Pub Date : 2024-09-28eCollection Date: 2024-01-01DOI: 10.2147/DDDT.S474275
Lin Lu, Bing Chen, Xueli Zhao, Jie Zhai, Pan Zhang, Zhen Hua
Purpose: We designed this trial to compare the recovery time of remimazolam and propofol in elderly patients undergoing painless gastrointestinal endoscopy.
Patients and methods: In this randomized, non-Inferiority trial, 360 patients aged 65 years or older, scheduled for elective outpatient gastrointestinal endoscopy, were randomly assigned to the remimazolam combined with fentanyl (RF) group or the propofol combined with fentanyl (PF) group. The primary outcome was the post-anesthesia care unit (PACU) stay time, defined as the time from the end of the examination to scoring 9 points using the Modified Post-Anesthetic Discharge Scoring System (MPADSS) criteria. Secondary outcomes included sedation-related adverse events, recall, injection pain, as well as postoperative Quality of Recovery-15 (QoR-15) scores and Pittsburgh Sleep Quality Index (PSQI) scores at 1 day, 1 week, and 1 month postoperatively.
Results: A total of 351 patients completed the study, with 174 receiving remimazolam and 177 receiving propofol. The PACU stay time in RF group was non-inferior to that in PF group [14 (11, 18) vs 13 (10, 17), mean difference 1 (95% confidence interval 0, 2), P=0.084 for noninferiority]. However, remimazolam was associated with lower rate of hypoxemia [4.7% (8/180) vs 12.4% (22/180), P=0.011], reduced use of vasoactive drugs [1 (0, 1) vs 1 (1, 2), P<0.001], less injection pain [2 (1.2%) vs 35 (21.3%), P<0.001], and lower recall [20 (11.8%) vs 36 (20.3%), P=0.034]. There were no differences in the QoR-15 scores and PSQI scores at postoperative 1 day, 1 week, and 1 month between groups.
Conclusion: This non-inferiority study revealed that in elderly outpatients undergoing gastrointestinal endoscopy, remimazolam achieved recovery times comparable to propofol, with fewer associated complications.
目的:我们设计了这项试验,以比较瑞马唑仑和异丙酚对接受无痛胃肠道内窥镜检查的老年患者的恢复时间:在这项随机、非劣效试验中,360 名 65 岁或以上的患者被随机分配到瑞马唑仑联合芬太尼(RF)组或异丙酚联合芬太尼(PF)组,这些患者都计划接受择期门诊胃肠道内窥镜检查。主要结果是麻醉后护理病房(PACU)停留时间,即从检查结束到使用改良麻醉后出院评分系统(MPADSS)标准评分达到 9 分的时间。次要结果包括镇静相关不良事件、回忆、注射疼痛以及术后1天、1周和1个月的术后恢复质量-15(QoR-15)评分和匹兹堡睡眠质量指数(PSQI)评分:共有351名患者完成了研究,其中174人接受了瑞马唑仑治疗,177人接受了异丙酚治疗。RF组的PACU停留时间不劣于PF组[14 (11, 18) vs 13 (10, 17),平均差异1(95%置信区间0, 2),P=0.084为不劣性]。然而,雷马唑仑与较低的低氧血症发生率[4.7% (8/180) vs 12.4% (22/180),P=0.011]、减少血管活性药物的使用[1 (0, 1) vs 1 (1, 2),PPP=0.034]相关。术后1天、1周和1个月的QoR-15评分和PSQI评分在组间无差异:这项非劣效性研究表明,对于接受消化道内窥镜检查的老年门诊患者,瑞马唑仑的恢复时间与异丙酚相当,相关并发症较少。
{"title":"Comparison of Remimazolam and Propofol in Recovery of Elderly Outpatients Undergoing Gastrointestinal Endoscopy: A Randomized, Non-Inferiority Trial.","authors":"Lin Lu, Bing Chen, Xueli Zhao, Jie Zhai, Pan Zhang, Zhen Hua","doi":"10.2147/DDDT.S474275","DOIUrl":"10.2147/DDDT.S474275","url":null,"abstract":"<p><strong>Purpose: </strong>We designed this trial to compare the recovery time of remimazolam and propofol in elderly patients undergoing painless gastrointestinal endoscopy.</p><p><strong>Patients and methods: </strong>In this randomized, non-Inferiority trial, 360 patients aged 65 years or older, scheduled for elective outpatient gastrointestinal endoscopy, were randomly assigned to the remimazolam combined with fentanyl (RF) group or the propofol combined with fentanyl (PF) group. The primary outcome was the post-anesthesia care unit (PACU) stay time, defined as the time from the end of the examination to scoring 9 points using the Modified Post-Anesthetic Discharge Scoring System (MPADSS) criteria. Secondary outcomes included sedation-related adverse events, recall, injection pain, as well as postoperative Quality of Recovery-15 (QoR-15) scores and Pittsburgh Sleep Quality Index (PSQI) scores at 1 day, 1 week, and 1 month postoperatively.</p><p><strong>Results: </strong>A total of 351 patients completed the study, with 174 receiving remimazolam and 177 receiving propofol. The PACU stay time in RF group was non-inferior to that in PF group [14 (11, 18) vs 13 (10, 17), mean difference 1 (95% confidence interval 0, 2), <i>P</i>=0.084 for noninferiority]. However, remimazolam was associated with lower rate of hypoxemia [4.7% (8/180) vs 12.4% (22/180), <i>P</i>=0.011], reduced use of vasoactive drugs [1 (0, 1) vs 1 (1, 2), <i>P</i><0.001], less injection pain [2 (1.2%) vs 35 (21.3%), <i>P</i><0.001], and lower recall [20 (11.8%) vs 36 (20.3%), <i>P</i>=0.034]. There were no differences in the QoR-15 scores and PSQI scores at postoperative 1 day, 1 week, and 1 month between groups.</p><p><strong>Conclusion: </strong>This non-inferiority study revealed that in elderly outpatients undergoing gastrointestinal endoscopy, remimazolam achieved recovery times comparable to propofol, with fewer associated complications.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-27eCollection Date: 2024-01-01DOI: 10.2147/DDDT.S471352
Ke-Qian Chen, Shu-Zhi Wang, Hai-Bo Lei, Xiang Liu
Background: Dauricine is an important natural organic compound in Menispermum dauricum, which often has significant biological activity.
