Effect of food and polymorphisms in SLCO2B1, CYP3A4 and UGT1A4 on pharmacokinetics of abiraterone and its metabolites in Chinese volunteers.

AIMS: Abiraterone acetate, a prodrug of abiraterone (ABI), provides an efficient therapeutic option for metastatic castration-resistant prostate cancer patients. ABI undergoes extensive metabolism in vivo and is transformed into active metabolites Δ4 -abiraterone and 3-keto-5α-abiraterone as well as inactive metabolites abiraterone sulfate and abiraterone N-oxide sulfate. We aimed to examine the effect of polymorphisms in SLCO2B1, CYP3A4 and UGT1A4 on the pharmacokinetics of ABI and its metabolites. METHODS: In this study, 81 healthy Chinese subjects were enrolled and divided into 2 groups for fasted (n = 45) and fed (n = 36) studies. Plasma samples were collected after administering a 250 mg abiraterone acetate tablet followed by liquid chromatography-tandem mass spectrometry analysis. Genotyping was performed on a MassARRAY system. The association between SLCO2B1, CYP3A4, UGT1A4 genotype and pharmacokinetic parameters of ABI and its metabolites was assessed. RESULTS: Food effect study demonstrated high fat meal remarkedly increased systemic exposure of ABI and its metabolites. The geometric mean ratio and 90% confidence interval of area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC0-t ) and maximum plasma concentration (Cmax ) of ABI in fed state vs. fasted state were 351.64% (286.86%-431.04%) and 478.45% (390.01%-586.94%), respectively, while the corresponding results were ranging from 145.11% to 269.42% and 150.10% to 478.45% for AUC0-t and Cmax of ABI metabolites in fed state vs. fasted state, respectively. The SLCO2B1 rs1077858 had a significant influence on AUC0-t and Cmax , while 7 other SLCO2B1 variants prolonged half-life of ABI under both fasted and fed conditions. As for ABI metabolites, the systemic exposure of Δ4 -abiraterone, abiraterone sulfate and abiraterone N-oxide sulfate as well as the elimination of 3-keto-5α-abiraterone were significantly affected by SLCO2B1 polymorphisms. Polymorphisms in CYP3A4 and UGT1A4 did not significantly affect pharmacokinetics of ABI and its metabolites. CONCLUSION: Polymorphisms in SLCO2B1 were significantly related to the pharmacokinetic variability of ABI and its metabolites under both fasted and fed conditions.

Global burden of ischemic stroke attributable to high body mass index in 204 countries and territories, 1990-2021.

BACKGROUND: A high body mass index (hBMI) is one of the major risk factors for ischemic stroke (IS), although independent estimates of the global burden and trend of IS attributable to hBMI are unclear. METHODS: Study data were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study and analysed by age, sex, year, and geographical location. The sociodemographic index (SDI) and the human development index (HDI) were used as indicators of national socioeconomic status. Geographic distributions and trends were assessed by calculating the estimated annual percentage change (EAPC). Associations between the age-standardized death rate (ASMR) or disability-adjusted life year rate (DALY) and socioeconomic status were analysed. RESULTS: Deaths and DALYs increased worldwide from 1990-2021, with increases of 95.74% for the former and 133.00% for the latter; the ASMR and ASDR decreased, with an ASMR and ASDR-related EAPCs of -1.10 (95% CI: -1.24--0.96) and 0.04 (95% CI:-0.47-0.55), respectively; women had greater numbers of deaths and DALYs, and the majority of deaths and DALYs were shared by those aged ≥ 70. The highest burden rates were shared by Eastern Europe, North Africa, the Middle East, and Central Asia. The ASMR-related EAPCs were associated with the ASMR in 1990 (R = -0.35, P < 0.001) and the SDI in 2021 in different countries (R = -0.66, P < 0.001); these patterns were similar to those of the ASDR; the HDI in 2021 was associated with the ASMR-related EAPC (R = -0.71, P < 0.001) and the ASDR-related EAPC in different countries (R = -0.71, P < 0.001). CONCLUSIONS: The number of deaths and DALYs from ischemic stroke attributable to hBMI worldwide increased substantially from 1990-2021. Successful population-wide initiatives targeting hBMI may mitigate a wide range of burdens on this disease. Taking into account variations in the SDI burden, future prevention and control strategies must be developed and implemented according to country-specific development status.

