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1初级保健中原发性醛固酮增多症的患病率和临床表现显示文摘原发性醛固酮增多症(primaryaldosteronism,PA)是一种异质性疾病,以高血压和相对自主于肾素血管紧张素系统产生过量醛固酮为特征。与心血管病风险相似的原发性高血压患者相比,PA患者发生心脑血管并发症的风险以及代谢综合征患病率增加,提示正确诊断PA的重要性。Monticone S Burrello J Tizzani D Bertello C Viola A Buffolo F Gabetti L Mengozzi G Williams TA Rabbia F Veglio F Mulatero P 练桂丽 叶鹏 2017中华高血压杂志2017,25,5:58
2最新AD研究用诊断标准:IWG-2标准显示文摘在过去的8年中,国际工作组织(IWG)和美国国立老化研究院-阿尔茨海默协会(NIA-AA)建立了阿尔茨海默病(AD)诊断标准,它能更好地定义AD的临床表型,整合了生物标记物于诊断流程中,并覆盖了疾病的全程。本意见书充分地权衡了IWG标准的优缺点,建议改进诊断框架。依据这些改进,AD的诊断变得简单,只要有恰当的AD临床表型(典型或不典型)和与AD的病理相一致的病理生理学生物标志物出现。我们认为疾病的下游的定位性生物标志,如容积性磁共振成像(MRI)和氟脱氧葡萄糖-正电子发射型计算机断层成像(FDG-PET)等,适合更好地测量和监测疾病过程。本文还详述了非典型性AD、混合性AD和AD临床前期的特异诊断标准。陈刚 曹雯炜 俞羚 糜建华 Dubois B Feldman HH Jacova C Hampel H Molinuevo JL Blennow K DeK osky ST Gauthier S Selkoe D Bateman R Cappa S Crutch S Engelborghs S Frisoni GB Fox NC Galasko D Habert MO Jicha GA Nordberg A Pasquier F Rabinovici G Robert P Rowe C Salloway S Sarazin M Epelbaum S de Souza LC Vellas B Visser PJ Schneider L Stern Y Scheltens P Cummings JL 2014神经病学与神经康复学杂志2014,11,3:31
3尿钠排泄、血压、心血管病与死亡率的关系:社区前瞻性流行病学队列研究显示文摘WHO建议人群钠摄人<2 g/d作为预防心血管病的措施之一,但这一目标在任何国家都没有实现。该建议主要基于短期血压试验的个体水平数据,没有来自随机试验或观察性研究的关于低钠摄入与降低心血管事件的数据。前瞻性城市农村流行病学研究目前正在21个国家进行。该文对其中18个国家的数据进行分析,其中包含了临床结果数据。Mente A O'Donnell M Rangarajan S McQueen M Dagenais G Wielgosz A Lear S Ah STL Wei L Diaz R Avezum A Lopez-Jaramillo P Lanas F Mony P Szuba A Iqbal R Yusuf R Mohammadifard N Khatib R Yusoff K Ismail N Gulec S Rosengren A Yusufali A Kruger L Tsolekile LP Chifamba J Dans A Alhabib KF Yeates K Teo K Yusuf S 刘莉 叶鹏 2018中华高血压杂志2018,26,12:29
4急性缺血性卒中的血管内治疗:神经介入外科学学会实践标准委员会的报告显示文摘目的总结采用血管内技术治疗急性缺血性卒中的有关证据并等级分类。方法对美国心脏协会(American Heart Association,AHA)以前发表的推荐意见进行审查并作为当前流程的基础。在此这基础上,进行系统的文献回顾以评估支持急性缺血性卒中血管内治疗的证据。根据AHA卒中委员会和牛津大学循证医学中心提出的循证医学证据分级指南进行评估。对操作安全性、技术效果以及对临床转归的影响进行特别审核。K A Blackham P M Meyers T A Abruzzo F C Alberquerque D Fiorella J Fraser D Frei C D Gandhi D V Heck J A Hirsch D P Hsu M Jayaraman S Narayanan C Prestigiacomo J L Sunshine 包元飞(译) 李永坤(译) 刘新峰(译) 2012国际脑血管病杂志2012,20,12:28
5OPTICAL PROPERTIES OF GeO_2 AND Ge NANOCRYSTALS显示文摘he co m pound m aterial of n m size particles Ge O2 Si O2 w as synthesied through hydrolysis of Si( O C2 H4) and Ge Cl4 . A heat treatm ent w as carried out for the sa m ples at 100 ~1200 ℃in air . Its optical property w as deter mined by U V Vis spectur m . We have found that theabsorption edge of spectru m shifted progressively to longer w avelengths . The quantu m size ef fect of nanocrystals appears because crystals gro w and energy of optical band gap reduces d ueto the influence of te m perature . By the analysis of X ray diffraction w e have observed theprocess in w hich the structure of particles changed fro m disorder into order .Y.H.Zhou 1) ,Y.Y.Feng 2) and H.Y.Lu 2) 1)Department of Physics Nanjing Normal University, Nanjing 210097,China 2)Physics and Ch寁O P T I C A L P R O P E R T I E S O F Ge O2 A N D Ge N A N O C R Y S T A L S Y. H. Zhou1) , Y. Y. Feng2) 1999Acta Metallurgica Sinica(English Letters)1999,12,5:22
6Non-alcoholic fatty liver disease and diabetes: From physiopathological interplay to diagnosis and treatment显示文摘Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in patients with diabetes mellitus and increasing evidence suggests that patients with type 2diabetes are at a particularly high risk for developing the progressive forms of NAFLD,non-alcoholic steatohepatitis and associated advanced liver fibrosis.Moreover,diabetes is an independent risk factor for NAFLD progression,and for hepatocellular carcinoma development and liver-related mortality in prospective studies.Notwithstanding,patients with