Purpose: The purpose of this review is to systemically summarize and discuss the pharmacological activity and underlying mechanisms of dauricine in recent years.
Methods: Web of Science (121 articles) and PubMed databases (97 articles) were used to search for articles related to "dauricine" published from 2000 to 2024. Meanwhile, we classified the pharmacological activity of dauricine by screening these articles.
Results: Emerging evidence suggests that dauricine possesses numerous pharmacological activities, including neuroprotection, anti-cancer, anti-arrhythmia, anti-inflammatory and anti-diabetes.
Conclusion: Dauricine has a potential value in the treatment of many diseases. We hope that this review will contribute to therapeutic development and future studies of dauricine.
背景:目的:本综述旨在系统总结和探讨近年来金丝桃碱的药理活性及其作用机制:方法:利用 Web of Science(121 篇)和 PubMed 数据库(97 篇)检索 2000 年至 2024 年间发表的与 "金丝桃碱 "相关的文章。同时,通过筛选这些文章,我们对道里碱的药理活性进行了分类:结果:新的证据表明,牛磺酸具有多种药理活性,包括神经保护、抗癌、抗心律失常、抗炎和抗糖尿病等:结论:牛磺酸具有治疗多种疾病的潜在价值。我们希望这篇综述能为金牛血碱的治疗开发和未来研究做出贡献。
{"title":"Dauricine: Review of Pharmacological Activity.","authors":"Ke-Qian Chen, Shu-Zhi Wang, Hai-Bo Lei, Xiang Liu","doi":"10.2147/DDDT.S471352","DOIUrl":"10.2147/DDDT.S471352","url":null,"abstract":"<p><strong>Background: </strong>Dauricine is an important natural organic compound in <i>Menispermum dauricum</i>, which often has significant biological activity.</p><p><strong>Purpose: </strong>The purpose of this review is to systemically summarize and discuss the pharmacological activity and underlying mechanisms of dauricine in recent years.</p><p><strong>Methods: </strong>Web of Science (121 articles) and PubMed databases (97 articles) were used to search for articles related to \"dauricine\" published from 2000 to 2024. Meanwhile, we classified the pharmacological activity of dauricine by screening these articles.</p><p><strong>Results: </strong>Emerging evidence suggests that dauricine possesses numerous pharmacological activities, including neuroprotection, anti-cancer, anti-arrhythmia, anti-inflammatory and anti-diabetes.</p><p><strong>Conclusion: </strong>Dauricine has a potential value in the treatment of many diseases. We hope that this review will contribute to therapeutic development and future studies of dauricine.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: We aimed to prepare a β-cyclodextrin (β-CD) polymer using radical polymerization with co-monomers, 6-deoxy-6-(2-methacryloyloxyethylsuccinamide)-β-cyclodextrin (CD-MSAm) and N,N,N-trimethyl-N-(2-hydroxy-3-metacryloyloxopropyl)-ammonium chloride (QA) to design cyclodextrins suitable for use in ophthalmology. In addition, we evaluated their solubility and inclusion properties with rebamipide (REB), a poorly soluble drug, and investigated the usefulness of the β-CD polymer and REB (REB@CDQA) combination in treating dry eye.
Methods: The β-CD polymer (CD-MSAm-co-QA, CDQA) based on CD-MSAm/QA was prepared via radical polymerization, and the usefulness of REB@CDQA in treating dry eye was evaluated using a rabbit treated with N-acetylcysteine (dry eye model).
Results: The solubility of the CDQA powder was higher than that of the β-CD powder, and 80 nm colloids were observed in the CDQA solution. No corneal toxicity was observed in human corneal epithelial cells or rat corneas treated with 0.2% CDQA solution. The levels of REB dissolved in the CDQA solution were higher than those of the β-CD solution. Moreover, the application of the CDQA solution enhanced REB retention in the cornea and attenuated the transcorneal penetration of REB. In addition, instillation of REB@CDQA enhanced the volume of the lacrimal fluid and normalized the reduced mucin levels in the dry eye model. The extent of tear film breakup was attenuated by REB@CDQA instillation.
