The function of microglia/macrophages after ischemic stroke is poorly understood. This study examines the role of microglia/macrophages in the focal infarct area after transient middle cerebral artery occlusion (MCAO) in rhesus monkeys. We measured infarct volume and neurological function by magnetic resonance imaging (MRI) and non-human primate stroke scale (NHPSS), respectively, to assess temporal changes following MCAO. Activated phagocytic microglia/macrophages were examined by immunohistochemistry in post-mortem brains (n=6 MCAO, n=2 controls) at 3 and 24 hours (acute stage), 2 and 4 weeks (subacute stage), and 4, and 20 months (chronic stage) following MCAO. We found that the infarct volume progressively decreased between 1 and 4 weeks following MCAO, in parallel with the neurological recovery. Greater presence of cluster of differentiation 68 (CD68)-expressing microglia/macrophages was detected in the infarct lesion in the subacute and chronic stage, compared to the acute stage. Surprisingly, 98~99% of transforming growth factor beta (TGFβ) was found colocalized with CD68-expressing cells. CD68-expressing microglia/macrophages, rather than CD206⁺ cells, may exert anti-inflammatory effects by secreting TGFβ after the subacute stage of ischemic stroke. CD68⁺ microglia/macrophages can therefore be used as a potential therapeutic target.
Brain ; Haplorhini ; Immunohistochemistry ; Infarction, Middle Cerebral Artery ; Inflammation ; Macaca mulatta ; Magnetic Resonance Imaging ; Microglia ; Middle Cerebral Artery ; Primates ; Stroke ; Transforming Growth Factor beta

Objective To evaluate the effect of ultraviolet (UV) irradiation and all-trans retinoic acid (ATRA) on expression of Hrd1 in human skin and fibroblasts,and to explore their mechanisms.Methods From December 2017 to June 2018,12 human skin tissue samples were collected from Department of Dermatology,The First Affiliated Hospital of Nanjing Medical University,including 3 sun-exposed and 3 non-sun-exposed skin tissue samples of patients aged 30-40 years,and 3 sun-exposed and 3 non-sun-exposed skin tissue samples of patients aged 60-70 years.Immunohistochemicai examination was performed to determine the expression of Hrd 1 in the above samples.A total of 40 BALB/c mice were randomly classified into 4 groups:UV group treated with UVA irradiation at 10 J/cm2 and UVB irradiation at 30 mJ/cm2 every day,ATRA group topically treated with 0.1 ml of ATRA 0.1％ cream once a day on the shaved back,UV + ATRA group treated with topical ATRA 0.1％ cream before the above UV irradiation,and control group receiving no treatment.After 14 weeks,these mice were sacrificed,skin tissues were excised from the back,and the expression of Hrd 1 was determined by immunohistochemical examination.In vitro cultured human fibroblasts were divided into 4 groups:UV group and ATRA + UV group covered with phosphate buffer saline (PBS) followed by UVA irradiation at 10 J/cm2 or UVB irradiation at 30 mJ/cm2,ATRA group treated with culture media containing 1.μmol/L ATRA for 24 hours,and ATRA + UV group also treated with culture media containing 1 μmol/L ATRA for 24 hours after the ultraviolet irradiation.Western blot analysis was performed to determine the expression of Hrd 1 in fibroblasts in the above groups,fluorescence microscopy to detect the levels of reactive oxygen species (ROS) in the above groups.Statistical analysis was carried out by one-way analysis of variance (ANOVA) for comparison among groups,and least significant difference (LSD)-t test for multiple comparisons.The difference was considered to be statistically significant when the P value was less than the significant level of 0.05.Results In both the groups of 30-40 years and 60-70 years,the expression of Hrd1 was significantly higher in the sun-exposed skin tissues (0.307 ± 0.256,0.486 ± 0.579,respectively) than in the non-sun-exposed skin tissues (0.196 ± 0.330,0.199 ± 0.375,respectively;t =5.486,10.579 respectively,both P ＜ 0.05).In the in vivo experiment,the expression of Hrd1 in the skin tissues of mice significantly differed among the control group,UV group,ATRA group and ATRA + UV group (0.189 ± 0.015,0.288 ± 0.017,0.187 ±0.020,0.226 ± 0.021 respectively,F =19.553,P ＜ 0.001),and the UV group showed significantly higher Hrd1 expression compared with the control group (t =5.337,P =0.033)and ATRA + UV group (t =4.891,P =0.039).In the in vitro experiment,the level of Hrd1 in the fibroblasts significantly differed among the 4 groups after the UVA or UVB irradiation (F =120.704,102.119,both P ＜ 0.001).The effect of the UVA and UVB irradiation on the expression of Hrd1 was basically consistent,and the Hrd1 level was significantly higher in the UV group than in the control group and ATRA + UV group (both P ＜ 0.05).After the UV irradiation,the ROS level was significantly higher in the UV group than in the control group and ATRA + UV group (both P ＜ 0.05).Conclusion ATRA can inhibit ultraviolet-induced Hrd1 expression in skin fibroblasts,likely by inhibiting the generation of cellular ROS.

