GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Frontiers Media SA  (65)
Material
Publisher
  • Frontiers Media SA  (65)
Person/Organisation
Language
Years
FID
  • 1
    Online Resource
    Online Resource
    Table_2.xlsx
    Frontiers Media SA ; 2021
    In:  Frontiers in Cellular and Infection Microbiology Vol. 11 ( 2021-10-7)
    Details
    In: Frontiers in Cellular and Infection Microbiology, Frontiers Media SA, Vol. 11 ( 2021-10-7)
    Abstract: Comprehensive analyses of multi-omics data may provide insights into interactions between different biological layers concerning distinct clinical features. We integrated data on the gut microbiota, blood parameters and urine metabolites of treatment-naive individuals presenting a wide range of metabolic disease phenotypes to delineate clinically meaningful associations. Trans-omics correlation networks revealed that candidate gut microbial biomarkers and urine metabolite feature were covaried with distinct clinical phenotypes. Integration of the gut microbiome, the urine metabolome and the phenome revealed that variations in one of these three systems correlated with changes in the other two. In a specific note about clinical parameters of liver function, we identified Eubacteriumeligens, Faecalibacteriumprausnitzii and Ruminococcuslactaris to be associated with a healthy liver function, whereas Clostridium bolteae, Tyzzerellanexills, Ruminococcusgnavus, Blautiahansenii, and Atopobiumparvulum were associated with blood biomarkers for liver diseases. Variations in these microbiota features paralleled changes in specific urine metabolites. Network modeling yielded two core clusters including one large gut microbe-urine metabolite close-knit cluster and one triangular cluster composed of a gut microbe-blood-urine network, demonstrating close inter-system crosstalk especially between the gut microbiome and the urine metabolome. Distinct clinical phenotypes are manifested in both the gut microbiome and the urine metabolome, and inter-domain connectivity takes the form of high-dimensional networks. Such networks may further our understanding of complex biological systems, and may provide a basis for identifying biomarkers for diseases. Deciphering the complexity of human physiology and disease requires a holistic and trans-omics approach integrating multi-layer data sets, including the gut microbiome and profiles of biological fluids. By studying the gut microbiome on carotid atherosclerosis, we identified microbial features associated with clinical parameters, and we observed that groups of urine metabolites correlated with groups of clinical parameters. Combining the three data sets, we revealed correlations of entities across the three systems, suggesting that physiological changes are reflected in each of the omics. Our findings provided insights into the interactive network between the gut microbiome, blood clinical parameters and the urine metabolome concerning physiological variations, and showed the promise of trans-omics study for biomarker discovery.
    Type of Medium: Online Resource
    ISSN: 2235-2988
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fcimb.2021.708088
    DOI: 10.3389/fcimb.2021.708088.s001
    DOI: 10.3389/fcimb.2021.708088.s002
    DOI: 10.3389/fcimb.2021.708088.s003
    DOI: 10.3389/fcimb.2021.708088.s004
    DOI: 10.3389/fcimb.2021.708088.s005
    DOI: 10.3389/fcimb.2021.708088.s006
    DOI: 10.3389/fcimb.2021.708088.s007
    DOI: 10.3389/fcimb.2021.708088.s008
    DOI: 10.3389/fcimb.2021.708088.s009
    DOI: 10.3389/fcimb.2021.708088.s010
    DOI: 10.3389/fcimb.2021.708088.s011
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2619676-1
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    FDA-Approved and Emerging Next Generation Predictive Biomarkers for Immune Checkpoint Inhibitors in Cancer Patients
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-6-7)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-6-7)