Conclusion: The CDQA solution enhanced the solubility of REB, and the combination of CDQA and REB enhanced the drug content in the corneal tissue. Moreover, the therapeutic effect on dry eye was higher than that of REB suspensions without CDQA.
{"title":"Copolymerized Polymers Based on Cyclodextrins and Cationic Groups Enhance Therapeutic Effect of Rebamipide in the N-Acetylcysteine-Treated Dry Eye Model.","authors":"Hiroko Otake, Ko Kobayashi, Reita Kadowaki, Taiyo Kosaka, Mizuki Itahashi, Masanobu Tsubaki, Masaru Matsuda, Norio Iwakiri, Eiji Harata, Noriaki Nagai","doi":"10.2147/DDDT.S469445","DOIUrl":"10.2147/DDDT.S469445","url":null,"abstract":"<p><strong>Purpose: </strong>We aimed to prepare a β-cyclodextrin (β-CD) polymer using radical polymerization with co-monomers, 6-deoxy-6-(2-methacryloyloxyethylsuccinamide)-β-cyclodextrin (CD-MSAm) and N,N,N-trimethyl-N-(2-hydroxy-3-metacryloyloxopropyl)-ammonium chloride (QA) to design cyclodextrins suitable for use in ophthalmology. In addition, we evaluated their solubility and inclusion properties with rebamipide (REB), a poorly soluble drug, and investigated the usefulness of the β-CD polymer and REB (REB@CDQA) combination in treating dry eye.</p><p><strong>Methods: </strong>The β-CD polymer (CD-MSAm-co-QA, CDQA) based on CD-MSAm/QA was prepared via radical polymerization, and the usefulness of REB@CDQA in treating dry eye was evaluated using a rabbit treated with N-acetylcysteine (dry eye model).</p><p><strong>Results: </strong>The solubility of the CDQA powder was higher than that of the β-CD powder, and 80 nm colloids were observed in the CDQA solution. No corneal toxicity was observed in human corneal epithelial cells or rat corneas treated with 0.2% CDQA solution. The levels of REB dissolved in the CDQA solution were higher than those of the β-CD solution. Moreover, the application of the CDQA solution enhanced REB retention in the cornea and attenuated the transcorneal penetration of REB. In addition, instillation of REB@CDQA enhanced the volume of the lacrimal fluid and normalized the reduced mucin levels in the dry eye model. The extent of tear film breakup was attenuated by REB@CDQA instillation.</p><p><strong>Conclusion: </strong>The CDQA solution enhanced the solubility of REB, and the combination of CDQA and REB enhanced the drug content in the corneal tissue. Moreover, the therapeutic effect on dry eye was higher than that of REB suspensions without CDQA.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26eCollection Date: 2024-01-01DOI: 10.2147/DDDT.S479700
Jing-Xian Cao, Jing-Yan Song
Purpose: The purpose of this study was to compare the efficacy of Follitropin alpha (Gonal-F) and Follitropin beta (Puregon) on cumulative live birth rate (CLBR), defined as the percentage of the number of patients who delivered for the first time in a single ovarian stimulation cycle and the number of patients in all oocyte retrieval cycles.
Methods: A retrospective cohort study including 2864 infertile patients who underwent ovarian stimulation with Puregon (group A, n=1313) and Gonal-F (group B, n=1551) was conducted between July 2015 and June 2021 at a university-affiliated reproductive medicine center. Reduce potential confounding factors between groups, propensity scores and multivariable logistic regression analyses were estimated to obtain unbiased estimates of outcomes. The primary outcome was the difference in CLBR between the two groups.
Results: Each group identified 1160 individuals after propensity score matching (PSM). Baseline characteristics were similar between groups after PSM. The total gonadotrophin (Gn) dose (2400 vs 2325), p=0.038) and cost of Gn usage (5327.9¥ vs 7547.2¥, p<0.001) between the Puregon and Gonal-F groups were statistically significant. Nevertheless, the pregnancy outcomes between the two groups were comparable after fresh embryo transfer and subsequent frozen-thawed embryo transfer. Additionally, there was also no difference observed in the primary outcome of CLBR (52.8% vs 55.7%, p=0.169). Multivariable regression analysis revealed that the type of Gn was not associated with CLBR (p = 0.912).
Conclusion: Gonal-F may be a reasonable option for infertile patients who are hesitant to receive more Gn dosage injections. Furthermore, Puregon can eliminate unneeded anxiety and expenses while also administering more flexibility. Taken together, these findings could well be utilized in everyday clinical practice to better inform patients when deciding on an ovarian stimulation strategy.
