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Purpose@#Alisol A is a bioactive triterpenoid isolated from the Rhizoma Alismatis. Previous studies have shown that alisol A has anticancer potential. In this study, we explored the effect of alisol A on the growth of nasopharyngeal carcinoma (NPC) cells. @*Materials and Methods@#MTT assay, colony formation assay, flow cytometry, transwell assay, wound healing assay, and western blotting were used to assess cell viability, proliferation, cell cycle, migration, invasion, and protein expression, respectively, in vitro.AutoDock Vina and Discovery Studio software were used for molecular docking. @*Results@#Alisol A inhibited the viability, proliferation, migration, and invasion of NPC cells. The molecular docking simulation assay confirmed that alisol A bound to YAP protein. In addition, alisol A promoted the phosphorylation of YAP and suppressed the expression of YAP in NPC cells. @*Conclusion@#Alisol A inhibited the proliferation, migration, and invasion of NPC cells by inhibiting the Hippo signaling pathway. Alisol A may be a candidate drug for NPC.
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Purpose@#Alisol A is a bioactive triterpenoid isolated from the Rhizoma Alismatis. Previous studies have shown that alisol A has anticancer potential. In this study, we explored the effect of alisol A on the growth of nasopharyngeal carcinoma (NPC) cells. @*Materials and Methods@#MTT assay, colony formation assay, flow cytometry, transwell assay, wound healing assay, and western blotting were used to assess cell viability, proliferation, cell cycle, migration, invasion, and protein expression, respectively, in vitro.AutoDock Vina and Discovery Studio software were used for molecular docking. @*Results@#Alisol A inhibited the viability, proliferation, migration, and invasion of NPC cells. The molecular docking simulation assay confirmed that alisol A bound to YAP protein. In addition, alisol A promoted the phosphorylation of YAP and suppressed the expression of YAP in NPC cells. @*Conclusion@#Alisol A inhibited the proliferation, migration, and invasion of NPC cells by inhibiting the Hippo signaling pathway. Alisol A may be a candidate drug for NPC.
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OBJECTIVES@#To investigate the level and significance of serum γ-glutamyl transferase-to-platelet ratio (GPR) and monocyte count to high-density lipoprotein ratio (MHR) in patients with essential hypertension (EH) and unstable angina (UA).@*METHODS@#A total of 218 patients with coronary angiography aged ≥60 years, who were admitted to the EH hospital of the Department of Cardiac Medicine, Affiliated Hospital of Chengde Medical College, were selected from September 2018 to September 2019. They were divided into an EH+UA group (@*RESULTS@#Compared with the control group, patients in the EH+UA group and the EH group had higher body mass index (BMI), tyiglyceride (TG), GPR, and MHR, and lower high-density lipoprotein-cholesterol (HDL-C) (all @*CONCLUSIONS@#There is a correlation between GPR, MHR and EH combined with UA pectoris, and the combined detection of the two indicators has adjuvant diagnostic value for elderly EH combined with UA.
