AIM: To study the protective effects of Shenmai injection, a Chinese medicine, on angiotensin Ⅱ (AngⅡ)-induced rat cardiomyocyte apoptosis in vitro and the probable mechanism. METHODS: Cultured cardiomyocytes from neonatal rats were stimulated with AngⅡ. Cell viability were measured by MTT, and apoptosis was evaluated suing Hoethst33258 fluorescent dye staining and flow cytometry. Fluo-3/AM was used to test the change in intracellular free calcium. RESULTS: It was found that incubation with AngⅡ (10 -7 mol/L) for 48 h increased cardiomyocyte apoptosis, Shenmai injection (0 5 g/L, 1 0 g/L) inceased myocyte viability ( P

AIM: To study the effects of Shenmai injection on cardiomyocytes apoptosis after acute anoxia-reoxygenation (A/R) and the possible mechanism. METHODS: In this experiment, cultured cardiomyocytes isolated from neonatal rat were used. Model of myocardial anoxia-reoxygenation injury was produced by depriving oxygen for 5 min and then restoring oxygen for 15 min. The apoptotic cells was detected by flow cytometry to detect labbled Annexin V-FITC/PI. The intracellular calcium level was observed by laser scanning confocal microscopy markered Fluo-3/AM. RESULTS: In anoxia-reoxygenation group, the percentage of apoptotic cells and fluorescent intensity of intracellular calcium were both prominently higher than those in control group (P

Platelets are the blood cells essential for human hemostasis, wound healing and human health. Drug-induced thrombopenia refers to a disease in which the drug causes platelet counts fall below the normal range (<100×109/L), resulting in a series of symptoms, including bleeding, nausea, vomiting, and abdominal pain, etc. The antineoplastic drugs-induced thrombopenia increases not only the potential bleeding risk of patients, but may also reduce the dose of anti-tumor drugs and prolong the treatment interval, or even lead to the ceasing of antitumor therapy in serious cases, which affects the clinical efficacy and survival of patients, leading to the increased medical costs. In recent years, a large number of studies have confirmed that antineoplastic drugs-induced thrombopenia is a disease caused through a non-immune-mediation, including platelet apoptosis. The research status has been reviewed in present paper of platelet apoptosis mechanism in antineoplastic drugs-induced thrombopenia to provide theoretical basis for clinical practice and scientific research.

Objective To research and prepare the individualized knee in vitro guided plate by 3D printing technique and to investigate the feasibility of its application in 8-plate epiphysiodesis.Methods Twelve children patients with knee varus or valgum in our hospital from January 2014 and November 2016,7 boys and 5 girls,average age of 8.2 years old,were performed the lower extremity continuous spiral CT scanning in the knee straight position.The Dicom format stored CT data were imported into software Mimics 15.0 for reconstructing the knee joint 3D model.The knee joint data after reconstruction were guided into software Geomagic1 1.0 with the.stl format.According to the demand that screws without perforating epiphyseal and joint surface,paralle ling to the epiphyseal and locating in the anterior-posterior median line of epiphyseal,the 8-plate placing screw navigation template was designed and printed by using the 3D printing technique;the 8-plate plate and screw internal fixation was conducted by intraoperative template location.The placed screw position was evaluated by postoperative CT.Results The imaging identification showed that 8-plate epiphysiodesis by using 3D printing individualized in vitro guided plate had accurate screw placement.The cases were followed from 6 months to 2 years,the satisfactory orthopedic effect was obtained in all cases.Conclusion Preparing the individualized knee in vitro guided plate by applying 3D printing technique in assisted 8-plate epiphysiodesis for treating child knee varus or valgum has accurate screw position and satisfactory effect.