目的:本研究旨在比较α型促性腺激素(Gonal-F)和β型促性腺激素(Puregon)对累积活产率(CLBR)的疗效,累积活产率是指在单个卵巢刺激周期中首次分娩的患者人数与所有取卵周期中患者人数的百分比:2015年7月至2021年6月期间,某大学附属生殖医学中心开展了一项回顾性队列研究,纳入了2864名接受Puregon(A组,人数=1313)和Gonal-F(B组,人数=1551)卵巢刺激的不孕患者。为减少组间潜在的混杂因素,对倾向评分和多变量逻辑回归分析进行了估计,以获得无偏的结果估计值。主要结果是两组之间的CLBR差异:经过倾向得分匹配(PSM)后,每组确定了 1160 人。经过倾向得分匹配后,两组的基线特征相似。促性腺激素(Gn)的总剂量(2400 vs 2325,P=0.038)和Gn的使用成本(5327.9¥ vs 7547.2¥,P=0.038):对于不愿接受更多 Gn 剂量注射的不孕患者来说,Gonal-F 可能是一个合理的选择。此外,Puregon 还能消除不必要的焦虑和费用,同时提供更大的灵活性。综上所述,这些研究结果完全可以用于日常临床实践,以便在患者决定卵巢刺激策略时提供更好的信息。
{"title":"Follitropin Alpha versus Follitropin Beta in IVF/ICSI Cycle: A Retrospective Cohort Study.","authors":"Jing-Xian Cao, Jing-Yan Song","doi":"10.2147/DDDT.S479700","DOIUrl":"10.2147/DDDT.S479700","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to compare the efficacy of Follitropin alpha (Gonal-F) and Follitropin beta (Puregon) on cumulative live birth rate (CLBR), defined as the percentage of the number of patients who delivered for the first time in a single ovarian stimulation cycle and the number of patients in all oocyte retrieval cycles.</p><p><strong>Methods: </strong>A retrospective cohort study including 2864 infertile patients who underwent ovarian stimulation with Puregon (group A, n=1313) and Gonal-F (group B, n=1551) was conducted between July 2015 and June 2021 at a university-affiliated reproductive medicine center. Reduce potential confounding factors between groups, propensity scores and multivariable logistic regression analyses were estimated to obtain unbiased estimates of outcomes. The primary outcome was the difference in CLBR between the two groups.</p><p><strong>Results: </strong>Each group identified 1160 individuals after propensity score matching (PSM). Baseline characteristics were similar between groups after PSM. The total gonadotrophin (Gn) dose (2400 vs 2325), p=0.038) and cost of Gn usage (5327.9¥ vs 7547.2¥, p<0.001) between the Puregon and Gonal-F groups were statistically significant. Nevertheless, the pregnancy outcomes between the two groups were comparable after fresh embryo transfer and subsequent frozen-thawed embryo transfer. Additionally, there was also no difference observed in the primary outcome of CLBR (52.8% vs 55.7%, p=0.169). Multivariable regression analysis revealed that the type of Gn was not associated with CLBR (p = 0.912).</p><p><strong>Conclusion: </strong>Gonal-F may be a reasonable option for infertile patients who are hesitant to receive more Gn dosage injections. Furthermore, Puregon can eliminate unneeded anxiety and expenses while also administering more flexibility. Taken together, these findings could well be utilized in everyday clinical practice to better inform patients when deciding on an ovarian stimulation strategy.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: EGFR-TKI resistance poses a significant challenge in the treatment landscape of non-small cell lung cancer (NSCLC), prompting extensive research into mechanisms and therapeutic strategies. In this study, we conduct a bibliometric analysis to elucidate evolving research hotspots and trends in EGFR-TKI resistance, offering insights for clinical interventions and scientific inquiries.
Methods: Publications spanning from 1996 to 2024, focusing on EGFR-TKI resistance in NSCLC, were sourced from the Web of Science Core Collection. Utilizing VOSviewer 1.6.19, CiteSpace 6.2. R2, and Scimago Graphica 1.0.35, we analyzed these articles to identify countries/regions and institutions, Journals, publications, key contributors, collaborations, and emerging topics.
Results: An analysis of 8051 articles by 38,215 researchers from 86 countries shows growing interest in EGFR-TKI resistance mechanisms. Since 1996, publications have steadily increased, surpassing 500 per year after 2016, with a sharp rise in citations. Research articles make up 84% of publications, emphasizing scholarly focus. Global collaboration, especially among researchers in China, the US, and Japan, is strong. Leading institutions like Dana-Farber and Harvard, along with journals such as "Lung Cancer", are key in sharing findings. Professors Yi-Long Wu and William Pao are prominent contributors. Keyword analysis reveals core themes, including first-generation EGFR-TKIs, emerging agents like osimertinib, and research on the T790M mutation.
Conclusion: EGFR-TKI resistance remains a critical issue in NSCLC treatment, driving ongoing research efforts worldwide. Focusing future research on clear identification of resistance mechanisms will guide post-resistance treatment strategies, necessitating further exploration, alongside the validation of emerging drugs through clinical trials. Moreover, "chemo+" treatments following EGFR-TKI resistance require more clinical data and real-world evidence for assessing safety and patient outcomes. As research advances, a multidisciplinary approach will be key to overcoming these challenges. Continued innovation in treatment could greatly enhance patient survival and quality of life.
