OBJECTIVEDoubly labeled water (DLW) method is the gold standard for measuring total energy expenditure (TEE). We used this method to measure TEE in Chinese young men.

METHODSSixteen healthy young men age 23±1 years with body mass index 22.0±1.4 kg/m2 were recruited. TEE was measured by the DLW method, and basal energy expenditure (BEE) was determined by indirect calorimetry. We also conducted 24-h activity, energy balance and factorial approach to estimate energy requirements of the subjects.

RESULTSTEE of subjects by DLW method was 9.45±0.57 MJ/day (2258±180 kcal/day). The 24-h activity was 10.80±0.33 MJ/day (2582±136 kcal/day). The energy requirement, derived from energy balance observations, was 9.93±1.32 MJ/day (2373±315 kcal/day). The BEE of 6.65±0.28 MJ/day (1589±67 kcal/day), calculated by the adjusted Schofield equation, was significantly higher (P<0.001) than that measured by indirect calorimetry, 5.99±0.66 MJ/day (1433±158 kcal/day). The TEE derived from the factorial approach was 10.31±0.43 MJ/day (2463±104 kcal/day).

CONCLUSIONThe TEE of Chinese young men measured by the DLW method was about 10% lower than the current recommended nutrient intake (RNI), suggesting that the RNI for Chinese men maybe overestimated. Further studies are warranted to determine the value of the estimated energy requirement.

Asian Continental Ancestry Group ; Energy Metabolism ; physiology ; Humans ; Isotope Labeling ; Male ; Motor Activity ; physiology ; Water ; Young Adult

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

The goal of this work was to establish a population pharmacokinetics (PPK) model of tacrolimus in idiopathic membranous nephropathy (IMN) patients and to identify potential covariates that influence pharmacokinetic of tacrolimus. A total of 610 data points on the blood concentration of tacrolimus were collected from 96 IMN patients in routine clinical settings. Nonlinear mixed-effect modeling (NONMEM) was used to investigate the effects of CYP3A5 genotype, age, gender, weight, laboratory tests and co-therapy medications on the pharmacokinetic of tacrolimus. The PPK model was evaluated by the goodness-of-fit (GOT), bootstrap and prediction corrected visual predictive check (pc-VPC). The pharmacokinetic of tacrolimus was described by a one-compartment model. The apparent clearance (CL/F) of CYP3A5*1/*3 and *1/*1 were 1.57 and 1.86 times of that of *3/*3, respectively. The CL/F of tacrolimus was 73.6% in patients undergoing co-therapy with Wuzhi capsules, and 1.2 times than that of the patients undergoing co-therapy with Jinshuibao capsules. The evaluation of the model shows that the model is stable and has satisfactory predictive performance. The clinical trial was approved by the Society of Ethics and conducted in Binzhou Medical University Hospital. The established PPK model can describe the pharmacokinetic characteristics of tacrolimus in Chinese patients with IMN, and can facilitate individualized therapy with tacrolimus.

OBJECTIVE: To analyze the differentially phosphorylated proteins in DENV-2-infected human umbilical venous endothelial cells (HUVECs) and explore the possible pathogenic mechanism of DENV-2 infection. METHODS: The total proteins were extracted from DENV-2-infected HUVECs and blank control HUVEC using SDT lysis method. The phosphorylated proteins were qualitatively and quantitatively analyzed using tandem mass spectrometry (TMT). The identified differentially phosphorylated proteins were analyzed by bioinformatics analyses such as subcellular localization analysis, GO enrichment analysis, KEGG pathway analysis and protein-protein interaction (PPI) analysis. Western blotting was used to detect the expressions of phosphorylated Jun, map2k2 and AKT1 proteins in DENV-2-infected HUVECs. RESULTS: A total of 2918 modified peptides on 1385 different proteins were detected, and among them 1346 were significantly upregulated (FC > 1.2, P < 0.05) and 1572 were significantly downregulated (FC < 0.83, P < 0.05). A total of 49 phosphorylated conserved motifs were obtained by amino acid conservative motif analysis. The most abundant differentially phosphorylated peptides in protein domain analysis included RNA recognition motif, protein kinase domain and PH domain. Subcellular localization analysis showed that the differentially modified peptides were mainly localized in the nucleus and cytoplasm. GO enrichment and KEGG pathway analysis showed that the differential peptides were mainly enriched in the regulation of stimulation response, biosynthesis of small molecules containing nuclear bases, and migration of phagosomes and leukocytes across the endothelium. PPI and KEGG joint analysis showed that the up-regulated and down-regulated differentially phosphorylated proteins were enriched in 15 pathways. In DENV-2-infected HUVECs, Western blotting detected differential expressions of phosphorylated proteins related with the autophagy pathway, namely JUN, MAP2K2 and AKT1, and among them p-JUN was significantly down-regulated and p-AKT1 and p-MAP2K2 were significantly upregulated (P < 0.01). CONCLUSION DENV-2 infected HUVECs show numerous differentially expressed proteins. The downregulation of p-JUN and upregulation of p-MAP2K2 and p-AKT1 suggest their potential roles in regulating autophagy, which is probably involved in the mechanism of DENV-2 infection.
Humans ; Autophagy ; Cell Death ; Cell Nucleus ; Human Umbilical Vein Endothelial Cells/virology* ; Dengue ; Proteome

OBJECTIVE：To know about the research status of health utility value obtained by mapping method in pharmacoeconomic evaluation ，and to provide reference for bibliometric study in pharmacoeconomic evaluation . METHODS ： Using“Mapping method ”“Health utility value ”“Cost-utility”“Utility point system ”as Chinese and English keywords ，retrieved from CNKI ，Wanfang database ，PubMed，Medline，Ebsco，Ovid and Wiley database ，empirical journal documents published from the inception to Dec. 31st，2018 about using mapping method to obtain health utility value were collected. The bibliometrics was used to statistically analyze basic information of included literature ，the construction and test of the model ，the type of the best model and so on. RESULTS ：The 124 included documents were all published in English journal. In the construction and testing of the mapping model ，the most frequently used econometric methods ，performance evaluation indicators and model testing methods were ordinary least squares （OLS），mean absolute error （MAE）and residual normality test ，application frequency of which were 97 times（31.60％），89 times（24.93％）and 62 times（21.09％）. There are 117 articles that define the best mapping model ，of which 101 articles（86.32％）have the best direct mapping effect. Most of the non-utility measurement scales adopted specific scales （92 articles，77.97％），and a few literatures adopted the universal scale （26 articles，22.03％）. The most utility measurement scales were 3-level European 5-dimensional health scale （79 articles，66.95％）. CONCLUSIONS ：The domestic empirical researches that use the mapping method to obtain health utility values need to be developed yet. A series of mapping models successfully developed by foreign scholars not only provide the feasibility of using non-utility measurement scales for cost-utility analysis ，but also provide more ideas for China to choose the corresponding econometric methods ，evaluation indicators and mapping methods in the empirical research of the mapping method in the future.