KIAA1199, a Target of MicoRNA-486-5p, Promotes Papillary Thyroid Cancer Invasion by Influencing Epithelial-Mesenchymal Transition (EMT).

BACKGROUND KIAA1199 has been reported to be associated with malignant progression and poor clinical outcomes in various human malignancies. However, its clinical role and molecular function remain unknown in papillary thyroid cancer (PTC). MATERIAL AND METHODS The Cancer Genome Atlas (TCGA) was used to investigate the expression profiles of KIAA1199 and miR-486-5p in PTC. Immunohistochemistry was used to validate the protein expression of KIAA1199 in PTC. The Weighted Gene Co-expression Network Analysis (WGCNA) and Gene Set Enrichment Analysis (GSEA) were used to explore the potential pathway underling KIAA1199 in PTC. In vitro and in vivo experiments were performed to investigate the biological role of KIAA1199 in PTC progression. Luciferase reporter assays and Western blot analysis were performed to determine whether KIAA1199 is a downstream target of miR-486-5p. RESULTS We found that KIAA1199 was aberrantly elevated in PTC tissues compared with normal tissues, and upregulation of KIAA1199 was positively correlated with more advanced clinical variables. Additionally, bioinformatic analysis indicated that KIAA1199 was involved in cell migration and invasion. KIAA1199 silencing inhibited the invasive ability of PTC cells by affecting epithelial-mesenchymal transition (EMT) in vitro and in vivo. Furthermore, miR-486-5p was identified as an upstream microRNA that directly targets the 3'-UTR region of KIAA1199. CONCLUSIONS The miR-486-5p/KIAA1199/EMT axis might play a critical role in PTC invasion and metastasis and offers a potential therapeutic strategy for PTC.

Population Pharmacokinetics in China: The Dynamics of Intravenous Voriconazole in Critically Ill Patients with Pulmonary Disease.

Pharmacokinetic research in China on the use of voriconazole in critically ill adult patients with different pulmonary diseases remains to be explored. This study evaluated the population pharmacokinetics of the use of voriconazole (VRC) in critically ill patients to determine covariate effects on VRC pharmacokinetics by NONMEM, which could further optimize VRC dosing in this population. A one-compartment model with first-order absorption and elimination best fit the data, giving 4.28 L/h clearance and 93.4 L volume of distribution of VRC. The model variability, described as an approximate percentage coefficient of interindividual variability in clearance and volume of distribution, was 72.94% and 26.50%, respectively. A significant association between Cmin and drug response or grade 2 hepatotoxicity was observed (p=0.002, <0.001, respectively, 1.5-4.0 µg/mL) via logistic multivariate regression. Monte Carlo simulations at 100, 150, 200, and 250 mg dosage predicted effectiveness at 45.99%, 99.76%, 98.76%, and 67.75% within the 1.5-4.0 µg/mL range, suggesting that a 150 or 200 mg intravenous dose twice daily is best suited to achieve the target steady state trough concentration range in critically ill patients with pulmonary disease.

Serum 25(OH)D and vitamin D status in relation to VDR, GC and CYP2R1 variants in Chinese.

Previous studies have identified several common genetic variants in VDR, GC and CYP2R1 to be associated with circulating levels of 25-hydroxyvitamin D [25(OH)D] and vitamin D deficiency in Western populations. We aimed to investigate the associations of these variants with serum levels of 25(OH)D and vitamin D status in 1,199 Chinese. Nine common variants of VDR, GC and CYP2R1 were genotyped using multiple SNaPshot assay, and serum 25(OH)D was detected by radioimmunoassay. The prevalence of vitamin D deficiency (<50 nmol/L) was 38.8%, which is higher in women (46.2%) than in men (34.3%, P<0.0001). The risk alleles of three common variants of GC (rs7041, rs4588, and rs2282679) were significantly associated with a lower serum levels of 25(OH)D (-1.789 ≤ß ≤-3.549, P ≤0.006), while common variants in VDR and CYP2R1 were not associated with serum levels of 25(OH)D after adjusted for covariates (P ≥0.30). None of the nine common variants were associated with the presence of vitamin D deficiency in multivariable adjusted logistic regression analyses (P ≥0.17). Haplotype-based analyses of GC-rs7041 and rs4588 showed that the haplotype Gc2-2 (rs7041 AA and rs4588 TT) had the lowest levels of 25(OH)D compared with other haplotypes that contained at least one copy of Gc1 allele (Ptrend <0.0001). Our results suggest that the common variants of GC are genetic determinants of serum 25(OH)D in Chinese.

