hepatitis B virus infection显示文摘The optimal approach to the management of several marginal cases with chronic hepatitis B virus (HBV) infection is controversial. Serum HBV DNA and ami-notransferase levels, and the degree of necroinflammation and fibrosis determine the therapeutic decisions. All patients with elevated aminotransferase (> twice the upper limit of normal) and serum HBV DNA above 20 000 IU/mL should be treated. Liver biopsy is important for therapeutic decisions in cases with mild aminotransferase elevations and serum HBV DNA below 20 000 IU/mL. Chronic HBV patients who do not receive treatment should be followed for life. There are seven agents licensed for chronic hepatitis B: standard and pegylated interferon-alpha, lamivudine, adefovir, entecavir, telbivudine and tenofovir. One-year courses with pegylated interferon-alpha induce sustained off-therapy remission in 30%-32% of patients with HBeAg-positive chronic hepatitis B and in a smaller proportion of patients with HBeAg-negative chronic hepatitis B. Oral antivirals achieve initial on-therapy responses in the majority of patients, but are intended as long-term therapies. Viral suppression has favourable effects on patients' outcome and modifies the natural course of the disease. Viral resistance, however, is the major drawback of long-term oral antiviral therapy. Lamivudine monotherapy is associated with the highest and ente-cavir monotherapy with the lowest resistance rate so far. There has been no resistance to tenofovir, but afteronly 18 mo of treatment to date. The optimal first-line anti-HBV therapy with the best long-term cost/benefit ratio remains unclear. If oral antiviral agents are used, compliance should always be ascertained and HBV DNA levels should be regularly tested. | George V Papatheodoridis Spilios Manolakopoulos Athanasios J Archimandritis | 2008 | World Journal of Gastroenterology2008，14，45： | 7 |
| 12 | Type 1 diabetes and polyglandular autoimmune syndrome: A review显示文摘Type 1 diabetes(T1D) is an autoimmune disorder caused by inflammatory destruction of the pancreatic tissue. The etiopathogenesis and characteristics of the pathologic process of pancreatic destruction are well described. In addition, the putative susceptibility genes for T1 D as a monoglandular disease and the relation to polyglandular autoimmune syndrome(PAS) have also been wellexplored. The incidence of T1 D has steadily increased in most parts of the world, especially in industrialized nations. T1 D is frequently associated with autoimmune endocrine and non-endocrine diseases and patients with T1 D are at a higher risk for developing several glandular autoimmune diseases. Familial clustering is observed, which suggests that there is a genetic predisposition. Various hypotheses pertaining to viral- and bacterialinduced pancreatic autoimmunity have been proposed, however a definitive delineation of the autoimmune pathomechanism is still lacking. In patients with PAS, pancreatic and endocrine autoantigens either colocalize on one antigen-presenting cell or are expressed on two/various target cells sharing a common amino acid, which facilitates binding to and activation of T cells. The most prevalent PAS phenotype is the adult type 3 variant or PAS type Ⅲ, which encompasses T1 D and autoimmune thyroid disease. This review discusses the findings of recent studies showing noticeable differences in the genetic background and clinical phenotype of T1 D either as an isolated autoimmune endocrinopathy or within the scope of polyglandular autoimmune syndrome. | Martin P Hansen Nina Matheis George J Kahaly | 2015 | World Journal of Diabetes2015，6，1： | 7 |
| 13 | Role of functional imaging in the development and refinement of invasive neuromodulation for psychiatric disorders显示文摘Deep brain stimulation(DBS) is emerging as a pow-erful tool for the alleviation of targeted symptoms in treatment-resistant neuropsychiatric disorders. Despite the expanding use of neuropsychiatric DBS, the mecha-nisms responsible for its effects are only starting to be elucidated. Several modalities such as quantitative elec-troencephalography as well a intraoperative recordings have been utilized to attempt to understand the under-pinnings of this new treatment modality, but functional imaging appears to offer several unique advantages. Functional imaging techniques like positron emission tomography, single photon emission computed tomog-raphy and functional magnetic resonance imaging have been used to examine the effects of focal DBS on activ-ity in a distributed neural network. These investigations are critical for advancing the field of invasive neuro-modulation in a safe and effective manner, particularly in terms of defining the neuroanatomical targets and refining the stimulation protocols. The purpose of this review is to summarize the current functional neuroim-aging findings from neuropsychiatric DBS implantation for three disorders: treatment-resistant depression, obsessive-compulsive disorder, and Tourette syndrome. All of the major targets will be discussed(Nucleus ac-cumbens, anterior limb of internal capsule, subcallosal cingulate, Subthalamic nucleus, Centromedial nucleus of the thalamus-Parafasicular complex, frontal pole, and dorsolateral prefrontal cortex). We will also address some apparent inconsistencies within this literature, and suggest potential future directions for this promis-ing area. | Nolan R Williams Joseph J Taylor Kayla Lamb Colleen A Hanlon E Baron Short Mark S George | 2014 | World Journal of Radiology2014，6，10： | 6 |
