202 research outputs found
Influence of CYP3A5 and MDR1(ABCB1) Polymorphisms on the Pharmacokinetics of Tacrolimus in Chinese Renal Transplant Recipients
No full textThe aims of this study were to investigate the influence of CYP3A5 and MDR1 genetic polymorphisms on tacrolimus pharmacokinetics in Chinese renal transplant recipients, so as to help rational administration in clinical practice. We calculated pharmacokinetic parameters of tacrolimus from blood concentrations in steady state at day 28. Polymerase chain reaction restriction fragment length polymorphisms were used for CYP3A5 and MDR1 analysis. The results showed that the dose-adjusted area under the concentration time curve (AUC(0-12)) and renal clearance showed a significant difference between CYP3A5*1 carriers and the CYP3A5*3/*3 genotype (P < .01). In the following study, a distinction was made between carriers of CYP3A5*1/ vs CYP3A5*3/*3 seeking to investigate the influence of the MDR13435T>C polymorphism on tacrolimus pharmacokinetics. MDR1 3435T>C polymorphism did not affect any tacrolimus pharmacokinetic parameter in either group. Renal transplant recipients who were CYP3A5*1 carriers required a higher dose of tacrolimus than CYP3A5*3/*3, indicating a significantly lower dose-adjusted AUC(0-12) of tacrolimus. In contrast, MDR1 3435T>C polymorphism was not an important factor in tacrolimus pharmacokinetics. Pharmacogenetic methods may be used prospectively to aid dose selection and individualize immunosuppressive therapy.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000284969800019&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701ImmunologySurgeryTransplantationSCI(E)11ARTICLE93455-34584
Cost-Effectiveness of First-Line Atezolizumab versus Chemotherapy in Non-Small-Cell Lung Cancer Patients Ineligible for Platinum-Containing Regimens
No full textLan-Fang Li,1 Ran Qi,1 Tian-Tian Wei,1 Lei Feng,1 Xin Zhang,1 Qiao Liu2 1Department of Clinical Pharmacy, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272029, People’s Republic of China; 2Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of ChinaCorrespondence: Qiao Liu, Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Email [email protected]: The IPSOS study provided evidence supporting the efficacy and tolerability of first-line atezolizumab compared to single-agent chemotherapy for non-small-cell lung cancer (NSCLC) patients ineligible for treatment with a platinum-containing regimen. This study aimed to assess the cost-effectiveness of atezolizumab specifically in this population, considering the perspective of the Chinese healthcare system.Patients and Methods: In this analysis, a three-state Markov model was utilized. The survival data were derived from the IPSOS clinical trial. Direct medical costs and utility values were collected from national authoritative database and published literature. The primary outcomes were costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). To ensure the robustness of our model, both one-way and probabilistic sensitivity analyses were conducted.Results: Atezolizumab monotherapy led to an increase in costs of $4139.23 compared to single-agent chemotherapy. Additionally, it resulted in a gain of 0.14 QALYs, leading to an ICER of $29,365.79 per QALY, which was below the willingness-to-pay threshold of $36,066 per QALY used in the model. One-way sensitivity analyses revealed cost of atezolizumab and utility of progressive disease (PD) as major influencing factors for ICER. Furthermore, probabilistic sensitivity analyses confirmed our base-case results.Conclusion: From the perspective of the Chinese healthcare system, atezolizumab emerges as a cost-effective choice for the first-line treatment of NSCLC patients ineligible for platinum-based chemotherapy.Keywords: atezolizumab, cost-effectiveness, NSCLC, IPSO
Cost-Effectiveness Analysis of Pembrolizumab Plus Chemotherapy in Squamous Non–Small-Cell Lung Cancer in China
