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1.
Daru ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060737

RESUMO

Pain represents an unpleasant sensation linked to actual or potential tissue damage. In the early phase, the sensation of pain is caused due to direct stimulation of the sensory nerve fibers. On the other hand, the pain in the late phase is attributed to inflammatory mediators. Current medicines used to treat inflammation and pain are effective; however, they cause severe side effects, such as ulcer, anemia, osteoporosis, and endocrine disruption. Increased attention is recently being focused on the examination of the analgesic potential of phytoconstituents, such as glycosides of traditional medicinal plants, because they often have suitable biological activities with fewer side effects as compared to synthetic drugs. The purpose of this article is to review for the first time the current state of knowledge on the use of glycosides from medicinal plants to induce analgesia and anti-inflammatory effect. Various databases and search engines, including PubMed, ScienceDirect, Scopus, Web of Science and Google Scholar, were used to search and collect relevant studies on glycosides with antinociceptive activities. The results led to the identification of several glycosides that exhibited marked inhibition of various pain mediators based on different well-established assays. Additionally, these glycosides were found to induce most of the analgesic effects through cyclooxygenase and lipoxygenase pathways. These findings can be useful to identify new candidates which can be clinically developed as analgesics with better bioavailability and reduced side effects. Graphical abstract Analgesic mechanisms of plant glycosides.

2.
J Pharm Biomed Anal ; 183: 113131, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-32058288

RESUMO

A battery of analytical methods is used to analyze recombinant monoclonal antibodies for lot release to ensure consistent product quality, safety, and efficacy. Additionally, state-of-the-art analytical methods have been used to thoroughly characterize various post-translational modifications and degradation pathways of those molecules. Scientifically sound and robust analytical methods are essential to providing reliable results for defining control strategy, including setting phase-appropriate specifications. Analytical artifacts can substantially impact analytical method performance, causing either overestimation or underestimation of the impacted attributes. However, these artifacts are often overlooked due to lack of the fundamental understanding of analytical methods. This review discusses several regularly encountered artifacts and provides a guidance on assessment and prevention of these artifacts. Understanding and preventing artifacts can help establish scientifically sound and robust methods with reliable performance throughout the method life cycle.

3.
Adv Mater ; 32(7): e1905923, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31930593

RESUMO

The reasonable design of electrode materials for rechargeable batteries plays an important role in promoting the development of renewable energy technology. With the in-depth understanding of the mechanisms underlying electrode reactions and the rapid development of advanced technology, the performance of batteries has significantly been optimized through the introduction of defect engineering on electrode materials. A large number of coordination unsaturated sites can be exposed by defect construction in electrode materials, which play a crucial role in electrochemical reactions. Herein, recent advances regarding defect engineering in electrode materials for rechargeable batteries are systematically summarized, with a special focus on the application of metal-ion batteries, lithium-sulfur batteries, and metal-air batteries. The defects can not only effectively promote ion diffusion and charge transfer but also provide more storage/adsorption/active sites for guest ions and intermediate species, thus improving the performance of batteries. Moreover, the existing challenges and future development prospects are forecast, and the electrode materials are further optimized through defect engineering to promote the development of the battery industry.

4.
Theranostics ; 10(1): 17-35, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903103

RESUMO

Approximately 10% of bone fractures do not heal satisfactorily, leading to significant clinical and socioeconomic implications. Recently, the role of macrophages in regulating bone marrow stem cell (BMSC) differentiation through the osteogenic pathway during fracture healing has attracted much attention. Methods: The tibial monocortical defect model was employed to determine the critical role of macrophage scavenger receptor 1 (MSR1) during intramembranous ossification (IO) in vivo. The potential functions and mechanisms of MSR1 were explored in a co-culture system of bone marrow-derived macrophages (BMDMs), RAW264.7 cells, and BMSCs using qPCR, Western blotting, immunofluorescence, and RNA sequencing. Results: In this study, using the tibial monocortical defect model, we observed delayed IO in MSR1 knockout (KO) mice compared to MSR1 wild-type (WT) mice. Furthermore, macrophage MSR1 mediated PI3K/AKT/GSK3ß/ß-catenin signaling increased ability to promote osteogenic differentiation of BMSCs in the co-culture system. We also identified proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) as the target gene for macrophage MSR1-activated PI3K/AKT/GSK3ß/ß-catenin pathway in the co-culture system that facilitated M2-like polarization by enhancing mitochondrial oxidative phosphorylation. Conclusion: Our findings revealed a previously unrecognized function of MSR1 in macrophages during fracture repair. Targeting MSR1 might, therefore, be a new therapeutic strategy for fracture repair.

