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Evaluating the Effectiveness and Safety of Fecal Management Systems among Severely Ill Patients Suffering from Fecal Incontinence: A Retrospective Cohort Study 评估大便失禁重症患者粪便管理系统的有效性和安全性:回顾性队列研究
IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-09 DOI: 10.1155/2024/7644383
Xiecheng Zhou, Ying Yue, Lifeng Gong, Huipeng Wang, Zhou Xin, Yuhui Cui, Wenjie Chen, Xin Wang, Jian Shi, Yuankun Cai

Background. Few large-sample studies have examined the use of fecal management systems (FMSs) in intensive care units (ICUs) or evaluated the associated complications. This study aims to assess the effectiveness and safety of FMS for stool diversion in ICU patients with fecal incontinence (FI). Methods. We enrolled 381 FI patients, assigning them to either an FMS group (n = 134), which used a fecal management device, or a usual care (UC) group (n = 247) that received standard care including regular perianal cleaning. Results. The FMS group reported lower incidence and severity of incontinence-associated dermatitis (IAD) and higher Braden Scale scores (10.42 ± 2.77) compared to the UC group (9.71 ± 2.56), indicating reduced pressure ulcer risk. Notably, FMS-associated complications were minimal, with only 5 patients (3.73%) affected; one required surgical intervention for rectal mucosal bleeding. Conclusions. FMS significantly reduced stool-associated skin irritation, lowered the incidence of IAD and pressure injuries, and improved nurses’ convenience compared to UC.

背景。很少有大样本研究对重症监护病房(ICU)中粪便管理系统(FMS)的使用情况或相关并发症进行评估。本研究旨在评估粪便管理系统在重症监护病房粪便失禁(FI)患者粪便转运中的有效性和安全性。方法。我们招募了 381 名大便失禁患者,将他们分配到使用粪便管理装置的 FMS 组(n = 134)或接受标准护理(包括定期清洗肛周)的常规护理(UC)组(n = 247)。结果显示与UC组(9.71 ± 2.56)相比,FMS组尿失禁相关皮炎(IAD)的发生率和严重程度较低,布莱登量表评分(10.42 ± 2.77)较高,表明压疮风险降低。值得注意的是,FMS 相关并发症极少,仅有 5 名患者(3.73%)受到影响;其中一名患者因直肠粘膜出血而需要手术治疗。结论与 UC 相比,FMS 大大减少了粪便对皮肤的刺激,降低了 IAD 和压伤的发生率,为护士提供了更多便利。
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引用次数: 0
Use of Tocolytic Agents in Preterm Labor: A Cross-Sectional Analysis from a Chinese Real-World Study from 2016 to 2021 在早产中使用促凝血剂:2016-2021年中国真实世界研究的横断面分析
IF 2 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-06-10 DOI: 10.1155/2024/3206060
Haoran Liu, Xianli Wang

What Is Known and Objective. Tocolytic agents are used to prolong gestational age and prevent immediate preterm birth (PTB). This study aims to provide an overview of the use of tocolytics among patients with PTB in China through retrospectively analyzing trends in application, influencing factors, and inappropriate prescriptions. Methods. The prescription data of five tocolytic agents from 2016 to 2021 were extracted from the database of the Hospital Prescription Analysis Cooperation Project. Drug consumption was expressed as number of prescriptions, cost of prescriptions, and DDDs (defined daily doses). Pearson correlation analysis was used to examine the association between DDDs and DDC (defined daily cost). The appropriateness of prescriptions was analyzed in terms of drug dosage form, administration, clinical diagnosis, and combined medication. Results. The total number of tocolytic prescriptions and the total cost of tocolytic agents increased by 6.12% and 387.58%, respectively, over the six-year duration of the study. From 2016 to 2021, the ranking of the number of prescriptions and DDDs of tocolytic agents was magnesium sulfate > ritodrine > nifedipine > indomethacin > atosiban. During the study period, the cost of tocolytic agents increased significantly, which was mainly related to the increased costs of magnesium sulfate in 2017 and atosiban in 2018 and 2019. The ranking of DDCs was atosiban > ritodrine > magnesium sulfate > nifedipine = indomethacin from 2016 to 2021. For atosiban, the DDC was negatively correlated with the DDDs. Inappropriate prescription, which accounted for 14.84% of all prescriptions, was mainly manifested in the inappropriate selection of nifedipine dosage form, low frequency of nifedipine and indomethacin, and overdosing of ritodrine. Furthermore, 22.87% of tocolytic prescriptions remained active after 34 weeks of gestation, and 7.24% of the prescriptions authorized the use of combination drugs, with magnesium sulfate and nifedipine being the most commonly prescribed combination. What Is New and Conclusion. Magnesium sulfate, ritodrine, and nifedipine were the top three tocolytic agents. As the inappropriate use of tocolytic agents continues to persist, it is important to intensify efforts to ensure the safety and the appropriateness of maternal medication.