This study aimed to assess the pharmacokinetics of cyclosporine A (CsA) in Asian children with renal impairment (RI) by developing a physiologically-based pharmacokinetic (PBPK) model with Simcyp Simulator. The PBPK model of Asian children with RI was developed by modifying the physiological parameters of the built-in population libraries in Simcyp Simulator. The ratio of healthy and RI populations was obtained for each parameter showing a difference between the populations. Each ratio was multiplied by the corresponding parameter in healthy Asian children. The model verification was performed with published data of Korean children with kidney disease given multiple CsA administrations. Simulations were performed with different combinations of ethnicity, age, and renal function to identify the net impact of each factor. The simulated results suggested that the effect of RI was higher in children than adults for both Caucasian and Asian. In conclusion, the constructed model adequately characterized CsA pharmacokinetics in Korean children with RI. Simulations with populations categorized by ethnicity, age, and renal function enabled to assess the net impact of each factor on specific populations.
Adult ; Asian Continental Ancestry Group ; Child ; Cyclosporine ; Humans ; Kidney Diseases ; Pediatrics ; Pharmacokinetics

Diemailing~® Kudiezi Injection( DKI) is widely used in the treatment of cerebral infarction,coronary heart disease and angina pectoris. Long-term clinical application and related research evidence showed that DKI has a good effect in improving the clinical symptoms of cardiovascular and cerebrovascular diseases. However,this injection has not been included in any clinical practice guideline. It has been found that the use of DKI is in wrong way in clinical practice in recent years. Therefore,clinical experts from the field of cardiovascular and cerebrovascular diseases nationwide are invited to compile this expert consensus in order to guide clinicians.GRADE system is used to grade the quality of evidence according to different outcomes according to degrading factors. Then it forms the recommendation or consensus suggestion through the nominal group method. The formation of expert consensus mainly considers six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on these six aspects,if the evidence is sufficient,a " recommendation" supported by evidence is formed,and GRADE grid voting rule is adopted. If the evidence is insufficient,a " consensus suggestions" will be formed,using the majority voting rule. In this consensus,the clinical indications,efficacy,safety evidences and related preliminary data of DKI were systematically and comprehensively summarized in a concise and clear format,which could provide valuable reference for the clinical use of DKI. This consensus has been approved by China association of Chinese medicine which is numbered GS/CACM 202-2019.
Angina Pectoris ; drug therapy ; Cerebral Infarction ; drug therapy ; China ; Consensus ; Coronary Disease ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Injections ; Medicine, Chinese Traditional

