首页 > 最新文献

Current Therapeutic Research-clinical and Experimental最新文献

英文 中文
The Effect of Anthocyanin Supplementation on Pro-Inflammatory Biomarkers in Patients With Metabolic Disorders: A Grade-Assessed Systematic Review and Meta-Analysis 补充花青素对代谢紊乱患者促炎生物标志物的影响:一项分级评估的系统评价和荟萃分析
IF 1.6 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 Epub Date: 2024-12-31 DOI: 10.1016/j.curtheres.2024.100772
Fatemeh Babaee Kiadehi MSc , Pegah Samani MSc , Sanaz Barazandeh MSc , Pedram Pam MSc , Ali Hajipour MSc , Narges Goli MSc , Ali Asadi PhD

Introduction and Aim

Patients with metabolic disorders benefit from using anthocyanins. Nevertheless, the findings drawn from extant trials remain contentious. Thus, this meta-analysis evaluated anthocyanin's effect on inflammatory biomarkers in patients with metabolic disorders.

Materials and Methods

We comprehensively searched electronic databases, including PubMed, Scopus, Web of Science, and CENTRAL, from their inception to June 14, 2024.

Findings

A total of 11 randomized controlled clinical trials with 14 arms were analyzed. There was no significant effect of anthocyanin supplementation on interleukin (IL)-1β levels (standardized mean difference [SMD] = –0.01, 95% CI: –0.33, 0.31; P = 0.941, I2 = 62.4%, P = 0.031), tumor necrosis factor-α (TNF-α) (SMD = –0.49, 95% CI: –1.07, 0.09; P = 0.098, I2 = 94.0%, P < 0.001) and IL-6 (SMD = –0.69, 95% CI: –1.45, 0.06; P = 0.073, I2 = 95.2%, P < 0.001), respectively. A significant between-study heterogeneity was identified, which was reduced when subgrouping by sample size, dosage, and study population. However, subgroup analysis showed that it might decrease TNF-α and IL-6 in patients with hypertension, and if the intervention lasted less than 12 weeks.

Conclusions

There was no significant impact of anthocyanin supplementation on IL-1β, TNF-α, and IL-6; however, it should be noted that the intervention has a decreasing impact on individuals with hypertension. Our observed effect sizes on IL-1β, TNF-α, and IL-6 are not clinically important.
介绍和目的代谢紊乱患者受益于使用花青素。然而,从现有试验中得出的结论仍然存在争议。因此,本荟萃分析评估了花青素对代谢紊乱患者炎症生物标志物的影响。材料与方法我们全面检索了PubMed、Scopus、Web of Science、CENTRAL等电子数据库,检索时间从建站到2024年6月14日。结果:共分析了11项随机对照临床试验,共14组。添加花青素对白介素(IL)-1β水平无显著影响(标准化平均差[SMD] = -0.01,95% CI: -0.33, 0.31;0.941 P = ,I2 = 62.4%,P = 0.031),肿瘤坏死因子-α(TNF -α)(SMD = -0.49,95%置信区间CI: -1.07, 0.09;0.098 P = ,I2 = 94.0%,P & lt; 0.001)和il - 6 (SMD = -0.69,95%置信区间CI: -1.45, 0.06;P = 0.073, I2 = 95.2%,P & lt;分别 0.001)。研究发现了显著的研究间异质性,当按样本量、剂量和研究人群进行亚分组时,这种异质性降低了。然而,亚组分析显示,如果干预持续时间少于12周,它可能会降低高血压患者的TNF-α和IL-6。结论补充花青素对IL-1β、TNF-α、IL-6无显著影响;然而,应该注意的是,干预对高血压患者的影响逐渐减弱。我们观察到的IL-1β、TNF-α和IL-6的效应大小在临床上并不重要。
{"title":"The Effect of Anthocyanin Supplementation on Pro-Inflammatory Biomarkers in Patients With Metabolic Disorders: A Grade-Assessed Systematic Review and Meta-Analysis","authors":"Fatemeh Babaee Kiadehi MSc ,&nbsp;Pegah Samani MSc ,&nbsp;Sanaz Barazandeh MSc ,&nbsp;Pedram Pam MSc ,&nbsp;Ali Hajipour MSc ,&nbsp;Narges Goli MSc ,&nbsp;Ali Asadi PhD","doi":"10.1016/j.curtheres.2024.100772","DOIUrl":"10.1016/j.curtheres.2024.100772","url":null,"abstract":"<div><h3>Introduction and Aim</h3><div>Patients with metabolic disorders benefit from using anthocyanins. Nevertheless, the findings drawn from extant trials remain contentious. Thus, this meta-analysis evaluated anthocyanin's effect on inflammatory biomarkers in patients with metabolic disorders.</div></div><div><h3>Materials and Methods</h3><div>We comprehensively searched electronic databases, including PubMed, Scopus, Web of Science, and CENTRAL, from their inception to June 14, 2024.</div></div><div><h3>Findings</h3><div>A total of 11 randomized controlled clinical trials with 14 arms were analyzed. There was no significant effect of anthocyanin supplementation on interleukin (IL)-1β levels (standardized mean difference [SMD] = –0.01, 95% CI: –0.33, 0.31; <em>P</em> = 0.941, <em>I</em><sup>2</sup> = 62.4%, <em>P</em> = 0.031), tumor necrosis factor-α (TNF-α) (SMD = –0.49, 95% CI: –1.07, 0.09; <em>P</em> = 0.098, <em>I</em><sup>2</sup> = 94.0%, <em>P</em> &lt; 0.001) and IL-6 (SMD = –0.69, 95% CI: –1.45, 0.06; <em>P</em> = 0.073, <em>I</em><sup>2</sup> = 95.2%, <em>P</em> &lt; 0.001), respectively. A significant between-study heterogeneity was identified, which was reduced when subgrouping by sample size, dosage, and study population. However, subgroup analysis showed that it might decrease TNF-α and IL-6 in patients with hypertension, and if the intervention lasted less than 12 weeks.</div></div><div><h3>Conclusions</h3><div>There was no significant impact of anthocyanin supplementation on IL-1β, TNF-α, and IL-6; however, it should be noted that the intervention has a decreasing impact on individuals with hypertension. Our observed effect sizes on IL-1β, TNF-α, and IL-6 are not clinically important.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100772"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cardiovascular Events and Heart Failure in Patients With Type 2 Diabetes Treated With Dipeptidyl Peptidase-4 Inhibitors: A Meta-Analysis 二肽基肽酶-4抑制剂治疗2型糖尿病患者的心血管事件和心力衰竭:一项荟萃分析
IF 1.5 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 Epub Date: 2025-07-15 DOI: 10.1016/j.curtheres.2025.100804
Adili Tuersun PhD , Shufen Cui BS , Li Han BS , Alimu Aikebaier BS , Yanyan Shi BS , Gang Cheng PhD , Lei Cheng BS , Guo Ma PhD

Background

The global prevalence of type 2 diabetes mellitus (T2DM) continues to rise, with patients facing significantly elevated risks of cardiovascular complications, particularly heart failure (HF).

Objective

This examination sought to methodically examine cardiovascular sequelae, notably heart failure, among users of dipeptidyl peptidase 4 (DPP-4) inhibitors when compared with nonusers.

Methods

Cochrane, Embase, and PubMed databases, which compared the use of DPP-4 inhibitors and reported cardiovascular outcomes and heart failure events in patients with type 2 diabetes mellitus (T2DM), were searched using specific terms. Studies were included if they satisfied the following inclusion criteria: they were randomized trials comparing DPP-4 inhibitor use in patients with T2DM; study duration was longer than 24 weeks; and they reported cardiovascular outcomes as their main or secondary end points. Stata 15 MP (StataCorp LLC, College Station, Texas, USA) was used to analyze the data, and odds ratios (ORs) with 95% CIs were used to represent the results.