NAFLD have an elevated prevalence of prediabetes.Recent studies have shown that NAFLD presence predicts the development of type2 diabetes.Diabetes and NAFLD have mutual pathogenetic mechanisms and it is possible that genetic and environmental factors interact with metabolic derangements to accelerate NAFLD progression in diabetic patients.The diagnosis of the more advanced stages of NAFLD in diabetic patients shares the same challenges as in non-diabetic patients and it includes imaging and serological methods,although histopathological evaluation is still considered the gold standard diagnostic method.An effective established treatment is not yet available for patients with steatohepatitis and fibrosis and randomized clinical trials including only diabetic patients are lacking.We sought to outline the published data including epidemiology,pathogenesis,diagnosis and treatment of NAFLD in diabetic patients,in order to better understand the interplay between these two prevalent diseases and identify the gaps that still need to be fulfilled in the management of NAFLD in patients with diabetes mellitus.Nathalie C Leite Cristiane A Villela-Nogueira Claudia R L Cardoso Gil F Salles 2014World Journal of Gastroenterology2014,20,26:21
7下肢浅静脉治疗术后的加压疗法:美国静脉论坛血管、外科学会、美国静脉学会、血管医学学会和国际静脉联盟的临床实践指南显示文摘一、指南的由来下肢浅静脉治疗术后应用压力治疗的方式是几代血管外科医师多年临床经验积累所得,现主要应用于大隐静脉剥脱术、下肢静脉点状剥脱术及静脉硬化治疗等。目前单就静脉硬化治疗而言,术后压力治疗的推荐也是基于相关文献及实验验证[1],但对于其他术式,尤其是对于大隐静脉的热消融术,目前还没有形成规范统一的建议,这也使得当前的压力治疗具有很大的临床差异性。Lurie F Lal BK Antignani PL Blebea J Bush R Caprini J Davies A Forrestal M Jacobowitz G Kalodiki E Killewich L Lohr J Ma H Mosti G Partsch H Rooke T Wakefield T 李丹(译) 陈程浩(译) 牛传强(译) 张靖(译) 黄建忠(译) 2020中华介入放射学电子杂志2020,8,4:16
8Chronic constipation in hemiplegic patients显示文摘AIM: To assess the prevalence of bowel dysfunction in hemiplegic patients, and its relationship with the site of neurological lesion, physical immobilization and pharmacotherapy. METHODS: Ninety consecutive hemiplegic patients and 81 consecutive orthopedic patients were investigated during physical motor rehabilitation in the same period, in the same center and on the same diet. All subjects were interviewed ≥ 3 mo after injury using a questionnaire inquiring about bowel habits before injury and at the time of the interview. Patients’ mobility was evaluated by the Adapted Patient Evaluation Conference System. Drugs considered for the analysis were nitrates, angiogenic converting enzyme (ACE) inhibitors, calcium antagonists, anticoagulants, antithrombotics, antidepressants, anti-epileptics. RESULTS: Mobility scores were similar in the two groups. De novo constipation (OR = 5.36) was a frequent outcome of the neurological accident. Hemiplegics showed an increased risk of straining at stool (OR: 4.33), reduced call to evacuate (OR: 4.13), sensation of incomplete evacuation (OR: 3.69), use of laxatives (OR: 3.75). Logistic regression model showed that constipation was significantly and independently associated with hemiplegia. A positive association was found between constipation and use of nitrates and antithrombotics in both groups. Constipation was not related to the site of brain injury. CONCLUSION: Chronic constipation is a possible outcome of cerebrovascular accidents occurring in 30% of neurologically stabilized hemiplegic patients. Its onset after a cerebrovascular accident appears to be independent from the injured brain hemisphere, and unrelated to physical inactivity. Pharmacological treatment with nitrates and antithrombotics may represent an independent risk factor for developing chronic constipation.F Bracci D Badiali P Pezzotti G Scivoletto U Fuoco L Di Lucente A Petrelli E Corazziari 2007World Journal of Gastroenterology2007,13,29:15
