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| 1 | 钠-葡萄糖共转运蛋白-2抑制剂或胰高血糖素样肽-1受体激动剂治疗成人2型糖尿病:临床实践指南显示文摘临床问题对于存在不同心血管风险及肾脏结局的2型糖尿病患者,在原有生活方式干预和/或其他降糖药物的基础上加用钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂的获益及风险是什么?现行做法几十年来,2型糖尿病的治疗决策都以控制血糖为主导。SGLT-2抑制剂和GLP-1受体激动剂在传统观念中常被用于二甲双胍治疗后血糖仍控制不佳的患者。目前这一现状已经发生了改变,这得益于多项临床研究结果。研究显示SGLT-2抑制剂和GLP-1受体激动剂拥有独立于药物降糖作用之外的对于动脉粥样硬化性心血管病(CVD)和慢性肾脏病(CKD)的获益。建议本指南阐述了针对不同风险分层的成人2型糖尿病患者使用SGLT-2抑制剂或GLP-1受体激动剂的建议。•伴有3种或更少的心血管风险因素且不存在CVD或CKD:不建议启动SGLT-2抑制剂或GLP-1受体激动剂治疗。(推荐等级:弱)•伴有3种以上心血管风险因素且不存在CVD或CKD:建议启动SGLT-2抑制剂治疗,不建议启动GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD或CKD:建议启动SGLT-2抑制剂治疗和GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD和CKD:建议启动SGLT-2抑制剂治疗(推荐等级:强)和GLP-1受体激动剂治疗。(推荐等级:弱)•对于那些想要进一步降低CVD和CKD结局风险的患者:推荐优先启用SGLT-2抑制剂治疗而非GLP-1受体激动剂治疗。(推荐等级:弱)这项指南是如何制订的一个由患者、临床医生和方法学家共同组成的国际小组提出了这些推荐意见。这些推荐意见基于可信度较高的指南的标准,并使用GRADE分级方法进行评估。该小组采用了息者个体化的观点。证据一项关于获益与风险的系统综述和网络meta分析(764项随机对照研究,包括421346例参与者)发现SGLT-2抑制剂和GLP-1受体激动剂可以降低总体死亡率、心肌梗死发生率、终末期肾病或肾衰竭的发生率(中等至高等质量的证据)。在不同的亚组中这些药物对卒中、因心力衰竭所致住院和其他主要不良事件有不同的影响。药物绝对获益的程度因患者个体风险的不同有很大的差异。(例如,对于接受了超过5年药物治疗的1000例患者,在最低风险人群中死亡人数减少了5人,在最高风险人群中死亡人数减少了48人)。一项关于预后的综述确认了14种风险预测模型,其中一种(RECODe)在证据总结中报告了大部分基线风险评估数据,小组利用该模型以支持风险分层的建议。考虑到患者的价值观及个体差异,指南推荐的支撑证据包括一项对已发表论文的系统综述、一项患者焦点小组研究、一项临床问题总结,以及一项指南调查。指南解读我们依据不同的CVD和CKD风险水平,综合考虑获益、风险和其他因素的平衡,以及每一个风险组别的实际问题,来对推荐意见进行分层。本指南强烈建议CVD和CKD患者使用SGLT-2抑制剂治疗,这说明专家组认为其具有显著的获益。而对于其他成人2型糖尿病患者,推荐等级较弱,这说明专家组想要在获益、风险及治疗花费上取得一个更好的平衡。临床医生通过该指南可以使用可靠的风险计算模型,如RECODe,来明确其患者的个体心血管和肾脏疾病风险。医患交互式总结临床证据和制订决策有助于患者知晓治疗选择,包括进行共同决策。2型糖尿病人群(全球患病率不断增长1-2)正面临着不断增加的心血管疾病、肾脏病和其他并发症的风险3。数十年来,2型糖尿病的管理始终以控制血糖及糖化血红蛋白(HbA1c)为治疗目标4-5,但是,最近的高质量随机对照研究已经对这种以血糖为中心的治疗模式发起了挑战。研究结果显示,强化血糖控制未必会降低大血管不良事件,它还可能带来不利影响监管机构现在要求新型糖尿病药物必须证明其具有心血管和肾脏获益才能获得批准。对两类新药--钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂(见框图1)的临床试验结果显示,在现有治疗方案(常规治疗)之上加用这些药物,对死亡、心肌梗死、卒中、心力衰竭和肾脏的结局(如进展为终末期肾病)都有获益8-12。 | Sheyu Li Per Olav Vandvik Lyubov Lytvyn Gordon H Guyatt Suetonia C Palmer Rene Rodriguez-Gutierrez Farid Foroutan Thomas Agoritsas Reed A C Siemieniuk Michael Walsh Lawrie Frere David J Tunnicliffe Evi V Nagler Veena Manja Bjφrn Olav Asvold Vivekanand Jha Mieke Vermandere Karim Gariani Qian Zhao Yan Ren Emma Jane Cartwright Patrick Gee Alan Wickes Linda Fems Robin Wright Ling Li Qiukui Hao Reem A Mustafa 无 郭鹤鸣(译) | 2021 | 英国医学杂志中文版2021，24，9： | 7 |
| 2 | Dynamic chromatin states in human ES cells reveal potential regulatory sequences and genes involved in pluripotency显示文摘Pluripotency,一个细胞的能力区分并且产生所有胚胎的系,定义象胚胎的茎(ES ) 那样的哺乳动物的细胞类型的一个小数字细胞。当它通常被保持了时,那 pluripotency 是 transcriptional 的产品激活并且维持关键干细胞基因的表达式的规章的网络,积累的证据在建立并且保卫 ES 房间的 pluripotency 为 epigenetic 进程正在指向一个关键角色,象维持区分的房间类型的身份一样。以便更好在 pluripotency 理解 epigenetic 机制的角色,我们检验了在经历区别进一个 mesendodermal 系的人的 ES 房间(hESCs ) 染色体宽的染色质修正的动力学。我们发现在倡导者的染色质修正在区别期间仍然保持大部分不变,除了在在在 H3K27 的 acetylation 和 methylation 之间的一个动态开关标记在基因表示的激活和 silencing 之间的转变的倡导者的一个小数字,建议在在大多数差别上的房间命运承诺的一个层次表示了基因。我们也在 50 000 潜在的 enhancers 上印射,并且在染色质修正,特别 H3K4me1 和 H3K27ac 观察了大得多的动力学,它与他们的潜在的目标基因的表示相关。这些 enhancers 的进一步的分析揭示了 pluripotency 和可以在 hESCs 授与发展胜任的一个平衡状态的一口染色质签名陈述语气的潜在地关键的 transcriptional 管理者。我们的结果提供在定义 enhancers 和 pluripotency 支持染色质修正的角色的新证据。 | R David Hawkins Gary C Hon Chuhu Yang Jessica E Antosiewicz-Bourget Leonard K Lee Que-Minh Ngo Sarit Klugman Keith A Ching Lee E Edsall Zhen Ye Samantha Kuan Pengzhi Yu Hui Liu Xinmin Zhang Roland D Green Victor V Lobanenkov Ron Stewart James A Thomson Bing Ren | 2011 | Cell Research2011，21，10： | 6 |