Comparison of Combined Dissipation Behaviors and Dietary Risk Assessments of Thiamethoxam, Bifenthrin, Dinotefuran, and Their Mixtures in Tea.

In the tea-planting process, insecticides are commonly combined, potentially prolonging the pre-harvest interval and heightening the risk of dietary exposure. This study focused on three frequently used insecticides in tea cultivation: thiamethoxam, bifenthrin, and dinotefuran, aiming to investigate their dissipation behaviors and associated dietary risks upon individual and simultaneous application. The dissipation kinetics of thiamethoxam, bifenthrin, and dinotefuran were successfully characterized by first-order kinetics, yielding respective half-lives of 5.44, 9.81, and 10.16 days. Upon joint application, the dissipation half-lives of thiamethoxam and bifenthrin were notably prolonged compared with their individual applications, resulting in final concentrations after 28 days that were correspondingly elevated by 1.41 and 1.29 times. Assessment of the dietary intake risk revealed that the chronic and acute risk quotients associated with thiamethoxam and bifenthrin escalated by 1.44-1.59 times following their combined application. Although dietary risks associated with Tianmuhu white tea, as determined by the exposure assessment model, were deemed acceptable, the cumulative risks stemming from pesticide mixtures across various dietary sources warrant attention. Molecular docking analyses further unveiled that thiamethoxam and bifenthrin competitively bound to glutathione S-transferase (GST) at amino acid residues, notably at the 76th GLU and the 25th PHE, pivotal in the metabolism and absorption of exogenous substances. Moreover, the interactions between P-glycoprotein and pesticides during transport and absorption were likely to influence dissipation behaviors post-joint application. This research offers valuable insights and data support for optimizing joint pesticide application strategies and assessing risks associated with typical pesticides used in tea cultivation.

No significant association between vitamin D and nonalcoholic fatty liver disease in a Chinese population.

BACKGROUND: Some research evidence from Western populations suggests that lower vitamin D is associated with the prevalence and histologically assessed severity of nonalcoholic fatty liver disease (NAFLD). AIMS: To investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] concentrations and vitamin D status (deficiency <20 ng/ml; insufficiency 20-30 ng/ml; sufficiency >30 ng/ml) with the prevalence of NAFLD in study population of Chinese. METHODS: Serum 25(OH)D, parathyroid hormone, lipids, liver enzymes, and anthropometric characteristics were measured in 1,248 subjects aged ≥ 20 years. NAFLD was diagnosed using abdominal ultrasound examination. RESULTS: The prevalence of NAFLD was 30.3 % in the total study population, 37.9 % in the male subjects, and 20.8 % in the female subjects (P < 0.0001). Subjects with NAFLD had a significantly higher body mass index, higher levels of fasting blood glucose and liver enzymes, and a more atherogenic lipid profile. However, serum 25(OH)D concentrations were not significantly different between subjects with and without NAFLD (22.1 vs. 22.8 ng/ml, respectively; P = 0.21). In addition, a 10 ng/ml higher serum 25(OH)D concentrations [odds ratio (OR) 1.02, 95 % confidence interval (CI) 0.84-1.25, P = 0.82] or vitamin D status (vs. sufficiency: deficiency OR 0.86, 95 % CI 0.54-1.37, P = 0.52; insufficiency OR 0.96, 95 % CI 0.61-1.52, P = 0.87) were not significantly associated with the presence of NAFLD in the multivariate logistic regression analyses. CONCLUSIONS: Serum 25(OH)D concentrations or vitamin D status were not significantly associated with the presence of NAFLD. More studies are needed to elucidate the relationship between vitamin D and the occurrence of NAFLD in Chinese.

Trends in deaths and disability-adjusted life-years of stroke attributable to high body-mass index worldwide, 1990-2019.