    Abstract: A patient’s response to immune checkpoint inhibitors (ICIs) is a complex quantitative trait, and determined by multiple intrinsic and extrinsic factors. Three currently FDA-approved predictive biomarkers (progra1mmed cell death ligand-1 (PD-L1); microsatellite instability (MSI); tumor mutational burden (TMB)) are routinely used for patient selection for ICI response in clinical practice. Although clinical utility of these biomarkers has been demonstrated in ample clinical trials, many variables involved in using these biomarkers have poised serious challenges in daily practice. Furthermore, the predicted responders by these three biomarkers only have a small percentage of overlap, suggesting that each biomarker captures different contributing factors to ICI response. Optimized use of currently FDA-approved biomarkers and development of a new generation of predictive biomarkers are urgently needed. In this review, we will first discuss three widely used FDA-approved predictive biomarkers and their optimal use. Secondly, we will review four novel gene signature biomarkers: T-cell inflamed gene expression profile (GEP), T-cell dysfunction and exclusion gene signature (TIDE), melanocytic plasticity signature (MPS) and B-cell focused gene signature. The GEP and TIDE have shown better predictive performance than PD-L1, and PD-L1 or TMB, respectively. The MPS is superior to PD-L1, TMB, and TIDE. The B-cell focused gene signature represents a previously unexplored predictive biomarker to ICI response. Thirdly, we will highlight two combined predictive biomarkers: TMB+GEP and MPS+TIDE. These integrated biomarkers showed improved predictive outcomes compared to a single predictor. Finally, we will present a potential nucleic acid biomarker signature, allowing DNA and RNA biomarkers to be analyzed in one assay. This comprehensive signature could represent a future direction of developing robust predictive biomarkers, particularly for the cold tumors, for ICI response.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2021.683419
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Table_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-12-20)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-12-20)
    Abstract: To analyzed the outcome of ETV6/RUNX1-positive pediatric acute B lymphoblastic leukemia (B-ALL) with the aim of identifying prognostic value. Method A total of 2,530 pediatric patients who were diagnosed with B-ALL were classified into two groups based on the ETV6/RUNX1 status by using a retrospective cohort study method from February 28, 2008, to June 30, 2020, at 22 participating ALL centers. Results In total, 461 (18.2%) cases were ETV6/RUNX1-positive. The proportion of patients with risk factors (age & lt;1 year or ≥10 years, WB≥50×10 9 /L) in ETV6/RUNX1-positive group was significantly lower than that in negative group ( P & lt;0.001), while the proportion of patients with good early response (good response to prednisone, D15 MRD & lt; 0.1%, and D33 MRD & lt; 0.01%) in ETV6/RUNX1-positive group was higher than that in the negative group ( P & lt;0.001, 0.788 and 0.004, respectively). Multivariate analysis of 2,530 patients found that age & lt;1 or ≥10 years, SCCLG-ALL-2016 protocol, and MLL were independent predictor of outcome but not ETV6/RUNX1. The EFS and OS of the ETV6/RUNX1-positive group were significantly higher than those of the negative group (3-year EFS: 90.11 ± 4.21% vs 82 ± 2.36%, P & lt;0.0001, 3-year OS: 91.99 ± 3.92% vs 88.79 ± 1.87%, P =0.017). Subgroup analysis showed that chemotherapy protocol, age, prednisone response, and D15 MRD were important factors affecting the prognosis of ETV6/RUNX1-positive children. Conclusions ETV6/RUNX1-positive pediatric ALL showed an excellent outcome but lack of independent prognostic significance in South China. However, for older patients who have the ETV6/RUNX1 fusion and slow response to therapy, to opt for more intensive treatment.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2021.797194
    DOI: 10.3389/fonc.2021.797194.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    A Nomogram for Predicting Event-Free Survival in Childhood Acute Lymphoblastic Leukemia: A Multicenter Retrospective Study
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-3-29)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-3-29)
    Abstract: Even though childhood acute lymphoblastic leukemia (ALL) has an encouraging survival rate in recent years, some patients are still at risk of relapse or even death. Therefore, we aimed to construct a nomogram to predict event-free survival (EFS) in patients with ALL. Method Children with newly diagnosed ALL between October 2016 and July 2021 from 18 hospitals participating in the South China children’s leukemia Group (SCCLG) were recruited and randomly classified into two subsets in a 7:3 ratio (training set, n=1187; validation set, n=506). Least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were adopted to screen independent prognostic factors. Then, a nomogram can be build based on these prognostic factors to predict 1-, 2-, and 3-year EFS. Concordance index (C-index), area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance and clinical utility of nomogram. Result The parameters that predicted EFS were age at diagnosis, white blood cell at diagnosis, immunophenotype, ETV6-RUNX1/TEL-AML1 gene fusion, bone marrow remission at day 15, and minimal residual disease at day 15. The nomogram incorporated the six factors and provided C-index values of 0.811 [95% confidence interval (CI) = 0.792-0.830] and 0.797 (95% CI = 0.769-0.825) in the training and validation set, respectively. The calibration curve and AUC revealed that the nomogram had good ability to predict 1-, 2-, and 3-year EFS. DCA also indicated that our nomogram had good clinical utility. Kaplan–Meier analysis showed that EFS in the different risk groups stratified by the nomogram scores was significant differentiated. Conclusion The nomogram for predicting EFS of children with ALL has good performance and clinical utility. The model could help clinical decision-making.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2022.854798
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    DataSheet6.PDF
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-5-13)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-5-13)
    Abstract: Koumine (KM), the most abundant alkaloid in Gelsemium elegans , has anti-neuropathic, anti-inflammatory, and analgesic activities; thus, it has the potential to be developed as a broad-spectrum analgesic drug. However, factors determining the relationship between analgesic efficacy and the corresponding plasma KM concentration are largely unclear. The pharmacokinetics and pharmacodynamics of KM and their optimization in the context of neuropathic pain have not been reported. We investigated the pharmacokinetics and pharmacodynamics of KM after oral administration in a streptozotocin-induced rat model of diabetic neuropathic pain (DNP) using a population approach. A first-order absorption and elimination pharmacokinetics model best described the plasma KM concentration. This pharmacokinetic model was then linked to a linear pharmacodynamic model with an effect compartment based on the measurement of the mechanical withdrawal threshold. KM was rapidly absorbed (time to maximum plasma concentration: 0.14–0.36 h) with similar values in both DNP and naïve rats, suggesting that DNP did not influence the KM absorption rate. However, the area under the curve (AUC 0–∞ ) of KM in DNP rats was over 3-fold higher than that in naïve rats. The systemic clearance rate and volume of KM distribution were significantly lower in DNP rats than in naïve rats. Blood glucose value prior to KM treatment was a significant covariate for the systemic clearance rate of KM and baseline value of the threshold. Our results suggest that streptozotocin-induced hyperglycemia is an independent factor for decreased KM elimination and its anti-allodynic effects in a DNP rat model. To the best of our knowledge, this is the first study to investigate the role of DNP in the pharmacokinetics and pharmacokinetics-pharmacodynamics of KM in streptozotocin-induced diabetic rats.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2021.640318
    DOI: 10.3389/fphar.2021.640318.s001
    DOI: 10.3389/fphar.2021.640318.s002
    DOI: 10.3389/fphar.2021.640318.s003
    DOI: 10.3389/fphar.2021.640318.s004
    DOI: 10.3389/fphar.2021.640318.s005
    DOI: 10.3389/fphar.2021.640318.s006
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Table_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 12 ( 2022-1-25)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2022-1-25)
    Abstract: Programmed death-ligand 1 (PD-L1) expression has been approved as an immune checkpoint inhibitor (ICI) response predictive biomarker; however, the clinicopathological and molecular features of HPV-positive oropharyngeal squamous cell carcinoma [HPV(+)OPSCC] based on PD-L1 expression are not well studied. We aimed to characterize clinicopathological, tumor immune microenvironmental, and molecular features of HPV(+)OPSCC with different PD-L1 expression scored by combined positive score (CPS). A total of 112 cases were collected from 2008-2021 and received PD-L1 and CD8 immunohistochemistry (IHC) staining. 