{"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}
Zhen Lu, Xiaoyan Huang, Yingjuan Ou, Qinbo Wang, Qirong Tan
{"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 (I<sup>2</sup>) = 29.53%), (p < 0.01, I<sup>2</sup> = 72.55%), (p = 0.03, I<sup>2</sup> = 46.54%), (p < 0.01, I<sup>2</sup> = 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":"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}
Mingtao Chen, Lin Zhou, Huijuan Yang, Mengmeng Wang
{"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}
Woongshik Nam, Ji-Hwan Bae, Jeongin Oh, Ju-Young Shin, Hoon Kim
{"title":"Cardiovascular safety profile of JAK inhibitors and ethnic factors in Asians: A signal detection study using the Global ICSR (WHO-UMC VigBase) database.","authors":"Woongshik Nam, Ji-Hwan Bae, Jeongin Oh, Ju-Young Shin, Hoon Kim","doi":"10.5414/CP204580","DOIUrl":"10.5414/CP204580","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to detect cardiovascular disease-related signals using Global Individual Case Safety Report data on JAK inhibitors.</p><p><strong>Materials and methods: </strong>A signal detection study was conducted using the WHO-UMC VigiBase.</p><p><strong>Results: </strong>This study identified four cardiovascular adverse event signals associated with JAK inhibitors in Asian populations, including pulmonary embolism, deep vein thrombosis, thrombosis, and cerebrovascular accidents.</p><p><strong>Conclusion: </strong>Analysis of Asian populations revealed a higher risk of thromboembolic events associated with JAK inhibitors than with TNF inhibitors. However, unlike in the Western populations, no myocardial infarction signal was detected in the Asian populations.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"160-163"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515621","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}
María Rodríguez Jorge, Loreto Domínguez Senín, Stephanie Saide Cobelas Cartagena, María Sánchez Esperilla, Juan Bayo Calero
{"title":"Severe genital cutaneous toxicity with sunitinib.","authors":"María Rodríguez Jorge, Loreto Domínguez Senín, Stephanie Saide Cobelas Cartagena, María Sánchez Esperilla, Juan Bayo Calero","doi":"10.5414/CP204697","DOIUrl":"10.5414/CP204697","url":null,"abstract":"<p><strong>Introduction: </strong>Sunitinib is an oral drug approved for the treatment of metastatic renal cell carcinoma. Serious cutaneous adverse reactions to sunitinib are rare, and when they occur, discontinuation of the treatment may be needed.</p><p><strong>Case report: </strong>A 70-year-old male patient was diagnosed with stage IV clear cell renal carcinoma and received treatment with sunitinib. After a second cycle with a 25% dose reduction, the patient was admitted with a diagnosis of grade 3 genital erythema. After ruling out other common causes, sunitinib was considered the cause of genital erythema and was stopped. Treatment with corticosteroids, topical applications, and morphine was started, with resolution after 18 days of evolution.</p><p><strong>Discussion: </strong>There are only a few published reports that describe erythema and scaling of the genital skin. As in those few cases, for our patient, the first clinical signs appeared on day 28 of sunitinib treatment, and the lesions disappeared after 2 weeks without the use of the drug. Erythema and scaling reappeared when the drug was reintroduced, with greater severity than what was described in some of the other cases, which even included cases for which the lesions did not reappear.</p><p><strong>Conclusion: </strong>Rare instances of severe and limiting skin toxicity may necessitate treatment suspension and compromise survival, as observed in our case. It is crucial to recognize these skin toxicities and understand their appropriate management strategies to initiate treatment as early as possible, thereby avoiding hospitalizations and enabling the resumption of sunitinib therapy.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"164-168"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948509","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}
Daoli Jiang, Fandong Meng, Xiaohua Chou, Jiaxin Shen, Miaoyan Liu
{"title":"Renoprotective effects of dulaglutide, a GLP-1 agonist, involving regulation of epithelial-mesenchymal transition in patients with type 2 diabetes and diabetic kidney disease.","authors":"Daoli Jiang, Fandong Meng, Xiaohua Chou, Jiaxin Shen, Miaoyan Liu","doi":"10.5414/CP204632","DOIUrl":"10.5414/CP204632","url":null,"abstract":"<p><strong>Aims: </strong>To assess the renoprotective effects of dulaglutide and identify mechanisms of action in patients with type 2 diabetes and diabetic kidney disease (DKD).</p><p><strong>Materials and methods: </strong>Outpatients/ambulant patients at the Department of Endocrinology, Affiliated Hospital of Xuzhou Medical University between October 2021 and July 2023, with type 2 diabetes and DKD, a urinary albumin-to-creatinine ratio (UACR) ≥ 3 mg/mmol and who were receiving hypoglycemic agents were prescribed dulaglutide at a dose rate of 0.75 - 1.5 mg once weekly (intervention group; n = 70). Patients receiving hypoglycemic agents other than glucagon-like peptide-1 (GLP-1) receptor agonists and who were not prescribed dulaglutide constituted the control group (n = 65). Observations/outcomes: The primary outcome was a change in the UACR and biomarkers of epithelial-mesenchymal transition (EMT) determined after 12 months of intervention treatment. Adverse events (estimates of tolerability and safety) were recorded during treatment and a follow-up period of 12 months.</p><p><strong>Results: </strong>UACR changes in the intervention group compared to the control group were significantly lower (p < 0.01 at 6 months and p < 0.05 at 12 months). The frequency of gastrointestinal adverse events in the two groups were not significantly different, and there were no significant increases in the number of hypoglycemic events. Dulaglutide significantly increased the epithelial marker E-cadherin and inhibited the mesenchymal marker periostin.</p><p><strong>Conclusion: </strong>It is concluded that dulaglutide causes significant reductions in urinary albumin and modulates EMT-related proteins thereby ameliorating the decline in kidney function in patients with type 2 diabetes and DKD.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"141-153"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948506","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}
