OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

OBJECTIVE: To investigate the therapeutic effects of total saponins from Panax notognseng (PNS) combined with cyclophosphamide (CTX) in mice bearing hepatocellular carcinoma H₂₂ cell xenograft. METHODS: We examined the effects of treatment with different concentrations of PNS on H₂₂ cell proliferation for 24 to 72 h in vitro using CCK8 colorimetric assay. Annexin V/PI double fluorescence staining was used to detect the effect of PNS on apoptosis of H₂₂ cells. Mouse models bearing H₂₂ cell xenograft were established and treated with CTX (25 mg/kg), PNS (120, 240 or 480 mg/kg), alone or in combinations. After treatments for consecutive 10 days, the mice were euthanized for examinations of carbon clearance ability of the monocytes and macrophages, splenic lymphocyte proliferation, tumor necrosis factor (TNF-α), interleukin-2 (IL-2), serum hemolysin antibody level, blood indicators, and the tumor inhibition rate. RESULTS: Treatment with PNS concentration-dependently inhibited the proliferation and significantly promoted apoptosis of cultured H₂₂ cells (P < 0.01). In the tumor-bearing mouse models, PNS alone and its combination with CTX both resulted in obvious enhancement of phagocytosis of the monocyte-macrophages, stimulated the proliferation of splenic lymphocytes, promoted the release of TNF-α and IL-2 and the production of serum hemolysin antibody, and increased the number of white blood cells, red blood cells and lymphocytes in the peripheral blood. Treatment with 480 mg/kg PNS combined with CTX resulted in a tumor inhibition rate of 83.28% (P < 0.01) and a life prolonging rate of 131.25% in the mouse models (P < 0.05). CONCLUSION PNS alone or in combination with CTX can improve the immunity and tumor inhibition rate and prolong the survival time of H₂₂ tumor-bearing mice.
Animals ; Carcinoma, Hepatocellular/pathology* ; Cyclophosphamide/therapeutic use* ; Hemolysin Proteins ; Heterografts ; Humans ; Interleukin-2 ; Liver Neoplasms/pathology* ; Mice ; Panax notoginseng ; Saponins/therapeutic use* ; Tumor Necrosis Factor-alpha

Objective: To explore the risk factors of low cardiac output syndrome (LCOS) after cardiac valvular surgery in elderly patients with valvular disease complicated with giant left ventricle. Methods: This was a retrospective study. The clinical data of patients over 60 years old with giant left ventricle who underwent cardiac valvular surgery in Henan Provincial People's Hospital (Fuwai Central China Cardiovascular Hospital) from January 2016 to January 2020 were collected in this study. Patients were divided into LCOS group and non-LCOS group. The clinical data, preoperative echocardiographic results and surgical data of all patients were collected. Taking LCOS as dependent variable and statistically significant variables in univariate analysis as independent variable, multivariate logistic regression equation was constructed to identify the risk factors of LCOS after cardiac valvular surgery in elderly patients with valvular disease complicated with giant left ventricle. On the basis of logistic regression, the risk factors of continuous variables were put into the regression model for trend test. Results: A total of 112 patients were included, among whom 76 patients were male, the mean age was (65.3±3.8) years. There were 21 cases in LCOS group and 91 cases in non LCOS group. Univariate analysis showed that age≥70 years, preoperative NYHA cardiac function class Ⅳ, preoperative renal dysfunction, preoperative cerebrovascular disease, preoperative LVEF<40%, blood loss/total blood volume>20%, cardiopulmonary bypass (CPB) time>130 minutes and aortic cross-clamp time>90 minutes all had statistically significant differences between the two groups (all P<0.05). Multivariate logistic regression analysis showed that age≥70 years (OR=5.067, 95%CI 1.320-19.456, P=0.018), preoperative NYHA cardiac function class Ⅳ (OR=3.100, 95%CI 1.026-9.368, P=0.045), renal dysfunction (OR=3.627, 95%CI 1.018-12.926, P=0.047), CPB time>130 minutes (OR=4.539, 95%CI 1.483-13.887, P=0.008) were the independent risk factors of LCOS after cardiac valvular surgery in elderly patients with giant left ventricle. Risk of LCOS was significantly higher in patients aged from 65 to 70 years (OR=1.784, 95%CI 0.581-5.476) and aged 70 years and above (OR=4.400, 95%CI 1.171-16.531) than in patients aged from 60 to 65 years. The trend test results showed that the risk of LCOS increased significantly in proportion with the increase of age (P for trend=0.024). Risk of LCOS was significantly higher in patients with CPB time between 90 and 110 minutes (OR=1.917, 95%CI 0.356-10.322), 110 and 130 minutes (OR=1.437, 95%CI 0.114-18.076) and 130 minutes and above (OR=5.750, 95%CI 1.158-28.551) than in patients with CPB time ≤ 90 minutes (P for trend=0.009). Conclusions: The risk factors of LCOS after cardiac valvular surgery are age≥70 years, preoperative NYHA cardiac function class Ⅳ, renal dysfunction, CPB time>130 minutes in elderly patients with giant left ventricle.
Aged ; Cardiac Output, Low/etiology* ; China ; Female ; Heart Valve Diseases ; Heart Ventricles/diagnostic imaging* ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors

Objective: To evaluate the auditory efficacy and subjective satisfaction of adhesive bone conduction hearing aid in children with unilateral congenital aural atresia (UCAA). Methods: Ten subjects (5 males and 5 females) diagnosed with UCAA with an average age of 8.3 years old (ranged from 5 to 15) were included in Beijing Tongren Hospital, Capital Medical University from January to August 2019. The free sound field hearing threshold, word recognition score in quiet, speech reception threshold in noise and sound localization ability (results were measured by RMS error) tests were performed in unaided and aided situation, respectively. Subjective satisfaction questionnaires were also distributed to subjects. Paired t test and Wilcoxon signed rank test were used as statistical analysis methods. Results: The average hearing threshold in aided condition was improved by (21.9±4.4) dB (t=15.8，P<0.05). Speech recognition abilities were generally improved both under quiet and noise (P<0.05);however, when the binaural summation, squelch and head shadow effects were analyzed respectively, the binaural squelch effect was not statistically improved (P>0.05), while the other effects were improved in aided condition (P<0.05). In sound localization test, there was no significant difference of the RMS error value between the unaided and aided situation (P>0.05). The subjects got high satisfaction rates in three subjective questionnaires. Conclusion: The adhesive bone conduction hearing aid can provide significant audiological benefit for children with UCAA as well as raising the quality of their life.
Adhesives ; Adolescent ; Bone Conduction ; Child ; Child, Preschool ; Female ; Hearing Aids ; Hearing Loss, Conductive ; Humans ; Male ; Speech Perception ; Treatment Outcome

AIM To investigate the effects of asiatic acid (AA) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD)-like motor symptoms in mice and its neuroprotective mechanism.METHODS Forty-five male C57BL/6 mice,except the nine mice in control group,were induced to be the PD models by peritoneal injection of 25 mg/kg MPTP for seven days and then were randomly assigned to model group,low-dose,high-dose AA groups and positive control group.Both the control group and the model group were administered with 0.5％ sodium carboxyl methyl cellulose (CMC-Na) solution,the AA groups were dosed with 12.5 mg/kg and 25 mg/kg AA,respectively,and the positive control group was given 75 mg/kg daily intragastric gavage of levodopa for eleven days.On the twelfth day,behavioral tests were performed.Tyrosine hydroxylase (TH) positive cells in substantia nigra were detected by immunohistochemistry.The mRNA expressions of iNOS,COX-2,TNF-α,IL-1β,and malonaldehyde (MDA) content in midbrain were measured.The levels of IL-1 β and TNF-α in the serum were detected using ELISA kits.RESULTS The mice treated with asiatic acid performed better in behavior tests than those in the model group (P ＜0.05,P ＜0.01).In addition,asiatic acid effectively protected the dopaminergic neurons in the substantia nigra due to upregulated TH expression and increased number of TH positive cells (P ＜ 0.05).The asiatic acid-treated mice had their mRNA expressions of IL-1β,TNF-α,iNOS and COX-2 in midbrain markedly suppressed (P ＜0.05,P ＜0.01),and a significant MDA level decrease in the midbrain tissue as well (P ＜ 0.01).Furthermore,reductions of IL-1 β and TNF-α contents in the serum were observed (P ＜ 0.05,P ＜ 0.01).CONCLUSION Asiatic acid attenuates motor dysfunction and dopaminergic neuronal deficits in PD mice,and the neuroprotective mechanisms may attribute to its anti-oxidative and anti-inflammatory activities.