Hydrazines

Hydrazines
  • 文章类型: Journal Article
    背景:癌症恶病质影响所有癌症患者的一半以上,降低生存率。迫切需要基于证据的方法来优化治疗。
    方法:进行系统评价和网络荟萃分析,以评估不同药物治疗癌症恶病质的有效性和安全性。三个数据库(PubMed,科克伦图书馆,和WebofScience)的搜索时间为2000年1月1日至2024年3月20日。使用R软件中的netmeta软件包计算合并效果,采用随机效应模型。
    结果:对涉及1421例患者的7项安慰剂对照随机试验进行分析。配对分析表明,奥氮平的体重增加为4.6kg(95%置信区间[CI]0.83-8.37kg),艾司吲哚洛尔(20mg)3.82kg(95%CI0.73-6.91kg),阿纳瑞林(100mg)为2.36kg(95%CI1.84-2.89kg),Anamorelin(50mg)为1.31kg(95%CI0.42-2.19kg)。在安全方面,与安慰剂相比,奥氮平显示出最低的比值比,在0.26(95%CI0.07-0.94),其次是0.86的anamorelin(50mg)(95%CI0.30-2.48),Anamorelin(100mg)为0.89(95%CI0.42-1.88)。然而,网络荟萃分析无法证实奥氮平在疗效和安全性方面优于阿纳瑞林.
    结论:奥氮平和阿纳瑞林对改善癌症恶病质患者的体重均有效。个性化可能对不同的患者有帮助。
    BACKGROUND: Cancer cachexia affects more than half of all cancer patients, reducing survival rates. Evidence-based approaches are urgently needed to optimize treatment.
    METHODS: A systematic review and network meta-analysis were conducted to assess the effectiveness and safety of different pharmacotherapies for cancer cachexia. Three databases (PubMed, Cochrane Library, and Web of Science) were searched for the period from January 1, 2000, to March 20, 2024. The netmeta package in R software was used to calculate the pooled effect, employing a random effects model.
    RESULTS: Seven placebo-controlled randomized trials involving 1421 patients were analyzed. Pairwise analysis showed that body weight increases were 4.6 kg (95% confidence interval [CI] 0.83-8.37 kg) for olanzapine, 3.82 kg (95% CI 0.73-6.91 kg) for espindolol (20 mg), 2.36 kg (95% CI 1.84-2.89 kg) for anamorelin (100 mg), and 1.31 kg (95% CI 0.42-2.19 kg) for anamorelin (50 mg). In terms of safety profiles, olanzapine demonstrated the lowest odds ratio when compared to placebo, at 0.26 (95% CI 0.07-0.94), followed by anamorelin (50 mg) at 0.86 (95% CI 0.30-2.48), and anamorelin (100 mg) at 0.89 (95% CI 0.42-1.88). However, network meta-analysis could not confirm the superiority of olanzapine over anamorelin in terms of efficacy and safety.
    CONCLUSIONS: Both olanzapine and anamorelin are useful in improving body weight in patients with cancer cachexia. Personalization may be helpful for different patients.
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  • 文章类型: Journal Article
    Exportin-1 (XPO1) is a major transporter for hundreds of proteins. Selinexor is the first generation XPO1 inhibitor. At present, selinexor has gained more attention in the application of multiple myeloma (MM). Meanwhile, the latest clinical trials have confirmed that whether it is a single agent or combined with other chemotherapy regimens, selinexor can also achieve good therapeutic effects in patients with leukemia and lymphoma. This review summarizes the results of preclinical studies and clinical trials of selinexor in treatment of non-MM hematological malignancies, aiming to explore how to choose single agent or in combination with other regimens as induction chemotherapy.
    UNASSIGNED: 塞利尼索在非多发性骨髓瘤血液肿瘤中的应用及研究进展.