No full textXin Zhang,1,* Huixian Zhang,1,* Lan-Fang Li,1 Lei Feng,1 Qiao Liu2 1Department of Clinical Pharmacy, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, People’s Republic of China; 2Department of Pharmacy, The Second Xiangya Hospital of Central South University, Central South University, Changsha, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiao Liu, Department of Pharmacy, The Second Xiangya Hospital of Central South University, Central South University, Changsha, Hunan, People’s Republic of China, Email [email protected]: The five-year update data from the KEYNOTE-407 study have unveiled noteworthy improvements in survival outcomes achieved with pembrolizumab plus chemotherapy (Pembro+Chemo) compared to placebo plus chemotherapy (Placebo+Chemo) for patients with previously untreated metastatic squamous non-small cell lung cancer (NSCLC). Building upon this finding, our study sought to evaluate the cost-effectiveness of Pembro+Chemo, utilizing the latest available data, from the perspective of the Chinese health care system.Patients and Methods: A Markov model was employed to compare the quality-adjusted life-year (QALY), life-year (LY), total cost, and incremental cost-effectiveness ratio (ICER) between Pembro+Chemo and Placebo+Chemo. The clinical and safety data were derived from the five-year update date of the KEYNOTE-407 study. Sensitivity analyses were conducted to assess the uncertainty of the model, and additional subgroup analyses were performed to explore specific subpopulations.Results: For patients with previously untreated metastatic squamous NSCLC, the utilization of Pembro+Chemo resulted in a improvement of 0.61 quality-adjusted life years (QALYs) along with a cost reduction of $17,491.52 when compared to Placebo+Chemo. Notably, across various subgroups with different tumor proportion scores (TPS), Pembro+Chemo demonstrated enhanced QALYs and lower total costs.Conclusion: From the perspective of the Chinese health care system, first-line Pembro+Chemo emerges as a dominant treatment option over Placebo+Chemo for the treatment of metastatic squamous NSCLC.Keywords: pembrolizumab, cost-effectiveness, squamous NSCLC, KEYNOTE-40
A Bibliometric Study of the Evidence About Applying Virtual Reality in Mental Health Care
No full textSaiyu Gao,1– 3 Pan Su,3,4 Aiming Wang,4 Yongfang Tao5 1Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, Hunan, 410008, People’s Republic of China; 4Emergency Department, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 5Emergency Medical Center, Hunan University of Medicine General Hospital, Huaihua, 418000, People’s Republic of ChinaCorrespondence: Yongfang Tao, Emergency Medical Center, Hunan University of Medicine General Hospital, Huaihua, 418000, People’s Republic of China, Tel +86-731-18774559185, Email [email protected]: Virtual reality (VR) technology has gained much traction related to mental health owing to its interactive features and immersive nature. A systematic bibliometric evaluation is necessary to guide researchers in identifying emerging trends and research priorities in VR technology applications for mental health, highlighting evolving challenges and research needs.Objective: This study aimed to analyze the bibliometric characteristics and scope of evidence on the application of virtual reality in mental health care, synthesizing findings and exploring potential innovations.Methods: We conducted a bibliometric analysis using CiteSpace to examine 1333 articles from the Web of Science Core Collection (from January 1, 1999, to February 14, 2025), retrieved via the search query TS=(“Mental health” AND “Virtual reality”). The study mapped key research trends, including international and institutional collaboration networks, author co-citation networks, and the evolution of keyword co-occurrence to identify influential contributors, thematic clusters, and emerging developments in VR-based mental health research.Results: The analysis revealed three key findings: (1) Exponential publication growth starting in 2020 with over 110 annual publications; (2) Robust collaboration networks featuring 3587 authors with Riva, G. as a central figure and the University of London as the most prominent institutional hub; (3) Virtual reality, exposure therapy, skin conductance, mild cognitive impairment, psychosis, augmented reality, and serious game are the main research clusters. Emergent word analysis of keywords from 2014 to early 2025 yielded 34 words/terms with the strongest citation bursts.Conclusion: This study demonstrates VR’s integration with traditional therapy and its expanding role in treating diverse mental health conditions, from anxiety to schizophrenia. Future research should focus on standardizing treatments and validating their efficacy.Keywords: virtual reality, mental health, bibliometrics, CiteSpac