To observe the effect of Tripterygium Glycosides Tablets on angiogenesis of rats with type Ⅱ collagen-induced arthritis( CIA) and on the tube formation of human umbilical vein endothelial cells( HUVEC) in vitro. The HUVEC were induced by 20 μg·L-1 vascular endothelial growth factor( VEGF) in vitro,and were treated with 0. 1,1,10 mg·L-1 Tripterygium Glycosides Tablets continuously for 7 hours. The numbers of branches of tube formation were measured. SD rats were immunized to establish CIA. CIA rats were treated with 9,18,36 mg·kg-1·d-1 Tripterygium Glycosides Tablets for 42 days. Histopathological examination( HE) was performed to observe the vascular morphology and vascular density in the synovial membrane of the inflamed joints. Immunohistochemistry and immunofluorescence were performed to observe the expression of platelets-endothelial cell adhesion molecule( CD31) and αsmooth muscle actin( αSMA) in synovial membrane. Immunohistochemistry and Western blot were performed to observe the expression of hypoxia-inducible factors 1α( HIF1α) and angiotensin 1( Ang1) in the synovial tissue. The results showed that the numbers of branches of tube formation of HUVEC induced by VEGF were improved,and declined significantly after treated by Tripterygium Glycosides Tablets. Compared with the normal group,the vascular density,CD31 positive expression,CD31 +/αSMA-immature and total vascular positive expression in the synovial membrane of the model group were significantly increased,and so as HIF1α and Ang1 in the synovium. Tripterygium Glycosides Tablets reduced the synovial vascular density and inhibited the positive expression of CD31,CD31+/αSMA-immature blood vessels and total vascular,but has no effect on CD31+/αSMA+mature blood vessels. Tripterygium Glycosides Tablets also inhibited the expression of HIF1α and Ang1 in synovial membrane of inflammatory joints. Our results demonstrated that Tripterygium Glycosides Tablets could inhibit the angiogenesis of synovial tissue in CIA rats and the tube formation of HUVEC,which is related to the down-regulation of HIF1α/Ang1 signal axis.
Angiogenesis Inhibitors ; pharmacology ; Angiotensin I ; metabolism ; Animals ; Arthritis, Experimental ; chemically induced ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Glycosides ; pharmacology ; Human Umbilical Vein Endothelial Cells ; drug effects ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Synovial Membrane ; drug effects ; Tablets ; Tripterygium ; chemistry ; Vascular Endothelial Growth Factor A

The intestinal absorption characteristics of ten iridoid glycosides and phenolic acids in the Pterocephali Herba were evaluated via rat intestinal valgus model. The intestinal sac fluids at different time after administration of high,medium and low concentrations of Pterocephali Herba extract were collected and ten chemical components in fluid samples were detected by UPLC-PDA. Accumulative absorbed doses( Q) and absorption rate constants( Ka) of ten chemical constituents were calculated,while proportions between Pterocephali Herba extract and intestinal absorption liquid were compared. The results showed that the intestinal absorption of 10 chemical components was linear absorption( R2>0. 9) at different concentrations,which accorded with the zero-order absorption rate. The absorption rate constant was related to the concentration of the drug and the intestinal site,which indicated that intestinal adsorption mechanism of the components were passive diffusion and active transport. Proportions of chemical constituents in intestinal sac fluid were different from those in Pterocephali Herba extract. Therefore,those ten chemical components in Pterocephali Herba extract can be absorbed in whole intestine. Everted intestinal sac model can be used to evaluate intestinal absorption characteristics of ingredients in Pterocephali Herba extract effectively.
Animals ; Caprifoliaceae ; chemistry ; Drugs, Chinese Herbal ; pharmacokinetics ; Intestinal Absorption ; Intestines ; Plant Extracts ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

In order to study the interaction between Pterocephalus hookeri and bitter taste receptors,three-dimensional structural models of bitter taste receptors TAS2 R16,TAS2 R14 and TAS2 R13 were established by homology modeling in this paper. Maestro software was used for docking the chemical constituents of P. hookeri with bitter taste receptors. The results showed that 25 chemical components of P. hookeri can regulate three bitter taste receptors. And these components were mainly iridoid glycosides and phenolic acids.This research focused on the comprehensive application of homology modeling and molecular docking technology to explore the interaction between bitter chemical constituents of P. hookeri and bitter taste receptors. This study provided assistance in revealing pharmacodynamic basis of bitter Tibetan medicine at molecular level. It also provided new ideas and methods for the study of Tibetan medicine.
Caprifoliaceae ; chemistry ; Correlation of Data ; Humans ; Medicine, Tibetan Traditional ; Molecular Docking Simulation ; Receptors, G-Protein-Coupled ; metabolism ; Taste

