Skeletal muscle plays a crucial role in maintaining metabolism,energy homeostasis,movement,as well as endocrine function.The gestation period is a critical stage for myogenesis and development of the skeletal muscle.Adverse environmental exposures during pregnancy may impose various effects on the skeletal muscle health of the offspring.Maternal obesity during pregnancy can mediate lipid deposition in the skeletal muscle of the offspring by affecting fetal skeletal muscle metabolism and inflammation-related pathways.Poor dietary habits during pregnancy,such as high sugar and high fat intake,can affect autophagy of skeletal muscle mitochondria and reduce the quality of the offspring skeletal muscle.Nutritional deficiencies during pregnancy can affect the development of the offspring skeletal muscle through epigenetic modifications.Gestational diabetes may affect the function of the offspring skeletal muscle by upregulating the levels of miR-15a and miR-15b in the offspring.Exposure to environmental endocrine disruptors during pregnancy may impair skeletal muscle function by interfering with insulin receptor-related signaling pathways.This article reviews the research progress on effects and possible mechanisms of adverse maternal exposures during pregnancy on the offspring skeletal muscle function based on clinical and animal studies,aiming to provide scientific evidence for the prevention and treatment strategies of birth defects in the skeletal muscle.

OBJECTIVE To explore the appropriate dosing regimen of meropenem in the elderly with renal insufficiency. METHODS The meropenem population pharmacokinetics of the two-compartment model of elderly patients were applied for Monte Carlo simulation. The model included the effect of renal function on the parameters. The designed dosages were 0.5， 1， 2 g； the administration modes included intravenous injection （lasting for 6 min） and intravenous drip （0.5， 3 h）； the administration frequencies were q12 h， q8 h. A total of 18 dosing regimens were designed. The probability of target attainment of %fT＞4MIC≥40% and Cmin≤27.5 mg/L were calculated respectively to optimize the dosing regimen. RESULTS For elderly patients with creatinine clearance （CLcr） ≤40 mL/min， when the minimum inhibitory concentration （MIC） was equaled to 1 mg/L， the suggested dosing regimens were “0.5 g， intravenous drip 0.5 h， q12 h”“ 1 g， intravenous injection， q12 h”. When the MIC was equaled to 2 mg/L， the suggested dosing regimens were “0.5 g， intravenous injection， q8 h”“ 1 g， intravenous drip 0.5 h， q12 h”. When the MIC was equaled to 4， 8 mg/L， the suggested dosing regimens were “1 g （or 2 g）， intravenous injection， q8 h”. For elderly patients with CLcr equal to 50 mL/min， when the MIC was equaled to 1 mg/L， the suggested dosing regimens were “0.5 g， intravenous injection， q8 h“”1 g， intravenous injection， q12 h”. When the MIC was equal to 2， 4， 8 mg/L，the suggested dosing regimens were“0.5 g （or 1 g， or 2 g）， intravenous drip for 0.5 h， q8 h”. The appropriate dosing regimens of all the above protocols were above 96.6%. In the dosing regimen of “2 g，intravenous injection or intravenous drip 0.5 h， q8 h”， Cmin＞27.5 mg/L occurred in 40 times among the 1 000 times of simulation， indicating adverse reactions of the nervous system may occur. CONCLUSIONS For the elderly patients with renal insufficiency， the dosing regimen of meropenem should be adjusted accordingly with CLcr＝40 mL/min as the boundary， and the toxicity of nervous system should be considered at the same time.

AIM: To build a meropenem population pharmacokinetic model for Chinese elderly through model-based meta-analysis. METHODS: Informations including dosing regimen, sampling times, concentrations, sample size, age, gender, body weight (BW) and creatinine clearance were extracted after the literature were retrieved. The model was built by NONMEM. Stepwise covariate modeling strategy was used for covariates analysis. RESULTS: A two-compartment model was applied to describe meropenem pharmacokinetics. After stepwise covariate modeling, covariates that remained significant in the final model were creatinine clearance (CLcr) on CL and the BW on V

To explore the clinical efficacy and possible mechanism of Tai Ji Quan for post-stroke depression (PSD), literature related to Tai Ji Quan and PSD were retrieved from China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full- text Database (Wanfang), Chongqing VIP Database (CQVIP), China Biology Medicine Disc (CBM), and PubMed, screened and then summarized. The results showed that Tai Ji Quan could effectively improve the depression and quality of life of stroke patients, and there were differences in the clinical efficacy among different training programs. Tai Ji Quan has the characteristics of "regulating mind", "regulating breath", and "regulating body". It may achieve the effect of "combined physique-spirit treatment" by improving social psychology, increasing the level of neurotrophin, regulating neuroendocrine, reducing inflammatory factors, and regulating neural circuits.