Background: High body mass index (HBMI) is an independent risk factor for stroke. Previous studies on the incremental burden of the rapid growth of stroke attributable to HBMI are incomplete and lag behind. We aim to assess the global burden of stroke attributable to HBMI based on a public database online. Materials and methods: Study data were taken from the Global Burden of Disease, Injuries, and Risk Factors Study; deaths, the Disability-Adjusted Life-Years (DALYs), and their age-standardized rates were screened. The join point regression was used, wherein age-standardized rates were referred to as temporal trends in disease burden. Results: Deaths from stroke attributable to HBMI worldwide were on the rise during 1990-2019, with an increase of 88.75%. Age-standardized DALYs were on the rise during 1990-2003 but declined during 2003-2013, with a turning point in 2013 and an increasing trend since then [the Annual Percentage Change (APC) = 0.30%, p < 0.05]. China, India, Indonesia, the Russian Federation, and the United States of America shared in sequence the rate of leading deaths and DALYs in 2019. The Socio-Demographic Index (SDI) was associated with an increasing trend in age-standardized deaths (R = -0.24, p < 0.001) and age-standardized DALYs (R = -0.22, p = 0.0018). Conclusion: A range of indicators for the global burden of stroke attributable to HBMI have been on the rise for the past three decades. Tremendous efforts worldwide should be in place to control and treat stroke attributable to HBMI, especially in regions with high-middle and middle SDIs and among middle-aged and aged populations.

Effects of Summer and Autumn Drought on Eutrophication and the Phytoplankton Community in Dongting Lake in 2022.

Since July 2022, the Yangtze River basin has experienced the most severe hydro-meteorological drought since record collection started in 1961, which has greatly affected the ecological environment of the Dongting Lake (DTL) basin. To investigate the effects of drought events on the eutrophication and phytoplankton community structure of DTL, the lake was sampled twice in August and September 2022 based on the water level fluctuations resulting in 47 samples. Furthermore, we combined the comprehensive trophic level index (TLI) and phytoplankton Shannon-Wiener diversity index (H) to characterize and evaluate the eutrophication status. The key influencing factors of the phytoplankton community were identified using redundancy analysis (RDA), hierarchical partitioning, and the Jaccard similarity index (J). Our results showed that the TLI of DTL changed from light-moderate eutrophication status (August) to mesotrophic status (September), whereas the H changed from light or no pollution to medium pollution. The phytoplankton abundance in August (122.06 × 104 cells/L) was less than that in September (351.18 × 104 cells/L) in DTL. A trend in phytoplankton community succession from Bacillariophyta to Chlorophyta and Cyanophyta was shown. The combination of physiochemical and ecological assessment more accurately characterized the true eutrophic status of the aquatic ecosystem. The RDA showed that the key influencing factors in the phytoplankton community were water temperature (WT), pH, nitrogen and phosphorus nutrients, and the permanganate index (CODMn) in August, while dissolved oxygen (DO) and redox potential (ORP) were the key factors in September. Hierarchical partitioning further indicated that temporal and spatial variations had a greater impact on the phytoplankton community. And the J of each region was slightly similar and very dissimilar, from August to September, which indicated a decreased hydrological connectivity of DTL during drought. These analyses indicated that the risk to the water ecology of DTL intensified during the summer-autumn drought in 2022. Safeguarding hydrological connectivity in the DTL region is a prerequisite for promoting energy flow, material cycle, and water ecosystem health.

[Driving Factors Analyze of Phytoplankton Community by Comparison of Population and Functional Groups and Water Quality Evaluation in Dongting Lake].

Phytoplankton is the most important component of water ecosystems, which could indicate the state of the water environment owing to its sensitivity to water environment variation. However, its response to the environment is influenced by classification methods. To understand the phytoplankton population(phyla and genera) and functional groups(FG) for driving response characteristics and applicability to the environment in Dongting Lake, a total of four samples were collected from the lake from March to December 2019, and the distribution characteristics of the phytoplankton population and functional groups and their responses to environmental factors were compared and analyzed. Meanwhile, the applicability of the TLI index, Shannon-Wiener index, and Q index was compared in Dongting Lake. The results showed that a total of 61 genera belonging to six phyla of phytoplankton were detected in Dongting Lake, which could be divided into 23 functional groups and nine dominant functional groups. The succession trend of functional groups was P/MP/D(March)→MP/P/J(June)→MP/H1(September)→Y/P/MP(December). The results of hierarchical segmentation showed that the population distribution and change in phytoplankton were driven by environmental factors more than the area in Dongting Lake. The main environmental factors affecting phytoplankton population and functional groups were water temperature(WT), permanganate index, dissolved oxygen(DO), conductivity(Cond), water level(WL), and total phosphorus(TP). RDA analysis showed that phytoplankton functional groups identified phytoplankton response to environmental factors better than phytoplankton population. It was shown that using the Q index to evaluate water quality had better applicability in Dongting Lake.