9Radioembolization for the treatment of unresectable hepatocellular carcinoma:A clinical review显示文摘Hepatocellular carcinoma(HCC)is the sixth most common cancer in the world.The majority of patients with HCC present with unresectable disease.These patients have historically had limited treatment options secondary to HCC demonstrating chemoresistance to the currently available systemic therapies.Additionally, normal liver parenchyma has shown intolerance to tumoricidal radiation doses,limiting the use of external beam radiation.Because of these limitations,novel percutaneous liver-directed therapies have emerged. The targeted infusion of radioactive microspheres (radioembolization)represents one such therapy. Radioembolization is a minimally invasive transcatheter therapy through which radioactive microspheres are infused into the hepatic arteries that supply tumor. Once infused,these microspheres traverse the hepatic vascular plexus and selectively implant within the tumor arterioles.Embedded within the arterioles, the 90Y impregnated microspheres emit high energy and low penetrating radiation doses selectively to the tumor.Radioembolization has recently shown promise for the treatment of patients with unresectable HCC. The objective of this review article is to highlight twocurrently available radioembolic devices(90Y,188Rh)and provide the reader with a recent review of the literature.Saad M Ibrahim Robert J Lewandowski Kent T Sato Vanessa L Gates Laura Kulik Mary F Mulcahy Robert K Ryu Reed A Omary Riad Salem 2008World Journal of Gastroenterology2008,14,11:14
10Serum cytokine profile in patients with hepatitis B e antigen-negative chronic active hepatitis B and inactive hepatitis B virus carriers显示文摘An insufficient cellular immune response seems to be critical for the immunopathogenesis of chronic hepatitis B virus infection.We have previously demonstrated no differences of T-lymphocyte subsets in blood between inactive hepatitis B s antigen(HBsAg) carriers and patients with HBeAg-negative chronic active hepatitis B.This study investigated the peripheral blood cytokine profile in patients with HBeAg-negative chronic active hepatitis B infection(Group A,n = 21) and inactive HBsAg carriers(Group B,n = 13).Serum cytokines [interferon(IFN)-γ,tumor necrosis factor-α,interleukin(IL)-1b,IL-4,IL-12,IL-10,IL-2,IL-5,IL-8] were analyzed by using flow cytometry.Patients with chronic active disease presented with significantly decreased levels of IFN-γ and IL-10 compared to inac-tive carriers(P = 0.048 and P = 0.008,respectively).In HBeAg-negative chronic active hepatitis B patients,a significant negative correlation of IFN-γ levels with serum hepatitis B viral load was noted(P = 0.021).In conclusion,patients with HBeAg-negative chronic active hepatitis B and HBsAg inactive carriers display a different cytokine profile.Decreased Th1 response observed in patients with chronic active hepatitis B could be implicated in the persistence of virus replication and ongoing progression of liver disease.Dimitra Dimitropoulou Marina Karakantza Georgios L Theodorou Lydia Leonidou Stelios F Assimakopoulos Athanasia Mouzaki Charalambos A Gogos 2013World Journal of Gastrointestinal Pathophysiology2013,4,1:13