| 3 | Enhanced expression of interleukin-18 in serum and pancreas of patients with chronic pancreatitis显示文摘AIM: To investigate interleukin-18 (IL-18) in patients with chronic panreatitis (CP). METHODS: We studied 29 patients with CP and 30 healthy controls. Peripheral blood mononuclear cells (PBMC) were isolated and incubated with 50 mmol/L ethanol, lipopolysaccharide (LPS) (doses 25 g/L, 250 g/L, 2500 g/L) and both agents for 24 h. Levels of IL-18 in the supernatants, and levels of IL-18, IL-12, interferon (IFN)-γ and soluble CD14 in the serum were analysed by ELISA technique. Expression of IL-18 in PBMC was investigated by reverse-transcription (RT)-PCR. IL-18 protein levels in CP tissue and in normal pancreas were studied by ELISA technique. IL-18 levels in PBMC and pancreatic tissue were determined by Westernblot. Im-munohistochemistry for pancreatic IL-18 expression was performed. RESULTS: In patients, IL-18 serum levels were signifi-cantly enhanced by 76% (mean: 289.9 ± 167.7 ng/L) compared with controls (mean: 165.2 ± 43.6 ng/L; P < 0.0005). IL-12 levels were enhanced by 25% in patients (18.3 ± 7.3 ng/L) compared with controls (14.7 ± 6.8ng/L, P = 0.0576) although not reaching the statistical significance. IFN-γ and soluble CD14 levels were not in-creased. In vitro, LPS stimulated significantly and dose-dependently IL-18 secretion from PBMC. Incubation with ethanol reduced LPS-stimulated IL-18 secretion by about 50%. The mRNA expression of IL-18 in PBMC and the response of PBMC to ethanol and LPS was similar in CP patients and controls. In PBMC, no significant differences in IL-18 protein levels were detected between patients and controls. IL-18 protein levels were increased in CP tissues compared to normal pancreatic tissues. IL-18 was expressed by pancreatic acinar cells and by infiltrating inflammatory cells within the pancreas. CONCLUSION: IL-18 originates from the chronically inflammed pancreas and appears to be involved in the fibrotic destruction of the organ. | Alexander Schneider Stephan L Haas Ralf Hildenbrand Sren Siegmund Iris Reinhard Helmut Nakovics Manfred V Singer Peter Feick | 2006 | World Journal of Gastroenterology2006，12，40： | 4 |
| 4 | The Treatment-Naive Microbiome in New-Onset Crohn’s Disease显示文摘 | Dirk Gevers Subra Kugathasan Lee A. Denson Yoshiki Vázquez-Baeza Will Van Treuren Boyu Ren Emma Schwager Dan Knights Se Jin Song Moran Yassour Xochitl C. Morgan Aleksandar D. Kostic Chengwei Luo Antonio González Daniel McDonald Yael Haberman Thomas Walter | 2014 | Cell Host & Microbe2014，，： | 3 |
| 5 | Improved Prediction of Signal Peptides: SignalP 3.0显示文摘 | Jannick Dyrl?v Bendtsen Henrik Nielsen Gunnar von Heijne S?ren Brunak | 2004 | Journal of Molecular Biology2004，，4： | 2 |
| 6 | 2021 Chinese consensus on the diagnosis and management of primary immune thrombocytopenia in pregnancy显示文摘Immune thrombocytopenia(ITP)is an acquired disease characterized by isolated thrombocytopenia,which is one of the most common causes of thrombocytopenia during pregnancy.Women with ITP who have severe thrombocytopenia are at an increased risk for life-threatening obstetric complications.Therefore,we established this consensus statement on the diagnosis and management of ITP during pregnancy(detailed