背景:表皮生长因子受体(EGFR)-TKI耐药是非小细胞肺癌(NSCLC)治疗领域的一个重大挑战,促使人们对其机制和治疗策略进行广泛研究。在本研究中,我们进行了文献计量分析,以阐明EGFR-TKI耐药方面不断演变的研究热点和趋势,为临床干预和科学探索提供见解:方法:从Web of Science Core Collection中获取1996年至2024年期间有关NSCLC中EGFR-TKI耐药的文献。利用 VOSviewer 1.6.19、CiteSpace 6.2.R2和Scimago Graphica 1.0.35对这些文章进行了分析,以确定国家/地区和机构、期刊、出版物、主要贡献者、合作和新出现的主题:对来自 86 个国家的 38,215 位研究人员发表的 8051 篇文章进行的分析表明,人们对表皮生长因子受体-TKI 的耐药机制越来越感兴趣。自1996年以来,论文发表量稳步增长,2016年后每年超过500篇,引用量也急剧上升。研究文章占出版物的84%,突出了学术重点。全球合作,尤其是中国、美国和日本研究人员之间的合作十分紧密。Dana-Farber 和哈佛等知名机构以及《肺癌》等期刊是分享研究成果的关键。吴一龙教授和 William Pao 教授是重要的撰稿人。关键词分析揭示了核心主题,包括第一代表皮生长因子受体-TKIs、奥西替尼等新兴药物以及有关T790M突变的研究:EGFR-TKI耐药性仍然是NSCLC治疗中的一个关键问题,推动着全球正在进行的研究工作。未来的研究重点是明确耐药机制,这将指导耐药后的治疗策略,需要进一步探索,同时通过临床试验验证新出现的药物。此外,EGFR-TKI 耐药后的 "化疗+"治疗需要更多的临床数据和实际证据来评估安全性和患者预后。随着研究的进展,多学科方法将成为克服这些挑战的关键。不断创新的治疗方法可以大大提高患者的生存率和生活质量。
{"title":"Deciphering the Dynamics of EGFR-TKI Resistance in Lung Cancer: Insights from Bibliometric Analysis.","authors":"Yinxue Zhou, Tingyu Wu, Jiaxing Sun, Huanhuan Bi, Yuting Xiao, Yanmei Shao, Weizhong Han, Hongmei Wang","doi":"10.2147/DDDT.S478910","DOIUrl":"10.2147/DDDT.S478910","url":null,"abstract":"<p><strong>Background: </strong>EGFR-TKI resistance poses a significant challenge in the treatment landscape of non-small cell lung cancer (NSCLC), prompting extensive research into mechanisms and therapeutic strategies. In this study, we conduct a bibliometric analysis to elucidate evolving research hotspots and trends in EGFR-TKI resistance, offering insights for clinical interventions and scientific inquiries.</p><p><strong>Methods: </strong>Publications spanning from 1996 to 2024, focusing on EGFR-TKI resistance in NSCLC, were sourced from the Web of Science Core Collection. Utilizing VOSviewer 1.6.19, CiteSpace 6.2. R2, and Scimago Graphica 1.0.35, we analyzed these articles to identify countries/regions and institutions, Journals, publications, key contributors, collaborations, and emerging topics.</p><p><strong>Results: </strong>An analysis of 8051 articles by 38,215 researchers from 86 countries shows growing interest in EGFR-TKI resistance mechanisms. Since 1996, publications have steadily increased, surpassing 500 per year after 2016, with a sharp rise in citations. Research articles make up 84% of publications, emphasizing scholarly focus. Global collaboration, especially among researchers in China, the US, and Japan, is strong. Leading institutions like Dana-Farber and Harvard, along with journals such as \"Lung Cancer\", are key in sharing findings. Professors Yi-Long Wu and William Pao are prominent contributors. Keyword analysis reveals core themes, including first-generation EGFR-TKIs, emerging agents like osimertinib, and research on the T790M mutation.</p><p><strong>Conclusion: </strong>EGFR-TKI resistance remains a critical issue in NSCLC treatment, driving ongoing research efforts worldwide. Focusing future research on clear identification of resistance mechanisms will guide post-resistance treatment strategies, necessitating further exploration, alongside the validation of emerging drugs through clinical trials. Moreover, \"chemo+\" treatments following EGFR-TKI resistance require more clinical data and real-world evidence for assessing safety and patient outcomes. As research advances, a multidisciplinary approach will be key to overcoming these challenges. Continued innovation in treatment could greatly enhance patient survival and quality of life.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of Propofol, Low and High Doses of Remimazolam on Hemodynamic and Inflammatory Response in Laparoscopic Surgery [Response to Letter].","authors":"Wenguang Deng, Zhiming Zeng, Qingyan Liu, Jingjing Deng, Liyu Wang, Hui Li, Yuenong Zhang","doi":"10.2147/DDDT.S493578","DOIUrl":"https://doi.org/10.2147/DDDT.S493578","url":null,"abstract":"","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-25eCollection Date: 2024-01-01DOI: 10.2147/DDDT.S480774
Cem Kaya, Alparslan Kapisiz, Sibel Eryilmaz, Ramazan Karabulut, Zafer Turkyilmaz, Mehmet Arda Inan, Gizem Yaz Aydin, Kaan Sonmez
Background: Ischemia-reperfusion (I/R) injury to the testis can lead to organ damage, infertility, and subfertility. The goal of this study was to investigate the effects of fasudil on this devastating condition.