已知信息和目标。促溶血药物用于延长胎龄和预防即刻性早产(PTB)。本研究旨在通过回顾性分析应用趋势、影响因素和不当处方,概述中国早产儿患者使用溶血剂的情况。方法从 "医院处方分析合作项目 "数据库中提取2016年至2021年五种解痉剂的处方数据。药物消耗量以处方数量、处方费用和DDD(定义日剂量)表示。皮尔逊相关分析用于研究DDDs与DDC(规定日剂量)之间的关联。从药物剂型、给药方式、临床诊断和合并用药等方面分析了处方的适当性。结果在研究的六年时间里,解痉剂处方总数和总费用分别增加了 6.12% 和 387.58%。从2016年到2021年,解痉剂处方数和DDD排名依次为硫酸镁> 利托君> 硝苯地平> 吲哚美辛> 阿托西班。在研究期间,溶血剂的成本明显增加,这主要与 2017 年硫酸镁和 2018 年、2019 年阿托西班的成本增加有关。2016年至2021年,DDCs的排名为阿托西班>利托君>硫酸镁>硝苯地平=吲哚美辛。就阿托西班而言,DDC 与 DDD 呈负相关。不恰当处方占所有处方的14.84%,主要表现为硝苯地平剂型选择不当、硝苯地平和吲哚美辛使用频率低、利多君用药过量等。此外,22.87%的促溶血处方在妊娠 34 周后仍在使用,7.24%的处方授权使用联合用药,其中硫酸镁和硝苯地平是最常见的联合用药。新内容和结论。硫酸镁、利托君和硝苯地平是前三种解痉剂。由于不适当使用促溶血药物的现象依然存在,因此必须加大力度确保孕产妇用药的安全性和适当性。
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引用次数: 0
The Catechol-O-Methyltransferase (COMT) Val158Met Polymorphism Is Associated with Oxycodone Requirements, Adverse Effects, and Pain Sensitivity in Cancer Patients 儿茶酚-O-甲基转移酶 (COMT) Val158Met 多态性与癌症患者的羟考酮需求量、不良反应和疼痛敏感性有关
IF 2 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-06-05 DOI: 10.1155/2024/9990112
Silu Xu, Nan Wu, Xin Liu, Jiali Zhu, Zhixian Liu

Purpose. Catechol-O-methyltransferase (COMT) participates in the regulation of dopaminergic and adrenergic neurotransmission. COMT Val158Met polymorphism influences the efficacy and safety of opioids, but its association with oxycodone treatment in patients with cancer pain is yet to be elucidated. Hence, this study aimed to investigate the influence of COMT Val158Met polymorphism on oxycodone requirements, drug adverse effects, and pain sensitivity in patients with cancer. Methods. Patients with moderate to severe cancer pain treated with oxycodone were enrolled, of which 101 patients completed the study. All patients were genotyped for COMT Val158Met polymorphism using DNA from blood samples and were categorized into the wild-type group (n = 50) comprising individuals with the Val/Val genotype and the mutant group (n = 51) encompassing those with the Val/Met or Met/Met genotype. Numerical rating scale (NRS) scores, oxycodone requirements, and the incidence of oxycodone-related adverse drug reactions were compared between the two groups. Results. Patients in the mutant group exhibited higher NRS scores (6.18 ± 1.40) before the oxycodone treatment than those in the wild-type (5.48 ± 1.54) group (P = 0.017). Patients in the wild-type group required more oxycodone (96.00 ± 146.19 mg/24 h) than those in the mutant (77.25 ± 83.91 mg/24 h) group (P = 0.0365). The incidence rates of dysuria (2.0% vs. 16.0%, P = 0.016) and fatigue (0.0% vs. 12.0%, P = 0.013) were significantly lower in the mutant group than those in the wild-type group. Moreover, patients with at least one Met allele showed a lower risk of suffering from oxycodone-related side effects than those with the wild homozygote (41.2% vs. 68.0%, P = 0.007). Conclusion. Genetic variations in the COMT Val158Met gene may contribute to variability in the efficacy and safety of oxycodone in cancer pain treatment. The findings from this study emphasize the potential of pharmacogenetics in personalizing pain management. Furthermore, oxycodone therapeutic strategies can be designed based on genetic polymorphisms.

目的:儿茶酚-O-甲基转移酶(COMT儿茶酚-O-甲基转移酶(COMT)参与多巴胺能和肾上腺素能神经递质的调节。COMT Val158Met 多态性会影响阿片类药物的疗效和安全性,但其与癌痛患者服用羟考酮治疗的关系尚未阐明。因此,本研究旨在探讨 COMT Val158Met 多态性对癌症患者的羟考酮需求量、药物不良反应和疼痛敏感性的影响。研究方法研究招募了接受羟考酮治疗的中重度癌痛患者,其中 101 名患者完成了研究。利用血液样本中的 DNA 对所有患者进行 COMT Val158Met 多态性基因分型,并将其分为野生型组(n = 50)和突变型组(n = 51),野生型组包括 Val/Val 基因型的患者,突变型组包括 Val/Met 或 Met/Met 基因型的患者。对两组患者的数字评分量表(NRS)评分、羟考酮需求量和羟考酮相关药物不良反应发生率进行了比较。结果显示突变体组患者在接受羟考酮治疗前的 NRS 评分(6.18 ± 1.40)高于野生型组(5.48 ± 1.54)(P = 0.017)。野生型组患者(96.00 ± 146.19 毫克/24 小时)比突变型组患者(77.25 ± 83.91 毫克/24 小时)需要更多的羟考酮(P = 0.0365)。突变体组的排尿困难发生率(2.0% vs. 16.0%,P = 0.016)和疲劳发生率(0.0% vs. 12.0%,P = 0.013)显著低于野生型组。此外,至少有一个 Met 等位基因的患者出现羟考酮相关副作用的风险低于野生同型基因患者(41.2% 对 68.0%,P = 0.007)。结论COMT Val158Met 基因的遗传变异可能会导致羟考酮在癌痛治疗中的疗效和安全性的变化。本研究的发现强调了药物遗传学在个性化疼痛治疗中的潜力。此外,还可以根据基因多态性设计羟考酮治疗策略。
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引用次数: 0
Elucidating the Immune Microenvironment and Therapeutic Targets in Nasopharyngeal Carcinoma through Bioinformatics 通过生物信息学阐明鼻咽癌的免疫微环境和治疗靶点
IF 2 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-06-05 DOI: 10.1155/2024/4239046
Shasha He, Yongbo Zheng