71 samples received DNA sequencing out of which 32 samples received RNA sequencing for immune-related gene alterations or expression analysis. The 32 samples were also subjected to analysis of CD20, CD4, CD8, CD68, Foxp3 and P16 by multiplex immunofluorescence (mIF) staining, and the immune markers were evaluated in the tumor body (TB), tumor margin (TM) and normal stroma (NS) regions separately. Our results showed that of 112 HPV(+)OPSCC tumors, high(CPS≥20), intermediate(1≤CPS & lt;20), and low(CPS & lt;1) PD-L1 expression was seen in 29.5%, 43.8% and 26.8% cases respectively. Non-smoking patients and patients with tumors occurring at the tonsils or having rich lymphocytes infiltration had significantly higher PD-L1 expression. Patients with CPS≥20 had significantly higher tumor mutation burden (TMB, p=0.0058), and PD-L1 expression correlated significantly with CD8 + T cells infiltration, which were ample in tumor regions than in NS in mIF. CD20 + , CD4 + , CD68 + , Foxp3 + CD4 + cells were demonstrated to infiltrate higher in TM while CD20 + and CD68 + cells were also enriched in NS and TB regions respectively. However, none of them showed correlations with PD-L1 expression. ARID1A, STK11 alterations were enriched in the low PD-L1 group significantly, while anti-viral immune associated APOBEC mutation signature and immune-related genes expression such as XCL1 and IL11 were positively associated with PD-L1 expression (p & lt;0.05). This is a comprehensive investigation revealing immune and molecular features of HPV(+)OPSCC based on PD-L1 expression. Our study suggested that 73.2% of HPV(+)OPSCC patients may benefit from immunotherapy, and high PD-L1 expression reflects immune-active status of HPV(+)OPSCC accompanied by higher immune effect factors such as TMB, CD8 + cytotoxic T cells and immune-related genomic alterations. Our study offers valuable information for understanding the immune features of HPV(+)OPSCC.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2021.798424
    DOI: 10.3389/fimmu.2021.798424.s001
    DOI: 10.3389/fimmu.2021.798424.s002
    DOI: 10.3389/fimmu.2021.798424.s003
    DOI: 10.3389/fimmu.2021.798424.s004
    DOI: 10.3389/fimmu.2021.798424.s005
    DOI: 10.3389/fimmu.2021.798424.s006
    DOI: 10.3389/fimmu.2021.798424.s007
    DOI: 10.3389/fimmu.2021.798424.s008
    DOI: 10.3389/fimmu.2021.798424.s009
    DOI: 10.3389/fimmu.2021.798424.s010
    DOI: 10.3389/fimmu.2021.798424.s011
    DOI: 10.3389/fimmu.2021.798424.s012
    DOI: 10.3389/fimmu.2021.798424.s013
    DOI: 10.3389/fimmu.2021.798424.s014
    DOI: 10.3389/fimmu.2021.798424.s015
    DOI: 10.3389/fimmu.2021.798424.s016
    DOI: 10.3389/fimmu.2021.798424.s017
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Table_1.DOC
    Frontiers Media SA ; 2020
    In:  Frontiers in Oncology Vol. 10 ( 2020-9-23)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 10 ( 2020-9-23)
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2020.571390
    DOI: 10.3389/fonc.2020.571390.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2649216-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Image_1.tif
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 10 ( 2021-1-26)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 10 ( 2021-1-26)
    Abstract: We investigated the locoregional effect of trastuzumab, and determined whether patients with human epidermal growth factor receptor (HER)2-positive breast cancer (BC) treated with trastuzumab could achieve comparable efficacy to that of patients with HER2-negative BC. Materials and Methods This was post hoc analyses of data of 793 BC patients from a randomized controlled trial comparing post-mastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy. Survival rates were analyzed by the Kaplan–Meier method and compared by the log-rank test. Results Patients were classified into three groups: HER2-negative (HER2 − ; n = 547), HER2-positve with trastuzumab (HER2 + + T; n = 136), and HER2-positive without trastuzumab (HER2 + − T; n = 110). The HER2 + + T group had significantly lower locoregional recurrence (LRR, 6.0% vs. 13.9%), distant metastasis (DM, 17.4% vs. 33.8%) and higher disease-free survival (DFS, 81.2% vs. 61.9%) at 5 years than that of the HER2 + − T group ( P & lt;.05). The HER2 − group had significantly lower LRR (6.8% vs. 13.9%), DM (22.4% vs. 33.8%) and higher DFS (76.1% vs. 61.9%) at 5 years than that of the HER2 + − T group ( P & lt;.05). The difference in LRR, DM and DFS at 5 years was not significant between the HER2 + + T group and HER2 − group ( P & gt;.05). Different annual LRR patterns was found among groups according to HR status. Conclusion Trastuzumab reduces LRR in patients with locally advanced HER2-positive BC who have received post-mastectomy radiotherapy. It provides comparable DFS to that with patients with HER2-negative BC.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2020.605750