    UNASSIGNED: .核输出蛋白1(XPO1)是数百种蛋白质的主要转运蛋白。塞利尼索是第一代XPO1抑制剂,目前在多发性骨髓瘤的治疗中获得了较多的关注,同时最新临床试验也证实,无论是单药还是联合其他化疗方案,塞利尼索在白血病、淋巴瘤中同样能取得较好的治疗效果。本文总结了塞利尼索治疗非多发性骨髓瘤血液肿瘤的临床前研究和临床试验结果,旨在探讨未来如何选择塞利尼索单药或联合其他方案进行诱导化疗。.
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  • 文章类型: Meta-Analysis
    暂无摘要。
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  • 文章类型: Meta-Analysis
    目的:免疫抑制治疗(IST)是造血干细胞移植(HSCT)受限的重型再生障碍性贫血(SAA)患者的首选治疗方法,而限制其疗效的主要因素是残余造血干/祖细胞(HSPC)过少。Eltrombopag(EPAG),作为一种小分子血小板生成素受体激动剂,能刺激残留HSPC的增殖,恢复患者骨髓造血功能。近年来,许多研究观察到IST联合EPAG治疗SAA的疗效和安全性,但结果仍有争议。本研究的目的是系统评估IST联合或不联合EPGA治疗SAA的疗效和安全性。
    方法:我们对截至2024年1月19日发表的所有相关文献进行了系统综述。计算汇总赔率比(OR)来比较这些比率,以及95%置信区间(CI)和p值,以评估ReviewManager5.4.1的结果是否具有统计学意义。通过Stata15.1计算每个亚组之间相互作用的p值。分别采用纽卡斯尔-渥太华量表和Cochrane偏倚风险评估工具,通过队列研究和随机对照试验评价文献质量。ReviewManager5.4.1和Stata15.1用于评估偏倚风险并进行荟萃分析。
    结果:共纳入16项研究,涉及2148名患者。IST联合EPAG组在3个月(合并OR=2.10,95%CI1.58-2.79,p<0.00001)和6个月(合并OR=2.13,95%CI1.60-2.83,p<0.00001)时的总体缓解率(ORR)高于IST组,但两组在12个月时差异无统计学意义(合并OR=1.13,95%CI0.75-1.72,p=0.55).完全缓解率(CRR)的结果(3个月时的合并OR=2.73,95%CI1.83-4.09,p<0.00001,6个月=2.76,95%CI2.08-3.67,p<0.00001和12个月=1.38,95%CI0.85-2.23,p=0.19)与ORR相似。与IST组相比,IST联合EPAG组有较好的总生存率(OSR)(合并OR=1.70,95%CI1.15-2.51,p=0.008),但无事件生存率(EFSR)差异无统计学意义(合并OR=1.40,95%CI0.93-2.13,p=0.11),两组间的克隆演变率(合并OR=0.68,95%CI0.46-1.00,p=0.05)和其他不良事件.亚组分析结果显示,不同年龄是异质性的来源,但不同的研究类型和不同的随访时间没有。此外,所有交互作用的p值均大于0.05,提示治疗效果不受亚组特征的影响.
    结论:在IST中添加EPAG使患者能够更早和更快地实现血液学反应,并具有更高的完全缓解率。虽然对整体EFSR没有影响,它改善了OSR,并且没有增加克隆进化和其他不良事件的发生率.
    OBJECTIVE: Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the main factor limiting its efficacy is too few residual hematopoietic stem/progenitor cells (HSPC). Eltrombopag (EPAG), as a small molecule thrombopoietin receptor agonist, can stimulate the proliferation of residual HSPC and restore the bone marrow hematopoietic function of patients. In recent years, many studies have observed the efficacy and safety of IST combined with EPAG in the treatment of SAA, but the results are still controversial. The aim of this study is to systematically evaluate the efficacy and safety of IST combined with or without EPGA in the treatment of SAA.
