International journal of clinical pharmacology and therapeutics最新文献

{"title":"Network pharmacology and experimental analysis of Yudantong decoction, a multi-immunomodulator for the treatment of intractable cholestatic liver disease: Identification of active agents, molecular targets, and mechanisms of action.","authors":"Xiaoming Wu, Linyi Hou, Jing Liu, Jing Hao, Chang Liu, Yan Hu, Qiang He","doi":"10.5414/CP204695","DOIUrl":"10.5414/CP204695","url":null,"abstract":"<p><strong>Background: </strong>Yudantong decoction (YDTD) is a therapeutic prescription for cholestatic liver disease (CLD) and is clinically effective in our medical institution. However, the exact constituents and mechanisms of YDTD in treating CLD remain unknown. This project aimed to explore the primary constituents and mechanism of YDTD in the treatment of CLD through ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS), network pharmacology, molecular docking technology, and in vivo experiments.</p><p><strong>Materials and methods: </strong>The chemical constituents of YDTD were identified via UPLC-HRMS, and Bioinformatics analysis tool for molecular mechANism of traditional Chinese medicine (BATMAN-TCM) was employed to screen target proteins. Cytoscape 3.7.1 was used to build the herbal component-target network. The CLD targets were identified by querying the OMIM and DisGeNET databases and determining the overlap between the targets of the YDTD chemical constituents and those of CLD. The STRING database was utilized to construct a protein-protein interaction (PPI) network for subsequent analysis. Gene ontology (GO) biological process enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis were carried out using the database for annotation, visualization and integrated discovery (DAVID) database. Molecular docking validation against core targets with PyMOL software was conducted for the active compounds. Finally, in vivo experiments were performed to investigate the therapeutic effect of YDTD in a murine model of α-naphthyl isothiocyanate (ANIT)-induced CLD.</p><p><strong>Results: </strong>YDTD has 112 major components, among which 59 have 1,478 potential targets. We identified a total of 1,957 potential therapeutic targets for CLD and 269 overlapping targets between CLD-associated targets and YDTD active component targets to construct a PPI network. Through topology analysis, IL-6, INS, IL1B, AKT1, BCL2, NFKB1, PTGS2, and TP53 were identified as key targets along with their corresponding primary chemical components. KEGG analysis revealed significant enrichment of the phosphoinositide 3-Kinase (PI3K)-Akt and nuclear factor Kappa-B (NF-κB) signaling pathways. The molecular docking results indicated strong binding affinities between glycyrrhizin-AKT1, l-arginine-IL1B, p-coumaric acid-IL1B, 2,4-dihydroxybenzoic acid-IL1B, p-coumaric acid-TNF, 2-hydroxycinnamic acid-TNF, uridine-AKT1, p-coumaric acid-IL6, and trigonelline-INS. In vivo experiments demonstrated that YDTD downregulated the expression of p-PI3K, p-AKT, p-NF-κB, IL-6, TNF-α, and IL-1β, and reduced immune cell infiltration in the liver to ameliorate liver damage in CLD patients.</p><p><strong>Conclusion: </strong>The present study clarified the active components and potential anti-inflammatory mechanism of YDTD in treating CLD, providing a solid foundation for future research on its therapeutic m","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"220-238"},"PeriodicalIF":0.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515332","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}

{"title":"Nano and liposome cancer chemotherapy: A review of advances in drug delivery with applications.","authors":"Lianmei Zhang, Xinglin Jin","doi":"10.5414/CP204715","DOIUrl":"10.5414/CP204715","url":null,"abstract":"<p><p>The high incidence of malignant tumors continues to pose a significant threat to public health. In recent years, there have been notable advancements in tumor treatment methods, leading to substantial changes in the concepts and clinical approaches to treatment. The primary clinical methods for treating malignant tumors currently include surgical resection, radiation therapy, and chemotherapy. Among these, chemotherapy is one of the most crucial and comprehensive treatment strategies. The rapid progress in nanoscience has fostered the development of nanocarrier compounds and their clinical applications in disease treatment. Notably, nanomedicines, including goserelin sustained-release implants, doxorubicin liposomes, albumin-bound paclitaxel, and paclitaxel liposomes, have been effectively utilized in tumor treatment in China [<xref-ref>1</xref-ref>]. The article presents a comprehensive overview of recent advancements in utilizing various nanocarriers for combination therapy in tumors. It also examines the clinical application and efficacy of drug delivery carriers. The development of efficient and safe co-delivery systems that facilitate the effective transport and precise release of drugs within the cancerous tissues while also elucidating the internalization of nanoparticles into tumor cells and their functional mechanisms represents critical areas for future research. Concurrently, advancements in nanocarriers and tumor treatment are anticipated to yield superior therapeutic outcomes and improved quality of life for cancer patients.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"208-216"},"PeriodicalIF":0.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673834","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}