Management and Anticoagulation Treatment of Non-Valvular Atrial Fibrillation in Elderly Patients: The Dali Study.

Background: Non-valvular atrial fibrillation (NVAF) is associated with increased stroke in elderly populations, yet anticoagulant therapy is underutilized. We analyzed clinical characteristics and anticoagulation treatment rates of elderly NVAF patients hospitalized in Dali, China, to identify potential contributing factors. Methods: We collected data for 155 elderly patients with NVAF aged ≥60 years, from July 01, 2020, to December 31, 2021. We analyzed the awareness rate, clinical characteristics, and anticoagulant treatment rate of atrial fibrillation (AF), and identified factors influencing treatment. Patients were followed up one year after discharge to assess vital status, cardiovascular events, and anticoagulation therapy status. Results: Among 155 patients, 52.26% were female, and the average age was 75.77 years. The awareness rate of AF was 47.74% at admission, and only 21.94% received anticoagulant therapy. After discharge, the rate of anticoagulant therapy significantly increased to 70.97%, and 89.09% used new oral anticoagulants. Thromboembolic history and persistent AF predicted anticoagulant therapy at discharge, while male gender, previous bleeding history, and antiplatelet therapy predicted non-anticoagulant therapy. Out of 133 patients who completed a one-year follow-up, 23.31% died, 3.01% had strokes, and 3.01% experienced bleeding. Anticoagulant therapy decreased to 51.96% during the follow-up year. Conclusion: Our findings highlight the low awareness rate and anticoagulant treatment rate, and high mortality among elderly NVAF patients in Dali. The development of comprehensive intervention strategies is critical to standardize AF management and improve prognosis.

Establishment and Validation of a Gene Signature-Based Prognostic Model to Improve Survival Prediction in Adrenocortical Carcinoma Patients.

BACKGROUND: The current guideline for the management of adrenocortical carcinoma (ACC) is insufficient for accurate risk prediction to guide adjuvant therapy. Given frequent and severe therapeutic side effects, a better estimate of survival is warranted for risk-specific assignment to adjuvant treatment. We attempted to construct an integrated model based on a prognostic gene signature and clinicopathological features to improve risk stratification and survival prediction in ACC. METHODS: Using a series of bioinformatic and statistical approaches, a gene-expression signature was established and validated in two independent cohorts. By combining the signature with clinicopathological features, a decision tree was generated to improve risk stratification, and a nomogram was constructed to personalize risk prediction. Time-dependent receiver operating characteristic (tROC) and calibration analysis were performed to evaluate the predictive power and accuracy. RESULTS: A three-gene signature could discriminate high-risk patients well in both training and validation cohorts. Multivariate regression analysis demonstrated the signature to be an independent predictor of overall survival. The decision tree could identify risk subgroups powerfully, and the nomogram showed high accuracy of survival prediction. Particularly, expression of a gene hitherto unknown to be dysregulated in ACC, TIGD1, was shown to be prognostically relevant. CONCLUSION: We propose a novel gene signature to guide decision-making about adjuvant therapy in ACC. The score shows unprecedented survival prediction and hence constitutes a huge step towards personalized management. As a secondary important finding, we report the discovery and validation of a new oncogene, TIGD1, which was consistently overexpressed in ACC. TIGD1 might shed further light on the biology of ACC and might give rise to targeted therapies that not only apply to ACC but potentially also to other malignancies.

Low-rank graph optimization for multi-view dimensionality reduction.

Graph-based dimensionality reduction methods have attracted substantial attention due to their successful applications in many tasks, including classification and clustering. However, most classical graph-based dimensionality reduction approaches are only applied to data from one view. Hence, combining information from different data views has attracted considerable attention in the literature. Although various multi-view graph-based dimensionality reduction algorithms have been proposed, the graph construction strategies utilized in them do not adequately take noise and different importance of multiple views into account, which may degrade their performance. In this paper, we propose a novel algorithm, namely, Low-Rank Graph Optimization for Multi-View Dimensionality Reduction (LRGO-MVDR), that overcomes these limitations. First, we construct a low-rank shared matrix and a sparse error matrix from the graph that corresponds to each view for capturing potential noise. Second, an adaptive nonnegative weight vector is learned to explore complementarity among views. Moreover, an effective optimization procedure based on the Alternating Direction Method of Multipliers scheme is utilized. Extensive experiments are carried out to evaluate the effectiveness of the proposed algorithm. The experimental results demonstrate that the proposed LRGO-MVDR algorithm outperforms related methods.