    METHODS: We conducted a systematic review of all relevant literature published up to January 19, 2024. Pooled odds ratio (OR) was calculated to compare the rates, along with 95% confidence intervals (CI) and p value to assess whether the results were statistically significant by Review Manager 5.4.1. The p values for the interactions between each subgroup were calculated by Stata 15.1. The Newcastle-Ottawa Scale and the Cochrane bias risk assessment tools were respectively used to evaluate the quality of the literature with cohort studies and randomized controlled trials. The Review Manager 5.4.1 and Stata 15.1 were used to assess bias risk and perform the meta-analysis.
    RESULTS: A total of 16 studies involving 2148 patients were included. The IST combined with the EPAG group had higher overall response rate (ORR) than the IST group at 3 months (pooled OR = 2.10, 95% CI 1.58-2.79, p < 0.00001) and 6 months (pooled OR = 2.13, 95% CI 1.60-2.83, p < 0.00001), but the difference between the two groups became statistically insignificant at 12 months (pooled OR = 1.13, 95% CI 0.75-1.72, p = 0.55). The results of complete response rate (CRR) (pooled OR at 3 months = 2.73, 95% CI 1.83-4.09, p < 0.00001, 6 months = 2.76, 95% CI 2.08-3.67, p < 0.00001 and 12 months = 1.38, 95% CI 0.85-2.23, p = 0.19) were similar to ORR. Compared with the IST group, the IST combined with the EPAG group had better overall survival rate (OSR) (pooled OR = 1.70, 95% CI 1.15-2.51, p = 0.008), but there were no statistically significant differences in event-free survival rate (EFSR) (pooled OR = 1.40, 95% CI 0.93-2.13, p = 0.11), clonal evolution rate (pooled OR = 0.68, 95% CI 0.46-1.00, p = 0.05) and other adverse events between the two groups. The results of subgroup analysis showed that different ages were a source of heterogeneity, but different study types and different follow-up times were not. Moreover, all p-values for the interactions were greater than 0.05, suggesting that the treatment effect was not influenced by subgroup characteristics.
    CONCLUSIONS: EPAG added to IST enables patients to achieve earlier and faster hematologic responses with a higher rate of complete response. Although it had no effect on overall EFSR, it improved OSR and did not increase the incidence of clonal evolution and other adverse events.
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  • 文章类型: Meta-Analysis
    本文对艾曲波帕联合免疫抑制治疗再生障碍性贫血(AA)的疗效进行了系统评价,证明艾曲波帕的有效性和安全性。
    PubMed,科克伦图书馆,Embase,OVID,WebofScience,中国国家知识基础设施,和万方数据库进行了搜索。收集符合纳入标准的研究,从数据库建立到2023年8月。两名评审员使用Cochrane系统评价方法和RevMan5.3软件进行荟萃分析。
    这项荟萃分析纳入了5项研究,共542例AA患者,其中实验组274个,对照组268个。对疗效和不良反应进行Meta分析。效果终点包括6个月完全缓解(CR),6个月部分反应(PR),6个月的总体反应(OR)。与免疫疗法相比,艾曲波帕格联合免疫疗法在6个月CR(OR:2.20;95%CI;1.54-3.12;P<0.0001)和6个月OR(OR=3.66,95%CI2.39-5.61,P<0.001)方面显着改善。在安全方面,与单纯免疫抑制治疗相比,艾曲波帕联合免疫抑制治疗显示色素沉积和肝功能异常显著增加。
    与单纯免疫抑制治疗相比,艾曲波帕联合免疫抑制治疗6个月CR和6个月OR均有显著改善。然而,在安全性方面,它还导致色素沉积增加和肝功能异常。
    UNASSIGNED: This article conducts a systematic review of eltrombopag combined with immunosuppressive therapy for the treatment of aplastic anemia (AA), to demonstrate the effectiveness and safety of eltrombopag.
    UNASSIGNED: PubMed, Cochrane Library, Embase, OVID, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched. Studies that met the inclusion criteria were collected, ranging from the establishment of the database to August 2023. Two reviewers performed meta-analyses using the Cochrane systematic review method and RevMan 5.3 software.