Background. Nasopharyngeal carcinoma (NPC), prevalent in East Asia and associated with EBV infection, poses unique challenges due to its complex immunological interactions. This study aims to dissect the molecular and immune mechanisms of NPC, providing a pathway to novel treatments. Methods. Through bioinformatics, we analyzed gene expression and immune cell infiltration in NPC tissues. Differential gene expression profiling, single-cell RNA sequencing, and gene set variation analysis (GSVA) were performed to understand the immune landscape and identify EBV-related molecular changes. Results. The differential gene expression analysis highlighted a diverse immune cell composition, suggesting an intricate immune evasion landscape. GSVA pinpointed pathways linked to tumor immunity and EBV pathogenesis. Notably, the expression of immune checkpoints, such as PD-L1, was significantly associated with NPC, offering a potential target for immunotherapy. Conclusions. Our findings underscore the potential of immunotherapeutic approaches in NPC, particularly those modulating the PD-1/PD-L1 axis. The integration of bioinformatics and immunology in NPC research provides a foundation for personalized medicine and warrants further exploration into combination therapies to enhance treatment efficacy.

背景。鼻咽癌(NPC)流行于东亚地区,与EB病毒感染有关,因其复杂的免疫相互作用而构成了独特的挑战。本研究旨在剖析鼻咽癌的分子和免疫机制,为新型治疗提供途径。研究方法通过生物信息学,我们分析了鼻咽癌组织中的基因表达和免疫细胞浸润。我们进行了差异基因表达谱分析、单细胞 RNA 测序和基因组变异分析 (GSVA),以了解免疫状况并确定与 EBV 相关的分子变化。结果。差异基因表达分析凸显了免疫细胞组成的多样性,表明存在错综复杂的免疫逃避格局。GSVA 确定了与肿瘤免疫和 EBV 发病机制相关的通路。值得注意的是,免疫检查点(如 PD-L1)的表达与鼻咽癌密切相关,为免疫疗法提供了潜在靶点。结论我们的发现强调了免疫治疗方法在鼻咽癌中的潜力,尤其是那些调节 PD-1/PD-L1 轴的方法。在鼻咽癌研究中整合生物信息学和免疫学为个性化医疗奠定了基础,值得进一步探索联合疗法以提高疗效。
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引用次数: 0
Factors Influencing Insulin Adherence among Outpatients with Type 2 Diabetes Mellitus and the Impact of Pharmaceutical Intervention: A Randomized Clinical Trial 影响门诊 2 型糖尿病患者胰岛素依从性的因素及药物干预的影响:随机临床试验
IF 2 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-05-27 DOI: 10.1155/2024/5518977
Ting He, Hao Wang, Wen Sun, Lintong Li, Li Li, Cheng Ji

Aims. This study aimed to identify and analyze the factors significantly influencing long-term insulin medication adherence among outpatients and to evaluate whether pharmaceutical interventions targeting these factors can improve patient medication adherence and glycemic control. Methods. A cohort of 180 patients was recruited from a tertiary hospital in Nanjing, China. Factors potentially influencing insulin adherence were scrutinized employing the KAP (knowledge, attitude/belief, and practice) health behavior model. Baseline characteristics were extracted from the hospital information system, while patient knowledge of the disease and medication, medication adherence, medication beliefs, and management self-efficacy were assessed, respectively, using self-developed questionnaires, MMAS-8, C-DMSES, and BMQ scales. Univariate and multivariate analyses were conducted to determine the impact of these factors on insulin adherence. Following this, participants were randomly allocated to either the intervention or control group. The intervention group received three months of weekly telephone sessions and educational interventions targeting facets such as medication knowledge and beliefs, while the control group received standard care. After the intervention, insulin adherence and glycemic control conditions of both groups were collected and re-evaluated. Results. After excluding lost-to-follow-up patients, 152 individuals were analyzed (intervention: 75 and control: 77). Multivariate analyses revealed factors influencing insulin adherence, including age, diabetes duration, health insurance status, HbA1c level, disease and medication knowledge, diabetes management self-efficacy, and medication beliefs (P < 0.05). Before targeted pharmaceutical care, no significant differences existed in insulin adherence, HbA1c levels, management self-efficacy, knowledge, or medication beliefs between intervention and control groups (P > 0.05). However, subsequent pharmaceutical intervention notably improved adherence, HbA1c levels, self-efficacy, knowledge, and medication beliefs (P < 0.05). Conclusion. This study examines the impact of glycemic control, health insurance status, management self-efficacy, level of knowledge, and medication beliefs on improving insulin medication adherence in patients with type 2 diabetes mellitus. Targeted pharmaceutical intervention can enhance medication adherence, improve glucose control, and promote rational insulin use. This trial is registered with ChiCTR2300074444.