Results

A total of 79,010 participants with T2DM were included. A total of 37,895 patients were assigned to the DPP-4 inhibitor group, whereas 41,115 patients were assigned to the control group. Results of the analysis showed that during a mean follow-up period ranging from 24 to 302 weeks, heart failure incidence did not differ significantly between T2DM patients treated with DPP-4 inhibitors and those who were not (OR = 1.06; 95% CI, 0.96–1.18; P = 0.452). Major adverse cardiovascular events (including nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death; OR = 1.01; 95% CI, 0.95–1.08; P = 0.354), stroke (OR = 1.01; 95% CI, 0.78–1.30; P = 0.968), myocardial infarction (OR = 0.89; 95% CI, 0.73–1.07; P = 0.49), and all-cause mortality (OR = 1.03; 95% CI, 0.96–1.11; P = 0.309) were also similarly manifested in both groups.

Conclusions

The present analysis showed that treatment with DPP-4 inhibitors did not significantly increase cardiovascular outcomes and heart failure in these patients with T2DM, indicating that these drugs may be safe to use in terms of cardiovascular events.
背景2型糖尿病(T2DM)的全球患病率持续上升,患者面临心血管并发症,特别是心力衰竭(HF)的风险显著升高。目的:本研究旨在系统地检查二肽基肽酶4 (DPP-4)抑制剂使用者与非使用者的心血管后遗症,特别是心力衰竭。方法使用特定术语对scochrane、Embase和PubMed数据库进行检索,这些数据库比较了2型糖尿病(T2DM)患者使用DPP-4抑制剂和报告的心血管结局和心力衰竭事件。满足以下纳入标准的研究被纳入:比较T2DM患者使用DPP-4抑制剂的随机试验;研究持续时间大于24周;他们报告了心血管结局作为主要或次要终点。使用Stata 15mp (StataCorp LLC, College Station, Texas, USA)分析数据,使用95% ci的优势比(or)来表示结果。结果共纳入T2DM患者79,010例。共有37,895名患者被分配到DPP-4抑制剂组,而41,115名患者被分配到对照组。分析结果显示,在24至302周的平均随访期间,接受DPP-4抑制剂治疗的T2DM患者与未接受DPP-4抑制剂治疗的T2DM患者的心力衰竭发生率无显著差异(OR = 1.06;95% ci, 0.96-1.18;P = 0.452)。主要不良心血管事件(包括非致死性心肌梗死、非致死性卒中和心血管性死亡);Or = 1.01;95% ci, 0.95-1.08;P = 0.354),中风(OR = 1.01;95% ci, 0.78-1.30;P = 0.968),心肌梗死(OR = 0.89;95% ci, 0.73-1.07;P = 0.49),全因死亡率(OR = 1.03;95% ci, 0.96-1.11;P = 0.309)。结论:本分析显示,DPP-4抑制剂治疗并没有显著增加这些T2DM患者的心血管结局和心力衰竭,表明这些药物在心血管事件方面可能是安全的。
{"title":"Cardiovascular Events and Heart Failure in Patients With Type 2 Diabetes Treated With Dipeptidyl Peptidase-4 Inhibitors: A Meta-Analysis","authors":"Adili Tuersun PhD ,&nbsp;Shufen Cui BS ,&nbsp;Li Han BS ,&nbsp;Alimu Aikebaier BS ,&nbsp;Yanyan Shi BS ,&nbsp;Gang Cheng PhD ,&nbsp;Lei Cheng BS ,&nbsp;Guo Ma PhD","doi":"10.1016/j.curtheres.2025.100804","DOIUrl":"10.1016/j.curtheres.2025.100804","url":null,"abstract":"<div><h3>Background</h3><div>The global prevalence of type 2 diabetes mellitus (T2DM) continues to rise, with patients facing significantly elevated risks of cardiovascular complications, particularly heart failure (HF).</div></div><div><h3>Objective</h3><div>This examination sought to methodically examine cardiovascular sequelae, notably heart failure, among users of dipeptidyl peptidase 4 (DPP-4) inhibitors when compared with nonusers.</div></div><div><h3>Methods</h3><div>Cochrane, Embase, and PubMed databases, which compared the use of DPP-4 inhibitors and reported cardiovascular outcomes and heart failure events in patients with type 2 diabetes mellitus (T2DM), were searched using specific terms. Studies were included if they satisfied the following inclusion criteria: they were randomized trials comparing DPP-4 inhibitor use in patients with T2DM; study duration was longer than 24 weeks; and they reported cardiovascular outcomes as their main or secondary end points. Stata 15 MP (StataCorp LLC, College Station, Texas, USA) was used to analyze the data, and odds ratios (ORs) with 95% CIs were used to represent the results.</div></div><div><h3>Results</h3><div>A total of 79,010 participants with T2DM were included. A total of 37,895 patients were assigned to the DPP-4 inhibitor group, whereas 41,115 patients were assigned to the control group. Results of the analysis showed that during a mean follow-up period ranging from 24 to 302 weeks, heart failure incidence did not differ significantly between T2DM patients treated with DPP-4 inhibitors and those who were not (OR = 1.06; 95% CI, 0.96–1.18; <em>P</em> = 0.452). Major adverse cardiovascular events (including nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death; OR = 1.01; 95% CI, 0.95–1.08; <em>P</em> = 0.354), stroke (OR = 1.01; 95% CI, 0.78–1.30; <em>P</em> = 0.968), myocardial infarction (OR = 0.89; 95% CI, 0.73–1.07; <em>P</em> = 0.49), and all-cause mortality (OR = 1.03; 95% CI, 0.96–1.11; <em>P</em> = 0.309) were also similarly manifested in both groups.</div></div><div><h3>Conclusions</h3><div>The present analysis showed that treatment with DPP-4 inhibitors did not significantly increase cardiovascular outcomes and heart failure in these patients with T2DM, indicating that these drugs may be safe to use in terms of cardiovascular events.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100804"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144809603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Meta-Analysis of the Efficacy and Safety of Sintilimab in Combination With Chemotherapy for Advanced Non–Small-Cell Lung Cancer 辛替单抗联合化疗治疗晚期非小细胞肺癌疗效和安全性的meta分析
IF 1.6 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 Epub Date: 2025-05-08 DOI: 10.1016/j.curtheres.2025.100796
Liling Pan MPharm , Qiongqing Chen MPharm , Ningsheng Liang PhD , Jinying Liang MBBS , Youjia Guo MMed

Objective

Sintilimab is an innovative immune checkpoint inhibitor (ICI), domestically produced in China, that exhibits significant efficacy in the treatment of lung cancer. However, due to the delayed initiation of ICI development in China, its use is currently restricted to domestic markets, resulting in a limited volume of clinical data, which poses a challenge in postmarketing evaluation. This study aimed to assess the safety and efficacy of sintilimab through a meta-analysis.

Methods

We conducted independent searches for relevant articles in both Chinese and international databases, followed by independent screening, after which the data were extracted from the selected studies. Statistical analysis was performed using RevMan software, version 5.4, and the results were estimated using the risk ratio with 95% confidence interval.

Results

Efficacy analysis revealed that sintilimab, when combined with chemotherapy, significantly enhanced the objective response rate and disease control rate in patients with non-small-cell lung cancer (NSCLC) while reducing the risk of disease progression. Evaluation of the safety of sintilimab revealed that the risks of hypothyroidism, pneumonia, and rash in patients with advanced NSCLC following treatment were higher than those of the control group by 3.70-fold, 2.22-fold, and 1.58-fold, respectively. There were no significant differences between the combination therapy and chemotherapy groups in terms of the incidence of blood system toxicity, impairment of liver function, and fever; however, nausea, vomiting, and diarrhea appeared to be less severe in the combination therapy group.

Conclusions

Sintilimab, combined with chemotherapy, demonstrates promising efficacy in the treatment of advanced NSCLC; however, it is imperative to closely monitor for adverse events, particularly immune-related adverse events.