    UNASSIGNED: This meta-analysis enrolled 5 studies with a total of 542 AA patients, including 274 in the experimental group and 268 in the control group. Meta-analyses were performed for efficacy and adverse reactions. The endpoint of effects included 6-month complete response (CR), 6-month partial response (PR), and 6-month overall response (OR). Eltrombopag combined with immunotherapy showed significant improvements in 6-month CR (OR: 2.20; 95% CI;1.54-3.12; P < 0.0001) and 6-month OR (OR = 3.66, 95% CI 2.39-5.61, P < 0.001)compared to immunosuppressive therapy for AA patients. In terms of safety, eltrombopag combined with immunosuppressive therapy showed significantly increased pigment deposition and abnormal liver function compared to immunosuppressive therapy alone.
    UNASSIGNED: Compared to immunosuppressive therapy alone, eltrombopag combined with immunosuppressive therapy showed significant improvements in 6-month CR and 6-month OR. However, it also resulted in increased pigment deposition and abnormal liver function in terms of safety.
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  • 文章类型: Journal Article
    作为一种新型的脱氮工艺,短程硝化和反硝化(SHARON)工艺,厌氧氨氧化(厌氧氨氧化)过程,亚硝酸盐(CANON)过程中的完全自养脱氮,部分硝化和厌氧氨氧化(PN/A)工艺和部分反硝化和厌氧氨氧化(PD/A)工艺由于其脱氮效率高(NRE)和低能耗等优点而进入公众视野。然而,上述过程还受到长期启动时间的限制,运行不稳定,复杂的过程调节等。作为上述过程中功能微生物的中间体或副产物,羟胺(NH2OH)和肼(N2H4)通过促进功能酶活性来改善上述过程的NRE,加速电子传输效率和调节微生物群落的分布。因此,本文讨论了NH2OH和N2H4对上述过程稳定性和NRE的影响,从功能性酶活性分析调控机制,电子传输效率和微生物群落分布。最后,讨论了由NH2OH和N2H4调节产生的一氧化氮(NO)和一氧化二氮(N2O)的挑战和局限性。Inadditional,对技术发展的未来趋势提出了展望。
    As the new fashioned nitrogen removal process, short-cut nitrification and denitrification (SHARON) process, anaerobic ammonium oxidation (anammox) process, completely autotrophic nitrogen removal over nitrite (CANON) process, partial nitrification and anammox (PN/A) process and partial denitrification and anammox (PD/A) process entered into the public eye due to its advantages of high nitrogen removal efficiency (NRE) and low energy consumption. However, the above process also be limited by long-term start-up time, unstable operation, complicated process regulation and so on. As intermediates or by-metabolites of functional microorganisms in above processes, hydroxylamine (NH2OH) and hydrazine (N2H4) improved NRE of the above processes by promoting functional enzyme activity, accelerating electron transport efficiency and regulating distribution of microbial communities. Therefore, this review discussed effects of NH2OH and N2H4 on stability and NRE of above processes, analyzed regulatory mechanism from functional enzyme activity, electron transport efficiency and microbial community distribution. Finally, the challenges and limitations for nitric oxide (NO) and nitrous oxide (N2O) produced from regulation of NH2OH and N2H4 are discussed. In additional, perspectives on future trends in technology development are proposed.