information is available in the Supplementary File,http://links.lww.com7CM9/A978). | Zhang Xiaohui Chen Fangping Chen Xiequn Cheng Yunfeng Fang Meiyun Feng Jianming Fu Haixia Gao Hong Han Yue He Aili Hou Ming Hu Yu Huang Ruibin Huang Wenrong Jing Zhicheng Kong Peiyan Liang Aibin Liang Meiying Liu Daihong Liu Junling Liu Lin Liu Xiaowei Ma Liangming Mei Heng Ni Heyu Niu Ting Peng Jun Qiao Jianlin Ren Jinhai Song Yongping Tang Liang V Tong Tong Wang Shaoyuan Wang Xin Wang Zhao Wei Hui Wu Depei Wu Guangsheng Xu Caigang Xu Xue Xu Yajing Yang Linhua Yang Renchi Yang Tonghua Yin Chenghong Yu Li Zhang Guangsen Zhang Lei Zhang Liansheng Zhang Xi Zhao Weili Zhao Yongqiang Zhou Daobin Zhou Hu Zhou Zeping Zhu Tienan Wang Jianliu Huang Xiaojun | 2022 | Chinese Medical Journal2022，，8： | 2 |
| 7 | Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake 显示文摘 | Zhang J V Ren P G Avsian-Kretehmer O 2005 | 2005 | Science2005，310，： | 1 |
| 8 | Semantic caching and query processing 显示文摘 | Ren Qun Dunham M H Kumar V | 2003 | IEEE Transactions on Knowledge and Data Engineering2003，15，1： | 1 |
| 9 | Synthesis and characterization of a mesoporous silica (MCM-48) membrane on a large-pore a-AI, 03 ceramic tube显示文摘 | LIU C v WANG L Q REN W Z | 2007 | Microporous and Mesoporous Materials2007，106，13： | 1 |
| 10 | Potential role of ixekizumab in the treatment of moderate-to-severe plaque psoriasis 显示文摘 | Ren V Dao H Jr | 2013 | Clin Cosmet Investig Dermatol2013，6，： | 1 |
| 11 | Obestatin, a peptide encoded by the ghrelin gene,opposes ghrelin's effects on food intake显示文摘 | Zhang J V Ren P G Avsian-Kretchmer O | 2005 | Science2005，310，5750： | 1 |
| 12 | The tribological performance and tribochemical analysis of novel borate esters as lubricant additives in rapeseedoil显示文摘 | YAN Jin-can ZENG Xiang-qiong HEIDE E V D REN Tian-hui | 2014 | Tribology International2014，71，： | 1 |
| 13 | Cytotoxic barrigenol-like triterpenoids from an extract of Cyrilla racemiflora housed in a repository 显示文摘 | Ren Y L Schoiack V A Chai H B | 2015 | JNat Prod2015，78，： | 1 |
| 14 | Cryosurgery in aggressive,benign,and low-grade malignant bone tumours显示文摘 | RenéV Bart S Hermanvan B | 2005 | Lancet Oncol2005，6，： | 1 |
| 15 | Associations of coagulation factor V Leiden and prothrombin G20210A mutations with Budd-Chiari syn- drome andporta! vein thrombosis: a systematic review and meta-analy- sis 显示文摘 | Qi x Ren W De Stefano V | 2014 | Clin Gastroenterol Hepatol2014，12，18： | 1 |
| 16 | Identification of two determinants that attenuate vaccine-related type 2poliovirus显示文摘 | Ren R B Moss E G Racaniello V R | 1991 | J Virol1991，65，3： | 1 |
| 17 | Three-dimensional fold of the human AQP1 water channel determined at 4 Aresolut ion by electron crystallography of two-dimensional crystals embedded in ice显示文摘 | Ren G Cheng A Reddy V | 2000 | J Mol Biol2000，301，： | 1 |
| 18 | Energy transduction on the nanosecond time scale:early structural events in a xanthopsin photocycle显示文摘 | PERMAN B SRAJER V REN Z | 1998 | Science1998，279，5358： | 1 |
| 19 | Semantic caching and query processing显示文摘 | REN Qun DUNHAM M H KUMAR V | 2003 | IEEE Trans on Knowledge and Data Engineering2003，15，1： | 1 |
| 20 | Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake显示文摘 | Zhang J V Ren P G Avsian K O | 2005 | Science2005，310，5750： | 1 |
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