Objective:To investigate the treatment effect of marrow mesenchymal stem cells (MSC)/endothelial progenitor cells (EPC) extracellular matrix-based tissue engineering bone (ECM-TEB) in repair of femoral defects in rats.Methods:Bone marrow-derived MSC and EPC were isolated and cultured for functional identification, and planted on the nanocrystalline collagen-based artificial bone particles. After culturing for 14 days, the cells were lyophilized to obtain MSC/EPC ECM-TEB and MSC ECM-TEB. A scanning electron microscope was used to observe the morphology of MSC and EPC on the surface of the scaffold. The protein extracts of MSC ECM-TEBs (control group) and the protein extracts of MSC/EPC ECM-TEBs (experimental group) were added to the EPC culture system for migration test, scratch repair assay, and tube formation detection; and to the MSC culture system for alizarin red staining and alkaline phosphatase? (ALP) staining detection. The cell recruitment, angiogenesis and osteogenic differentiation were observed. A total of 12 SD rats were selected to establish a femoral defect model. According to the random number table, the rats were divided into: (1) sham group: debridement treatment was performed only at the defect; (2) MSC ECM -TEB group: MSC ECM-TEB was implanted at the defect; (3) MSC/EPC ECM-TEB group: MSC/EPC ECM-TEB was implanted at the defect, with 4 rats per group. Two months later, micro-computed tomography (Micro-CT) and Masson's tricolor staining were performed to observe the treatment effect of the bone defect. When the cells were stored at low temperature for three months after lyophilization, the different protein profile between MSC ECM-TEB and MSC/EPC ECM-TEB in vascularization was detected by isotope relative labeling and absolute quantification technology (iTRAQ). The gene ontology/Kyoto Encyclopedia of Gene and Genome Technology (GO/ KEGG) function enrichment was used to analyze the key differences.Results:MSC and EPC grew well and formed a smooth cell layered structure on the surface of the scaffold. The number of cell migration, ratio of scratch repair, and length of the tube in experimental group were respective 121.6±8.3, (61.5±5.9)%, (11.3±0.6)mm, significantly increased compared with control group [85.0±6.7, (39.3±3.6)%, (5.9±0.4)mm] (all P<0.01). Alizarin red staining and ALP staining results showed that the proportion of calcium nodule mineralized area in experimental group increased significantly compared with control group [(38.8±3.3)%∶(49.9±3.0)%, (38.8±2.4)%∶(45.3±3.3)%] (all P<0.05). Base on the Micro-CT and Masson staining, bone defect healing was good in MSC/EPC ECM-TEB group, only a small amount of new bone was formed in MSC ECM-TEB group, and there was almost no new bone regenerated in sham group. Significant differences were found in bone volume/total volume, trabecular number and trabecular thickness among groups (all P<0.05), which were in line with Micro-CT and Masson staining results. The protein profile analysis showed that 83 angiogenesis-related factors in MSC/EPC ECM-TEB group were significantly up-regulated compared with MSC ECM-TEB group (fold change>2, P<0.05). GO/KEGG function enrichment analysis showed that MSC/EPC ECM-TEB group had projecting ascendancy in "vascular development" and in "vascular smooth muscle contraction pathway" compared with MSC ECM-TEB group (both P<0.01). Conclusion:MSC/EPC ECM-TEB has advantages in cell recruitment, angiogenesis, and new bone formation compared with MSC ECM-TEB, and is a better construction strategy for repair of traumatic bone defect.

Objective To summarize the characteristic of projects accepted by human genetic resources management office in 2016 and put forward further measures.Methods Statistic analyses were carried out based on the overall projects application,then Chinese application units and partners were analyzed separately.Results 1 138 international cooperation projects were approved in total,mainly on clinical research.24 countries were involved with increasing trend of globalization.Conclusions The human genetic resources management played a positive role in the development of the biomedical research and industry.