研究目的本研究旨在确定和分析对门诊患者长期胰岛素用药依从性有重大影响的因素,并评估针对这些因素的药物干预措施能否改善患者的用药依从性和血糖控制。研究方法从中国南京的一家三级甲等医院招募了180名患者。采用KAP(知识、态度/信念和实践)健康行为模型对可能影响胰岛素依从性的因素进行了仔细研究。基线特征从医院信息系统中提取,而患者对疾病和药物的知识、用药依从性、用药信念和管理自我效能则分别通过自主开发的问卷、MMAS-8、C-DMSES和BMQ量表进行评估。通过单变量和多变量分析来确定这些因素对胰岛素依从性的影响。随后,参与者被随机分配到干预组或对照组。干预组接受为期三个月的每周电话会议和针对用药知识和信念等方面的教育干预,而对照组则接受标准护理。干预结束后,收集并重新评估两组受试者的胰岛素依从性和血糖控制情况。结果显示剔除失去随访的患者后,共分析了 152 人(干预组 75 人,对照组 77 人)。多变量分析显示,影响胰岛素依从性的因素包括年龄、糖尿病病程、医疗保险状况、HbA1c水平、疾病和用药知识、糖尿病管理自我效能和用药信念(P < 0.05)。在进行有针对性的药物治疗之前,干预组和对照组在胰岛素依从性、HbA1c水平、管理自我效能、知识或用药信念方面没有明显差异(P >0.05)。然而,随后的药物干预显著改善了患者的依从性、HbA1c 水平、自我效能、知识和用药信念(P < 0.05)。结论本研究探讨了血糖控制、医疗保险状况、管理自我效能感、知识水平和用药信念对改善 2 型糖尿病患者胰岛素用药依从性的影响。有针对性的药物干预可以提高用药依从性,改善血糖控制,促进胰岛素的合理使用。本试验注册号为 ChiCTR2300074444。
{"title":"Factors Influencing Insulin Adherence among Outpatients with Type 2 Diabetes Mellitus and the Impact of Pharmaceutical Intervention: A Randomized Clinical Trial","authors":"Ting He,&nbsp;Hao Wang,&nbsp;Wen Sun,&nbsp;Lintong Li,&nbsp;Li Li,&nbsp;Cheng Ji","doi":"10.1155/2024/5518977","DOIUrl":"https://doi.org/10.1155/2024/5518977","url":null,"abstract":"<div>\u0000 <p><i>Aims</i>. This study aimed to identify and analyze the factors significantly influencing long-term insulin medication adherence among outpatients and to evaluate whether pharmaceutical interventions targeting these factors can improve patient medication adherence and glycemic control. <i>Methods</i>. A cohort of 180 patients was recruited from a tertiary hospital in Nanjing, China. Factors potentially influencing insulin adherence were scrutinized employing the KAP (knowledge, attitude/belief, and practice) health behavior model. Baseline characteristics were extracted from the hospital information system, while patient knowledge of the disease and medication, medication adherence, medication beliefs, and management self-efficacy were assessed, respectively, using self-developed questionnaires, MMAS-8, C-DMSES, and BMQ scales. Univariate and multivariate analyses were conducted to determine the impact of these factors on insulin adherence. Following this, participants were randomly allocated to either the intervention or control group. The intervention group received three months of weekly telephone sessions and educational interventions targeting facets such as medication knowledge and beliefs, while the control group received standard care. After the intervention, insulin adherence and glycemic control conditions of both groups were collected and re-evaluated. <i>Results</i>. After excluding lost-to-follow-up patients, 152 individuals were analyzed (intervention: 75 and control: 77). Multivariate analyses revealed factors influencing insulin adherence, including age, diabetes duration, health insurance status, HbA1c level, disease and medication knowledge, diabetes management self-efficacy, and medication beliefs (<i>P</i> &lt; 0.05). Before targeted pharmaceutical care, no significant differences existed in insulin adherence, HbA1c levels, management self-efficacy, knowledge, or medication beliefs between intervention and control groups (<i>P</i> &gt; 0.05). However, subsequent pharmaceutical intervention notably improved adherence, HbA1c levels, self-efficacy, knowledge, and medication beliefs (<i>P</i> &lt; 0.05). <i>Conclusion</i>. This study examines the impact of glycemic control, health insurance status, management self-efficacy, level of knowledge, and medication beliefs on improving insulin medication adherence in patients with type 2 diabetes mellitus. Targeted pharmaceutical intervention can enhance medication adherence, improve glucose control, and promote rational insulin use. This trial is registered with ChiCTR2300074444.</p>\u0000 </div>","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"2024 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/5518977","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141246106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bioequivalence and Safety of Two Formulations of Tofacitinib Citrate Tablets in Healthy Chinese Volunteers under Fasting and Fed Conditions: Randomized, Open-Label, 2-Period, Single-Dose, Crossover Trials 枸橼酸托法替尼片两种制剂在中国健康志愿者空腹和进食条件下的生物等效性和安全性:随机、开放标签、两阶段、单剂量、交叉试验
IF 2 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-05-23 DOI: 10.1155/2024/7914586
Yanping Liu, Yuping Ning, Yan Shi, Man Xu, Juanmin Tao, Yafen Dong, Jun Ma, Yan Qiu

Purpose. To evaluate the bioequivalence of two different tofacitinib citrate tablets formulations among healthy Chinese subjects under fasting and fed conditions and to observe the safety of test preparation and reference preparation in healthy subjects. Method. This randomized, open-label, 2-period, crossover, bioequivalence study included 64 healthy Chinese subjects (fasting: n = 32, fed: n = 32). The subjects were assigned to receive a single 5-mg dose of the test or a reference tofacitinib citrate tablets. Blood samples were collected at predose and up to 24 hours after dosing. Area under the plasma concentration time curve from zero to the last measurable concentration (AUC0-t), the area from time zero to infinite (AUC0-∞), and maximum plasma concentration (Cmax) were used for bioequivalence assessment. Safety assessment was conducted by vital signs, physical examination, laboratory examination, and 12-lead electrocardiogram during the study, from the time the subject receiving the test drug to the end of the last visit. Results. Under fed condition, the 90% CIs of the geometric mean ratios of the test/reference for tofacitinib citrate tablets were 98.40–104.16% for AUC0-t, 89.96–116.70% for Cmax, and 98.50–104.15% for AUC0-∞. Under fasting condition, the 90% CIs of the geometric mean ratios of the test/reference for tofacitinib citrate tablets were 93.65–101.60% for AUC0-t, 90.06–109.15% for Cmax, and 93.88–101.51% for AUC0-∞. There were no serious events. Conclusion. The 90% CI for the geometric mean ratio (test/reference) of Cmax, AUC0-t, and AUC0-∞ were within the range of 80.00%–125.00%, indicating that the test formulation was equivalent to the reference formulation in healthy Chinese subjects under both fasting and fed conditions. They are similar in terms of safety. This trial is registered with CTR20190366.