11Liver expression of steroid hormones and Apolipoprotein D receptors in hepatocellular carcinoma显示文摘AIM: To evaluate the tissular expression of Androgen (A), Estrogen (E) and Progesterone (Pg) receptors, and Apolipoprotein D (ApoD), in liver tumors from resected hepatocellular carcinoma (HCC) cases in order to assess their possible relationship to prognosis. METHODS: We performed an immunohistochemical study using tissue microarrays (containing more than 260 cancer specimens, from 31 HCC patients and controls) to determine the presence of specif ic antibodies against AR, ER, PgR and ApoD, correlating their findings with several clinico-pathological and biological variables. The staining results were categorized using a semi-quantitive score based on their intensity, and the percentage of immunostained cells was measured. RESULTS: A total of 21 liver tumors (67.7%) were positive for AR; 16 (51.6%) for ER; 26 (83.9%) for PgR and 12 (38.7%) stained for ApoD. We have found a wide variability in the immunostaining score values for each protein, with a median (range) of 11.5 (11.5-229.5) for AR; 11.1 (8.5-65) for ER; 14.2 (4-61) for PgR; and 37.7 (13.8-81.1) for ApoD. A history of heavy ethanol consumption, correlated positively with AR and PgR and negatively with ER status. HCV chronic infection also correlated positively with AR and PgR status. However, the presence of ApoD immunostaining did not correlate with any of these variables. Tumors with a positive immuno-staining for PgR showed a better prognosis. CONCLUSION: Our results indicate a moderate clinical value of the steroid receptor status in HCC, emphasizing the need to perform further studies in order to evaluate the possible role of new hormonal-based therapies.FJ Vizoso M Rodriguez A Altadill ML González-Diéguez A Linares LO González S Junquera F Fresno-Forcelledo MD Corte L Rodrigo 2007World Journal of Gastroenterology2007,13,23:11
12Contribution of galectin-1, a glycan-binding protein, to gastrointestinal tumor progression显示文摘Gastrointestinal cancer is a group of tumors that affect multiple sites of the digestive system, including the stomach, liver, colon and pancreas. These cancers are very aggressive and rapidly metastasize, thus identifying effective targets is crucial for treatment. Galectin-1(Gal-1) belongs to a family of glycan-binding proteins, or lectins, with the ability to cross-link specific glycoconjugates. A variety of biological activities have been attributed to Gal-1 at different steps of tumor progression. Herein, we summarize the current literature regarding the roles of Gal-1 in gastrointestinal malignancies. Accumulating evidence shows that Gal-1 is drastically up-regulated in human gastric cancer, hepatocellular carcinoma, colorectal cancer and pancreatic ductal adenocarcinoma tissues, both in tumor epithelial and tumor-associated stromal cells. Moreover, Gal-1 makes a crucial contribution to the pathogenesis of gastrointestinal malignancies, favoring tumor development, aggressiveness, metastasis, immunosuppression and angiogenesis. We also highlight that alterations in Gal-1-specific glycoepitopes may be relevant for gastrointestinal cancer progression. Despite the findings obtained so far, further functional studies are still required. Elucidating the precise molecular mechanisms modulated by Gal-1 underlying gastrointestinal tumor progression, might lead to the development of novel Gal-1-based diagnostic methods and/or therapies.maría l bacigalupo pablo carabias maría f troncoso 2017World Journal of Gastroenterology2017,23,29:11
13Effect of human skin-derived stem cells on vessel architecture, tumor growth, and tumor invasion in brain tumor animal models显示文摘Pisati F Belicchi M Acerbi F Marchesi C Giussani C Gavina M Javerzat S Hagedorn M Carrabba G Lucini V Gaini SM Bresolin N Bello L Bikfalvi A Torrente Y 2007中国神经肿瘤杂志2007,5,2:10