BACKGROUND: The immunosuppressant drugs (ISDs), tacrolimus and cyclosporine, are vital for solid organ transplant patients to prevent rejection. However, toxicity is a concern, and absorption is highly variable across patients; therefore, ISD levels need to be precisely monitored. In the Asia-Pacific (APAC) region, tacrolimus and cyclosporine concentrations are typically measured using immunoassays. The objective of this study was to assess the analytical performance of Roche Elecsystacrolimus and cyclosporinee electrochemiluminescence immunoassays (ECLIAs). METHODS: This evaluation was performed in seven centers across China, South Korea, and Malaysia. Imprecision (repeatability and reproducibility), assay accuracy, and lot-to-lot reagent variability were tested. The Elecsys ECLIAs were compared with commercially available immunoassays (Architect, Dimension, and Viva-E systems) using whole blood samples from patients with various transplant types (kidney, liver, heart, and bone marrow). RESULTS: Coefficients of variation for repeatability and reproducibility were ≤5.4% and ≤12.4%, respectively, for the tacrolimus ECLIA, and ≤5.1% and ≤7.3%, respectively, for the cyclosporine ECLIA. Method comparisons of the tacrolimus ECLIA with Architect, Dimension, and Viva-E systems yielded slope values of 1.01, 1.14, and 0.897, respectively. The cyclosporine ECLIA showed even closer agreements with the Architect, Dimension, and Viva-E systems (slope values of 1.04, 1.04, and 1.09, respectively). No major differences were observed among the different transplant types. CONCLUSIONS: The tacrolimus and cyclosporine ECLIAs demonstrated excellent precision and close agreement with other immunoassays tested. These results show that both assays are suitable for ISD monitoring in an APAC population across a range of different transplant types.
Absorption ; China ; Cyclosporine* ; Drug Monitoring ; Heart ; Humans ; Immunoassay* ; Korea ; Liver ; Malaysia ; Methods ; Tacrolimus* ; Transplants

Objective To investigate the value of local myocardial blood flow and myocardial function parameters in monitoring the dynamic changes of radiation induced heart disease (RIHD) using 13NNH3 PET gated myocardial perfusion imaging(GMPI).Methods Six healthy male Beagle dogs underwent 13N-NH3 PET GMPI 1 week before irradiation and 3,6 and 12 months after irradiation in the anterior wall of the left ventricle with a single dose of 20 Gy.Global myocardial function parameters including left ventricular ejection fraction (LVEF),end-diastolic volume (EDV),end-systolic volume (ESV),and regional myocardial function parameters including wall motion (WM),wall thickening (WT),end-diastolic perfusion (EDP),end-systolic perfusion (ESP) before and after irradiation were compared by repeated measures analysis of variance and paired t test.Results There were no significant changes between EDV,ESV and LVEF at baseline and those at 3 months after irradiation.EDV at 6 months after irradiation still had no change,compared with baseline value and EDV at 3 months after irradiation,but ESV was increased and LVEF was decreased.Twelve months after irradiation,ESV was further expanded,LVEF was further reduced,and EDV began to increase (F values:20.974-177.846,all P＜0.05).Compared with the baseline,WM,WT,EDP and ESP were increased in 10％(2/20),20％(4/20),10％(2/20) and 15％(3/20) of myocardial segments at 3 months after irradiation (t values:14.446-672.315,all P＜0.05);those parameters were decreased in 15％(3/20),20％(4/20),15％(3/20) and 25％(5/20) of myocardial segments at 6 months after irradiation (t values:18.171-723.156,all P＜0.05),and were decreased in 35％(7/20),45％(9/20),40％(8/20) and 60％ (12/20) of myocardial segments at 12 months after irradiation (t values:14.783-711.259,all P＜0.05).Conclusions 13N-NH3 PET GMPI could be used to detect RIHD early and monitor the dynamic development of RIHD.Compared with the global left ventricular function parameters,regional myocardial function parameters (WM,WT,EDP and ESP) are more sensitive,which may be served as the early monitoring indicators for RIHD.

Objective To explore the association between the genetic polymorphism of CYP3A4,CYP2D6 and response to methadone maintenance treatment(MMT)among heroin-dependent patients.Methods Patients undergoing MMT in 6 MMT clinics were randomly selected,information about general socia-demographic characteristics,drug abuse history,and MMT data of patients were collected,genotypes of peripheral blood CYP3A4 and CYP2D6 polymorphic loci were detected.Results A total of 820 patients were enrolled in the study,210 cases were with good response and 610 cases with poor response to MMT.Difference in age between different response groups was statistically significant(P<0.05).Distribution of genotype frequency and allele frequency of CYP3A4 rs2242480 and CYP2D6 rs16947 between good response and poor response groups was not significantly different(both P>0.05).Conclusion The association between CYP3A4 rs2242480,CYP2D6 rs16947 and response to MMT has not yet found in heroin-dependent patients.