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  • 文章类型: Journal Article
    除了具有关键的生物活性外,腙和酰肼-腙还可以作为合成1,3-苯并噻嗪-4-酮等杂环系统的有用中间体,1,3-噻唑烷-4-酮,氮杂环丁烷-2-酮和1,3,4-恶二唑衍生物。氮杂环丁烷-2-酮衍生物主要显示抗菌,抗结核和抗真菌活性以及抗炎,抗氧化剂,抗惊厥和抗抑郁活性和抗帕金森病活性。这篇综述集中在考虑氮杂环丁烷-2-酮衍生物的合成和生物学特性的文献报道上。
    The hydrazones and hydrazide-hydrazones beside possessing crucial bioactivity can serve as useful intermediates in the synthesis of heterocyclic systems like 1,3-benzothiazin-4-one, 1,3-thiazolidin-4-one, azetidin-2-one and 1,3,4-oxadiazole derivatives. The azetidin-2-one derivatives show mainly antibacterial, antitubercular and antifungal activity as well as anti-inflammatory, antioxidant, anticonvulsant and antidepressant activity and activity against Parkinson\'s disease. This review is focused on the literature reports which consider the synthesis and biological properties of azetidin-2-one derivatives.
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  • 文章类型: Journal Article
    这篇综述着重于过渡金属在氨基硫脲络合中的一些有趣和最新应用,硫代碳酰肼,和它们相应的卡巴酮。我们从选择的五种金属的描述开始审查,包括Cu[Cu(I),Cu(II),Co(II),Ni(II),Pd(II),和Ag(I)及其电子配置。还讨论了指定复合物的稳定性。我们阐明了描述这些配体合成的不同路线。我们还报道了Cu(I)合成的不同实例,Cu(II),Co(II),Ni(II),Ag(I),以及氨基硫脲和硫代碳酰肼络合物的Pd(II)(直到2022年)。本文还总结了缩氨基硫脲和硫代脲酮配体的金属配合物在催化领域的卓有成效的应用。最后,这篇最近的综述集中在这些复合物的应用与它们的生物学重要性。
    This review focuses on some interesting and recent applications of transition metals towards the complexation of thiosemicarbazides, thiocarbohydrazides, and their corresponding carbazones. We started the review with a description of the chosen five metals, including Cu[Cu(I), Cu(II], Co(II), Ni(II), Pd(II), and Ag(I) and their electronic configurations. The stability of the assigned complexes was also discussed. We shed light on different routes describing the synthesis of these ligands. We also reported on different examples of the synthesis of Cu(I), Cu(II), Co(II), Ni(II), Ag(I), and Pd(II) of thiosemicarbazide and thiocarbohydrazide complexes (until 2022). This review also deals with a summary of the fruitful use of metal complexes of thiosemicarbazones and thiocarbazones ligands in the field of catalysis. Finally, this recent review focuses on the applications of these complexes related to their biological importance.
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  • 文章类型: Systematic Review
    目前有三种血小板生成素受体激动剂(TPO-RA)在欧洲被批准用于治疗免疫性血小板减少症(ITP)患者:romiplostim(Nplate®),eltrombopag(Revolade®),和avatrombopag(Doptelet®)。然而,这些TPO-RA之间的比较临床数据有限。因此,这项研究的目的是进行文献综述,并就有关在成人ITP患者中使用TPO-RA的证据的相关性和强度寻求专家意见。在过去的10年中,直到2022年6月20日,在PubMed和Embase进行了系统的搜索。共检索并审查了478篇独特文章的相关性。专家共识小组由来自中欧八个国家的ITP高级血液学家组成。改进的德尔菲法,由两轮调查组成,电话会议和电子邮件通信,是用来达成共识的。40篇文章符合相关性标准,作为支持证据,包括5项荟萃分析,分析了所有3项欧洲许可的TPO-RA,包括总共31项独特的随机对照试验(RCT).就TPO-RA在成人ITP患者管理中的二线使用达成了七项共识。此外,专家小组讨论了一线治疗慢性ITP伴轻度/中度COVID-19患者和ITP患者的TPO-RA治疗,但未能达成共识.这项工作将有助于医疗保健提供者对使用TPO-RA治疗成年ITP患者的知情决策。然而,需要进一步研究TPO-RA在一线环境和特定患者人群中的应用.