Methods: Thirty male Long-Evans rats were divided into five groups: a control group (no torsion), rats administered fasudil (30 mg/kg, no torsion), rats subject to ischemia with no treatment (I) (I/R injury), injured rats that received treatment 1 (T1) (I/R with 30 mg/kg fasudil before detorsion), and injured rats that received treatment 2 (T2) (I/R with 30 mg/kg fasudil after detorsion). Serum levels of TNF-ɑ and IL-6, along with tissue levels of glutathione (GSH), malondialdehyde (MDA), caspase-3, and Johnsen Tubular Biopsy Score (JTBS), were measured.
Results: Group I exhibited significantly higher levels of MDA and caspase-3 than all other groups except T2 (p ˂ 0.05). Although the difference was not statistically significant, Group T2 exhibited lower MDA and caspase-3 levels than Group I (p ˃ 0.05). Additionally, Group I displayed significantly higher TNF-ɑ and IL-6 levels, and lower GSH and JTBS values, than the other groups (p ˂ 0.05).
Conclusion: Our findings indicate that fasudil protects the testis from I/R injury, particularly when administered early.
{"title":"Protective Effect of Fasudil on Testicular Ischemia-Reperfusion Injury in Rats.","authors":"Cem Kaya, Alparslan Kapisiz, Sibel Eryilmaz, Ramazan Karabulut, Zafer Turkyilmaz, Mehmet Arda Inan, Gizem Yaz Aydin, Kaan Sonmez","doi":"10.2147/DDDT.S480774","DOIUrl":"https://doi.org/10.2147/DDDT.S480774","url":null,"abstract":"<p><strong>Background: </strong>Ischemia-reperfusion (I/R) injury to the testis can lead to organ damage, infertility, and subfertility. The goal of this study was to investigate the effects of fasudil on this devastating condition.</p><p><strong>Methods: </strong>Thirty male Long-Evans rats were divided into five groups: a control group (no torsion), rats administered fasudil (30 mg/kg, no torsion), rats subject to ischemia with no treatment (I) (I/R injury), injured rats that received treatment 1 (T1) (I/R with 30 mg/kg fasudil before detorsion), and injured rats that received treatment 2 (T2) (I/R with 30 mg/kg fasudil after detorsion). Serum levels of TNF-ɑ and IL-6, along with tissue levels of glutathione (GSH), malondialdehyde (MDA), caspase-3, and Johnsen Tubular Biopsy Score (JTBS), were measured.</p><p><strong>Results: </strong>Group I exhibited significantly higher levels of MDA and caspase-3 than all other groups except T2 (p ˂ 0.05). Although the difference was not statistically significant, Group T2 exhibited lower MDA and caspase-3 levels than Group I (p ˃ 0.05). Additionally, Group I displayed significantly higher TNF-ɑ and IL-6 levels, and lower GSH and JTBS values, than the other groups (p ˂ 0.05).</p><p><strong>Conclusion: </strong>Our findings indicate that fasudil protects the testis from I/R injury, particularly when administered early.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142336339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease that lacks effective treatments. Qingchang Wenzhong Decoction (QCWZD) is a clinically effective herbal prescription that has been proven to attenuate intestinal inflammation in IBD. However, its molecular mechanism of action has not been clearly elucidated.
Purpose: We aimed to probe the mechanism of QCWZD for the treatment of IBD.
Methods: The dextran sulfate sodium (DSS)-induced mouse model of IBD was used to identify the molecular targets involved in the mechanism of action of QCWZD. Metagenomics sequencing was utilized to analyze the differences in gut microbiota and the functional consequences of these changes. Network pharmacology combined with RNA sequencing (RNA-seq) were employed to predict the molecular targets and mechanism of action of QCWZD, and were validated through in vivo experiments.
Results: Our results demonstrated that QCWZD treatment alleviated intestinal inflammation and accelerated intestinal mucosal healing that involved restoration of microbial homeostasis. This hypothesis was supported by the results of bacterial metagenomics sequencing that showed attenuation of gut dysbiosis by QCWZD treatment, especially the depletion of the pathogenic bacterial genus Bacteroides, while increasing the beneficial microorganism Akkermansia muciniphila that led to altered bacterial gene functions, such as metabolic regulation. Network pharmacology and RNA-seq analyses showed that Th17 cell differentiation plays an important role in QCWZD-based treatment of IBD. This was confirmed by in vivo experiments showing a marked decrease in the percentage of CD3+CD4+IL-17+ (Th17) cells. Furthermore, our results also showed that the key factors associated with Th17 cell differentiation (IL-17, NF-κB, TNF-α and IL-6) in the colon were significantly reduced in QCWZD-treated colitis mice.
Conclusion: QCWZD exerted beneficial effects in the treatment of IBD by modulating microbial homeostasis while inhibiting Th17 cell differentiation and its associated pathways, providing a novel and promising therapeutic strategy for the treatment of IBD.