Clinical trial registration

Not available.
目的:intilimab是一种创新的免疫检查点抑制剂(ICI),在中国国内生产,在治疗肺癌方面表现出显著的疗效。然而,由于ICI在中国的开发起步较晚,其使用目前仅限于国内市场,导致临床数据量有限,这给上市后评价带来了挑战。本研究旨在通过荟萃分析评估辛替单抗的安全性和有效性。方法分别在国内外数据库中独立检索相关文献,进行独立筛选,并从所选研究中提取数据。采用RevMan 5.4版软件进行统计分析,采用95%置信区间的风险比对结果进行估计。结果疗效分析显示,辛替单抗联合化疗可显著提高非小细胞肺癌(NSCLC)患者的客观有效率和疾病控制率,同时降低疾病进展风险。对辛替单抗的安全性评价显示,晚期NSCLC患者治疗后发生甲状腺功能减退、肺炎和皮疹的风险分别比对照组高3.70倍、2.22倍和1.58倍。联合治疗组与化疗组在血液系统毒性、肝功能损害和发热发生率方面无显著差异;然而,在联合治疗组中,恶心、呕吐和腹泻似乎不那么严重。结论辛替单抗联合化疗治疗晚期非小细胞肺癌疗效良好;然而,必须密切监测不良事件,特别是与免疫有关的不良事件。临床试验注册不可用。
{"title":"Meta-Analysis of the Efficacy and Safety of Sintilimab in Combination With Chemotherapy for Advanced Non–Small-Cell Lung Cancer","authors":"Liling Pan MPharm ,&nbsp;Qiongqing Chen MPharm ,&nbsp;Ningsheng Liang PhD ,&nbsp;Jinying Liang MBBS ,&nbsp;Youjia Guo MMed","doi":"10.1016/j.curtheres.2025.100796","DOIUrl":"10.1016/j.curtheres.2025.100796","url":null,"abstract":"<div><h3>Objective</h3><div>Sintilimab is an innovative immune checkpoint inhibitor (ICI), domestically produced in China, that exhibits significant efficacy in the treatment of lung cancer. However, due to the delayed initiation of ICI development in China, its use is currently restricted to domestic markets, resulting in a limited volume of clinical data, which poses a challenge in postmarketing evaluation. This study aimed to assess the safety and efficacy of sintilimab through a meta-analysis.</div></div><div><h3>Methods</h3><div>We conducted independent searches for relevant articles in both Chinese and international databases, followed by independent screening, after which the data were extracted from the selected studies. Statistical analysis was performed using RevMan software, version 5.4, and the results were estimated using the risk ratio with 95% confidence interval.</div></div><div><h3>Results</h3><div>Efficacy analysis revealed that sintilimab, when combined with chemotherapy, significantly enhanced the objective response rate and disease control rate in patients with non-small-cell lung cancer (NSCLC) while reducing the risk of disease progression. Evaluation of the safety of sintilimab revealed that the risks of hypothyroidism, pneumonia, and rash in patients with advanced NSCLC following treatment were higher than those of the control group by 3.70-fold, 2.22-fold, and 1.58-fold, respectively. There were no significant differences between the combination therapy and chemotherapy groups in terms of the incidence of blood system toxicity, impairment of liver function, and fever; however, nausea, vomiting, and diarrhea appeared to be less severe in the combination therapy group.</div></div><div><h3>Conclusions</h3><div>Sintilimab, combined with chemotherapy, demonstrates promising efficacy in the treatment of advanced NSCLC; however, it is imperative to closely monitor for adverse events, particularly immune-related adverse events.</div></div><div><h3>Clinical trial registration</h3><div>Not available.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100796"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparison of Bioavailability of Nitrates and Nitrites in 3 Species of Amaranthus: A Randomized, Double-Blind, Placebo-Controlled, 4-Way Crossover Study in Healthy Subjects Under Fasting Conditions 3种苋属植物中硝酸盐和亚硝酸盐的生物利用度比较:一项随机、双盲、安慰剂对照、空腹条件下健康受试者的4向交叉研究
IF 1.6 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 Epub Date: 2025-05-10 DOI: 10.1016/j.curtheres.2025.100789
Deepa Suhag , Aparna Nilesh Kodre

Background

Amaranthus is a significant source of dietary nitrates, which have been known to improve aerobic capacity and exercise performance in physically active individuals. There is a significant data gap on nonpartitive pharmacokinetics and bioequivalence studies of nitrate and nitrite from 3 species of Amaranth (A. hybridus, A. hypochondriacus, and A. tricolor).

Objective

This study aimed to assess the bioavailability of nitrates and nitrites from 3 Amaranthus species in a randomized, placebo-controlled design, thereby filling this gap.

Methods

A double-blinded, 4-way crossover study was conducted in 16 healthy participants. Each participant enrolled in the study received a single dose of 2000 mg of Amaranthus extract or a placebo. The plasma and saliva samples were collected at specific intervals over 24 hours. Nitrate and nitrite concentrations were analyzed using a validated LCMS/MS method.

Results

After the administration of amaranth extracts, both plasma and saliva samples were observed significantly higher levels of nitrate and nitrite compared with the placebo group. Pharmacokinetic variables (Cmax, AUC0-t24, and AUC0-∞) found a similar pattern for nitrite and nitrate in the 3 amaranth products but were significantly different from placebo (P < 0.05), in both plasma and saliva samples. Bioequivalence analysis confirmed significant bioequivalence among the 3 amaranth extracts for nitrite and nitrate.

Conclusions

This study concludes that the 3 species of AmaranthusA. hybridus, A. hypochondriacus, and A. tricolor are bioequivalent in terms of plasma and saliva nitrate and nitrite levels from a single dose of 2000 mg amaranth extract and have higher bioavailability than placebo. These findings report that Amaranthus extracts could potentially act as a daily diet supplement for improving the cardiovascular and neurogenerative health of the body, particularly aging people.
马兰花是膳食硝酸盐的重要来源,已知硝酸盐可以改善身体活跃个体的有氧能力和运动表现。3种苋菜(a . hybridus、a . hypochondriacus和a . tricolor)中硝酸盐和亚硝酸盐的非参与药代动力学和生物等效性研究存在明显的数据缺口。目的采用随机、安慰剂对照设计,对3种苋属植物中硝酸盐和亚硝酸盐的生物利用度进行评价,以填补这一空白。方法对16例健康受试者进行双盲、四向交叉研究。参加研究的每个参与者都接受了单剂量的2000毫克苋菜提取物或安慰剂。血浆和唾液样本在24小时内每隔一段时间采集一次。采用经验证的LCMS/MS法分析硝酸盐和亚硝酸盐浓度。结果服用苋菜提取物后,血浆和唾液样本的硝酸盐和亚硝酸盐水平均明显高于安慰剂组。药代动力学变量(Cmax, AUC0-t24和AUC0-∞)发现3种苋菜产品中亚硝酸盐和硝酸盐的模式相似,但与安慰剂显著不同(P <;0.05),在血浆和唾液样本中。生物等效性分析证实3种苋菜提取物对亚硝酸盐和硝酸盐具有显著的生物等效性。结论苋菜属的3种植物属属植物具有较强的多样性。单剂量2000 mg苋菜提取物对马齿苋、苋籽苋和三色苋的血浆和唾液硝酸盐和亚硝酸盐水平具有生物等效性,并且具有比安慰剂更高的生物利用度。这些研究结果表明,苋菜提取物可以作为日常饮食补充剂,改善身体的心血管和神经系统健康,尤其是老年人。
{"title":"Comparison of Bioavailability of Nitrates and Nitrites in 3 Species of Amaranthus: A Randomized, Double-Blind, Placebo-Controlled, 4-Way Crossover Study in Healthy Subjects Under Fasting Conditions","authors":"Deepa Suhag ,&nbsp;Aparna Nilesh Kodre","doi":"10.1016/j.curtheres.2025.100789","DOIUrl":"10.1016/j.curtheres.2025.100789","url":null,"abstract":"<div><h3>Background</h3><div><em>Amaranthus</em> is a significant source of dietary nitrates, which have been known to improve aerobic capacity and exercise performance in physically active individuals. There is a significant data gap on nonpartitive pharmacokinetics and bioequivalence studies of nitrate and nitrite from 3 species of Amaranth (<em>A. hybridus, A. hypochondriacus</em>, and <em>A. tricolor</em>).</div></div><div><h3>Objective</h3><div>This study aimed to assess the bioavailability of nitrates and nitrites from 3 <em>Amaranthus</em> species in a randomized, placebo-controlled design, thereby filling this gap.</div></div><div><h3>Methods</h3><div>A double-blinded, 4-way crossover study was conducted in 16 healthy participants. Each participant enrolled in the study received a single dose of 2000 mg of <em>Amaranthus</em> extract or a placebo. The plasma and saliva samples were collected at specific intervals over 24 hours. Nitrate and nitrite concentrations were analyzed using a validated LCMS/MS method.</div></div><div><h3>Results</h3><div>After the administration of amaranth extracts, both plasma and saliva samples were observed significantly higher levels of nitrate and nitrite compared with the placebo group. Pharmacokinetic variables (C<sub>max</sub>, AUC<sub>0-t24</sub>, and AUC0-∞) found a similar pattern for nitrite and nitrate in the 3 amaranth products but were significantly different from placebo (<em>P</em> &lt; 0.05), in both plasma and saliva samples. Bioequivalence analysis confirmed significant bioequivalence among the 3 amaranth extracts for nitrite and nitrate.</div></div><div><h3>Conclusions</h3><div>This study concludes that the 3 species of <em>Amaranthus</em>—<em>A. hybridus, A. hypochondriacus</em>, and <em>A. tricolor</em> are bioequivalent in terms of plasma and saliva nitrate and nitrite levels from a single dose of 2000 mg amaranth extract and have higher bioavailability than placebo. These findings report that <em>Amaranthus</em> extracts could potentially act as a daily diet supplement for improving the cardiovascular and neurogenerative health of the body, particularly aging people.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100789"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unleashing the Potential of Givinostat: A Novel Therapy for Duchenne Muscular Dystrophy 释放吉维司他的潜能:一种治疗杜氏肌营养不良症的新疗法
IF 1.6 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 Epub Date: 2025-03-25 DOI: 10.1016/j.curtheres.2025.100787
Ahmad Furqan Anjum MBBS, BSc , Muhammad Burhan Anjum MBBS , Raza ur Rehman MBBS, Bsc