目的评价枸橼酸托法替尼片两种不同制剂在中国健康受试者空腹和进食条件下的生物等效性,并观察试验制剂和参比制剂在健康受试者中的安全性。研究方法这项随机、开放标签、两阶段、交叉、生物等效性研究纳入了64名中国健康受试者(空腹:32人,进食:32人)。受试者被分配接受单次5毫克剂量的枸橼酸托法替尼试验药片或参比药片。在用药前和用药后 24 小时内采集血样。生物等效性评估采用了从零到最后可测量浓度的血浆浓度时间曲线下面积(AUC0-t)、从零时到无限时的面积(AUC0-∞)和最大血浆浓度(Cmax)。在研究期间,从受试者接受试验药物到最后一次访问结束,通过生命体征、体格检查、实验室检查和 12 导联心电图进行安全性评估。研究结果在进食条件下,枸橼酸托法替尼片的AUC0-t、Cmax和AUC0-∞的试验/参考几何平均比值的90%CI分别为98.40%-104.16%、89.96%-116.70%和98.50%-104.15%。在空腹条件下,枸橼酸托法替尼片的AUC0-t、Cmax和AUC0-∞的试验/参考几何平均比值的90%CI分别为93.65-101.60%、90.06-109.15%和93.88-101.51%。没有发生严重事件。结论Cmax、AUC0-t和AUC0-∞的几何平均比值(试验/参比)的90% CI在80.00%-125.00%范围内,表明在空腹和进食条件下,中国健康受试者的试验制剂与参比制剂具有等效性。就安全性而言,两者相似。该试验的注册号为 CTR20190366。
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引用次数: 0
Echinatin Inhibits Oxidative Stress and Inflammatory Processes in Trophoblast Cells by Inhibiting TLR4-MyD88-NF-κB Pathway in Preeclampsia 刺五加通过抑制子痫前期 TLR4-MyD88-NF-κB 通路抑制滋养层细胞的氧化应激和炎症过程
IF 2 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-05-20 DOI: 10.1155/2024/2296727
Xiangyun Deng, Hu Chen, Yang Zhang, Fengmei Xu, Qian Zhou

Background. Preeclampsia (PE) is a common obstetric disorder hallmarked by impaired trophoblast invasion and a skew toward an inflammatory immune response. Echinatin, a flavonoid with established anti-inflammatory, antioxidant, and anticancer activities, may offer therapeutic benefits in PE. Our study aimed to investigate the effect of echinatin on preeclampsia in vitro and in vivo and to reveal the potential molecular mechanism of its action. Methods. Eighteen adult female Sprague Dawley rats were randomized into three experimental groups: a PE model group, a PE + echinatin treatment group, and a PE + echinatin treatment group with TLR4 overexpression. Placental tissue CK7 expression was assessed by immunohistochemistry. TUNEL immunofluorescence staining quantified placental cell apoptosis. Cell viability, proliferation, and migration were evaluated using cell counting kit-8, EdU incorporation, and Transwell assays, respectively. Oxidative stress parameters of malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured. Flow cytometry determined cell apoptosis and intracellular reactive oxygen species (ROS) levels. Western blotting evaluated the expression of proteins related to the TLR4-MyD88-NF-κB signaling pathway, and the concentrations of TNF-α, IL-6, and IL-18 were measured with ELISA kits. Results. Echinatin mitigated placental damage, reduced apoptosis, and increased CK7 expression. It significantly enhanced HTR-8/SVneo cell viability and migration. Echinatin also counteracted H2O2-induced ROS production and cell death in HTR-8/SVneo cells. Moreover, it inhibited the expression of proteins within the TLR4-MyD88-NF-κB signaling cascade. Overexpression of TLR4 negated echinatin’s protective effects. Conclusion. Echinatin exerts protective effects against oxidative stress and inflammation in PE by targeting the TLR4-MyD88-NF-κB pathway, suggesting its therapeutic potential for the management of preeclampsia.

背景。子痫前期(PE)是一种常见的产科疾病,其特点是滋养细胞侵袭能力受损,并偏向于炎症性免疫反应。Echinatin是一种黄酮类化合物,具有公认的抗炎、抗氧化和抗癌活性,可能对子痫前期有治疗作用。我们的研究旨在探讨紫锥菊素在体外和体内对子痫前期的影响,并揭示其潜在的分子作用机制。研究方法将18只成年雌性Sprague Dawley大鼠随机分为三个实验组:子痫模型组、子痫+紫锥菊素治疗组和子痫+紫锥菊素治疗并TLR4过表达组。通过免疫组化评估胎盘组织 CK7 的表达。TUNEL 免疫荧光染色可量化胎盘细胞凋亡。细胞活力、增殖和迁移分别通过细胞计数试剂盒-8、EdU结合和Transwell试验进行评估。还测量了丙二醛、超氧化物歧化酶和谷胱甘肽过氧化物酶等氧化应激参数。流式细胞术测定了细胞凋亡和细胞内活性氧(ROS)水平。Western 印迹法评估了与 TLR4-MyD88-NF-κB 信号通路相关的蛋白质表达,并用 ELISA 试剂盒测定了 TNF-α、IL-6 和 IL-18 的浓度。结果棘白苷减轻了胎盘损伤,减少了细胞凋亡,增加了CK7的表达。它能明显增强 HTR-8/SVneo 细胞的活力和迁移。棘白还能抵消 H2O2 诱导的 ROS 生成和 HTR-8/SVneo 细胞的死亡。此外,它还抑制了 TLR4-MyD88-NF-κB 信号级联中蛋白质的表达。过量表达 TLR4 会抵消棘白蛋白的保护作用。结论刺五加通过靶向TLR4-MyD88-NF-κB途径对子痫前期的氧化应激和炎症产生保护作用,这表明刺五加具有治疗子痫前期的潜力。
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引用次数: 0
Population Pharmacokinetic Analysis of Selumetinib and Its N-desmethyl Metabolite in Japanese and Non-Japanese Pediatric Patients with Neurofibromatosis Type 1 and Inoperable Plexiform Neurofibromas 塞卢米替尼及其 N-去甲基代谢物在日本和非日本籍 1 型神经纤维瘤病和无法手术的丛状神经纤维瘤儿科患者中的群体药代动力学分析
IF 2 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-05-14 DOI: 10.1155/2024/4939254
Takumi Shinbo, Mitsuo Higashimori, Ignacio González-García, Maria Learoyd