{"title":"Taken from the Radio Times newspaper (U.K.) December 18, 1931.","authors":"Barrington G Woodcock-Kloberdanz","doi":"10.5414/CPP63177","DOIUrl":"10.5414/CPP63177","url":null,"abstract":"","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"177-178"},"PeriodicalIF":0.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730010","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}

{"title":"Differentiation of bone marrow mesenchymal stem cells modulated by Bushen Tian Sui decoction via the TGF-β1-Smad2/3 signaling pathway: In vitro evidence and potential clinical application in delayed fracture healing.","authors":"Wei Xiong, Bingru Li, Jiamin Chen, Zichen Shao, Wei-Kang Sun, Song Li, Hualong Lu, Ling Cheng","doi":"10.5414/CP204746","DOIUrl":"10.5414/CP204746","url":null,"abstract":"<p><strong>Background: </strong>Bone-related disorders pose significant challenges in clinical practice. Bone marrow mesenchymal stem cells (BMSCs), as multipotent stem cells, play a pivotal role in bone regeneration. The TGF-β1-Smad2/3 signaling pathway is a well-recognized regulator of BMSC osteogenic differentiation. Traditional Chinese medicine (TCM), such as Bushen Tian Sui decoction (BSTSD), has shown potential in enhancing bone health; however, its molecular mechanisms remain poorly understood.</p><p><strong>Objective: </strong>Investigating the effects and underlying mechanisms of BSTSD on the osteogenic differentiation of BMSCs.</p><p><strong>Materials and methods: </strong>The impact of BSTSD on BMSCs was comprehensively analyzed using Cell Counting Kit-8 (CCK8), quantitative polymerase chain reaction (qPCR), western blot (WB), and immunofluorescence assays.</p><p><strong>Results: </strong>CCK8 results revealed the highest optical density (OD) values in the BSTSD + activator group at 24, 48, and 72 hours, indicating enhanced cell proliferation. qPCR analysis showed significantly increased expression levels of TGF-β1, Smad2, Smad3, SOX9, and RUNX2 in the BSTSD + activator group, suggesting a synergistic effect in promoting osteogenic and chondrogenic differentiation. WB results demonstrated elevated phosphorylation levels of Smad2 and Smad3 (p-Smad2, p-Smad3) in the BSTSD + activator group, while total Smad2 and Smad3 protein levels remained consistent among groups. Immunofluorescence assays confirmed the highest fluorescence intensity, positive area ratio, and cell count containing Smad2 and Smad3 proteins in the BSTSD + activator group, validating the synergistic effect of BSTSD and TGF-β1.</p><p><strong>Conclusion: </strong>BSTSD exhibits promising effects on BMSC differentiation and bone regeneration, mediated through the TGF-β1-Smad2/3 signaling pathway.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"197-207"},"PeriodicalIF":0.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515624","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}

{"title":"Liver dysfunction and long-acting aripiprazole: The importance of tolerability assessment.","authors":"Noboru Hokama, Kazuki Ota, Hideo Shiohira, Yoshikazu Takaesu, Katsunori Nakamura","doi":"10.5414/CP204687","DOIUrl":"10.5414/CP204687","url":null,"abstract":"","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"217-219"},"PeriodicalIF":0.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596962","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}