Purpose

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder with limited treatment options beyond corticosteroids, which have significant adverse effects. Givinostat, a histone deacetylase inhibitor, has recently emerged as a promising disease-modifying therapy. This commentary examines the therapeutic potential of givinostat, its mechanism of action, and the clinical evidence supporting its role in DMD treatment.

Methods

A review of the EPIDYS Phase 3 trial and supporting clinical studies was conducted. The study included boys aged 6 to 17 years with genetically confirmed DMD, assessing givinostat's efficacy and safety over 18 months. Key endpoints included the North Star Ambulatory Assessment (NSAA), MRI-based muscle preservation, and adverse event (AE) profiles.

Findings

Givinostat-treated patients demonstrated a 1.9-point higher NSAA score compared to placebo (P = 0.03), with significant reductions in muscle fat infiltration (40% lower than placebo; P < 0.05). Functional tests showed trends toward improved stair-climbing ability, though not statistically significant. AEs included thrombocytopenia (20%) and hypertriglyceridemia (10%), necessitating monitoring but remaining manageable.

Implications

Givinostat represents a paradigm shift in DMD management, offering benefits beyond corticosteroids by reducing fibrosis and promoting muscle regeneration. While its long-term safety and cost-effectiveness require further evaluation, its combination potential with gene therapies highlights its importance in future DMD treatment strategies. Ongoing studies aim to refine its role in broader neuromuscular disorders.
目的:杜氏肌营养不良症(DMD)是一种进行性神经肌肉疾病,除皮质类固醇外,治疗选择有限,皮质类固醇有明显的不良反应。吉维诺司他是一种组蛋白去乙酰化酶抑制剂,最近作为一种有前景的疾病改善疗法出现。本评论探讨了吉维司他的治疗潜力,其作用机制,以及支持其在DMD治疗中的作用的临床证据。方法对EPIDYS 3期临床试验及相关临床研究进行综述。该研究包括6至17岁的男孩,遗传上证实患有DMD,在18个月的时间里评估givinostat的有效性和安全性。主要终点包括北极星动态评估(NSAA)、基于mri的肌肉保存和不良事件(AE)概况。研究结果:与安慰剂相比,接受吉维诺他治疗的患者的NSAA评分高1.9分(P = 0.03),肌肉脂肪浸润显著减少(比安慰剂低40%;P & lt;0.05)。功能测试显示,他们的爬楼梯能力有提高的趋势,但在统计上并不显著。ae包括血小板减少症(20%)和高甘油三酯血症(10%),需要监测,但仍可控制。givinostat代表了DMD治疗的范式转变,通过减少纤维化和促进肌肉再生提供皮质类固醇以外的益处。虽然其长期安全性和成本效益需要进一步评估,但其与基因疗法的联合潜力突出了其在未来DMD治疗策略中的重要性。正在进行的研究旨在完善其在更广泛的神经肌肉疾病中的作用。
{"title":"Unleashing the Potential of Givinostat: A Novel Therapy for Duchenne Muscular Dystrophy","authors":"Ahmad Furqan Anjum MBBS, BSc ,&nbsp;Muhammad Burhan Anjum MBBS ,&nbsp;Raza ur Rehman MBBS, Bsc","doi":"10.1016/j.curtheres.2025.100787","DOIUrl":"10.1016/j.curtheres.2025.100787","url":null,"abstract":"<div><h3>Purpose</h3><div>Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder with limited treatment options beyond corticosteroids, which have significant adverse effects. Givinostat, a histone deacetylase inhibitor, has recently emerged as a promising disease-modifying therapy. This commentary examines the therapeutic potential of givinostat, its mechanism of action, and the clinical evidence supporting its role in DMD treatment.</div></div><div><h3>Methods</h3><div>A review of the EPIDYS Phase 3 trial and supporting clinical studies was conducted. The study included boys aged 6 to 17 years with genetically confirmed DMD, assessing givinostat's efficacy and safety over 18 months. Key endpoints included the North Star Ambulatory Assessment (NSAA), MRI-based muscle preservation, and adverse event (AE) profiles.</div></div><div><h3>Findings</h3><div>Givinostat-treated patients demonstrated a 1.9-point higher NSAA score compared to placebo (<em>P</em> = 0.03), with significant reductions in muscle fat infiltration (40% lower than placebo; <em>P</em> &lt; 0.05). Functional tests showed trends toward improved stair-climbing ability, though not statistically significant. AEs included thrombocytopenia (20%) and hypertriglyceridemia (10%), necessitating monitoring but remaining manageable.</div></div><div><h3>Implications</h3><div>Givinostat represents a paradigm shift in DMD management, offering benefits beyond corticosteroids by reducing fibrosis and promoting muscle regeneration. While its long-term safety and cost-effectiveness require further evaluation, its combination potential with gene therapies highlights its importance in future DMD treatment strategies. Ongoing studies aim to refine its role in broader neuromuscular disorders.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100787"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Investigating the Effect of Reducing the Signs and Symptoms of Lid Wiper Epitheliopathy in Patients With Dry Eye Disease With Perfluorohexyloctane 研究全氟己基辛烷减轻干眼症患者眼睑拭泪器表皮病变症状的效果
IF 1.6 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 Epub Date: 2025-03-20 DOI: 10.1016/j.curtheres.2025.100786
Chris Lievens OD, MS, PhD, FNAP, FAAO , Andrew D. Pucker OD, PhD, FAAO , Quentin Franklin BS , Stephen M. Montaquila OD, FAAO , Brad Giedd OD, MS, FAAO , Gina Wesley OD, MS, FAAO , Morgan Bromley PhD , Zackarias Coker MS , John Meyers MS , Marta Vianya-Estopa PhD

Background

Perfluorohexyloctane (PFHO) acts to prevent the evaporation of the tear film. It has the potential to limit friction related issues between the eye lid margin and the ocular surface. Prior to the present work, this had not yet been evaluated.