Background. Selumetinib, a mitogen-activated protein kinase kinase 1/2 inhibitor, has been approved in several countries and regions, including Japan, for the treatment of pediatric patients with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas at a body surface area (BSA)-based dose of 25 mg/m2 twice daily. The objective of this population pharmacokinetic analysis was to evaluate ethnic sensitivity in the pharmacokinetics of selumetinib and N-desmethyl selumetinib between Japanese and non-Japanese pediatric patients. Methods. This population pharmacokinetic analysis was based on data from 80 pediatric patients enrolled in two clinical trials, one conducted in Japan and one conducted in the United States, comprising 12 Japanese participants and 68 non-Japanese participants. Both clinical trials used BSA-based dosing schemes. A two-compartment model with first-order elimination and sequential zero-order and first-order delayed absorption for selumetinib, combined with a one-compartment model with first-order elimination for N-desmethyl selumetinib, was used for this analysis. Ethnic sensitivity in pharmacokinetics was evaluated by covariate modeling and comparison of model-predicted exposures. Results. Covariate modeling showed that BSA had a clinically relevant impact on the pharmacokinetics of selumetinib. None of the other investigated covariates, such as race, had a significant impact. The predicted exposure in Japanese and non-Japanese patients showed a considerably overlapping distribution, and no clinically relevant difference in exposure was apparent. Conclusions. These findings support the use of the same BSA-based dosing regimen for Japanese and non-Japanese pediatric patients with neurofibromatosis type 1 and inoperable plexiform neurofibromas. Subsequent to this analysis, selumetinib was approved at the BSA-based dose of 25 mg/m2 in Japan, which is consistent with the recommended dosage and administration in other regions and countries. This analysis used data from trial registered with NCT04495127, and NCT01362803.

背景介绍塞卢米替尼是一种丝裂原活化蛋白激酶激酶1/2抑制剂,已在包括日本在内的多个国家和地区获批用于治疗患有症状性、无法手术的丛状神经纤维瘤的1型神经纤维瘤病儿科患者,体表面积(BSA)剂量为25毫克/平方米,每天两次。该群体药代动力学分析的目的是评估日本和非日本儿科患者对塞鲁米替尼和N-去甲基塞鲁米替尼药代动力学的种族敏感性。方法这项群体药代动力学分析基于参加两项临床试验的 80 名儿科患者的数据,其中一项在日本进行,另一项在美国进行,包括 12 名日本参与者和 68 名非日本参与者。两项临床试验都采用了基于 BSA 的给药方案。本分析采用了塞卢米替尼的一阶消除、顺序零阶和一阶延迟吸收的二室模型,以及N-去甲基塞卢米替尼的一阶消除的一室模型。通过协变量建模和比较模型预测的暴露量,评估了药代动力学的种族敏感性。结果显示协变量建模显示,BSA对色瑞替尼的药代动力学具有临床相关性影响。种族等其他协变量均无显著影响。日本患者和非日本患者的预测暴露量呈现出相当大的重叠分布,暴露量没有明显的临床相关性差异。结论。这些研究结果支持对患有 1 型神经纤维瘤病和无法手术的丛状神经纤维瘤的日本和非日本儿科患者使用相同的基于 BSA 的给药方案。在本分析之后,日本批准了赛鲁替尼的 BSA 剂量为 25 mg/m2,这与其他地区和国家的推荐剂量和给药方式一致。本分析使用了NCT04495127和NCT01362803登记的试验数据。
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引用次数: 0
Exploring the Impact of Preoperative Sleep Fragmentation on Cognitive Function in Mice: The Role of Microglial Activation and Iron Metabolism 探索术前睡眠不足对小鼠认知功能的影响:微胶质细胞活化和铁代谢的作用
IF 2 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-05-08 DOI: 10.1155/2024/4376698
Yong Chen, Peng Yao, Yujuan You, Xianliang Xing, Xifeng Wang, Weijian Zhou, Yanhui Hu, Enjun Lei

Background. Perioperative neurocognitive disorders (PND) are a significant concern, particularly for aged individuals. Sleep fragmentation (SF), a common condition in older adults, is considered a risk factor for PND. The present study explored the impact of SF on cognitive function and its association with microglial activation and iron metabolism. Methods. Adult and aged C57BL/6J mice were subjected to tibial fracture surgery (TFS) and varying durations of SF. Cognitive function was assessed using the Morris water maze and fear conditioning experiments. Microglial activation was evaluated by measuring CD68 protein expression and inflammatory cytokine levels. Iron metabolism and ferroptosis-related proteins were also examined. Results. SF significantly impacted spatial memory and conditioned fear responses in mice, with aged mice showing greater susceptibility. Microglial activation, indicated by changes in CD68 protein expression and inflammatory cytokine levels, was observed in mice exposed to SF. Alterations in iron metabolism, as evidenced by changes in hippocampal iron content and expression of ferroptosis-related proteins, were also observed in these mice. Conclusion. SF can lead to significant cognitive impairment, particularly in aged mice, likely mediated through microglial activation and dysregulated iron metabolism. These findings provide novel insights into the pathogenesis of PND and suggest potential targets for intervention. Significance. This study illuminates the complex interactions between SF, microglial activation, and cognitive function. It highlights the importance of sleep quality for cognitive health in older adults and points to potential therapeutic strategies for preventing PND, including targeting microglial activation and iron metabolism.