microRNA-99a Reduces Lipopolysaccharide-Induced Oxidative Injury by Activating Notch Pathway in H9c2 Cells
No full textmicroRNA-99a (miR-99a) is recently recognized as a key regulator in various cancers and cardiovascular diseases. In the present study, we sought to investigate the effects of miR-99a in rat cardiomyocyte H9c2 cells against oxidative injury induced by lipopolysaccharide (LPS). MTT assay, reactive oxygen species (ROS) assay, flow cytometry and lactate dehydrogenase (LDH) assay were respectively used to explore viability, ROS levels, apoptosis, and cell death in H9c2 cells. Quantitative PCR (qRT-PCR) was performed to confirm the expression of miR-99a. Western blot was performed to determine the expression of Notch pathway factors. LPS could significantly suppress viability and increase cell death, apoptosis, and ROS level (P < 0.05). However, miR-99a could significantly increase the viability and decrease apoptosis and ROS level of H9c2 cells (P < 0.05). Over expression of miR-99a could activate a Notch pathway and regulate the expression of B-cell CLL/lymphoma 2 (BCL2) and cleaved caspase 3. Our study found that overexpression of miR-99a could attenuate LPS-induced oxidative injury in H9c2 cells, possibly via a Notch pathway. These findings suggest that miR-99a may be a key factor in cardiomyocyte oxidative injury and could be a new therapeutic strategy for cardiovascular diseases.National Natural Science Foundation of China [8157021091]SCI(E)ARTICLE3422-4275
Cold Exposure Alleviates T2DM Through Plasma-Derived Extracellular Vesicles
No full textFu-Xing-Zi Li,1 Feng Xu,1 Chang-Chun Li,1 Li-Min Lei,1 Su-Kang Shan,1 Ming-Hui Zheng,1 Xiao Lin,2 Bei Guo,1 Ke-Xin Tang,1 Jia-Yue Duan,1 Yun-Yun Wu,1 Ye-Chi Cao,1 Jun-Jie Liu,3 Ling-Qing Yuan1 1Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Department of Periodontal Division, Hunan Xiangya Stomatological Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of ChinaCorrespondence: Ling-Qing Yuan, Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Email [email protected]: Anecdotal reports have praised the benefits of cold exposure, exemplified by activities like winter swimming and cold water immersion. Cold exposure has garnered acclaim for its potential to confer benefits and potentially alleviate diabetes. We posited that systemic cold temperature (CT, 4– 8°C) likely influences the organism’s blood components through ambient temperature, prompting our investigation into the effects of chronic cold exposure on type 2 diabetic (T2DM) mice and our initial exploration of how cold exposure mitigates the incidence of T2DM.Methods: The effects of CT (4– 8°C) or room temperature (RT, 22– 25°C) on T2DM mice were investigated. Mice blood and organ specimens were collected for fully automated biochemical testing, ELISA, HE staining, immunohistochemistry, and immunofluorescence. Glucose uptake was assessed using flow cytometry with 2-NBDG. Changes in potential signaling pathways such as protein kinase B (AKT), phosphorylated AKT (p-AKT), insulin receptor substrates 1 (IRS1), and phosphorylated IRS1 (p-IRS1) were evaluated by Western blot.Results: CT or CT mice plasma-derived extracellular vesicles (CT-EVs) remarkably reduced blood glucose levels and improved insulin sensitivity in T2DM mice. This treatment enhanced glucose metabolism, systemic insulin sensitivity, and insulin secretion function while promoting glycogen accumulation in the liver and muscle. Additionally, CT-EVs treatment protected against the streptozocin (STZ)-induced destruction of islets in T2DM mice by inhibiting β-cell apoptosis. CT-EVs also shielded islets from destruction and increased the expression of p-IRS1 and p-AKT in adipocytes and hepatocytes. In vitro experiments further confirmed its pro-insulin sensitivity effect.Conclusion: Our data indicate that cold exposure may have a potentially beneficial effect on the development of T2DM, mainly through the anti-diabetic effect of plasma-derived EVs released during cold stimulation. This phenomenon could significantly contribute to understanding the lower prevalence of diabetes in colder regions.Keywords: cold exposure, plasma-derived extracellular vesicles, type 2 diabetes, insulin sensitivity, β‑cell destructio