    There are currently three thrombopoietin receptor agonists (TPO-RAs) approved in Europe for treating patients with immune thrombocytopenia (ITP): romiplostim (Nplate®), eltrombopag (Revolade®), and avatrombopag (Doptelet®). However, comparative clinical data between these TPO-RAs are limited. Therefore, the purpose of this study was to perform a literature review and seek expert opinion on the relevance and strength of the evidence concerning the use of TPO-RAs in adults with ITP. A systematic search was conducted in PubMed and Embase within the last 10 years and until June 20, 2022. A total of 478 unique articles were retrieved and reviewed for relevance. The expert consensus panel comprised ITP senior hematologists from eight countries across Central Europe. The modified Delphi method, consisting of two survey rounds, a teleconference and email correspondence, was used to reach consensus. Forty articles met the relevancy criteria and are included as supporting evidence, including five meta-analyses analyzing all three European-licensed TPO-RAs and comprising a total of 31 unique randomized controlled trials (RCTs). Consensus was reached on seven statements for the second-line use of TPO-RAs in the management of adult ITP patients. In addition, the expert panel discussed TPO-RA treatment in chronic ITP patients with mild/moderate COVID-19 and ITP patients in the first-line setting but failed to reach consensus. This work will facilitate informed decision-making for healthcare providers treating adult ITP patients with TPO-RAs. However, further studies are needed on the use of TPO-RAs in the first-line setting and specific patient populations.
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  • 文章类型: Review
    背景:Eltrombopag,血小板生成素受体(TPO-R)激动剂,被认为是难治性免疫性血小板减少症(ITP)患者的二线治疗。系统性红斑狼疮(SLE)通常与ITP相关。在某些情况下,SLE患者的血小板减少症归因于并发抗磷脂抗体(APLA)。目前,关于SLE或APLA患者使用TPO-R激动剂治疗ITP的数据有限.在使用TPO-R激动剂时,SLE发作或抗磷脂综合征的发生率尚未得到充分研究。
    方法:我们报告2例女性SLE患者并发三阳性APLA,在他们的病史中没有血栓性事件,在我们的风湿病诊所,用艾曲波帕治疗难治性ITP。在开始使用eltrombopag治疗几周后,两者都出现了灾难性的抗磷脂综合征。他们被送进重症监护室接受solumedrol治疗,血浆置换,抗凝和利妥昔单抗。
    结论:我们描述了艾曲波帕的严重可能的副作用作为灾难性抗磷脂综合征的触发因素,一种罕见的抗磷脂综合征的初始表现,在患有APLA的SLE患者中。我们建议在SLE相关ITP患者开始使用eltrombopag之前测试APLA。在这些情况下,应考虑这种治疗的安全性。
    BACKGROUND: Eltrombopag, a thrombopoietin receptor (TPO-R) agonist, is considered a second-line treatment for patients with refractory immune thrombocytopenia (ITP). Systemic lupus erythematosus (SLE) is frequently associated with ITP. In some cases, thrombocytopenia in SLE patients is attributed to concurrent antiphospholipid antibodies (APLA). Currently, data regarding treatment with TPO-R agonists for ITP in SLE or APLA patients are limited. The incidence of SLE flare or antiphospholipid syndrome while on TPO-R agonists has not been well-studied.
    METHODS: We report 2 cases of female patients with SLE and concurrent triple positive APLA, without thrombotic events in their medical history, in our rheumatology clinic, who were treated for refractory ITP with eltrombopag. Both developed catastrophic antiphospholipid syndrome a few weeks after beginning treatment with eltrombopag. They were admitted to the intensive care unit and treated with solumedrol, plasmapheresis, anticoagulation and rituximab.
    CONCLUSIONS: We describe a severe possible side-effect of eltrombopag as a trigger of catastrophic antiphospholipid syndrome, a rare initial manifestation of antiphospholipid syndrome, in SLE patients with APLA. We suggest that APLA should be tested before initiating eltrombopag in patients with SLE-associated ITP. The safety of this treatment should be considered in these cases.
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