OBJECTIVE: To investigate the incidence of neonatal asphyxia and possible contributing factors for the development of severe asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture, China. METHODS: A total of 16 hospitals in Hubei Enshi Tujia and Miao Autonomous Prefecture were selected as research centers. A retrospective analysis was performed for the clinical data of 22 294 live births in these 16 hospitals from January to December, 2016 to investigate the incidence rate of neonatal asphyxia and possible contributing factors for the development of severe asphyxia. RESULTS: Of the 22 294 neonates born alive, 733 (3.29%) were diagnosed with neonatal asphyxia, among whom 627 had mild asphyxia and 106 had severe asphyxia. The neonates with low maternal education level, maternal anemia during pregnancy, chorioamnionitis, abnormal amniotic fluid, abnormal umbilical cord, placenta previa, placental abruption, Tujia Minority, preterm birth, and low birth weight had a higher incidence of severe asphyxia (P<0.05). CONCLUSIONS The incidence rate of neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture is higher. Low maternal education level, maternal anemia during pregnancy, chorioamnionitis, abnormal amniotic fluid, abnormal umbilical cord, placenta previa, placental abruption, Tujia Minority, preterm birth, and low birth weight may be related to the development of severe neonatal asphyxia.
Asphyxia Neonatorum ; epidemiology ; China ; Humans ; Incidence ; Infant, Newborn ; Retrospective Studies

Objective To analyze the clustering of major cardiovascular risk factors among population with different level of fasting blood glucose (FBG) in Jiangsu provincial communities. Methods A population-based screening project was conducted during 2015-2017, with 83 522 residents aged 35-75 years from 6 areas included in the study. Prevalence and the clustering of four cardiovascular risk factors (hypertension, obesity, dyslipidemia and smoking) were analyzed. Binary Logistic regression analysis was performed to explore the relationship between FBG and cardiovascular risk factor clustering. Results The prevalence of diabetes was 18.9% among adults aged 35-75 years in Jiangsu province, and 41.4% of them were aware of their disease. Among undiagnosed population, the odd ratios (OR) of cardiovascular risk factors clustering in impaired fasting glucose (IFG) and hyperglycemia group was 1.29 (OR=1.29，95% CI:1.24-1.36，P<0.001) and 1.99 (OR=1.99，95% CI:1.89-2.08，P<0.001), compared with normal FBG group. The control rate of FBG was 15.5% among diagnosed cases. There was no difference in the risk clustering between diabetes patient with and without control of FBG. Conclusions Hyperglycemia and IFG increase the risk of cardiovascular risk factor clustering. Comprehensive interventions should be served as an important role to keep blood glucose at a normal level in high-risk population.

Objective The aim is to investigate the association between body mass index (BMI) and risk of all-cause mortality among patients with type 2 diabetes. Methods A total of 17 638 patients with type 2 diabetes registered in the management of National Basic Public Health Services in two areas of southern and northern Jiangsu were recruited. Cox proportional risk regression model was used to calculate the hazard ratio(HR) value and 95% confidence interval (95% CI) of different BMI groups in the follow-up period. Results The subjects were followed up for a total of 77 451 person-years with an average duration of 4.39 years, and 1 274 patients died during the follow-up period. The number of death in low weight group (BMI<18.5 kg/m2), normal weight group (18.5 kg/m2≤BMI<24 kg/m2), overweight (24 kg/m2≤BMI<28 kg/m2) and obese group (BMI≥28 kg/m2) were 39, 575, 484 and 176 respectively.The corresponding mortalities were 15.6%, 9.5%, 6.2% and 5.1%, respectively. Compared to normal weight group, the adjusted HR of all-cause mortality in low weight, overweight and obese group were 1.66 (95% CI: 1.20-2.30), 0.68 (95% CI: 0.61-0.77), 0.58 (95% CI: 0.48-0.68), respectively. Conclusions Low-weight patients have the highest risk of all-cause mortality compared with normal counterparts, while both overweight and obese people have a lower risk of death. Overweight and obesity may reduce the risk of all-cause mortality in type 2 diabetic patients.