Objective

To examine the potential of using perfluorohexyloctane for reducing the signs and symptoms of lid wiper epitheliopathy (LWE).

Methods

Data were collected at 4 visits spanning 2 months. Patients who had symptomatic dry eye and a LWE score of ≥1.0 on the Korb LWE scale were recruited. Participants were randomized to PFHO 4 times a day or no treatment. Lid wiper epitheliopathy was graded at each visit with the Korb and photographic LWE (PLWE) scales. Symptoms were assessed using the Standard Patient Evaluation of Eye Dryness questionnaire and visual analog scales (0–100).

Results

A total of 52 participants were enrolled (mean ± SD age, 49.7 ± 15.7 years; 79% female). Right eyes in the treatment group were significantly more likely to show an improvement of ≥0.5-units in PLWE scores at 2 months than the no treatment group (P = 0.04), but no left eye differences were noted. Korb and PLWE scores were significantly better in the treatment group compared with the no treatment group starting at 2 weeks and remained so for the duration of the study (all P < 0.001). Standard Patient Evaluation of Eye Dryness scores and dry eye symptoms were significantly better in the treatment than in the no treatment group at the 2-month visit (all P ≤ 0.01).

Conclusions

Perfluorohexyloctane significantly reduced LWE and improved dry eye symptoms compared with no treatment, suggesting that PFHO may enhance ocular lubrication and reduce friction-related damage. Masked, randomized, trials are still needed to compare PFHO to other treatments in participants with LWE to support generalizability of results. ClinicalTrials.gov study NCT06671041.
背景全氟己基辛烷(PFHO)具有防止泪膜蒸发的作用。它有可能限制眼睑边缘和眼球表面之间的摩擦问题。在本研究之前,还没有人对此进行过评估。目的 研究使用全氟己基辛烷减轻睑板腺上皮炎(LWE)症状的潜力。招募的患者均为有症状的干眼症患者,且在 Korb LWE 量表中 LWE 评分≥1.0。参与者被随机分配到每天 4 次的 PFHO 或无治疗。每次就诊时,均使用 Korb 和摄影 LWE(PLWE)量表对睑板腺上皮病变进行评分。使用标准眼干患者评估问卷和视觉模拟量表(0-100)对症状进行评估。结果 共有 52 名参与者(平均年龄为 49.7±15.7 岁;79% 为女性)参加了研究。2个月后,治疗组右眼的PLWE评分改善≥0.5个单位的几率明显高于未治疗组(P = 0.04),但左眼无差异。从 2 周开始,治疗组的 Korb 和 PLWE 评分明显优于未治疗组,并且在整个研究期间保持不变(所有 P 均为 0.001)。结论与不治疗相比,全氟己基辛烷能显著降低LWE并改善干眼症状,这表明全氟己基辛烷可能会增强眼部润滑并减少与摩擦相关的损伤。目前仍需进行掩蔽、随机试验,将PFHO与其他治疗方法在干眼症患者中进行比较,以证明试验结果的普遍性。ClinicalTrials.gov研究NCT06671041。
{"title":"Investigating the Effect of Reducing the Signs and Symptoms of Lid Wiper Epitheliopathy in Patients With Dry Eye Disease With Perfluorohexyloctane","authors":"Chris Lievens OD, MS, PhD, FNAP, FAAO ,&nbsp;Andrew D. Pucker OD, PhD, FAAO ,&nbsp;Quentin Franklin BS ,&nbsp;Stephen M. Montaquila OD, FAAO ,&nbsp;Brad Giedd OD, MS, FAAO ,&nbsp;Gina Wesley OD, MS, FAAO ,&nbsp;Morgan Bromley PhD ,&nbsp;Zackarias Coker MS ,&nbsp;John Meyers MS ,&nbsp;Marta Vianya-Estopa PhD","doi":"10.1016/j.curtheres.2025.100786","DOIUrl":"10.1016/j.curtheres.2025.100786","url":null,"abstract":"<div><h3>Background</h3><div>Perfluorohexyloctane (PFHO) acts to prevent the evaporation of the tear film. It has the potential to limit friction related issues between the eye lid margin and the ocular surface. Prior to the present work, this had not yet been evaluated.</div></div><div><h3>Objective</h3><div>To examine the potential of using perfluorohexyloctane for reducing the signs and symptoms of lid wiper epitheliopathy (LWE).</div></div><div><h3>Methods</h3><div>Data were collected at 4 visits spanning 2 months. Patients who had symptomatic dry eye and a LWE score of ≥1.0 on the Korb LWE scale were recruited. Participants were randomized to PFHO 4 times a day or no treatment. Lid wiper epitheliopathy was graded at each visit with the Korb and photographic LWE (PLWE) scales. Symptoms were assessed using the Standard Patient Evaluation of Eye Dryness questionnaire and visual analog scales (0–100).</div></div><div><h3>Results</h3><div>A total of 52 participants were enrolled (mean ± SD age, 49.7 ± 15.7 years; 79% female). Right eyes in the treatment group were significantly more likely to show an improvement of ≥0.5-units in PLWE scores at 2 months than the no treatment group (<em>P</em> = 0.04), but no left eye differences were noted. Korb and PLWE scores were significantly better in the treatment group compared with the no treatment group starting at 2 weeks and remained so for the duration of the study (all <em>P</em> &lt; 0.001). Standard Patient Evaluation of Eye Dryness scores and dry eye symptoms were significantly better in the treatment than in the no treatment group at the 2-month visit (all <em>P</em> ≤ 0.01).</div></div><div><h3>Conclusions</h3><div>Perfluorohexyloctane significantly reduced LWE and improved dry eye symptoms compared with no treatment, suggesting that PFHO may enhance ocular lubrication and reduce friction-related damage. Masked, randomized, trials are still needed to compare PFHO to other treatments in participants with LWE to support generalizability of results. ClinicalTrials.gov study NCT06671041.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100786"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reversing Morphine Induced Tolerance: Insights Into Cetirizine and Green Tea Extract Efficacy 逆转吗啡诱导的耐受性:西替利嗪和绿茶提取物疗效的见解
IF 1.6 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 Epub Date: 2025-03-04 DOI: 10.1016/j.curtheres.2025.100783
Tahereh Eteraf-Oskouei Phd , Adel Mahmoudi Gharehbaba Phd , Solmaz Asnaashari Phd , Zahra Fazli Phd , Bohloul Habibi Asl Phd

Background

The treatment of chronic pain presents a considerable difficulty, particularly due to opioid dependence, which is marked by tolerance and withdrawal symptoms. Opioids primarily target mu (μ) opioid receptors, providing pain relief while also leading to various side effects. This research aimed to examine the effectiveness of cetirizine and green tea hydroalcoholic extract (EXT) in altering morphine tolerance and improving analgesic effects.

Methods

Adult male mice were divided into nine groups. In order to investigate the analgesic tolerance, animals received morphine on 14 consecutive days. Cetirizine (5, 10, 20 mg/kg, i.p.) and EXT (50, 100, 200 mg/kg, i.p.) were given before a test dose of morphine (9 mg/kg, i.p.). The analgesic effects were evaluated by the hot plate test.

Results

Cetirizine with doses of 5, 10, 20 mg/kg, and 10 mg/kg showed a significant effect in reducing morphine tolerance 30 min (P < 0.0001) and 45 to 60 min (P < 0.0001) after test dose of morphine (9 mg/kg, i.p.) respectively. While the injection of different doses of the extract did not show any effect on tolerance to morphine. In the combined injection of these two drugs, there was no reduction in tolerance to morphine.