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Aged , Humans , Angina, Unstable , Cholesterol, HDL , Coronary Angiography , Essential Hypertension , Lipoproteins, HDL , MonocytesABSTRACT
Objective:To investigate the correlation of the gamma-glutamyl transpeptidase to platelet ratio(GPR)and monocyte count to high-density lipoprotein cholesterol(HDL-C)ratio(MHR)with the severity of coronary artery disease in elderly patients with essential hypertension(EH)combined with unstable angina pectoris(UA).Methods:A total of 218 EH patients aged 60 years and over undergoing coronary arteriography admitted to cardiology department of our hospital were enrolled from September 2018 to September 2019.They were divided into the EH plus UA group(n=113)and the simple EH group(n=105)according to whether UA was combined.In addition, 106 patients with normal coronary angiography who were suspected with coronary heart disease were selected as the healthy group.General data of patients between three groups were compared.Severity of coronary artery disease was evaluated using a Gensini score.The correlation of GPR and MHR with coronary Gensini scores was analyzed in the EH plus UA group.Patients in the EH plus UA group were sub-grouped into the single-, double- and triple-vessel disease groups according to the number of disease branches.Differences in coronary Gensini scores, GPR and MHR were compared among subgroups.A receiver operating characteristic(ROC)curve was used to evaluate the auxiliary diagnostic efficacy of GPR, MHR and the combined GPR and MHR in the EH plus UA group.Results:Compared with the healthy group, both EH plus UA group and EH group showed that the BMI(25.8±3.4 kg/m 2, 25.4±3.6 kg/m 2vs.24.2±2.3 kg/m 2), triglyceride(1.9±1.2, 2.0±1.2 vs.1.5±1.1 mmol/L), and MHR(6.6±1.4, 5.8±1.7 vs.4.9±1.7)were increased, and the HDL-C(1.1±0.2 mmol/L, 1.1±0.3 mmol/L vs.1.3±0.3 mmol/L)were reduced( P<0.05), and only EH plus UA group showed that white blood cells(6.7±1.5×10 9/L vs.6.1±1.8×10 9/L), LDL-C(2.3±0.6 mmol/L vs.2.1±0.6 mmol/L)and GPR(0.3±0.1 vs.0.2±0.1)were higher than in the healthy group( P<0.05). Compared with the EH group, the EH plus UA group showed that the GPR(0.3±0.1 vs.0.2±0.1), and MHR(6.6±1.4 vs.5.8±1.7)were increased( P<0.05). The correlation analysis showed that the levels of GPR and MHR were positively correlated with Gensini scores in the EH plus UA group( r=0.537, 0.333, P<0.05), and the correlation was better along with the increased number of diseased branches( P<0.05). The ROC curve analysis showed that GPR had a high specificity and positive predictive value with the specificity of 68.9% and the area under the ROC curve( AUC)of 0.842, while MHR had a high sensitivity with the sensitivity of 92.9%.The combined detection of GPR and MHR had a higher specificity and positive predictive value with a specificity of 84.0% and the AUC of 0.871. Conclusions:The increase of GPR and MHR can be used as a marker to assist the diagnosis of EH combined with UA, and to assess the severity of coronary artery disease in the elderly.
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Objective To study the audiological characteristics of large vestibular aqueduct syndrome (LVAS)and provide evidence for early diagnosis and prevention.Methods Tympanometry,Otoacoustic emission , auditory brainstem response (ABR),auditory steady-state response(ASSR)were performed on the 49 cases of LVAS which were diagnosed by CT scanning from May,2010 to October,2013.Among them,23 cases(46ears)were examined by pure tone andiometry at the same time.ResuIts Pure tone andiometry showed that 33 ears were mixed hearing loss in the 23 cases(46 ears),the air-bone gap was larger at low frequencies than that of at high frequen-cies,15 ears were senserineural hearing loss with no air-bone gap;96 ears were type A tympanogram.Acoustic re-flex were present in 5 ears ;34 cases (68 ears)of LVAS group were detected with ASNR in 3 -4 ms by the ABR testing,the positive rate was 70.8%.ConcIusion Our study indicates that for confirmed LAVS,if the pure tone andiometry shows significant air-bone gaps at low frequencies with the normal tympanograms,and ASNR is e-voked during the routine ABR testing.
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Objective To explore the relationship between adenoid vegetation children with different types of tympanograms and secretory otitis media in children and diagnosis of secretory otitis media .Methods A retrospec-tive study was carried out among 328 cases with adenoid vegetation in children ,including simple adenoid vegetation and associated with chronic tonsillitis and tonsillar hypertrophy ,from August 2010 to May 2012 .The incidence of secretory otitis media and outcomes of tympanometry for the diagnosis were analyzed .Results 104 cases were diag-nosed with secretory otitis media by tympanic membrane puncture or tympanostomy tube in 328 cases with adenoid vegetation (32 .31% );86 cases (147 ears) were finally diagnosed as secretory otitis media among 89 cases (152 ears) with type B tympanogram (147/152 ,96 .63% );16 cases (20 ears) were finally diagnosed secretory otitis media among 33 cases (49 ears) with type C tympanogram (20/49 ,40 .82% );2 cases (2 ears) with type As tympa-nogram were finally diagnosed .Conclusion With or without complaint of hearing loss ,children with adenoid vegeta-tion should be checked by routine tympanometry .Careful physical examinations and electric otoscope or ear endosco-py combined tympanometry can greatly reduce the rate of misdiagnosis of secretory otitis media .