5.
Int J Equity Health ; 19(1): 6, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906960

RESUMO

BACKGROUND: Aging and the chronic non-communicable diseases (NCDs) challenge the Chinese government in the process of providing hospitalization services fairly and reasonably. The Chinese government has developed the basic medical insurance system to solve the problem of "expensive medical cost and difficult medical services" for vulnerable groups and alleviate the unfair phenomenon. However, few studies have confirmed its effect through longitudinal comparison. This study aimed to explore the trend in the inequity of inpatient use among middle-aged and elderly individuals with NCDs in China. METHODS: This longitudinal comparative study was based on CHARLS data in 2011, 2013 and 2015. Concentration index (CI) was used to measure the variation trend of inequity of inpatient services utilization, while the decomposition method of the CI was applied to measure the factors contributing to inequity in inpatient services utilization. The effect of each factor on the change of inequity in inpatient services utilization was divided into the change of the elasticity and the change of inequality using the Oaxaca-type decomposition method. RESULTS: The affluent middle-aged and elderly patients with NCDs used more inpatient services than poor groups. The per capita household consumption expenditure (PCE) and Urban Employee Basic Medical Insurance (UEBMI) contributed to the decline in pro-rich inequality of inpatient use, while the New Rural Cooperative Medical Scheme (NRCMS) contributed to the decline in pro-poor inequality of inpatient use. CONCLUSIONS: There was a certain degree of pro-rich unfairness in the probability and frequency of inpatient services utilization for middle-aged and elderly individuals with NCDs in China. The decrease of pro-wealth contribution of PCE and UEBMI offset the decrease of pro-poor contribution of NRCMS, and improved the equity of inpatient services utilization, favoring poor people.

6.
Nat Commun ; 11(1): 357, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953423

RESUMO

Hypoxia of solid tumor compromises the therapeutic outcome of photodynamic therapy (PDT) that relies on localized O2 molecules to produce highly cytotoxic singlet oxygen (1O2) species. Herein, we present a safe and versatile self-assembled PDT nanoagent, i.e., OxgeMCC-r single-atom enzyme (SAE), consisting of single-atom ruthenium as the active catalytic site anchored in a metal-organic framework Mn3[Co(CN)6]2 with encapsulated chlorin e6 (Ce6), which serves as a catalase-like nanozyme for oxygen generation. Coordination-driven self-assembly of organic linkers and metal ions in the presence of a biocompatible polymer generates a nanoscale network that adaptively encapsulates Ce6. The resulted OxgeMCC-r SAE possesses well-defined morphology, uniform size distribution and high loading capacity. When conducting the in situ O2 generation through the reaction between endogenous H2O2 and single-atom Ru species of OxgeMCC-r SAE, the hypoxia in tumor microenvironment is relieved. Our study demonstrates a promising self-assembled nanozyme with highly efficient single-atom catalytic sites for cancer treatment.