Identification of CD159A as a prognostic and immune biomarker in kidney renal clear cell carcinoma
No full textAbstract Kidney renal clear cell carcinoma (KIRC) is a highly aggressive malignant tumor, and its occurrence and progression are influenced by tumor microenvironment (TME). CD159A, a natural killer (NK) cell inhibitory receptor, has emerged as a critical immune checkpoint in TME. We conducted a comprehensive multi-omics analysis of CD159A expression, prognostic significance, and functional enrichment in KIRC. Additionally, quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were employed to perform CD159A expression in the Xiangya KIRC validation cohort. Furthermore, in vitro experiments were evaluated through cell proliferation, colony formation, and flow cytometry (FC) analysis of apoptosis in KIRC cell lines. Our study found that CD159A expression was significantly upregulated in KIRC tissues compared to normal tissues, as confirmed by TCGA data and the Xiangya KIRC validation cohort. In machine learning analyses, the biological significance of the regulatory network risk factors of the CD159A-HLA-E pathway is immunosuppressive receptors or abnormal antigen presentation that may promote immune escape. Elevated CD159A levels were observed in NK cells and CD8+ T cells infiltrating KIRC by single-cell RNA sequencing analysis. A positive correlation between CD159A and NK/CD8+ T cell infiltration was observed, and higher CD159A expression in KIRC patients receiving anti-PD-1/PD-L1 immunotherapy was associated with improved outcomes. In vitro experiments demonstrated that silencing CD159A significantly suppressed proliferation, colony formation and induced apoptosis in KIRC cells. Our research highlights the critical role of CD159A as a key immune checkpoint in KIRC progression and immune evasion, suggesting its potential as a prognostic and immunotherapy biomarker
Diagnostic models of the pre-test probability of stable coronary artery disease: A systematic review
No full textA comprehensive search of PubMed and Embase was performed in January 2015 to examine the available literature on validated diagnostic models of the pre-test probability of stable coronary artery disease and to describe the characteristics of the models. Studies that were designed to develop and validate diagnostic models of pre-test probability for stable coronary artery disease were included. Data regarding baseline patient characteristics, procedural characteristics, modeling methods, metrics of model performance, risk of bias, and clinical usefulness were extracted. Ten studies involving the development of 12 models and two studies focusing on external validation were identified. Seven models were validated internally, and seven models were validated externally. Discrimination varied between studies that were validated internally (C statistic 0.66-0.81) and externally (0.49-0.87). Only one study presented reclassification indices. The majority of better performing models included sex, age, symptoms, diabetes, smoking, and hyperlipidemia as variables. Only two diagnostic models evaluated the effects on clinical decision making processes or patient outcomes. Most diagnostic models of the pre-test probability of stable coronary artery disease have had modest success, and very few present data regarding the effects of these models on clinical decision making processes or patient outcomes.Fundamental Research Funds of Central South University [2016zzts565]; National Science Foundation of China [81273594]; National Key Technology RD Program [2012BAI37B05]SCI(E)REVIEW3188-1967
IL-3 and CTLA4 gene polymorphisms may influence the tacrolimus dose requirement in Chinese kidney transplant recipients