| 14 | Osteoclast activity modulates B-cell development in the bone marrow显示文摘B 房间开发开是依赖的在 B 房间先锋和骨头髓 stromal 房间之间的相互作用,而是在这的骨破折(OCL ) 的角色处理未知的遗体。B lymphocytopenia 是 osteopetrosis 的一个特征,建议由 OCL 活动的 B 淋巴细胞增殖的调整。探讨这个问题,我们首先由树枝状的房间转移在 osteopetrotic oc/oc 鼠标救了 OCL 功能,导致骨头显型和 B 房间开发的恢复。为了推进,探索在 OCL 活动和 B 淋巴细胞增殖之间的连接,我们由 zoledronic 酸(ZA ) 的注射在正常老鼠导致了 osteopetrosis,骨头再吞的一个禁止者。B 房间数字在对待 ZA 的老鼠的骨头髓明确地减少了。ZA 直接没影响 B 房间区别,增长和 apoptosis,但是由 stromal 房间在 CXCL12 和 IL-7 的表示导致减少,与减少的 osteoblastic 约会联系了。在 oc/oc 老鼠的相等的低 osteoblastic 约会证实它在造骨细胞上源于减少的 OCL 活动而非从 ZA 的直接效果。骨头微型环境的这些戏剧的改变为 B 淋巴细胞增殖是不利的,导致在他们在导致 ZA 的 osteopetrotic 模型的骨头髓壁龛外面的 B 房间祖先的保留。总的来说,我们的数据表明 OCL 由控制骨头微型环境和造骨细胞的命运在骨头髓调制 B 房间开发。他们由 OCL 活动在他们的壁龛为 B 房间的保留的规定提供新奇基础。 | Anna Mansour | 2011 | Cell Research2011，21，7： | 6 |
| 15 | It is safe to use transdermal glyceryl trinitrate to lower blood pressure in patients with acute ischaemic stroke with carotid stenosis显示文摘Background There is concern that blood pressure(BP)lowering in acute stroke may compromise cerebral perfusion and worsen outcome in the presence of carotid stenosis.We assessed the effect of glyceryl trinitrate(GTN)in patients with carotid stenosis using data from the Efficacy of Nitric Oxide in Stroke(ENOS)Trial.Methods ENOS randomised 4011 patients with acute stroke and raised systolic BP(140-220 mm Hg)to transdermal GTN or no GTN within 48 hours of onset.Those on prestroke antihypertensives were also randomised to stop or continue their medication for 7 days.The primary outcome was the modified Rankin Scale(mRS)at day 90.Ipsilateral carotid stenosis was split:<30%;30-<50%;50-<70%;≥70%.Data are ORs with 95%CIs adjusted for baseline prognostic factors.results 2023(60.5%)ischaemic stroke participants had carotid imaging.As compared with<30%,≥70%ipsilateral stenosis was associated with an unfavourable shift in mRS(worse outcome)at 90 days(OR 1.88,95%CI 1.44 to 2.44,p<0.001).Those with≥70%stenosis who received GTN versus no GTN had a favourable shift in mRS(OR 0.56,95%CI 0.34 to 0.93,p=0.024).In those with 50-<70%stenosis,continuing versus stopping prestroke antihypertensives was associated with worse disability,mood,quality of life and cognition at 90 days.Clinical outcomes did not differ across bilateral stenosis groups.Conclusions Following ischaemic stroke,severe ipsilateral carotid stenosis is associated with worse functional outcome at 90 days.GTN appears safe in ipsilateral or bilateral carotid stenosis,and might improve outcome in severe ipsilateral carotid stenosis. | Jason P Appleton Lisa J Woodhouse Andrew Belcher Daniel Bereczki Eivind Berge Valeria Caso Hui Meng Chang Hanne K Christensen Ronan Collins John Gommans Ann C Laska George Ntaios Serefnur Ozturk Gillian M Sare Szabolcs Szatmari Yongjun Wang Joanna M Wardlaw Nikola Sprigg Philip M Bath for the ENOS investigators | 2019 | Stroke & Vascular Neurology2019，4，1： | 6 |
| 16 | Palliative chemotherapy for gastroesophageal cancer in old and very old patients: A retrospective cohort study at the National Center for Tumor Diseases, Heidelberg显示文摘AIM:To investigate the outcome of palliative chemotherapy in old patients with gastroesophageal cancer at the National Center for Tumor Diseases,Heidelberg.METHODS:Using a prospectively generated database,we retrospectively analyzed 55 patients≥70years under palliative chemotherapy for advanced gastroesophageal cancer at the outpatient clinic of the National Center for Tumor Diseases Heidelberg,Germany between January 2006 and December2013.Further requirements for inclusion were(1)histologically proven diagnosis of gastroesophageal cancer;(2)advanced(metastatic or inoperable)disease;and(3)no history of radiation or radiochemotherapy.The clinical information included Eastern Cooperative Oncology Group performance status(ECOG PS),presence and site of metastases at diagnosis,date of previous surgery and perioperative chemotherapy,start and stop date of first-line treatment,toxicities and consecutive dosage reductions of first-line treatment,response to first-line therapy,date of progression,usage of second-line therapies and date and cause of death.Survival times[progression-free survival(PFS),overall survival(OS)and