7.
BMC Musculoskelet Disord ; 21(1): 34, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31948409

RESUMO

BACKGROUND: Intertrochanteric femoral fractures are prevalent among the elderly, and usually demands surgical treatments. Proximal femoral nail antirotation Asian version (PFNA-II) is widely used for intertrochanteric fracture treatment. The computer-assisted preoperative planning (CAPP) system has the potential to reduce the difficulty of PFNA-II in the treatment of intertrochanteric fractures. The aim of the study was to investigate and compare the learning curves of PFNA-II treatment with CAPP and conventional preoperational planning methods for intertrochanteric femoral fractures. METHODS: A total of 125 patients with intertrochanteric fracture who were treated with PFNA-II between March 2012 and June 2015 were retrospectively analyzed. Patients who underwent surgery with CAPP procedure by a junior surgeon were regarded as group A (n = 53); patients who underwent the conventional surgery by another junior surgeon were regarded as group B (n = 72). Each group was divided into three subgroups (case 1-20, case 21-40, case 41-53 or case 41-72). RESULTS: The average operation time of group A was 45.00(42.00, 50.00) minutes, and in group B was 55.00 (50.00, 60.00) minutes (P < 0.01). Average radiation frequency and blood loss were 13.02 ± 2.32, 160.00 (140.00, 170.00) ml and 20.92 ± 3.27, 250.00 (195.00, 279.50) ml, respectively, with significant differences (P < 0.01). The learning curve of the surgical procedure in group A was steeper than that in group B. There were no significant differences in patient reported outcomes, hospital stay and complication rate between the two groups. Significant differences were observed between group A and B in Harris score at last follow-up in the AO/OTA type 31-A2 intertrochanteric fracture (P < 0.05). CONCLUSION: Compared with conventional preoperative planning methods, CAPP system significantly reduced operation time, radiation frequency and blood loss, thus reshaped the learning curve of PFNA-II treatment with lower learning difficulty. TRIAL REGISTRATION: researchregistry4770. Registered 25 March 2019.

8.
Int J Mol Sci ; 21(3)2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31979310

RESUMO

Epidemiological results revealed that there is an inverse correlation between high-density lipoprotein (HDL) cholesterol levels and risks of atherosclerotic cardiovascular disease (ASCVD). Mounting evidence supports that HDLs are atheroprotective, therefore, many therapeutic approaches have been developed to increase HDL cholesterol (HDL-C) levels. Nevertheless, HDL-raising therapies, such as cholesteryl ester transfer protein (CETP) inhibitors, failed to ameliorate cardiovascular outcomes in clinical trials, thereby casting doubt on the treatment of cardiovascular disease (CVD) by increasing HDL-C levels. Therefore, HDL-targeted interventional studies were shifted to increasing the number of HDL particles capable of promoting ATP-binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux. One such approach was the development of reconstituted HDL (rHDL) particles that promote ABCA1-mediated cholesterol efflux from lipid-enriched macrophages. Here, we explore the manipulation of rHDL nanoparticles as a strategy for the treatment of CVD. In addition, we discuss technological capabilities and the challenge of relating preclinical in vivo mice research to clinical studies. Finally, by drawing lessons from developing rHDL nanoparticles, we also incorporate the viabilities and advantages of the development of a molecular imaging probe with HDL nanoparticles when applied to ASCVD, as well as gaps in technology and knowledge required for putting the HDL-targeted therapeutics into full gear.

9.
Semin Cancer Biol ; 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31935456

RESUMO

Scavenger receptor class B type I (SR-BI) protein is an integral membrane glycoprotein. SR-BI is emerging as a multifunctional protein, which regulates autophagy, efferocytosis, cell survival and inflammation. It is well known that SR-BI plays a critical role in lipoprotein metabolism by mediating cholesteryl esters selective uptake and the bi-directional flux of free cholesterol. Recently, SR-BI has also been identified as a potential marker for cancer diagnosis, prognosis, or even a treatment target. Natural products are a promising source for the discovery of new drug leads. Multiple natural products were identified to regulate SR-BI protein expression. There are still a number of challenges in modulating SR-BI expression in cancer and in using natural products for modulation of such protein expression. In this review, our purpose is to discuss the relationship between SR-BI protein and cancer, and the molecular mechanisms regulating SR-BI expression, as well as to provide an overview of natural products that regulate SR-BI expression.