{"title":"Cost-utility analysis of pembrolizumab versus nivolumab in the treatment of metastatic colorectal cancer from the perspective of the healthcare payer.","authors":"Zhen Lu, Xiaoyan Huang, Yingjuan Ou, Qinbo Wang, Qirong Tan","doi":"10.5414/CP204665","DOIUrl":"10.5414/CP204665","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is a malignant tumor with the third highest incidence worldwide. The comprehensive economic evaluation of programmed cell death protein-1 inhibitors in China, however, has not yet been carried out. The aim of this study is to assess the cost-utility of pembrolizumab and nivolumab in the treatment of metastatic colorectal cancer (mCRC).</p><p><strong>Materials and methods: </strong>A Markov model microsimulation of efficacy and cost-utility analysis (CUA) was carried out, and efficacy and safety data were compared using network meta-analysis. Literature screening and data extraction were performed according to established criteria where the main outcome indicators, complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were compared between two treatments. The lifetime cost and outcomes of mCRC treatment were estimated, and quality-adjusted life years (-QALYs) and incremental cost-effectiveness ratio (ICER) were used to evaluate the economy of each program.</p><p><strong>Results: </strong>A total of 442 studies were evaluated of which 15, with a total of 798 patients, were included in the analysis. Of these, 13 evaluated PD, and total patients for CR, PR, SD, and PD were 82, 283, 160, and 180 respectively. The corresponding heterogeneity values were (p = 0.13, heterogeneity index as percentage (I²) = 29.53%), (p < 0.01, I² = 72.55%), (p = 0.03, I² = 46.54%), (p < 0.01, I² = 80.31%), and (p = 0.13 > 0.05). The proportion of patients classified as CR in the pembrolizumab group was greater than in the nivolumab group (0.105 vs. 0.085). However, the number of patients classified as PR and SD in the nivolumab group exceeded those in the pembrolizumab group. The number of patients classified as PD were similar in the two groups. Combination therapy nivolumab + ipilimumab yielded an incremental gain of 0.04 QALYs at an additional cost of 356,723 ¥. The ICER reached 8,918,075 ¥/QALYs, surpassing three times the per capita gross domestic product (GDP).</p><p><strong>Conclusion: </strong>Both pembrolizumab and nivolumab showed beneficial effects in patients with mCRC. Nivolumab in combination with ipilimumab led to improved progression-free survival, but the values for ICER reached 8,918,075 ¥/QALYs. Treatment of non-resectable or metastatic microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) advanced solid tumors CRC with pembrolizumab alone, in the Chinese population examined, was the most cost-effective, where the willingness-to-pay threshold was 242,928 ¥/QALY (100 ¥ = 13.75 US$ and 12.63 €).</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"179-189"},"PeriodicalIF":0.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596961","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}

{"title":"Augmented renal clearance in neurosurgical patients receiving vancomycin: Limited prognostic value for the duration of hospitalization, treatment course, fever, and changes in the CSF test and CRP.","authors":"Lu Sun, Yunchuan Sun","doi":"10.5414/CP204743","DOIUrl":"https://doi.org/10.5414/CP204743","url":null,"abstract":"<p><strong>Objective: </strong>In patients with augmented renal clearance (ARC) receiving vancomycin, therapeutic drug monitoring (TDM) is recommended in accordance with the 2020 guidelines. This study was conducted to delineate the profile of ARC and TDM in non-critically ill, non-trauma, non-stroke neurosurgical patients receiving vancomycin, thereby elucidating the additional risk factors and prognostic implications of ARC.</p><p><strong>Materials and methods: </strong>A single-center retrospective review of clinical data was performed from patients who were consecutively admitted to the Neurosurgical Department of Beijing Tongren Hospital, Capital Medical University, Beijing, China, from November 1, 2017, to October 31, 2022, and received vancomycin. 62 patients with a maximum ICU stay of 72 hours were included. ARC was defined as an estimated glomerular filtration rate (eGFR) of > 130 mL/min/1.73m² in the main analysis. A difference analysis based on ARC risk factors, correlation analysis, and multiple linear regression was conducted.</p><p><strong>Results: </strong>The eGFR of the total patient cohort was 115.41 ± 13.39 mL/min/1.73m² (mean ± SD), whereas 10 patients (16.13%) had eGFRs > 130 mL/min/1.73m². Younger ages and mannitol co-administration were risk factors for ARC, whereas increased eGFR was not associated with prognostic implications for hospital stay, treatment course, fever duration, or duration to normalization of the CSF test or CRP level.</p><p><strong>Conclusion: </strong>A minimum of 16.13% of non-critical, non-trauma, non-stroke neurosurgical patients exhibit ARC. ARC was not associated with anti-infection prognosis. This finding suggests that further evaluation of ARC-guided TDM of these populations is warranted.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999554","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}