Xuechun Gu, Liyuan Zhang, Xiangyi Chen, Lingyan Kong
{"title":"Bisphosphonates in combination with alendronate sodium increase bone mineral density and modulate IL-6, TNF-α, and IGF-1 in patients with osteoporosis.","authors":"Xuechun Gu, Liyuan Zhang, Xiangyi Chen, Lingyan Kong","doi":"10.5414/CP204706","DOIUrl":"10.5414/CP204706","url":null,"abstract":"<p><strong>Objective: </strong>To assess the effects of bisphosphonates (zoledronic acid injection) plus alendronate sodium on bone mineral density (BMD) and levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and insulin-like growth factor I (IGF-I) in patients with osteoporosis.</p><p><strong>Materials and methods: </strong>A total of 94 patients recruited from osteoporosis patients hospitalized in the period October 2021 to December 2022 were assigned to either a control group or an observation group using a random number table. The control group was treated with alendronate sodium alone, whereas the observation group received zoledronic acid injection in combination with alendronate sodium administered orally.</p><p><strong>Results: </strong>Pre-treatment values for BMD, serum levels of IL-6, TNF-α, and IGF-I did not differ between the two groups (p > 0.05). However, post-treatment BMD measured at the femoral neck, in lumbar vertebrae, and Ward's triangle were increased, as was serum IGF-I level (p < 0.05). In contrast, in comparison with the control group, reductions were observed in serum IL-6 and TNF-α (p < 0.05). The incidence of adverse reactions such as nausea and vomiting, diarrhea, musculoskeletal pain, and hypocalcemia was significantly lower in the observation group (p < 0.05).</p><p><strong>Conclusion: </strong>Zoledronic acid injection in combination with alendronate sodium increases the expression of IL-6, TNF-α, and IGF-I, suppresses bone resorption and promotes bone recovery in patients with osteoporosis.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":"154-159"},"PeriodicalIF":0.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515618","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":"Advantages of an abdominal anticoagulant subcutaneous injection procedure based on a personal digital assistant and positioning card system: A clinical trial with a historical control cohort.","authors":"Xue-Fen Xia, Zhi-Bo Chen, Chan-Chan Fang, Yu-Jie Xie, Fei-Fan Yan, Sui-Li Yang","doi":"10.5414/CP204754","DOIUrl":"10.5414/CP204754","url":null,"abstract":"<p><strong>Objective: </strong>Our aim in this study is to investigate the advantages of a mobile personal digital assistant (PDA)-based anticoagulant abdominal injection positioning card in the subcutaneous injection process of low molecular weight heparin (LMWH).</p><p><strong>Materials and methods: </strong>This was a historical control study. Convenience sampling was used to include 210 patients diagnosed with venous thromboembolism who received dalteparin sodium (Fragmin) injections in our department between January 2021 and December 2022. Patients were categorized into the control group and the experimental group based on the time period before and after the implementation of the PDA-based anticoagulant abdominal injection positioning card that was developed by the information research and development department of our hospital. The control group consisted of 105 patients treated before the introduction of the PDA-based card (January to December 2021), while the experimental group comprised 105 patients treated after its introduction (January to December 2022). Patients in the control group used subcutaneous injection positioning cards made of paper to determine injection sites, while those in the experimental group used the PDA-based cards to determine injection sites. Outcome measures, including the incidence of subcutaneous bleeding, time spent on the subcutaneous injection procedure, and patient satisfaction, were compared between the two groups.</p><p><strong>Results: </strong>The incidence of subcutaneous bleeding was 5.59% in the experimental group vs. 5.61% in the control group, with no statistically significant difference between the two groups (p > 0.05). The time required for the subcutaneous injection was significantly shorter in the experimental group (63.11 ± 3.59 seconds) than in the control group (83.38 ± 6.96 seconds) (p < 0.05). The patient satisfaction rate was higher in the experimental group (94.3%) than in the control group (80.0%) (p < 0.05).</p><p><strong>Conclusion: </strong>Use of the PDA-based anticoagulant abdominal injection positioning card to determine the abdominal subcutaneous injection site for LMWH does not increase the occurrence of adverse reactions of subcutaneous bleeding, and can ensure the accuracy of medication use and the safety of medication for patients, reduce the time of nursing operations, optimize the nursing process, and improve patient satisfaction.</p>","PeriodicalId":13963,"journal":{"name":"International journal of clinical pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":0.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673764","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}