Serum N(1)-Methylnicotinamide Is Associated With Obesity and Diabetes in Chinese.

CONTEXT: Nicotinamide N-methyltransferase (NNMT) is a novel histone methylation modulator that regulates energy metabolism, and NNMT knockdown prevents diet-induced obesity in mice. However, whether NNMT plays a role in human obesity and type 2 diabetes (T2DM) remains to be elucidated. OBJECTIVE: NNMT catalyzes methylation of nicotinamide to generate N(1)-methylnicotinamide (me-NAM). We aimed to investigate the associations of serum me-NAM with obesity and T2DM in Chinese. DESIGN, SETTING, AND PARTICIPANTS: The study subjects (n = 1160) were recruited from Dali, a city of Yunnan Province, in southwest China. Anthropometric phenotypes, fasting glucose, and serum lipids were measured. Serum me-NAM was measured by liquid chromatography-mass spectrometry. RESULTS: Serum me-NAM was positively correlated with body mass index and waist circumference and negatively with high-density lipoprotein (P ≤ .03). The correlations remained highly significant in the multivariate adjusted correlation analyses. In men (n = 691), positive correlations between me-NAM and fasting glucose, low-density lipoprotein, liver function, and serum creatinine levels were also observed in both simple and multivariate adjusted correlation analyses. In multiple logistic regression analyses, elevated serum me-NAM was associated with higher risks for overweight/obesity (odds ratios, 2.36 and 5.78; 95% confidence intervals, 1.10-5.08 and 1.78-18.76 for men and women, respectively; P ≤ .03) and diabetes (odds ratios, 1.56 and 1.86; 95% confidence intervals, 1.10-2.22 and 1.05-3.31 for men and women, respectively; P ≤ .03). CONCLUSIONS: This first large-scale population study shows that me-NAM, as an indicator of NNMT activity, is strongly associated with obesity and diabetes, supporting NNMT as a potential target for treating obesity and diabetes in humans.

The compatibility of swine BMDC-derived bile duct endothelial cells with a nanostructured electrospun PLGA material.

PURPOSE: To investigate the production of bile duct endothelial cells via directed differentiation of porcine bone marrow mesenchymal stem cells (BMSCs) down the hepatic lineage in vitro and the biocompatibility of differentiated bile duct endothelial cells with electrospun nanofibers. METHODS: Porcine BMSCs were differentiated in vitro into bile duct endothelial cells, which were identified by morphology and RT-PCR. PLGA nanofiber membranes were prepared by electrospinning. The morphology was detected by scanning electron microscopy and the short-term (two weeks) in vitro degradation rate was determined. Adhesion and proliferation of the bile duct endothelial cells on the nanofiber surface were analyzed by calculating the cell adhesion rate and MTT assay, respectively. Cell growth, morphology and distribution on the material surface were observed by fluorescence staining and scanning electron microscopy, respectively. RESULTS: After four weeks of directed differentiation of BMSCs in vitro, cells showed the typical morphology of dendritic bile duct endothelial cells and had the expression of CK19. Scanning electron micrographs showed that electrospun materials were continuous nanofibers with diameters between 200 and 500 nm. No significant degradation of the PLGA nanofibers was observed within two weeks. Based on the measured cell adhesion rate, MTT assay, fluorescence staining, and scanning electron microscopy, the differentiated cells possess a good proliferative capacity on PLGA nanofibers. CONCLUSIONS: BMSCs can be differentiated into the bile duct endothelial cells in vitro. Materials prepared by the electrospinning method have a nanofiber structure, which does not significantly degrade within two weeks. Differentiated cells exhibit good biocompatibility with the nanofibers.

Serum 25-hydroxyvitamin D, parathyroid hormone, and their association with metabolic syndrome in Chinese.