Conclusions

Cetirizine but not EXT reversed morphine tolerance. Furthermore, the co-administration of cetirizine and EXT did not yield any significant benefits compared to the individual treatments.
慢性疼痛的治疗呈现出相当大的困难,特别是由于阿片类药物依赖,其特征是耐受性和戒断症状。阿片主要靶向mu (μ)阿片受体,在缓解疼痛的同时也会导致各种副作用。本研究旨在探讨西替利嗪和绿茶水酒精提取物(EXT)改变吗啡耐受性和改善镇痛效果的有效性。方法将成年雄性小鼠分为9组。为了观察小鼠的镇痛耐受性,连续14天给予吗啡。在吗啡试验剂量(9 mg/kg, i.p)之前给予西替利嗪(5、10、20 mg/kg, i.p)和EXT(50、100、200 mg/kg, i.p)。采用热板法评价镇痛效果。结果西替利嗪剂量为5、10、20 mg/kg和10 mg/kg时,分别在吗啡试验剂量(9 mg/kg, i.p)后30 min (P <; 0.0001)和45 ~ 60 min (P <; 0.0001)显著降低吗啡耐受性。而注射不同剂量的提取物对吗啡耐受性没有任何影响。在联合注射这两种药物时,对吗啡的耐受性没有降低。结论西替利嗪对吗啡耐受有逆转作用,EXT对吗啡耐受无逆转作用。此外,与单独治疗相比,西替利嗪和EXT联合使用没有产生任何显著的益处。
{"title":"Reversing Morphine Induced Tolerance: Insights Into Cetirizine and Green Tea Extract Efficacy","authors":"Tahereh Eteraf-Oskouei Phd ,&nbsp;Adel Mahmoudi Gharehbaba Phd ,&nbsp;Solmaz Asnaashari Phd ,&nbsp;Zahra Fazli Phd ,&nbsp;Bohloul Habibi Asl Phd","doi":"10.1016/j.curtheres.2025.100783","DOIUrl":"10.1016/j.curtheres.2025.100783","url":null,"abstract":"<div><h3>Background</h3><div>The treatment of chronic pain presents a considerable difficulty, particularly due to opioid dependence, which is marked by tolerance and withdrawal symptoms. Opioids primarily target mu (μ) opioid receptors, providing pain relief while also leading to various side effects. This research aimed to examine the effectiveness of cetirizine and green tea hydroalcoholic extract (EXT) in altering morphine tolerance and improving analgesic effects.</div></div><div><h3>Methods</h3><div>Adult male mice were divided into nine groups. In order to investigate the analgesic tolerance, animals received morphine on 14 consecutive days. Cetirizine (5, 10, 20 mg/kg, i.p.) and EXT (50, 100, 200 mg/kg, i.p.) were given before a test dose of morphine (9 mg/kg, i.p.). The analgesic effects were evaluated by the hot plate test.</div></div><div><h3>Results</h3><div>Cetirizine with doses of 5, 10, 20 mg/kg, and 10 mg/kg showed a significant effect in reducing morphine tolerance 30 min (<em>P</em> &lt; 0.0001) and 45 to 60 min (<em>P</em> &lt; 0.0001) after test dose of morphine (9 mg/kg, i.p.) respectively. While the injection of different doses of the extract did not show any effect on tolerance to morphine. In the combined injection of these two drugs, there was no reduction in tolerance to morphine.</div></div><div><h3>Conclusions</h3><div>Cetirizine but not EXT reversed morphine tolerance. Furthermore, the co-administration of cetirizine and EXT did not yield any significant benefits compared to the individual treatments.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100783"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Oral Cyclosporine Treatment for Four Pediatric Patients With Toxic Epidermal Necrolysis That Showed No Response to High-dose Corticosteroids in Combination With Intravenous Immunoglobulin: A Case Series 口服环孢素治疗4例对大剂量皮质类固醇联合静脉注射免疫球蛋白无反应的中毒性表皮坏死松解患儿:一个病例系列
IF 1.6 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 Epub Date: 2024-12-02 DOI: 10.1016/j.curtheres.2024.100767
Peijing Li MD , Qin Yao MD , Yuanyuan Wang MD , Xipeng Xu MD

Background

Immunosuppressive agents like cyclosporine have proven effective in some pediatric cases, although there are limited case reports considering potential risks such as secondary infections.

Objective

This study investigated the safety and efficacy of Cyclosporine A in children who did not respond to high-dose corticosteroids combined with intravenous immunoglobulin (IVIG).

Methods

We reported four pediatric patients diagnosed with toxic epidermal necrolysis (TEN) received treatment at our institution. All patients were previously healthy children with a median age of 7 years, comprising three boys and one girl (Table 1). Epidermal exfoliation and vesicular lesions ranged from 32.5% to 54.5% of the body surface area (BSA). Despite the administration of treatment comprising high-dose corticosteroids and intravenous immunoglobulin (IVIG), new cutaneous herpes continually emerged. This prompted a transition to cyclosporine treatment (3–5 mg/kg/d) administered in 1–2 oral doses.

Results

Lesions stopped progressing, and bullous lesions started epithelialization after 13–27 days of hospitalization. Cases 1 and 2 faced secondary bacterial and fungal infections, respectively, and their temperatures stabilized after administration of antibiotics. Cases 3 and 4 experienced fever again when the dosage of corticosteroids was tapered off, with no discernible evidence of infection. The patients’ temperatures normalized upon the continuation of cyclosporine therapy. Among the patients, three presented asymptomatic elevated serum amylase, one of which met the diagnostic criteria for acute pancreatitis. Two children showed mildly raised aminotransferases, with one experiencing mild coronary artery dilation, two contracted onychomadesis, and three developed corneal ulceration/keratitis and atretoblepharia, which eventually resolved after vigorous ophthalmologic treatment. None of the children had any permanent sequelae after being discharged from the hospital for six months.