背景。围手术期神经认知障碍(PND)是一个值得关注的重要问题,尤其是对老年人而言。睡眠片段化(SF)是老年人的常见病,被认为是导致围手术期神经认知障碍的一个危险因素。本研究探讨了 SF 对认知功能的影响及其与小胶质细胞活化和铁代谢的关系。研究方法成年和老龄 C57BL/6J 小鼠接受胫骨骨折手术(TFS)和不同持续时间的 SF。使用莫里斯水迷宫和恐惧条件反射实验评估认知功能。通过测量 CD68 蛋白表达和炎性细胞因子水平评估了小胶质细胞的活化情况。此外还检测了铁代谢和铁蛋白相关蛋白。结果SF 明显影响小鼠的空间记忆和条件性恐惧反应,老年小鼠更易受影响。在暴露于 SF 的小鼠中,CD68 蛋白表达和炎性细胞因子水平的变化表明小胶质细胞活化。在这些小鼠中还观察到铁代谢的改变,表现为海马铁含量和铁变态反应相关蛋白表达的变化。结论SF 可导致严重的认知障碍,尤其是在老年小鼠中,这可能是通过小胶质细胞激活和铁代谢失调介导的。这些发现为 PND 的发病机制提供了新的见解,并提出了潜在的干预目标。意义重大。这项研究揭示了SF、小胶质细胞活化和认知功能之间复杂的相互作用。它强调了睡眠质量对老年人认知健康的重要性,并指出了预防 PND 的潜在治疗策略,包括针对小胶质细胞活化和铁代谢的治疗策略。
{"title":"Exploring the Impact of Preoperative Sleep Fragmentation on Cognitive Function in Mice: The Role of Microglial Activation and Iron Metabolism","authors":"Yong Chen,&nbsp;Peng Yao,&nbsp;Yujuan You,&nbsp;Xianliang Xing,&nbsp;Xifeng Wang,&nbsp;Weijian Zhou,&nbsp;Yanhui Hu,&nbsp;Enjun Lei","doi":"10.1155/2024/4376698","DOIUrl":"10.1155/2024/4376698","url":null,"abstract":"<p><i>Background</i>. Perioperative neurocognitive disorders (PND) are a significant concern, particularly for aged individuals. Sleep fragmentation (SF), a common condition in older adults, is considered a risk factor for PND. The present study explored the impact of SF on cognitive function and its association with microglial activation and iron metabolism. <i>Methods</i>. Adult and aged C57BL/6J mice were subjected to tibial fracture surgery (TFS) and varying durations of SF. Cognitive function was assessed using the Morris water maze and fear conditioning experiments. Microglial activation was evaluated by measuring CD68 protein expression and inflammatory cytokine levels. Iron metabolism and ferroptosis-related proteins were also examined. <i>Results</i>. SF significantly impacted spatial memory and conditioned fear responses in mice, with aged mice showing greater susceptibility. Microglial activation, indicated by changes in CD68 protein expression and inflammatory cytokine levels, was observed in mice exposed to SF. Alterations in iron metabolism, as evidenced by changes in hippocampal iron content and expression of ferroptosis-related proteins, were also observed in these mice. <i>Conclusion</i>. SF can lead to significant cognitive impairment, particularly in aged mice, likely mediated through microglial activation and dysregulated iron metabolism. These findings provide novel insights into the pathogenesis of PND and suggest potential targets for intervention. <i>Significance</i>. This study illuminates the complex interactions between SF, microglial activation, and cognitive function. It highlights the importance of sleep quality for cognitive health in older adults and points to potential therapeutic strategies for preventing PND, including targeting microglial activation and iron metabolism.</p>","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"2024 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141000498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Neoadjuvant Administration of PD-1 Inhibitor plus Concurrent Chemoradiotherapy in Patients with Locally Advanced Esophageal Squamous-Cell Carcinoma 局部晚期食管鳞状细胞癌患者新辅助治疗 PD-1 抑制剂和同期化放疗的研究
IF 2 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-04-12 DOI: 10.1155/2024/5542947
Yong Chen, Shuangmei Zhu, Xiang Lan, Tianzhen Hu, Lele Ma, Hong Ye, Baoqiang Wang, Xiao He, Hanying Wang