10.
Breast Cancer Res ; 22(1): 3, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910867

RESUMO

BACKGROUND: Breast cancer metastasis is driven by a profound remodeling of the cytoskeleton that enables efficient cell migration and invasion. Anillin is a unique scaffolding protein regulating major cytoskeletal structures, such as actin filaments, microtubules, and septin polymers. It is markedly overexpressed in breast cancer, and high anillin expression is associated with poor prognosis. The aim of this study was to investigate the role of anillin in breast cancer cell migration, growth, and metastasis. METHODS: CRISPR/Cas9 technology was used to deplete anillin in highly metastatic MDA-MB-231 and BT549 cells and to overexpress it in poorly invasive MCF10AneoT cells. The effects of anillin depletion and overexpression on breast cancer cell motility in vitro were examined by wound healing and Matrigel invasion assays. Assembly of the actin cytoskeleton and matrix adhesion were evaluated by immunofluorescence labeling and confocal microscopy. In vitro tumor development was monitored by soft agar growth assays, whereas cancer stem cells were examined using a mammosphere formation assay and flow cytometry. The effects of anillin knockout on tumor growth and metastasis in vivo were determined by injecting control and anillin-depleted breast cancer cells into NSG mice. RESULTS: Loss-of-function and gain-of-function studies demonstrated that anillin is necessary and sufficient to accelerate migration, invasion, and anchorage-independent growth of breast cancer cells in vitro. Furthermore, loss of anillin markedly attenuated primary tumor growth and metastasis of breast cancer in vivo. In breast cancer cells, anillin was localized in the nucleus; however, knockout of this protein affected the cytoplasmic/cortical events, e.g., the organization of actin cytoskeleton and cell-matrix adhesions. Furthermore, we observed a global transcriptional reprogramming of anillin-depleted breast cancer cells that resulted in suppression of their stemness and induction of the mesenchymal to epithelial trans-differentiation. Such trans-differentiation was manifested by the upregulation of basal keratins along with the increased expression of E-cadherin and P-cadherin. Knockdown of E-cadherin restored the impaired migration and invasion of anillin-deficient breast cancer cells. CONCLUSION: Our study demonstrates that anillin plays essential roles in promoting breast cancer growth and metastatic dissemination in vitro and in vivo and unravels novel functions of anillin in regulating breast cancer stemness and differentiation.

11.
Biomed Res Int ; 2020: 6745626, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31998795

RESUMO

The aim of this study was to compare the values of six methods in measuring the involvement of posterior malleolus and to demonstrate the reliability and reproducibility of each method. Three independent orthopaedic surgeons, retrospectively, measured 106 cases. The difference between the six methods was analyzed using Bonferroni-corrected paired t-tests after one-way ANOVA. The agreement between the six methods was analyzed using Bland-Altman analysis. The intraclass correlation coefficient (ICC) was used to assess intraobserver reproducibility and interobserver reliability. Significant differences were observed between values of any two of the six measurement methods (P < 0.0033), except between any two of the plane radiograph linear, axial CT linear, sagittal CT linear, and 3D CT linear. The Bland-Altman plots demonstrated poor agreement between values of any two of the six methods. The lowest intraobserver reproducibility was 0.46 (moderate) for resident surgeon using plain radiographs. The intraobserver reproducibility for three surgeons using two-dimensional (2D) and 3D images was almost perfect (ICC, 0.82-0.96). The lowest interobserver reliability was 0.41 (moderate) between chief and attending surgeon using plain radiographs, and it improved to almost perfect (ICC, 0.81-0.95) with the use of 3D CT images. The standard error of measurement showed almost the same results as ICC values. The existing operative indications which were determined based on plain radiography are neither reliable nor suitable for other measurement methods. Both 3D linear and 3D surface measurement methods are reliable and reproducible in measuring posterior fragment involvement, and experience is not so crucial. Operative indications for posterior malleolar fractures need to be redefined based on the 3D measurement method.