{"title":"Combining Metagenomics, Network Pharmacology and RNA-Seq Strategies to Reveal the Therapeutic Effects and Mechanisms of Qingchang Wenzhong Decoction on Inflammatory Bowel Disease in Mice.","authors":"Yali Yuan, Hairong Hu, Zhongmei Sun, Wenting Wang, Zhibin Wang, Mengyu Zheng, Yunqi Xing, Wenji Zhang, Muyuan Wang, Xinyu Lu, Yitong Li, Chengtao Liang, Zhengdao Lin, Chune Xie, Junxiang Li, Tangyou Mao","doi":"10.2147/DDDT.S473688","DOIUrl":"https://doi.org/10.2147/DDDT.S473688","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease that lacks effective treatments. Qingchang Wenzhong Decoction (QCWZD) is a clinically effective herbal prescription that has been proven to attenuate intestinal inflammation in IBD. However, its molecular mechanism of action has not been clearly elucidated.</p><p><strong>Purpose: </strong>We aimed to probe the mechanism of QCWZD for the treatment of IBD.</p><p><strong>Methods: </strong>The dextran sulfate sodium (DSS)-induced mouse model of IBD was used to identify the molecular targets involved in the mechanism of action of QCWZD. Metagenomics sequencing was utilized to analyze the differences in gut microbiota and the functional consequences of these changes. Network pharmacology combined with RNA sequencing (RNA-seq) were employed to predict the molecular targets and mechanism of action of QCWZD, and were validated through in vivo experiments.</p><p><strong>Results: </strong>Our results demonstrated that QCWZD treatment alleviated intestinal inflammation and accelerated intestinal mucosal healing that involved restoration of microbial homeostasis. This hypothesis was supported by the results of bacterial metagenomics sequencing that showed attenuation of gut dysbiosis by QCWZD treatment, especially the depletion of the pathogenic bacterial genus <i>Bacteroides</i>, while increasing the beneficial microorganism <i>Akkermansia muciniphila</i> that led to altered bacterial gene functions, such as metabolic regulation. Network pharmacology and RNA-seq analyses showed that Th17 cell differentiation plays an important role in QCWZD-based treatment of IBD. This was confirmed by in vivo experiments showing a marked decrease in the percentage of CD3<sup>+</sup>CD4<sup>+</sup>IL-17<sup>+</sup> (Th17) cells. Furthermore, our results also showed that the key factors associated with Th17 cell differentiation (IL-17, NF-κB, TNF-α and IL-6) in the colon were significantly reduced in QCWZD-treated colitis mice.</p><p><strong>Conclusion: </strong>QCWZD exerted beneficial effects in the treatment of IBD by modulating microbial homeostasis while inhibiting Th17 cell differentiation and its associated pathways, providing a novel and promising therapeutic strategy for the treatment of IBD.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24eCollection Date: 2024-01-01DOI: 10.2147/DDDT.S474850
Kamrin Kamalpersad, Giuseppe Luna, Bruce Sunderland, Petra Czarniak
Purpose: Amoxicillin/clavulanate antibiotic combination is suitable for treating a range of infections, including some suited for Outpatient Parenteral Antimicrobial Therapy (OPAT). The aim of the study was to evaluate shelf-life values of amoxicillin at clinical concentrations in the presence of clavulanate for use in OPAT.
Methods: A stability-indicating HPLC assay was developed and validated. Kinetic studies were performed at 1 mg/mL and 15 mg/mL amoxicillin at 40-60 °C. Studies in elastomeric infusers included the pH lowered from 8.73 to 6.52 for 1 mg/mL; 8.85 to 7.69 for 7.5 mg/mL and 8.68 to 8.40 for 15 mg/mL amoxicillin plus clavulanate and stored at 2.9 °C.
Results: Amoxicillin and clavulanate eluted at 5.2 and 3.0 minutes, respectively, with linear concentration relationships. Forced degradation retained base-line separation of each component in the presence of degradation products. Amoxicillin 1 mg/mL had a shelf-life of 4.85 hours at pH 6.53 and 40 °C which on extrapolation to 25 °C was 22.8 h. Clavulanate was 1.38 h at 40 °C and 4.0 h at 25 °C. Amoxicillin 15 mg/mL at pH 8.34 gave a shelf-life of 0.11 h at 40 °C and clavulanate 0.41 h. In elastomeric infusers, amoxicillin 1 mg/mL, with lowering pH from 8.73 to 6.52, improved the shelf-life at 2.9 °C from 72 to >263.8 h and similarly for clavulanate. At 7.5 mg/mL amoxicillin, lowering pH from 8.85 to 7.69 improved the shelf-life from 4.2 to 51.8 h and clavulanate from 4.2 to 48.0 h. At 15 mg/mL amoxicillin, the shelf-life values at pH 8.68 or 8.40 were 3.8 h and 1.6 h and similarly for clavulanate.
Conclusion: Amoxicillin and clavulanate showed adequate stability at 2.9 °C for OPAT storage at 1 mg/mL and possibly 7.5 mg/mL, but not 15 mg/mL. Low shelf-life values at 25 °C also limit administration times.