14酒精摄入、心脏生物标志物和心房颤动风险与不良结局显示文摘酒精摄入和新发心房颤动相关性证据不一,尤其是在低剂量下。该研究评估欧洲队列在整个饮酒范围内酒精摄入、生物标志物和新发心房颤动的关系。方法和结果:在一个以社区为基础的汇集队列中,研究者随访107845人,以评估酒精摄入(酒精种类和饮酒方式)与新发心房颤动的关系。研究者收集经典心血管病危险因素和新发心力衰竭的信息,并检测生物标记物氨基末端脑钠肽前体和高敏肌钙蛋白I。陈嘉睿(译) 练桂丽((审校) Csengeri D Sprünker NA Di Castelnuovo A Niiranen T Vishram-Nielsen JK Costanzo S S derberg S Jensen SM Vartiainen E Donati MB Magnussen C Camen S Gianfagna F L chen ML Kee F Kontto J Mathiesen EB Koenig W Stefan B de Gaetano G J rgensen T Kuulasmaa K Zeller T Salomaa V Iacoviello L Schnabel RB 2021中华高血压杂志2021,29,2:9
15Dietary and metabolomic determinants of relapse in ulcerative colitis patients: A pilot prospective cohort study显示文摘AIM To identify demographic, clinical, metabolomic, and lifestyle related predictors of relapse in adult ulcerative colitis(UC) patients.METHODS In this prospective pilot study, UC patients in clinical remission were recruited and followed-up at 12 mo to assess a clinical relapse, or not. At baseline information on demographic and clinical parameters was collected. Serum and urine samples were collected for analysis of metabolomic assays using a combined direct infusion/liquid chromatography tandem mass spectrometry and nuclear magnetic resolution spectroscopy. Stool samples were also collected to measure fecal calprotectin(FCP). Dietary assessment was performed using a validated self-administered food frequency questionnaire. RESULTS Twenty patients were included(mean age: 42.7 ± 14.8 years, females: 55%). Seven patients(35%) experienced a clinical relapse during the follow-up period. While 6 patients(66.7%) with normal body weight developed a clinical relapse, 1 UC patient(9.1%) who was overweight/obese relapsed during the follow-up(P = 0.02). At baseline, poultry intake was significantly higher in patients who were still in remission during follow-up(0.9 oz vs 0.2 oz, P = 0.002). Five patients(71.4%) with FCP > 150 μg/g and 2 patients(15.4%) with normal FCP(≤ 150 μg/g) at baseline relapsed during the follow-up(P = 0.02). Interestingly, baseline urinary and serum metabolomic profiling of UC patients with or without clinical relapse within 12 mo showed a significant difference. The most important metabolites that were responsible for this discrimination were trans-aconitate, cystine and acetamide in urine, and 3-hydroxybutyrate, acetoacetate and acetone in serum. CONCLUSION A combination of baseline dietary intake, fecal calprotectin, and metabolomic factors are associated with risk of UC clinical relapse within 12 mo.Ammar Hassanzadeh Keshtel iFloris F van den Brand Karen L Madsen Rupasri Mandal Rosica ValchevaKaren I Kroeker Beomsoo Han Rhonda C Bell Janis Cole Thomas Hoevers David S Wishart Richard N Fedorak Levinus A Dieleman 2017World Journal of Gastroenterology2017,23,21:9
16Oligodendroglioma: CD44 as a possible prognostic opportunity显示文摘CD44, in its standard form as well in its isoforms, is a cell surface adhesion glycoprotein which occurs in a widevariety of non-neoplastic and neoplastic ceils. CD44 has been considered to be implicated in tumoral growth andin metastatic potential. We studied the immunohistochemical expression of CD44 standard in 30 oligodendrogliomas(19 primary lesions and 11 recurrences) in order to verify its possible prognostic role. Twelve primary oligoden-Buccoliero AM Caldarella A Arganini L Mennonna P Ammanati F Taddei A Taddei GL 2003中国神经肿瘤杂志2003,1,3:8