To investigate the protective effect of preconditioning with hyperoside ( Hyp) against myocardial ischemia-reperfusion injury (MIRI) in rats and the role of PI3K/Akt signaling pathway. MIRI was established by ligation of left anterior descending coronary artery for 30 min followed by reperfusion for 120 min in rats. Male SD rats were randomly divided into five groups: sham group,model group (MIRI),Hyp preconditioning group(Hyp), Hyp preconditioning + LY294002 (a PI3K/Akt signaling pathway inhibitor) group (Hyp + LY), and LY294002 group (LY). At the end of reperfusion, hemodynamic parameters were recorded as left ventricular systolic pressure (LVSP) , left ventricular end-diastolic pressure ( LVEDP) and maximal rate of increase and decrease of left ventricular pressure (± dP/dt(max)). Myocardial infaret size, the oxidative stress markers, myocardial enzymes indicators and inflammatory factors were also analyzed. The expressions of Akt, p-Akt, Bax and Bcl-2 proteins was detected by using Western blot method. The results showed that Hyp preconditioning remarkably improved cardiac constriction and relaxation function, reduced myocardial infarct size and enhanced the activities of oxidative stress markers about correlated to MIRI, such as superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GSH-Px) and decreased the contents of malondialdehyde (MDA) as compared with MIRI group. Simultaneouly, the levels of myocardial enzymes, i. e. creatine kinase ( CK) and creatine kinase MB isoenzyme (CK-MB), and inflammatory factors, for instance tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were decreased. Hyp pretreatment apparently restrained myocardial apoptosis as evidenced by decreasing the level of Bax expression, increasing the levels of phosphorylation of Akt and Bcl-2 expression. These effects were inhibited by LY294002, a blocker of PI3K/Akt signaling pathway. These findings indicated that the cardioprotection of Hyp preconditioning against MIRI may be related to activating PI3K/Akt signaling pathway, upregulating the expression of BCL-2 protein and down-regulating the expression of Bax protein.
Animals ; Creatine Kinase ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Heart ; drug effects ; Humans ; Interleukin-6 ; genetics ; metabolism ; Ischemic Preconditioning, Myocardial ; Male ; Malondialdehyde ; metabolism ; Myocardial Reperfusion Injury ; drug therapy ; enzymology ; genetics ; prevention & control ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Quercetin ; administration & dosage ; analogs & derivatives ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; genetics ; metabolism

To investigate the effects and potential mechanisms of hyperoside (Hyp) on the vascular endothelium function in middle cerebral artery (MCA) ex vivo in rats. Isolated arterial segments from MCAs of rats were used for surveying vasomotoricity in a pressurized chamber. Transmembrane potential was recorded by using glass microelectrodes to evaluate hyperpolarization. Hyp (1 x 10(-6)-1 x 10(-4) mol . L-1) was utilized to observe the effect on 1 x 10(-7) mol . L-1 U46619-preconstricted MCA in rats. The results showed that 1 x 10(-6)-1 x 10(-4) mol . L-1 Hyp significantly induced concentration-dependent vasodilatation and hyperpolarization, leading to the maximal diastolic ratio of (73. 2 ± 6. 1)% and maximal changes in membrane potentials of (-13. 2 ± 2. 2) mV. Hyp still elicited vasorelaxation and hyperpolarization by removal of endothelium in MCA of rat, which was notably attenuated as compared with vascular endothelium-intact group (P <0. 01). In the MCAs preconstricted by U46619 (1 x 10(-7) mol . L-1), Hyp (1 x 10(-6)-1 x 10(-4) mol . L-1) produced concentration-dependent vasorelaxation and hyperpolarizition that were partially attenuated by 3 x 10(-5) mol . L-1 L-NAME(a NOS inhibitor) plus 1 x 10(-5) mol . L-1 PGI2 ,(a synthetase inhibitor). The residual effects were further decreased by 1 x 10(-3) mol . L-1 TEA (an inhibitor of Ca2+-activated potassium channel) or 1 x 10(-5) mol . L-1 PPG (a blocker of endogenous H2S synthese-CSE). Similarly, 1 x 10(-5)-1 x 10(-3) mol . L-1 NaHS (a donor of exogenous H2S) or 1 x 10(-5)-1 x 10(-3) mol . L-1 L-Cys (the substrate of endogenous H2S synthesis) obviously evoked dose-dependent vasodilatation and hyperpolarization of MCA in rats. These findings indicated that Hyp may induce endothelium-dependent and endothelium-independent responses. And the endothelium-dependent vasodilatation may be related to the increases of endogenous H2S that has been promoted Hyp in the endotheliocyte of MCAs, and activated Kca and opening of Kca channels, resulting in the hyperpolarization of vascular smooth muscle cell membrane and subsequent reduction of Ca2+ influx and vasodilation.
Animals ; Endothelium, Vascular ; drug effects ; Enzyme Inhibitors ; pharmacology ; Female ; Male ; Middle Cerebral Artery ; Muscle, Smooth, Vascular ; drug effects ; Nitric Oxide ; metabolism ; Potassium Channels ; metabolism ; Quercetin ; analogs & derivatives ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Sulfides ; metabolism ; Vasodilation ; drug effects ; Vasodilator Agents ; pharmacology