{"title":"An Evaluation of Amoxicillin/Clavulanate Stability in Aqueous Systems, Including Its Suitability for Outpatient Parenteral Antimicrobial Therapy (OPAT).","authors":"Kamrin Kamalpersad, Giuseppe Luna, Bruce Sunderland, Petra Czarniak","doi":"10.2147/DDDT.S474850","DOIUrl":"10.2147/DDDT.S474850","url":null,"abstract":"<p><strong>Purpose: </strong>Amoxicillin/clavulanate antibiotic combination is suitable for treating a range of infections, including some suited for Outpatient Parenteral Antimicrobial Therapy (OPAT). The aim of the study was to evaluate shelf-life values of amoxicillin at clinical concentrations in the presence of clavulanate for use in OPAT.</p><p><strong>Methods: </strong>A stability-indicating HPLC assay was developed and validated. Kinetic studies were performed at 1 mg/mL and 15 mg/mL amoxicillin at 40-60 °C. Studies in elastomeric infusers included the pH lowered from 8.73 to 6.52 for 1 mg/mL; 8.85 to 7.69 for 7.5 mg/mL and 8.68 to 8.40 for 15 mg/mL amoxicillin plus clavulanate and stored at 2.9 °C.</p><p><strong>Results: </strong>Amoxicillin and clavulanate eluted at 5.2 and 3.0 minutes, respectively, with linear concentration relationships. Forced degradation retained base-line separation of each component in the presence of degradation products. Amoxicillin 1 mg/mL had a shelf-life of 4.85 hours at pH 6.53 and 40 °C which on extrapolation to 25 °C was 22.8 h. Clavulanate was 1.38 h at 40 °C and 4.0 h at 25 °C. Amoxicillin 15 mg/mL at pH 8.34 gave a shelf-life of 0.11 h at 40 °C and clavulanate 0.41 h. In elastomeric infusers, amoxicillin 1 mg/mL, with lowering pH from 8.73 to 6.52, improved the shelf-life at 2.9 °C from 72 to >263.8 h and similarly for clavulanate. At 7.5 mg/mL amoxicillin, lowering pH from 8.85 to 7.69 improved the shelf-life from 4.2 to 51.8 h and clavulanate from 4.2 to 48.0 h. At 15 mg/mL amoxicillin, the shelf-life values at pH 8.68 or 8.40 were 3.8 h and 1.6 h and similarly for clavulanate.</p><p><strong>Conclusion: </strong>Amoxicillin and clavulanate showed adequate stability at 2.9 °C for OPAT storage at 1 mg/mL and possibly 7.5 mg/mL, but not 15 mg/mL. Low shelf-life values at 25 °C also limit administration times.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11440154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Obesity represents a substantial risk factor for a multitude of metabolic disorders, which seriously threatens human life and health. As the global obesity epidemic intensifies, obesity-related nephropathy (ORN) has attracted great attention. ORN arises from both physical/mechanical and non-physical insults to the glomerular and tubular structures precipitated by obesity, culminating in structural impairments and functional aberrations within the kidneys. Physical injury factors include changes in renal hemodynamics, renal compression, and mechanical stretching of podocytes. Non-physical injury factors include overactivation of the RAAS system, insulin resistance, lipotoxicity, inflammation, and dysregulation of bile acid metabolism. Exploring molecules that target modulation of physical or nonphysical injury factors is a potential approach to ORN treatment. ORN is characterized clinically by microproteinuria and pathologically by glomerulomegaly, which is atypical and makes early diagnosis difficult. Investigating early diagnostic markers for ORN thus emerges as a critical direction for future research. Additionally, there is no specific drug for ORN in clinical treatment, which mainly focuses on weight reduction, mitigating proteinuria, and preserving renal function. In our review, we delineate a progressive therapeutic approach involving enhancements in lifestyle, pharmacotherapy, and bariatric surgery. Our emphasis underscores glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as poised to emerge as pivotal therapeutic modalities for ORN in forthcoming clinical avenues.
{"title":"New Perspectives on Obesity-Associated Nephropathy from Pathophysiology to Therapeutics: Revealing the Promise of GLP-1 RA Therapy.","authors":"Linan Ren, Feng Ju, Siyuan Liu, Yunjia Cai, Xiaokun Gang, Guixia Wang","doi":"10.2147/DDDT.S476815","DOIUrl":"https://doi.org/10.2147/DDDT.S476815","url":null,"abstract":"<p><p>Obesity represents a substantial risk factor for a multitude of metabolic disorders, which seriously threatens human life and health. As the global obesity epidemic intensifies, obesity-related nephropathy (ORN) has attracted great attention. ORN arises from both physical/mechanical and non-physical insults to the glomerular and tubular structures precipitated by obesity, culminating in structural impairments and functional aberrations within the kidneys. Physical injury factors include changes in renal hemodynamics, renal compression, and mechanical stretching of podocytes. Non-physical injury factors include overactivation of the RAAS system, insulin resistance, lipotoxicity, inflammation, and dysregulation of bile acid metabolism. Exploring molecules that target modulation of physical or nonphysical injury factors is a potential approach to ORN treatment. ORN is characterized clinically by microproteinuria and pathologically by glomerulomegaly, which is atypical and makes early diagnosis difficult. Investigating early diagnostic markers for ORN thus emerges as a critical direction for future research. Additionally, there is no specific drug for ORN in clinical treatment, which mainly focuses on weight reduction, mitigating proteinuria, and preserving renal function. In our review, we delineate a progressive therapeutic approach involving enhancements in lifestyle, pharmacotherapy, and bariatric surgery. Our emphasis underscores glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as poised to emerge as pivotal therapeutic modalities for ORN in forthcoming clinical avenues.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}