Increasing evidence suggests that 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) levels are associated with metabolic syndrome (MetS). In 2010, we explored the association of serum 25(OH)D and PTH levels with MetS in 1,390 Chinese participants, aged 20-83 years. Anthropometric phenotypes, blood pressure, and the incidence of MetS were evaluated. In addition, serum lipids, 25(OH)D, and PTH were measured. The median concentration of 25(OH)D and PTH were 55.3 nmol/l and 2.8 pmol/l, respectively. The prevalence of vitamin D deficiency (<50 nmol/l) was 39.9 %, with 34.5 % in men and 47.8 % in women. After accounting for confounding factors and serum PTH, a 10 nmol/l higher serum 25(OH)D level was associated with a 10 % lower risk of MetS (OR = 0.90, 95 % CI 0.84-0.96, P = 0.0007). Furthermore, participants with vitamin D sufficiency had a 35 % lower risk of MetS than those with vitamin D deficiency (OR = 0.65, 95 % CI 0.51-0.84, P = 0.0009). PTH was not associated with the risk of MetS after adjustment for confounding factors. These results were confirmed in both men and women. Thus in this cohort of Chinese individuals, vitamin D deficiency is common and optimal vitamin D level is inversely associated with MetS, independent of several confounders and PTH level. The clinical significance of these findings warrants further study.

Vitamin D, parathyroid hormone and their associations with hypertension in a Chinese population.

BACKGROUND: Conflicting reports support or refute an association between vitamin D deficiency with high levels of parathyroid hormone (PTH) and raised blood pressure or hypertension. OBJECTIVE: To explore the associations of serum vitamin D and PTH levels with blood pressure and risk of hypertension in a Chinese population. METHODS: A population-based cross-sectional study was conducted among 1,420 Chinese participants, aged 20-83 years, in 2010. Anthropometric phenotypes and blood pressure were evaluated. Serum lipids, 25-hydroxyvitamin D [25(OH)D] and PTH were measured. RESULTS: One thousand four hundred and twenty participants, including 566 women (39.9%), were evaluated in 2010. Four hundred and eighty seven were hypertensive (34.3%), of whom 214 (43.9%) received antihypertensive treatment. The median concentrations of serum 25(OH)D and PTH were 22.0 ng/ml and 2.83 pmol/l, respectively. Serum 25(OH)D and natural log of PTH levels were not independently associated with blood pressure in a multivariable adjusted linear regression analysis of 1,206 participants not receiving antihypertensive treatment (P>0.05). In logistic regression analyses, serum 25(OH)D levels were not associated with risk of hypertension in single and multiple regression models. One unit increments of natural log of PTH levels were significantly associated with risk of hypertension in the crude model (OR = 1.78, 95% confidence interval 1.38-2.28, P<0.0001) and model adjusted for age and sex (OR = 1.41, 95% confidence interval 1.08-1.83, P = 0.01). However, these associations were attenuated and became nonsignificant (OR = 1.29, 95% confidence interval 0.98-1.70, P = 0.07) after further adjustment for body mass index, current alcohol intake, current smoking, glomerular filtration rate and family history of hypertension. CONCLUSIONS: Serum vitamin D and PTH levels are not independently associated with blood pressure or risk of hypertension in a Chinese population.

Development and validation of a nylon6 nanofibers mat-based SPE coupled with HPLC method for the determination of docetaxel in rabbit plasma and its application to the relative bioavailability study.

A simple and sensitive HPLC method was established and validated for the determination of docetaxel (DTX) in rabbit plasma. Biosamples were spiked with paclitaxel (PCX) as an internal standard (I.S.) and pre-treated by solid-phase extraction (SPE). The SPE procedure followed a simple protein digestion was based on nylon6 electrospun nanofibers mats as sorbents. Under optimized conditions, target analytes in 500 microL of plasma sample can be completely extracted by only 2.5mg nylon6 nanofibers mat and eluted by 100 microL solvent. The HPLC separation was obtained on C18 column and UV detector was used to quantify the target analytes. The extraction recovery was more than 85%; the standard curve was linear over the validated concentrations range of 10-5000 ng/mL and the limit of detection was 2 ng/mL. The inter-day coefficient of variation (CV%) of the calibration standards was below 5.0% and the mean accuracy was in the range of 92.8-113.4%. Moreover, analysing quality control plasma samples in 3 days, the results showed that the method was precise and accurate, for the intra- and inter-day CV% within 10% and the accuracy from 96.0% to 114.0%. The developed and validated method was successfully applied to relative bioavailability study for the preclinical evaluation of a new injectable DTX-sulfobutyl ether beta-cyclodextrin (DTX-SBE-beta-CD) inclusion complex freeze-dried powder (test preparation), compared with the reference preparation (DTX injection, Taxotere) in healthy rabbits. On the basis of the mean AUC(0-t) and AUC(0-infinity), the relative bioavailability of the test preparation was found to be 113.1%.