17Ultrafine Grained HSLA Steels for Cold Forming显示文摘The industrial level production of ultrafine grained(or ultrafine ferrite)ferrous alloys was investigated through three examples of steels that complied with the EN 10149-2 Euronorm and were produced by advanced controlled hot rolling techniques.The steel samples were tension tested and chemically analyzed,and the microstructure was evaluated through quantitative metallographic techniques to determine parameters such as yield stress,amount of microalloying elements,strain hardening coefficient,grain size,and grain size distribution.These steels were microalloyed with Ti,Nb,and Mn with ASTM grain sizes of approximately 13-15.The careful control of chemical composition and deformation during production,giving a specific attention to the deformation sequences,austenite non-recrystallization temperatures and allotropic transformations during cooling,are indispensable to obtain steels with an adequate strain hardening coefficient that allows cold working operations such as bending,stretching or drawing.R González J O García M A Barbés M J Quintana L F Verdeja J I Verdeja 2010Journal of Iron and Steel Research(International)2010,17,10:7
18Concordance of non-invasive mechanical and serum tests for liver fibrosis evaluation in chronic hepatitis C显示文摘AIM To determine the sensitivity and specificity of liver stiffness measurement(LSM) and serum markers(SM) for liver fibrosis evaluation in chronic hepatitis C.METHODS Between 2012 and 2014,81 consecutive hepatitis C virus(HCV) patients had METAVIR score from liver biopsy compared with concurrent results from LSM [transient elastography(TE) [FibroS can~/ARFI technology(Virtual Touch~)] and SM [FIB-4/aspartate aminotransferase-toplatelet ratio index(APRI)].The diagnostic performance of these tests was assessed using receiver operating characteristic curves.The optimal cut-off levels of each test were chosen to define fibrosis stages F ≥ 2,F ≥ 3 and F = 4.The Kappa index set the concordance analysis.RESULTS Fifty point six percent were female and the median age was 51 years(30-78).Fifty-six patients(70%) weretreatment-na?ve.The optimal cut-off values for predicting F ≥ 2 stage fibrosis assessed by TE were 6.6 kP a,for acoustic radiation force impulse(ARFI) 1.22 m/s,for APRI 0.75 and for FIB-4 1.47.For F ≥ 3 TE was 8.9 kP a,ARFI was 1.48 m/s,APRI was 0.75,and FIB-4 was 2.For F = 4,TE was 12.2 kP a,ARFI was 1.77 m/s,APRI was 1.46,and FIB-4 was 3.91.The APRI could not distinguish between F2 and F3,P = 0.92.The negative predictive value for F = 4 for TE and ARFI was 100%.Kappa index values for F ≥ 3 METAVIR score for TE,ARFI and FIB-4 were 0.687,0.606 and 0.654,respectively.This demonstrates strong concordance between all three screening methods,and moderate to strong concordance between them and APRI(Kappa index = 0.507).CONCLUSION Given the costs and accessibility of LSM methods,and the similarity with the outcomes of SM,we suggest that FIB-4 as well as TE and ARFI may be useful indicators of the degree of liver fibrosis.This is of particular importance to developing countries.Denise C Paranaguá-Vezozzo Adriana Andrade Daniel F C Mazo Vinicius Nunes Ana L Guedes Taisa G Ragazzo Renata Moutinho Lucas S Nacif Suzane K Ono Venancio A F Alves Flair J Carrilho 2017World Journal of Hepatology2017,9,8:7
19纤维蛋白相关性EBV阳性大B细胞淋巴瘤:一种不同于慢性炎症相关性弥漫大B细胞淋巴瘤而特征明显的惰性肿瘤显示文摘目前,罕见部位局限性纤维蛋白相关性EB病毒(EBV)阳性大B细胞增生淋巴瘤已有报道。本组12例患者中位年龄55.5岁,男女比为3:1。12例纤维蛋白相关性EBV阳性大B细胞增生淋巴瘤中,镜下见淋巴瘤为偶发,包含3例心房黏液瘤,3例血管内移植物相关性血栓,2例慢性血肿和4例假性囊肿。病变均为非生发中心B细胞来源,Boyer D F McKelvie P A de Leval L 解建军 张仁亚 2017临床与实验病理学杂志2017,33,7:7
20健康领域的文化能力显示文摘1背景 尽管人类对其他社会的兴趣纵贯历史的各个阶段,但是检验不同文化概念对人类健康实践的影响从20世纪才开始,当时是伴随着长期的人类学田野调查产生的,这些田野调查揭露了不同文化之间相关卫生实践的多样性、复杂性和连续性。Napier A D Ancarno C Butler B Calabrese j Chater A Chatterjee H Guesnet F Home R Jacyna S Jadhav S Macdonald A Neuendorf U Parkhurst A Reynolds R Scambler G Shamdasani S Smith S Z Stougaard-Nielsen J Thomson L Tyler N Volkmann A M Walker T Watson J Williams AC Willott C Wilson J Woolf K 2016中国卫生政策研究2016,9,2:5
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