{"title":"Exacerbations, mortality risk, and pharmacotherapy in COPD: Effect of 17 different drug combinations in a cohort of 495 patients.","authors":"Guoxin Wu, Ziyun Guan, Quankun Lv, Yi Ye, Jiacheng He, Jianwen Luo, Yanglin Cai, Zhixin Wu","doi":"10.5414/CP204727","DOIUrl":"https://doi.org/10.5414/CP204727","url":null,"abstract":"<p><strong>Objective: </strong>To assess the association between the severity of recent exacerbations and 90-day mortality risk in chronic obstructive pulmonary disease patients (COPD) with acute symptoms, focusing on the impact of the treatment regimen and involving 17 different drug combinations.</p><p><strong>Materials and methods: </strong>A longitudinal, retrospective analysis was carried out in 495 hospitalized COPD patients aged 40 - 75 years. Patients' clinical characteristics were recorded and the effects of drug regimens, administered pre and post hospitalization, comprising various combinations of long-acting muscarinic antagonists (LAMA), long-acting beta agonists (LABA), inhaled corticosteroids (ICS), and antibiotics, were compared. A statistical analysis of the primary outcome, 90-day mortality was used to identify patient attributes best predicting mortality.</p><p><strong>Results: </strong>At discharge, 65% of patients were receiving a 3-drug combination, 33% a 2-drug regimen, and 9% a single-drug therapy. Patients discharged on a 3-drug combination treatment had the lowest 90-day mortality rate (4%) compared to 22% for those treated with single-drug regimens. Multivariate analysis revealed that the risk of death on single-drug therapy was more than 5-fold greater (odds ratio 5.08) than in the case of patients discharged on a multi-drug combination regimen.</p><p><strong>Conclusion: </strong>Patients treated and discharged from hospital on a multi-drug regimen following recent COPD exacerbations had significantly better 90-day survival than patients discharged on monotherapy. The severity of exacerbations and nature of the pharmacotherapy were the main predictors of mortality and were indicative for the importance of disease assessment and multi-drug treatment strategies.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011448","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}

{"title":"Evidence for a loss of analgesia when hydromorphone is administered in combination with hange-shashin-to: Enterohepatic circulation and β-glucuronidase inhibition.","authors":"Masakazu Ozaki, Hiroshi Yamagata, Hiroto Matsui, Naoto Okada, Mishiya Matsumoto, Hiroaki Nagano, Takashi Kitahara","doi":"10.5414/CP204702","DOIUrl":"10.5414/CP204702","url":null,"abstract":"","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"174-176"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515363","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}

{"title":"Niraparib-related severe refractory thrombocytopenia in ovarian cancer patients receiving paclitaxel/carboplatin chemotherapy: A report on three cases.","authors":"Mingtao Chen, Lin Zhou, Huijuan Yang, Mengmeng Wang","doi":"10.5414/CP204724","DOIUrl":"10.5414/CP204724","url":null,"abstract":"<p><p>A characteristic toxicity of niraparib is a decrease in blood platelets (PLT), with an incidence of ~ 34% for grades 3 - 4 conditions. However, exceedingly severe cases have been reported infrequently. This paper describes three patients with acute and refractory severe PLT deficiency due to niraparib administration. The symptom characteristics, treatment course, and outcomes have also been analyzed, and the potential for the involvement of immune-related factors is considered. Therefore, it is recommended to comprehensively assess bone marrow hematopoietic function and high-risk variables before administering niraparib, intensify self-management and monitoring of patients, track changes in indicators, and intervene promptly. Additionally, if standard PLT-elevating therapies are ineffective, early full-dose administration of thrombopoietin receptor agonists, preferably avatrombopag, may be beneficial for reversing PLT loss of control.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"169-173"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382260","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}