12.
J Ethnopharmacol ; 249: 112444, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31805338

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In different countries and areas of the world, traditional medicine has been and is still used for the treatment of various disorders, including chest pain or liver complaints, of which we now know that they can be linked with altered lipid and cholesterol homeostasis. As ATP-binding cassette transporter A1 (ABCA1) plays an essential role in cholesterol metabolism, its modulation may be one of the molecular mechanisms responsible for the experienced benefit of traditional recipes. Intense research activity has been dedicated to the identification of natural products from traditional medicine that regulate ABCA1 expression. AIMS OF THE REVIEW: This review surveys natural products, originating from ethnopharmacologically used plants, fungi or marine sources, which influence ABCA1 expression, providing a reference for future study. MATERIALS AND METHODS: Information on regulation of ABCA1 expression by natural compounds from traditional medicine was extracted from ancient and modern books, materia medica, and electronic databases (PubMed, Google Scholar, Science Direct, and ResearchGate). RESULTS: More than 60 natural compounds from traditional medicine, especially traditional Chinese medicine (TCM), are reported to regulate ABCA1 expression in different in vitro and in vivo models (such as cholesterol efflux and atherosclerotic animal models). These active compounds belong to the classes of polyketides, terpenoids, phenylpropanoids, tannins, alkaloids, steroids, amino acids and others. Several compounds appear very promising in vivo, which need to be further investigated in animal models of diseases related to ABCA1 or in clinical studies. CONCLUSION: Natural products from traditional medicine constitute a large promising pool for compounds that regulate ABCA1 expression, and thus may prevent/treat diseases related to cholesterol metabolism, like atherosclerosis or Alzheimer's disease. In many cases, the molecular mechanisms of these natural products remain to be investigated.

13.
Xenobiotica ; 50(2): 178-185, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30938547

RESUMO

1. Several tacrolimus population pharmacokinetic (PPK) models in hematopoietic stem cell transplantation (HSCT) patients have been set up to recommend an optimal dosage schedule. However, the PPK model of Chinese pediatric HSCT patients has not been reported. The study is to investigate whether published PPK models of HSCT patients can be used to simulate Chinese pediatric HSCT patients and establish the tacrolimus PPK model of Chinese pediatric HSCT patients.2. Published PPK models were collected from the literature and assessed using Chinese pediatric HSCT patients via the individual prediction error method. The establishment of tacrolimus PPK model in Chinese pediatric HSCT patients was characterized with nonlinear mixed-effects modeling (NONMEM).3. Three published HSCT PPK models were identified, two of which could be applied to our external dataset. However, these models were dissatisfactory in terms of individual prediction error and, hence, inadequate for extrapolation. Finally, a new tacrolimus PPK model in Chinese pediatric HSCT patients was established. Based on the simulation results of our model, new initial dosage suggestions were recommended. In conclusion, the tacrolimus PPK model in Chinese pediatric HSCT patients was presented and the model could be used to predict individualized dosing regimens in children with HSCT.

14.
Anal Chem ; 92(2): 1850-1855, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31867957

RESUMO

Highly efficient cellular transfection and intracellular signal amplification is a prerequisite for low-abundant microRNA (miRNA) imaging and biomedical application. Herein, we report a functional cancer cell membrane (CM) vesicle, Au-P/DSN@CM (DSN, double-specific nucleases), which consists of Au nanoparticles modified with three types of fluorescent miRNA detection probes (Au-P) and DSN that simultaneously encapsulate in cancer CM. We find that the Au-P/DSN@CM could specifically target the cancer cell and transfect the cell with higher efficiency than Au nanoparticles. The internalized Au-P/DSN@CM could further specifically recognize the target miRNA and induce DSN-assisted target recycle signal amplification, leading to multiple miRNA simultaneous detection with high sensitivity. It successfully detects oncogenic miRNAs in MCF-7 cells with high sensitivity and is amenable to monitor the dynamic expression change of oncogenic miRNAs in cancer cells. Our study represents a promising gene delivery vector for cancer diagnosis and potential therapy.