residual survival(RS)]were calculated.Toxicity and safety were examined.Prognostic factors including ECOG PS,age and previousperioperative treatment were analyzed.RESULTS:Median age of our cohort was 76 years.86%of patients received a combination of two cytotoxic drugs.76 percent of patients had an oxaliplatin-based first-line therapy with the oxaliplatin and 5-fluorouracil regimen being the predominantely chosen regimen(69%).Drug modifications due to toxicity were necessary in 56%of patients,and 11%of patients stopped treatment due to toxicities.Survival times of our cohort are in good accordance with the major phaseⅢtrials that included mostly younger patients:PFS and OS were 5.8 and 9.5 mo,respectively.Survival differed significantly between patient groups with low(≤1)and high(≥2)ECOG PS(12.7 mo vs 3.8 mo,P<0.001).Very old patients(≥75 years)did not show a worse outcome in terms of survival.Patients receiving secondline treatment(51%)had a significantly longer RS than patients with best supportive care(6.8 vs 1.4 mo,P=0.001).Initial ECOG PS was a strong prognostic factor for PFS,OS and RS.CONCLUSION:Old patients with non-curable gastroesophageal cancer should be offered chemotherapy,and ECOG PS is a tool for balancing benefit and harm upfront.Second-line treatment is reasonable. | Anne Katrin Berger Stefanie Zschaebitz Christine Komander Dirk Jger Georg Martin Haag | 2015 | World Journal of Gastroenterology2015，21，16： | 6 |
| 17 | Effects of glycaemic management on diabetic kidney disease显示文摘Hyperglycaemia contributes to the onset and progression of diabetic kidney disease(DKD). Observational studies have not consistently demonstrated a glucose threshold, in terms of HbA1c levels, for the onset of DKD. Tight glucose control has clearly been shown to reduce the incidence of micro-or macroalbuminuria. However, evidence is now also emerging to suggest that intensive glucose control can slow glomerular filtration rate loss and possibly progression to end stage kidney disease. Achieving tight glucose control needs to be balanced against the increasing appreciation that glucose targets for the prevention of diabetes related complications need be individualised for each patient. Recently, empagliflozin which is an oral glucose lowering agent of the sodium glucose cotransporter-2 inhibitor class has been shown to have renal protective effects. However, the magnitude of empagliflozin's reno-protective properties are over and above that expected from its glucose lowering effects and most likely largely result from mechanisms involving alterations in intra-renal haemodynamics. Liraglutide and semaglutide, both injectable glucose lowering agents which are analogues of human glucagon like peptide-1 have also been shown to reduce progression to macroalbuminuria through mechanisms that remain to be fully elucidated. Here we review the evidence from observational and interventional studies that link good glucose control with improved renal outcomes. We also briefly review the potential reno-protective effects ofnewer glucose lowering agents. | Richard J MacIsaac George Jerums Elif I Ekinci | 2017 | World Journal of Diabetes2017，8，5： | 6 |
| 18 | Acute upper gastrointestinal bleeding in patients on long-term oral anticoagulation therapy: Endoscopic findings, clinical management and outcome显示文摘AIM: Acute gastrointestinal bleeding is a severe complication in patients receiving long-term oral anticoagulant therapy.The purpose of this study was to describe the causes and clinical outcome of these patients.METHODS: From January 1999 to October 2003, 111patients with acute upper gastrointestinal bleeding (AUGIB)were hospitalized while on oral anticoagulants. The causes and clinical outcome of these patients were compared with those of 604 patients hospitalized during 2000-2001with AUGIB who were not taking warfarin.RESULTS: The most common cause of bleeding was peptic ulcer in 51 patients (45%) receiving anticoagulants compared to 359/604 (59.4%) patients not receiving warfarin (P<0.05). No identifiable source of bleeding could be found in 33 patients (29.7%) compared to 31/604(5.1%) patients not receiving anticoagulants (P= 0.0001).The majority of patients with concurrent use of non-steroidal anti-inflammatory drugs (NSATDs) (26/35, 74.3%) had a peptic ulcer as a cause of bleeding while 32/76 (40.8%)patients not taking a great dose of NSATDs had a negative upper and lower gastrointestinal endoscopy. Endoscopic hemostasis was applied and no complication was reported.Six patients (5.4%) were operated due to continuing or recurrent hemorrhage, compared to 23/604 (3.8%) patients not receiving anticoagulants. Four patients died, the overall mortality was 3.6% in patients with AUGIB due to anticoagulants, which was not different from that in patients not receiving anticoagulant therapy.CONCLUSION: Patients with AUGIB while on long-term anticoagulant therapy had a clinical outcome, which is not different from that of patients not taking anticoagulants.Early endoscopy is important for the management of these patients and endoscopic hemostasis can be safely applied. | Konstantinos C Thomopoulos Konstantinos P Mimidis George J Theocharis Anthie G Gatopoulou Georgios N Kartalis Vassiliki N Nikolopoulou | 2005 | World Journal of Gastroenterology2005，11，9： | 5 |