    DOI: 10.3389/fonc.2020.605750.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    CaM/CaMKII mediates activation and proliferation of hepatic stellate cells regulated by ASIC1a
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-12-15)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-12-15)
    Abstract: The activation of hepatic stellate cells (HSCs) is closely related to hepatic fibrosis and plays a key role in its occurrence and development. In the damaged liver, inhibition of the activation, proliferation, and clearance of HSCs is an important therapeutic strategy. However, the mechanism underlying the activation of HSCs is not completely clear. Acid-sensitive ion channel 1a (ASIC1a) is a cation channel activated by extracellular acid, which is responsible for the transport of Ca 2+ and Na + and participates in the activation of HSCs and the occurrence and development of many inflammatory diseases, suggesting that ASIC1a plays an important role in liver fibrosis. A previous study by the project team found that when the membrane channel protein ASIC1a was opened, intracellular Ca 2+ levels increased, the expression of CaM/CaMKII in HSCs was high, and HSC was activated and proliferated. Therefore, we established an SD rat model of hepatic fibrosis and induced HSC-T6 activation by stimulating ASIC1a with acid in vitro. In vivo, CCl 4 was used to induce liver fibrosis in rats, and different doses of KN93 (0.5, 1, and 2 mg/kg/d) and colchicine (0.1 mg/kg/d) were administered. Eight weeks later, the activities of ALT and AST in serum were measured and hematoxylin-eosin and Masson staining in liver tissue, and immunohistochemistry analysis were performed in SD rats. The expressions of ASIC1a, α-SMA, Collagen-1, CaM, and CaMKII were detected. In vitro, we activated HSC-T6 cells by stimulating ASIC1a with acid. The results showed that inhibition of ASIC1a could improve acid-induced HSCs activation. In addition, CaM/CaMKII was expressed in HSC of rats with hepatic fibrosis regulated by ASIC1a. After blocking or silencing the expression of CaMKII, the fibrosis marker protein can be down-regulated. KN93 also reduced inflammation and improved the activation, proliferation and fibrosis of HSC. In summary, we concluded that CaM/CaMKII participates in ASIC1a regulation of the proliferation and activation of HSC and promotes the occurrence of liver fibrosis.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2022.996667
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Population Pharmacokinetics of Cyclosporine in Chinese Pediatric Patients With Acquired Aplastic Anemia
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-7-26)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-7-26)
    Abstract: Cyclosporine (CsA) is a component of the first-line treatment for acquired aplastic anemia (acquired AA) in pediatric patients. This study aimed to develop a population pharmacokinetic (PK) model of CsA in Chinese pediatric patients with acquired AA to inform individual dosage regimens. A total of 681 CsA whole blood concentrations and laboratory data of 157 pediatric patients with acquired AA were retrospectively collected from two hospitals in Shanghai. A nonlinear mixed-effect model approach was used to build the population PK model. Potential covariate effects of age, body weight, and biochemical measurements (renal and liver functions) on CsA PK disposition were evaluated. Model fit was assessed using the basic goodness of fit and a visual predictive check. The CsA concentration data were accurately described using a two-compartment disposition model with first-order absorption and elimination. Body weight value was implemented as a fixed allometric function on all clearance and volume of distribution parameters. Total bilirubin level was identified as a significant covariate on apparent clearance (CL/F), with a 1.07% reduction per 1 nmol/L rise in total bilirubin level. The final estimates for CL/F and central volume (Vc/F) were 29.1 L/h and 325 L, respectively, for a typical 28 kg child. Other covariates (e.g., gender, age, albumin, hemoglobin, hematocrit, serum creatinine, and concomitant medication) did not significantly affect the PK properties of CsA. This population PK model, along with a maximum a posteriori Bayesian approach, could estimate individual PK parameters in pediatric patients with acquired AA to conduct individual CsA therapy.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2022.933739
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...