15.
Plant Methods ; 15: 145, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798671

RESUMO

Background: Potato, the third most important crop worldwide, plays a critical role in human food security. Brown rot, one of the most destructive potato diseases caused by Ralstonia solanacearum, results in huge economic losses every year. A quick, stable, low cost and high throughout method is required to meet the demands of identification of germplasm resistance to bacterial wilt in potato breeding programs. Results: Here we present a novel R. solanacearum hydroponic infection assay on potato plants grown in vitro. Through testing wilt symptom appearance and bacterial colonization in aerial part of plants, we found that the optimum conditions for in vitro potato infection were using an OD600 0.01 bacterial solution suspended with tap water for infection, broken potato roots and an open container. Infection using R. solanacearum strains with differential degree of aggressivity demonstrated that this infection system is equally efficient as soil-drench inoculation for assessment of R. solanacearum virulence on potato. A small-scale assessment of 32 potato germplasms identified three varieties highly resistant to the pathogen, which indicates this infection system is a useful method for high-throughout screening of potato germplasm for resistance. Furthermore, we demonstrate the utility of a strain carrying luminescence to easily quantify bacterial colonization and the detection of latent infections in hydroponic conditions, which can be efficiently used in potato breeding programs. Conclusions: We have established a quick and efficient in vitro potato infection system, which may facilitate breeding for new potato cultivars with high resistance to R. solanacearum.

17.
Int J Food Microbiol ; 317: 108463, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31809966

RESUMO

Paocai is a widely consumed Chinese traditional fermented vegetable product. To understand the effect of temperature on paocai fermentation flora, the bacterial community structure of paocai fermented at 10 °C, 15 °C, 25 °C and 35 °C was analyzed by culture-dependent and culture-independent methods. The results showed that increasing the fermentation temperature in a certain range is beneficial for rapid paocai acid production and shortening of the maturity period. Illumina Miseq sequencing was performed on 56 samples at different fermentation process temperatures using a culture-independent method. A total of 1,964,231 high-quality reads of 16S rRNA V3-V4 regions were obtained, and they were divided into 405 operational taxonomic units (OTUs) and identified as 213 bacterial genera. The bacterial diversity decreased with the progression of fermentation, and some spoiled samples had an increased diversity. The culture-independent method found that at 10 °C, Lactococcus appeared at the start of fermentation, Leuconostoc and Weissella appeared in the middle of fermentation, and Lactobacillus and Leuconostoc dominated fermentation in the late stage. At 15 °C, Lactococcus started fermentation, Leuconostoc appeared in the middle stage, and Lactobacillus was dominant in the late stage. At 25 °C, Lactococcus started fermentation, Weissella and Lactobacillus appeared in the middle stage, and Lactobacillus dominated fermentation in the late stage. Finally, at 35 °C, Lactococcus, Weissella, and Lactobacillus started fermentation, Weissella and Lactobacillus appeared in the middle stage, and Lactobacillus dominated fermentation in the late stage. A total of 647 strains of bacteria were isolated by culture-dependent methods and were divided into 12 genera and 19 species by randomly amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) and 16S ribosomal RNA gene (rDNA) sequencing technology. More types of bacteria were isolated in the early stage of fermentation. At 10 °C, Lactococcus lactis began fermentation, and Lactobacillus brevis and Leuconostoc mesenteroides dominated acid production in the middle and late stages of paocai fermentation. At 15 °C, L. lactis initiates fermentation, while Lactobacillus plantarum dominates the acid fermentation of paocai. At 25 °C and 35 °C, there were a large number of Enterobacteriaceae bacteria in the start-up fermentation stage, and L. plantarum was dominant after 1-2 days of fermentation. Redundancy analysis (RDA) found that the lower the temperature, the more bacterial species that are produced, and the higher the temperature and the longer the time, the more obvious are the effects of L. plantarum on paocai. The results of dominant bacteria studied by culture-dependent and culture-independent methods are similar. The results indicate that most of the dominant microorganisms in the paocai fermentation system are culturable. This discovery can provide data and physical support for modernization and regulation of different types of paocai production.