No full textThe highly variable pharmacokinetics and narrow therapeutic window of tacrolimus (TAC) has hampered its clinical use. Genetic polymorphisms may contribute to the variable response, but the evidence is not compelling, and the explanation is unclear. In this study we attempted to find previously unknown genetic factors that may influence the TAC dose requirements. The association of 105 pathway-related single nucleotide polymorphisms (SNPs) with TAC dose-adjusted concentrations (C0/D) was examined at 7, 30 and 90 d post-operation in 382 Chinese kidney transplant recipients. In CYP3A5 non-expressers, the patients carrying the IL-3 rs181781 AA genotype showed a significantly higher TAC logC0/D than those with the AG genotype at 30 and 90 d post-operation (AA vs AG, 2.21+/-0.06 vs 2.01+/-0.03, P=0.004; and 2.17+/-0.06 vs 2.03+/-0.03, P=0.033, respectively), and than those with the GG genotype at 30 d (AA vs GG, 2.21+/-0.06 vs 2.04+/-0.03, P=0.011). At 30 d, the TAC logC0/D in the grouped AG+ GG genotypes of CTLA4 rs4553808 was significantly lower than that in the AA genotype (P=0.041) in CYP3A5 expressers, but it was higher (P=0.008) in the non-expressers. We further validated the influence of CYP3A5 rs776746, CYP3A4 rs2242480 and rs4646437 on the TAC C0/D; other candidate SNPs were not associated with the differences in TAC C0/D. In conclusion, genetic polymorphisms in the immune genes IL-3 rs181781 and CTLA4 rs4553808 may influence the TAC C0/D. They may, together with CYP3A5 rs776746, CYP3A4 rs2242480 and rs4646437, contribute to the variation in TAC dose requirements. When conducting individualized therapy with tacrolimus, these genetic factors should be taken into account.National Key Research and Development Program [2016YFC0905000]; National High Technology Research and Development Program of China, the "863" Project [2012AA02A518]; National Natural Science Foundation of China [81522048, 81573511, 81273595]; Innovation Driven Project of Central South University [2016CX024]SCI(E)中国科学引文数据库(CSCD)ARTICLE3415-4233
Optimized Sampling Strategies for Isoniazid in East Asian Pediatric Populations Using Population Pharmacokinetics-Informed Approaches
No full textGehang Ju,1– 3 Xin Liu,4 Yeheng Peng,4 Wenyu Yang,4 Nuo Xu,4 Qingfeng He,4 Chenchen Zhang,5 Lulu Chen,3,6 Nan Yang,3,6,7 Gufen Zhang,3,6,7 Chao Li,3,6,7 Pan Su,8 Xiao Zhu,4 Dongsheng Ouyang1– 3,6 1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Institute of Clinical Pharmacology, Central South University, Changsha, People’s Republic of China; 3Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd., Changsha, People’s Republic of China; 4Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China; 5School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 6Changsha Duxact Biotech Co., Ltd., Changsha, People’s Republic of China; 7Phamark Data Technology Co., Ltd., Changsha, People’s Republic of China; 8Hunan Chest Hospital, Changsha, People’s Republic of ChinaCorrespondence: Dongsheng Ouyang, Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Lutian Road 28, Changsha, People’s Republic of China, Tel +86 0731 84805380, Email [email protected] Xiao Zhu, Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Jinke Road 3728, Shanghai, People’s Republic of China, Tel +86 21 51980025, Email [email protected]: Isoniazid exposure in vivo is significantly affected by NAT2 genotypes and has ethnic differences. To optimize the sampling strategy for isoniazid in East Asian pediatric populations. We employed a model-informed optimization approach based on INH population pharmacokinetic (PopPK) models.Methods: We selected PopPK models for children and East Asian adults and optimized the sampling strategy using PopED (Population Experimental Design), a method that helps identify the most efficient sampling points for maximizing parameter estimation accuracy. Virtual patients with varying NAT2 phenotypes were created, and real-world pediatric scenarios were evaluated using questionnaire data, sampling windows, and stochastic simulations.Results: From eight analyzed models (four for East Asian adults and four for non-East Asian pediatrics), we simplified two over-parameterized models using lumping without loss of performance. The optimized clinical sampling strategy involved collecting samples at 0.25 [0– 0.5], 1.5 [1– 2], 6 [3– 8], 12 [9– 14], and 24 [22– 24] hours post-dose. Simulation verification showed that re-estimated major PK parameters had acceptable relative biases and relative standard error (< 30%).Conclusion: Traditional adult sampling strategies are inadequate for East Asian pediatric populations. A tailored strategy involving up to five samples can accurately estimate INH PopPK parameters and should be considered for clinical implementation to optimize treatment and reduce patient sampling burden.Keywords: isoniazid, optimal sampling design, population pharmacokinetics, stochastic simulation and estimatio
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