| 19 | Octreotide induces caspase activation and apoptosis in human hepatoma HepG2 cells显示文摘AIM: To investigate the role of octreotide on cellular proliferation and apoptosis of human hepatoma (HepG2) cells. METHODS: We studied cellular proliferation, apoptosis and the possible internal caspase-mediated apoptosis pathway involved, after treatment of HepG2 carcinoma cells with octreotide in comparison with the apoptosis caused by tumor necrosis factor-α (TNF-α). Activities of caspase-3, caspase-9, caspase-8 and caspase-2 were studied, while apoptosis was investigated through detection of DNA fragmentation and through identification of apoptotic cells with the annexin-V/propidium iodide flow cytometric method. RESULTS: After an initial increase in HepG2 cellular proliferation, a significant inhibition was observed with 10-8 mol/L octreotide, while TNF-α dose-dependently decreased proliferation. Early and late apoptosis was significantly increased with both substances. Octreotide significantly increased caspase-3, caspase-8 and caspase-2 activity. TNF-α signifi cantly increased only caspase-2. Cellular proliferation was decreased after treatment with octreotide or TNF-α alone but, in contrast to TNF-α, octreotide decreased proliferation only at concentrations of 10-8 mol/L, while lower concentrations increased proliferation. CONCLUSION: Our findings are suggestive of caspasemediated signaling pathways of octreotide antitumor activity in HepG2 cells, and indicate that measurements of serum octreotide levels may be important, at least in clinical trials, to verify optimal therapeutic drug concentrations. | Nikos J Tsagarakis Ioannis Drygiannakis Antonis G Batistakis George Kolios Elias A Kouroumalis | 2011 | World Journal of Gastroenterology2011，17，3： | 5 |
| 20 | New developments and controversies in iron metabolism and iron chelation therapy显示文摘Iron is essential for all organisms including microbial,cancer and human cells. More than a quarter of the human population is affected by abnormalities of iron metabolism, mainly from iron deficiency and iron overload. Iron also plays an important role in free radical pathology and oxidative damage which is observed in almost all major diseases, cancer and ageing. New developments include the complete treatment of iron overload and reduction of morbidity and mortality in thalassaemia using deferiprone and selected deferiprone/deferoxamine combinations and also the use of the maltol iron complex in the treatment of iron deficiency anaemia. There is also a prospect of using deferiprone as a universal antioxidant in non iron overloaded diseases such as neurodegenerative, cardiovascular, renal, infectious diseases and cancer. New regulatory molecules of iron metabolism such as endogenous and dietary chelating molecules, hepcidin, mitochondrial ferritin and their role in health and disease is under evaluation. Similarly, new mechanisms of iron deposition, removal, distribution and toxicity have been identified using new techniques such as magnetic resonance imaging increasing our understanding of iron metabolic processes and the targeted treatment of related diseases. The uniform distribution of iron in iron overload between organs and within each organ is no longer valid. Several other controversies such as the toxicity impact of non transferrin bound iron vs injected iron, the excess levels of iron in tissues causing toxicity and the role of chelation on iron absorption need further investigation. Commercial interests of pharmaceutical companies and connections to leading journals are playing a crucial role in shaping worldwide medical opinion on drug sales and use but also patients' therapeutic outcome and safety. Major controversies include the selection criteria and risk/benefit assessment in the use of deferasirox in thalassaemia and more so in idiopathic haemochromatosis, thalassaemia intermedia and ex-thalassaemia transplanted patients who are safely treated with venesection. Iron chelating drugs can override normal regulatory pathways, correct iron imbalance and minimise iron toxicity. The use of iron chelating drugs as main, alternative or adjuvant therapy is in progress in many conditions, especially those with non established or effective therapies. | Christina N Kontoghiorghe George J Kontoghiorghes | 2016 | World Journal of Methodology2016，6，1： | 5 |
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