Conclusions

Cyclosporine A is generally safe and effective for children who fail to respond to high-dose corticosteroids in combination with IVIG.
背景:免疫抑制剂如环孢素已被证明对一些儿科病例有效,尽管考虑到继发感染等潜在风险的病例报告有限。目的:本研究探讨环孢素A对大剂量皮质类固醇联合静脉注射免疫球蛋白(IVIG)无反应的儿童的安全性和有效性。方法:我们报告了4例诊断为中毒性表皮坏死松解症(TEN)的儿科患者在我院接受治疗。所有患者均为健康儿童,中位年龄为7岁,包括3名男孩和1名女孩(表1)。表皮脱落和水疱病变占体表面积(BSA)的32.5%至54.5%。尽管给予高剂量皮质类固醇和静脉注射免疫球蛋白(IVIG)治疗,新的皮肤疱疹仍不断出现。这促使改用环孢素治疗(3-5 mg/kg/d),分1-2次口服。结果:13 ~ 27 d后病变停止进展,大疱性病变开始上皮化。病例1和2分别面临继发性细菌和真菌感染,并在给予抗生素后体温稳定。病例3和4在皮质类固醇剂量逐渐减少时再次出现发热,没有明显的感染证据。继续环孢素治疗后患者体温恢复正常。3例患者血清淀粉酶无症状升高,其中1例符合急性胰腺炎诊断标准。2例患儿转氨酶轻度升高,1例发生轻度冠状动脉扩张,2例发生甲发育,3例发生角膜溃疡/角膜炎和眼膜粘连,经大力眼科治疗后最终消退。出院6个月后,所有患儿均无永久性后遗症。结论:环孢素A对于大剂量皮质类固醇联合IVIG治疗无效的儿童通常是安全有效的。
{"title":"Oral Cyclosporine Treatment for Four Pediatric Patients With Toxic Epidermal Necrolysis That Showed No Response to High-dose Corticosteroids in Combination With Intravenous Immunoglobulin: A Case Series","authors":"Peijing Li MD ,&nbsp;Qin Yao MD ,&nbsp;Yuanyuan Wang MD ,&nbsp;Xipeng Xu MD","doi":"10.1016/j.curtheres.2024.100767","DOIUrl":"10.1016/j.curtheres.2024.100767","url":null,"abstract":"<div><h3>Background</h3><div>Immunosuppressive agents like cyclosporine have proven effective in some pediatric cases, although there are limited case reports considering potential risks such as secondary infections.</div></div><div><h3>Objective</h3><div>This study investigated the safety and efficacy of Cyclosporine A in children who did not respond to high-dose corticosteroids combined with intravenous immunoglobulin (IVIG).</div></div><div><h3>Methods</h3><div>We reported four pediatric patients diagnosed with toxic epidermal necrolysis (TEN) received treatment at our institution. All patients were previously healthy children with a median age of 7 years, comprising three boys and one girl (<span><span>Table 1</span></span>). Epidermal exfoliation and vesicular lesions ranged from 32.5% to 54.5% of the body surface area (BSA). Despite the administration of treatment comprising high-dose corticosteroids and intravenous immunoglobulin (IVIG), new cutaneous herpes continually emerged. This prompted a transition to cyclosporine treatment (3–5 mg/kg/d) administered in 1–2 oral doses.</div></div><div><h3>Results</h3><div>Lesions stopped progressing, and bullous lesions started epithelialization after 13–27 days of hospitalization. Cases 1 and 2 faced secondary bacterial and fungal infections, respectively, and their temperatures stabilized after administration of antibiotics. Cases 3 and 4 experienced fever again when the dosage of corticosteroids was tapered off, with no discernible evidence of infection. The patients’ temperatures normalized upon the continuation of cyclosporine therapy. Among the patients, three presented asymptomatic elevated serum amylase, one of which met the diagnostic criteria for acute pancreatitis. Two children showed mildly raised aminotransferases, with one experiencing mild coronary artery dilation, two contracted onychomadesis, and three developed corneal ulceration/keratitis and atretoblepharia, which eventually resolved after vigorous ophthalmologic treatment. None of the children had any permanent sequelae after being discharged from the hospital for six months.</div></div><div><h3>Conclusions</h3><div>Cyclosporine A is generally safe and effective for children who fail to respond to high-dose corticosteroids in combination with IVIG.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100767"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Innovative Solutions for Multidrug-Resistant Organisms’ Infections in Intensive Care Unit: A Joint Efficacy Evaluation of Multidisciplinary Team and SHEL (Software, Hardware, Environment, Liveware) Model 重症监护病房多重耐药菌感染的创新解决方案:多学科团队与SHEL(软件、硬件、环境、活体)模型的联合疗效评估。
IF 1.6 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 Epub Date: 2024-12-03 DOI: 10.1016/j.curtheres.2024.100766
Xiaoyan Kang MD , Ping Zhang DNP , Qing Xu MD , Zhengqun Feng MD , Bei Yin MD

Background

The escalating threat of multidrug-resistant organisms (MDROs) in intensive care unit (ICU) demands innovative management strategies to curb the rising infection rates and associated clinical challenges.

Objective

To assess the effectiveness of integrating the multidisciplinary team (MDT) approach with the SHEL (Software, Hardware, Environment, Liveware) model in reducing MDRO infections within ICU settings.

Methods

From January 2021 to April 2024, a prospective, randomized controlled study was conducted in the ICU of Nantong Fourth People's Hospital, enrolling 411 patients with MDRO infections. These patients were randomly assigned into 3 groups: the MDT group, the SHEL model group, and a combined group. The intervention lasted for 4 weeks, during which the effects on the MDRO detection rate, infection rate, health care staff's infection control execution scores, and the rationality of antibiotic use were assessed, aiming to determine the efficacy of each approach in managing MDROs in the ICU setting.

Results

The overall infection rate of MDROs in the ICU of our hospital from 2021 to 2024 was 60.18%, with sputum infection sources accounting for 68.37% of the total sources, making it the primary source of infection. The detection rate of MDROs in the combined group was significantly higher than that in the MDT and the SHEL groups, with the SHEL group having a higher detection rate than the MDT group (P < 0.05). The infection rate of MDROs in the combined group was significantly lower than that in both the MDT and the SHEL groups, with the SHEL group having a lower detection rate than the MDT group (P < 0.05). The implementation scores of the combination group in standard prevention, hand hygiene, antibiotic management, and isolation measures were significantly higher than those of the MDT and SHEL groups, with the SHEL group scoring higher than the MDT group (P < 0.05). The rational use of antibiotics in the combined group was also higher than in both the MDT and the SHEL groups, with the SHEL group having a higher level than the MDT group (P < 0.05).

Conclusions

The integrated MDT and SHEL model significantly reduced MDRO infections in ICU, improved health care workers' infection prevention and nursing quality, and promoted the appropriate use of antibiotics, advocating for its clinical application.
背景:重症监护病房(ICU)耐多药菌(mdro)的威胁不断升级,需要创新的管理策略来遏制感染率的上升和相关的临床挑战。目的:评估多学科团队(MDT)方法与SHEL (Software, Hardware, Environment, Liveware)模式相结合在减少重症监护室MDRO感染中的有效性。方法:于2021年1月至2024年4月在南通市第四人民医院ICU开展前瞻性、随机对照研究,纳入411例MDRO感染患者。将这些患者随机分为3组:MDT组、SHEL模型组和联合组。干预时间为4周,评估干预对MDRO检出率、感染率、医护人员感染控制执行得分、抗生素使用合理性的影响,旨在确定各干预方式对ICU MDRO管理的效果。结果:2021 - 2024年我院ICU MDROs总体感染率为60.18%,痰液感染源占总感染源的68.37%,为主要感染源。联合治疗组MDROs检出率显著高于MDT组和SHEL组,且SHEL组检出率高于MDT组(P < 0.05)。联合用药组MDROs感染率均显著低于MDT组和SHEL组,且SHEL组检出率低于MDT组(P < 0.05)。联合用药组在标准预防、手卫生、抗生素管理、隔离措施执行得分均显著高于MDT组和SHEL组,且SHEL组得分高于MDT组(P < 0.05)。联合用药组抗菌药物合理使用率也高于MDT组和SHEL组,且SHEL组高于MDT组(P < 0.05)。结论:MDT与SHEL相结合的模式显著降低了ICU MDRO感染,提高了医护人员的感染预防和护理质量,促进了抗生素的合理使用,提倡其临床应用。
{"title":"Innovative Solutions for Multidrug-Resistant Organisms’ Infections in Intensive Care Unit: A Joint Efficacy Evaluation of Multidisciplinary Team and SHEL (Software, Hardware, Environment, Liveware) Model","authors":"Xiaoyan Kang MD ,&nbsp;Ping Zhang DNP ,&nbsp;Qing Xu MD ,&nbsp;Zhengqun Feng MD ,&nbsp;Bei Yin MD","doi":"10.1016/j.curtheres.2024.100766","DOIUrl":"10.1016/j.curtheres.2024.100766","url":null,"abstract":"<div><h3>Background</h3><div>The escalating threat of multidrug-resistant organisms (MDROs) in intensive care unit (ICU) demands innovative management strategies to curb the rising infection rates and associated clinical challenges.</div></div><div><h3>Objective</h3><div>To assess the effectiveness of integrating the multidisciplinary team (MDT) approach with the SHEL (Software, Hardware, Environment, Liveware) model in reducing MDRO infections within ICU settings.</div></div><div><h3>Methods</h3><div>From January 2021 to April 2024, a prospective, randomized controlled study was conducted in the ICU of Nantong Fourth People's Hospital, enrolling 411 patients with MDRO infections. These patients were randomly assigned into 3 groups: the MDT group, the SHEL model group, and a combined group. The intervention lasted for 4 weeks, during which the effects on the MDRO detection rate, infection rate, health care staff's infection control execution scores, and the rationality of antibiotic use were assessed, aiming to determine the efficacy of each approach in managing MDROs in the ICU setting.</div></div><div><h3>Results</h3><div>The overall infection rate of MDROs in the ICU of our hospital from 2021 to 2024 was 60.18%, with sputum infection sources accounting for 68.37% of the total sources, making it the primary source of infection. The detection rate of MDROs in the combined group was significantly higher than that in the MDT and the SHEL groups, with the SHEL group having a higher detection rate than the MDT group (<em>P</em> &lt; 0.05). The infection rate of MDROs in the combined group was significantly lower than that in both the MDT and the SHEL groups, with the SHEL group having a lower detection rate than the MDT group (<em>P</em> &lt; 0.05). The implementation scores of the combination group in standard prevention, hand hygiene, antibiotic management, and isolation measures were significantly higher than those of the MDT and SHEL groups, with the SHEL group scoring higher than the MDT group (<em>P</em> &lt; 0.05). The rational use of antibiotics in the combined group was also higher than in both the MDT and the SHEL groups, with the SHEL group having a higher level than the MDT group (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>The integrated MDT and SHEL model significantly reduced MDRO infections in ICU, improved health care workers' infection prevention and nursing quality, and promoted the appropriate use of antibiotics, advocating for its clinical application.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100766"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nano-Amounts of Glucagon Premixed With Fast-Acting Insulin Lispro: Effect on Insulin Absorption in Pigs 纳米级胰高血糖素与速效胰岛素利斯普罗预混:对猪胰岛素吸收的影响
IF 1.6 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2025-01-01 Epub Date: 2025-06-24 DOI: 10.1016/j.curtheres.2025.100803
Ilze Dirnena-Fusini PhD , Misbah Riaz MSc , Sverre Christian Christiansen MD, PhD , Sven Magnus Carlsen MD, PhD