Objective. Programmed cell death-1 (PD-1) inhibitors have shown potency for neoadjuvant therapy in several cancers, while their administration combined with concurrent chemoradiotherapy (CCRT) as a neoadjuvant therapy for locally advanced esophageal squamous-cell carcinoma (ESCC) is seldom reported. The current study aimed to investigate the pathological response, survival, and safety of neoadjuvant PD-1 inhibitor plus CCRT in locally advanced ESCC patients. Methods. Twenty-five locally advanced ESCC patients who underwent PD-1 inhibitor plus CCRT neoadjuvant therapy were retrospectively reviewed. Data regarding radiological response, pathological response, disease-free survival (DFS), overall survival (OS), and adverse events were retrieved. Results. Two (8.0%), 14 (56.0%), 9 (36.0%), and 0 (0.0%) patients had a clinical response of complete response, partial response, stable disease, and progressive disease after neoadjuvant therapy by radiological evaluations, respectively. Notably, 25 (100.0%) patients had successful tumor resections, 24 (96.0%) patients realized R0 resection, and 13 (52.0%) patients achieved pathological complete response (pCR) by pathological evaluations. Regarding survival profiles, the 1-year and 2-year accumulating DFS rates were 90.0% and 74.6%, respectively; then, the 1-year and 2-year accumulating OS rates were 95.5% and 90.4%, respectively. The top prevalent adverse events were fatigue (48.0%), nausea and vomiting (40.0%), leukopenia (36.0%), neutropenia (36.0%), and peripheral neuropathy (36.0%). In addition, grades 3-4 adverse events included peripheral neuropathy (12.0%), nausea and vomiting (4.0%), leukopenia (4.0%), neutropenia (4.0%), anemia (4.0%), and pruritus (4.0%). Conclusion. Neoadjuvant PD-1 inhibitor plus CCRT shows a good efficacy and acceptable tolerance for locally advanced ESCC treatment, but further large-scale study validation is needed.

目的程序性细胞死亡-1(PD-1)抑制剂已在多种癌症的新辅助治疗中显示出疗效,但将其与同期化放疗(CCRT)联合作为局部晚期食管鳞状细胞癌(ESCC)的新辅助治疗却鲜有报道。本研究旨在探讨新辅助 PD-1 抑制剂联合 CCRT 治疗局部晚期 ESCC 患者的病理反应、生存率和安全性。研究方法回顾性研究了25例接受PD-1抑制剂加CCRT新辅助治疗的局部晚期ESCC患者。检索了有关放射学反应、病理学反应、无病生存期(DFS)、总生存期(OS)和不良事件的数据。结果显示通过放射学评估,2 例(8.0%)、14 例(56.0%)、9 例(36.0%)和 0 例(0.0%)患者在新辅助治疗后的临床反应分别为完全反应、部分反应、疾病稳定和疾病进展。值得注意的是,25 例(100.0%)患者成功切除了肿瘤,24 例(96.0%)患者实现了 R0 切除,13 例(52.0%)患者通过病理评估获得了病理完全反应(pCR)。在生存率方面,1年和2年累计DFS率分别为90.0%和74.6%,1年和2年累计OS率分别为95.5%和90.4%。最常见的不良反应是疲劳(48.0%)、恶心和呕吐(40.0%)、白细胞减少(36.0%)、中性粒细胞减少(36.0%)和周围神经病变(36.0%)。此外,3-4 级不良事件包括周围神经病变(12.0%)、恶心呕吐(4.0%)、白细胞减少(4.0%)、中性粒细胞减少(4.0%)、贫血(4.0%)和瘙痒(4.0%)。结论新辅助PD-1抑制剂联合CCRT治疗局部晚期ESCC显示出良好的疗效和可接受的耐受性,但还需要进一步的大规模研究验证。
{"title":"The Neoadjuvant Administration of PD-1 Inhibitor plus Concurrent Chemoradiotherapy in Patients with Locally Advanced Esophageal Squamous-Cell Carcinoma","authors":"Yong Chen,&nbsp;Shuangmei Zhu,&nbsp;Xiang Lan,&nbsp;Tianzhen Hu,&nbsp;Lele Ma,&nbsp;Hong Ye,&nbsp;Baoqiang Wang,&nbsp;Xiao He,&nbsp;Hanying Wang","doi":"10.1155/2024/5542947","DOIUrl":"10.1155/2024/5542947","url":null,"abstract":"<p><i>Objective</i>. Programmed cell death-1 (PD-1) inhibitors have shown potency for neoadjuvant therapy in several cancers, while their administration combined with concurrent chemoradiotherapy (CCRT) as a neoadjuvant therapy for locally advanced esophageal squamous-cell carcinoma (ESCC) is seldom reported. The current study aimed to investigate the pathological response, survival, and safety of neoadjuvant PD-1 inhibitor plus CCRT in locally advanced ESCC patients. <i>Methods</i>. Twenty-five locally advanced ESCC patients who underwent PD-1 inhibitor plus CCRT neoadjuvant therapy were retrospectively reviewed. Data regarding radiological response, pathological response, disease-free survival (DFS), overall survival (OS), and adverse events were retrieved. <i>Results</i>. Two (8.0%), 14 (56.0%), 9 (36.0%), and 0 (0.0%) patients had a clinical response of complete response, partial response, stable disease, and progressive disease after neoadjuvant therapy by radiological evaluations, respectively. Notably, 25 (100.0%) patients had successful tumor resections, 24 (96.0%) patients realized R0 resection, and 13 (52.0%) patients achieved pathological complete response (pCR) by pathological evaluations. Regarding survival profiles, the 1-year and 2-year accumulating DFS rates were 90.0% and 74.6%, respectively; then, the 1-year and 2-year accumulating OS rates were 95.5% and 90.4%, respectively. The top prevalent adverse events were fatigue (48.0%), nausea and vomiting (40.0%), leukopenia (36.0%), neutropenia (36.0%), and peripheral neuropathy (36.0%). In addition, grades 3-4 adverse events included peripheral neuropathy (12.0%), nausea and vomiting (4.0%), leukopenia (4.0%), neutropenia (4.0%), anemia (4.0%), and pruritus (4.0%). <i>Conclusion</i>. Neoadjuvant PD-1 inhibitor plus CCRT shows a good efficacy and acceptable tolerance for locally advanced ESCC treatment, but further large-scale study validation is needed.</p>","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"2024 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140710045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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