Humans ; Supranuclear Palsy, Progressive ; Acupuncture Therapy

Objective To observe the characteristics of hepatic progenitor cells(HPCs)activation in liver tissues of patients with hepatitis B cirrhosis,and to investigate the relationship between the number of HPCs and HBV infection.Methods Cytokeratin 7(CK7)-was stained immunohistochemically in liver tissues of 16 patients with hepatitis B cirrhosis.HPCs and duetular reactions were quantitively analyzed.The expression of HBsAg and HBcAg were also detected to evaluate its relationship with HPCs activation.Results HPCs were extensively activated and marked duetular reactions can be observed in cirrhotic liver tissues.Tlle expression of HBsAg was positively correlated with HPCs activation.Conclusions HPCs are extensively activated in cirrhotic liver tissues,and HBV infection may facilitate its activation.

Objective To investigate the daily total fluoride intake in relating to the prevalence of skeletal fluorosis in two villages in Jiangsu Province,in order to provide the scientific evidences for the control and prevention of endemic fluorosis.Methods Adults sampled from a high-fluoride Village,Wamiao,and a low-fluoride Village,Xinhuai,were surveyed in this study according to the fluoride concentration in their household shallow well.The average daily total fluoride intake from difierent sources and the skeletal fluorosis were investigated in each subject.Then the subjects from two villages were allocated into five subgroups(＜2.00,2.00～,3.00～,4.00～,≥5.00 mg/d),the relation fluoride intake and prevalence of osteofluorosis was analyzed.Results The prevalence of skeletal fluorosis in Wamiao Village was 31.06%(41/132),but no skeletal fluorosis case(0/35)was found in Xinhuai Village.According to the daily total fluoride intake,subjects with higher daily total fluoride intake tended to associated with a higher prevalence of skeletal fluorosis in a significant dose-response relationship(regression equation:y=2.624-6.855x+3.424x2:r=0.997).The benchmark dose lower limitation of daily total fluoride intake with 95% confidencewas 2.50 mg/d calculated according to this dose-response relationship,the reference dose(RfD)was 2.50 mg/d.In Wamiao Village a significant difference was also found between daily total fluoride intake in 41 subjects[(5.09±1.20)mg/d]with X-ray detectable skeletal fluorosis and in 91 subjects[(3.08±1.12)mg/d]without X-ray detectable skeletal fluorosis(t=-9.32,P＜0.01).Conclusions These findings indicate that the daily total fluoride intake has a significant dose-response relationship with the prevalence of skeletal fluorosis in an endemic fluorosis area associated with high-fluoride drinking water;and the RfD in this study was lower than that in the national standard of"Chinese hygienic standard for daily total fluoride intake(WS/T 87-1996)"(3.50 mg/d).

The clinical tumor therapy was greatly challenged due to the complex characteristics of tumor microenvironment, however, which also provide arena for novel therapeutic strategies. In this study, poly(2-ethyl-2-oxazoline)-poly(lactic acid)-SS-poly(β-amino ester (PEOz-PLA-SS-PBAE) triblock copolymers with pH and GSH double response were synthesized, polymer micelles were prepared by thin film hydration method for loading of silybin to improve its antitumor activity. The critical micelle concentration was determined by pyrene fluorescence method as 1.8 μg·mL^-1. The particle size was 155.30 ± 1.80 nm as determined by dynamic light scattering, with polydispersity index of 0.168 ± 0.004. The drug loading and entrapment efficiency of the micelles were determined by HPLC as (5.48 ± 0.04)% and (68.52 ± 0.48)%, respectively. The in vitro drug release profiles showed that the micelles have low pH sensitivity and high GSH responsiveness, and exhibited sustained release profiles. The good biocompatibility of the material was proved by measuring the hemolysis rate and cytotoxicity of the blank micelle. The cytotoxicity and apoptosis rate of tumor cells showed that the drug loaded PEOz-PLA-SS-PBAE micelles had significant inhibitory effect and apoptosis-inducing effect on MDA-MB-231 cells. The results of wounding healing assay and Transwell invasion test showed that the drug loaded PEOz-PLA-SS-PBAE micelles could significantly inhibit the metastasis of MDA-MB-231 cells. The PEOz-PLA-SS-PBAE drug-loaded micelles prepared in this study have good inhibitory effect on tumor growth and anti-tumor metastasis in vitro, which lays the foundation for the further application of silybin.