Background

Glucagon leads to substantial but short-lived subcutaneous vasodilation. Using micro-amounts of glucagon at the insulin injection site increases insulin absorption.

Objective

We hypothesized that a premixed solution of insulin and nanogram doses of glucagon would improve the pharmacokinetic and pharmacodynamic properties of subcutaneously injected insulin.

Methods

In this series of proof-of-concept experiments, 17 anesthetized pigs were included. Nine pigs were included in the control groups; they received a subcutaneous injection of 10 U of insulin lispro (Lyumjev or Humalog). Eight pigs were included in the glucagon groups; they received 10 U of a premixed insulin (Lyumjev or Humalog)/glucagon solution (5 ng glucagon/unit of insulin). Arterial blood was frequently sampled for 210 minutes to assess insulin and glucose concentrations. The impact on glucose metabolism was evaluated through euglycemic clamp investigation.

Results

When premixed insulin Lyumjev/glucagon was injected, insulin Tmax decreased from 33 to 20 minutes (SE = 6.6, P = 0.08), and Cmax was 2-fold higher than that in the control group (100 mU/L vs 46 mU/L, SE = 4.8, P = 0.007). When premixed insulin Humalog/glucagon was injected, Tmax and Cmax did not change significantly (P = 0.53 and P = 0.83, respectively). Insulin AUC for the first 15 minutes increased two-fold when insulin Lyumjev/glucagon was injected (946 mU×min/L vs 337 mU×min/L, SE = 196, P = 0.02). A similar trend was observed when Humalog/glucagon was injected (306 mU×min/L vs 65 mU×min/L, SE = 125), although this difference did not reach statistical significance (P = 0.102) compared with the control groups.

Conclusions

This series of proof-of-concept experiments in anesthetized pigs indicate that premixing nanogram doses of glucagon in fast-acting insulin lispro formulations may speed up the absorption of subcutaneously injected insulin.
背景:胰高血糖素导致大量但短暂的皮下血管扩张。在胰岛素注射部位使用微量胰高血糖素可以增加胰岛素的吸收。目的假设胰岛素与毫微克胰高血糖素的预混溶液可以改善皮下注射胰岛素的药动学和药效学特性。方法在这一系列的概念验证实验中,选取17头麻醉猪。9头猪作为对照组;皮下注射10u胰岛素lispro (LyumjevⓇ或HumalogⓇ)。8头猪分为胰高血糖素组;他们接受10单位胰岛素(LyumjevⓇ或HumalogⓇ)/胰高血糖素溶液(5 ng胰高血糖素/单位胰岛素)的预混合。经常抽取动脉血210分钟,以评估胰岛素和葡萄糖浓度。通过正糖钳法观察对糖代谢的影响。结果注射Lyumjev胰岛素Ⓡ/胰高血糖素预混剂后,胰岛素Tmax从33 min降低至20 min (SE = 6.6, P = 0.08), Cmax比对照组提高2倍(100 mU/L vs 46 mU/L, SE = 4.8, P = 0.007)。注射预混合胰岛素HumalogⓇ/胰高血糖素时,Tmax和Cmax无显著变化(P = 0.53和P = 0.83)。Lyumjev胰岛素Ⓡ/胰高血糖素组前15分钟胰岛素AUC升高2倍(946 mU×min/L vs 337 mU×min/L, SE = 196, P = 0.02)。注射HumalogⓇ/胰高血糖素组也有类似的趋势(306 mU×min/L vs 65 mU×min/L, SE = 125),但与对照组相比差异无统计学意义(P = 0.102)。结论在麻醉猪身上进行的一系列概念验证实验表明,在速效胰岛素制剂中预混纳克剂量的胰高血糖素可以加速皮下注射胰岛素的吸收。
{"title":"Nano-Amounts of Glucagon Premixed With Fast-Acting Insulin Lispro: Effect on Insulin Absorption in Pigs","authors":"Ilze Dirnena-Fusini PhD ,&nbsp;Misbah Riaz MSc ,&nbsp;Sverre Christian Christiansen MD, PhD ,&nbsp;Sven Magnus Carlsen MD, PhD","doi":"10.1016/j.curtheres.2025.100803","DOIUrl":"10.1016/j.curtheres.2025.100803","url":null,"abstract":"<div><h3>Background</h3><div>Glucagon leads to substantial but short-lived subcutaneous vasodilation. Using micro-amounts of glucagon at the insulin injection site increases insulin absorption.</div></div><div><h3>Objective</h3><div>We hypothesized that a premixed solution of insulin and nanogram doses of glucagon would improve the pharmacokinetic and pharmacodynamic properties of subcutaneously injected insulin.</div></div><div><h3>Methods</h3><div>In this series of proof-of-concept experiments, 17 anesthetized pigs were included. Nine pigs were included in the control groups; they received a subcutaneous injection of 10 U of insulin lispro (Lyumjev<sup>Ⓡ</sup> or Humalog<sup>Ⓡ</sup>). Eight pigs were included in the glucagon groups; they received 10 U of a premixed insulin (Lyumjev<sup>Ⓡ</sup> or Humalog<sup>Ⓡ</sup>)/glucagon solution (5 ng glucagon/unit of insulin). Arterial blood was frequently sampled for 210 minutes to assess insulin and glucose concentrations. The impact on glucose metabolism was evaluated through euglycemic clamp investigation.</div></div><div><h3>Results</h3><div>When premixed insulin Lyumjev<sup>Ⓡ</sup>/glucagon was injected, insulin T<sub>max</sub> decreased from 33 to 20 minutes (SE = 6.6, <em>P</em> = 0.08), and C<sub>max</sub> was 2-fold higher than that in the control group (100 mU/L vs 46 mU/L, SE = 4.8, <em>P</em> = 0.007). When premixed insulin Humalog<sup>Ⓡ</sup>/glucagon was injected, T<sub>max</sub> and C<sub>max</sub> did not change significantly (<em>P</em> = 0.53 and <em>P</em> = 0.83, respectively). Insulin AUC for the first 15 minutes increased two-fold when insulin Lyumjev<sup>Ⓡ</sup>/glucagon was injected (946 mU×min/L vs 337 mU×min/L, SE = 196, <em>P</em> = 0.02). A similar trend was observed when Humalog<sup>Ⓡ</sup>/glucagon was injected (306 mU×min/L vs 65 mU×min/L, SE = 125), although this difference did not reach statistical significance (<em>P</em> = 0.102) compared with the control groups.</div></div><div><h3>Conclusions</h3><div>This series of proof-of-concept experiments in anesthetized pigs indicate that premixing nanogram doses of glucagon in fast-acting insulin lispro formulations may speed up the absorption of subcutaneously injected insulin.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100803"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Current Therapeutic Research-clinical and Experimental
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1