18.
Exp Ther Med ; 18(6): 4653-4660, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31772640

RESUMO

Pediatric patients with systemic-onset juvenile idiopathic arthritis (SOJIA) may be treated with tacrolimus. However, the therapeutic range for tacrolimus is narrow with considerable inter- and intra-individual variability, making it difficult to formulate an ideal dosage regimen for personalized treatment. The purpose of the present study was to set up a population pharmacokinetics (PPK) model of tacrolimus treatment for SOJIA to determine the optimal initial dosage. Patients with SOJIA were analyzed using non-linear mixed-effects modeling. Different regimens were analyzed using Monte Carlo simulation with concentration profiles. A first-order absorption and elimination one-compartment model was selected as the most appropriate model for SOJIA. Based on initial dosage recommendations, the regimen of 0.5 mg every 24 h (q24h) appeared to be most suitable for subjects with a body weight of 5 kg, while the 0.5 mg q12h regimen was most suitable for subjects with a body weight of 15-25 kg, the 1/0.5 mg q24h regimen was appropriate for the 26-35 kg group and the 1 mg q12h regimen was suitable for the subjects with a body weight of 36-50 kg. To the best of our knowledge, the present study established the first PPK model of tacrolimus treatment that may be used for the selection of the initial dose based on body weight of pediatric patients with SOJIA.

19.
J Clin Pharm Ther ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31755126

RESUMO

WHAT IS KNOWN AND OBJECTIVES: Tacrolimus, an immunosuppressant, has been used to treat paediatric systemic lupus erythematosus, but the optimal initial regimen is not clear. The purpose of this study was to explore the optimal initial dose of tacrolimus for children with systemic lupus erythematosus using population pharmacokinetics and pharmacogenomics. METHODS: Clinical information, tacrolimus concentrations and related genetic polymorphisms were incorporated into a model using non-linear mixed-effects modelling (NONMEM) analysis. RESULTS AND DISCUSSION: The results showed that weight, the CYP3A5 genotype and combined treatment with Wuzhi capsule can affect tacrolimus clearance in children with systemic lupus erythematosus. Furthermore, at the same weight, the ratios of tacrolimus clearance were 1:2.49:0.57:1.4193 from people who were CYP3A5*3/*3 and did not take Wuzhi capsule, people who had the CYP3A5*1 allele and did not take Wuzhi capsule, people who were CYP3A5*3/*3 and took Wuzhi capsule, and people who had the CYP3A5*1 allele and took Wuzhi capsule, respectively. In addition, we found that 0.10 mg/kg split into two doses was suitable for people with weights from 10 to 60 kg who were CYP3A5*3/*3 and did not take Wuzhi capsule, who were CYP3A5*3/*3 and took Wuzhi capsule, and who had the CYP3A5*1 allele and took Wuzhi capsule. In people who had the CYP3A5*1 allele and did not take Wuzhi capsule, 0.15 mg/kg split into two doses was appropriate for those with weights from 10 to 40 kg and 0.10 mg/kg split into two doses was appropriate for those with weights from 40 to 60 kg. WHAT IS NEW AND CONCLUSION: This study is the first study to recommend an optimal initial regimen of tacrolimus for children with systemic lupus erythematosus based on the CYP3A5 polymorphism and coadministration of Wuzhi capsule.

20.
Acta Neurol Belg ; 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31734794

RESUMO

The computed tomography angiography (CTA) Spot Sign is an effective means of predicting hematoma expansion (HE) in the context of spontaneous intracerebral hemorrhage (ICH). We investigated whether continuous CTA source images could differentiate the Spot Sign and blood vessels in the hematoma, and whether it would improve Spot Sign accuracy as an HE predictor. We screened for the presence of CTA Spot Sign in individuals affected by spontaneous ICH within 24 h of symptom development. Based on our findings, we determined the sensitivity, specificity, and positive/negative predictive values of this sign as a predictor of HE both on its own and following the exclusion of blood vessels. In addition, a receiver-operating characteristic approach was used to assess the accuracy of Spot Sign with and without elimination of vascular interference. A total of 265 patients were included in this study. The Spot Sign was observed in 100 patients, including in 29 patients wherein it was confirmed to be blood vessels as determined based upon continuous CTA source images. With respect to predicting HE, Spot Sign sensitivity, specificity, positive predictive values, and negative predictive values were 57%, 71%, 48% and 78%, respectively. Following the exclusion of blood vessels, these values were 57%, 87%, 68% and 81%, respectively. Spot Sign area under the curve after excluding blood vessels was 0.718, which was higher than that of the Spot Sign (0.638). After continuous CTA, source images are used to exclude blood vessels in the hematoma, the Spot Sign is thus more accurate in predicting HE.

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