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Objective To investigate the regulatory effects of umbilical cord-derived mesenchymal stem cells (UC -MSCs) on Th17 cells and related cytokines in patients with systemic lupus erythematosus (SLE). Methods Human UC-MSCs were isolated and expanded and infused into fourteen SLE patients. Clinical changes were evaluated before and after transplantation by SLE disease activity index (SLEDAI), 24-hour urine protein, serum albumin and complement C3. The percentages of CD3 +CD8-IL17A + T cells in peripheral blood were detected by flow cytometry. Concentrations of plasma IL-6, TGF-β, IL-17A, IL-22were determined by enzyme-linked immunosorbent assay (ELISA). UC-MSCs and peripheral blood mononindependent samples t-test. Results SLEDAI scores decreased significantly at 3 month (7.8±1.2, t=2.19) and 6 month (6.9±0.9, t=4.2) after UC-MSCs transplantation than pre-transplantation level (10.4±0.9, P0.05).Conclusion UC-MSCs transplantation down-regulates the percentages of CD3+CD8-IL17A+T cells in SLE patients, which may be one of the mechanisms for its therapeutic effect in refractory SLE.
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ObjectiveTo investigate the effect of IκB kinase (IKK-β) on migration and proliferation of bone marrow mesenchymal stem cells(BMSCs) from patients with systemic lupus erythematosus (SLE).MethodsHuman bone marrow aspirates were collected from iliac of six donors and six SLE patients and cultured in vitro.Migration of BMSCs were observed by wound healing and transwell migration assays.Proliferation of BMSCs was quantified by cell counting kit-8 assay.Total RNA was extracted and reverse transcribed into complementary DNA.Real-time PCR technique was used to determine the gene expression of IKK-β at transcription level.The expression of IKK-β and phospho-IKK-β(p-IKK-β) protein were determined by Western blotting analysis.Statistical analysis was conducted with or Mann-Whitney rank test.Results① The migration rate of BMSCs from SLE patients(5.2±3.8)‰ were significantly reduced as compared with normal controls (7.0±2.9)‰(P＜0.05 ).The proliferation of BMSCs of SLE patients (0.21±0.49)was lower than that from healthy controls ( 1.00±0.35 )(P＜0.05 ).②) No difference in IKK-β3 mRNA expression between SLE ( 1.9± 1.4) subjects and normal controls (1.9±2.4) (P＞0.05).IKK-β protein expression of BMSCs from SLE patients (1.41 ±0.19) increased significantly compared with healthy controls (0.93±1.24) (P＜0.05).③ Inhibitor of IKK-β caused a significant increase in cell migration (3.3±1.6)‰ and proliferation (1.13±0.26) of BMSCs from SLE patients compared with untreated cells (2.3±1.1)‰ and (0.81±0.17),respectively (P＜0.05).ConclusionMigration and proliferation of BMSCs are significantly decreased in SLE patients.IKK-β may be involved in migration and proliferation of BMSCs.
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Objective To investigate the effect and mechanism of murine bone marrow mesenchymal stem cells(BM-MSCs)transplantation on B-cell activating factor(BAFF)expression and B cell activation of MRL/Ipr mice.Methods Eighteen female MRL/Ipr mice were divided into the treatment group and the control group.Five female BAL B/C mice were used as negative controls.At the age of 18 weeks,the treatment group was transplanted with 1×10~6 murine BM-MSCs through vena caudalis,the control group was treated with 0.5ml sodium chloride.Enzyme linked immunoserbent assay(ELISA)was used to measure the level of the BAFF,IFN-γ,IL-2 and IL-10 in the serum.The percentage and numbers of Marginal zone,T1 and T2 B cells in spleen were detected by flow cytometry.Results①Eight weeks after transplantation,the level of BAFF [(32±14)ng/ml]in serum of the treatment group decreased significantly than the control group[(47±13)ng/ml](P＜0.05)as well as the level of serum IL- 10,IFN-γ and IL-2 levels[(19±7)vs(40±13)pg/ml](P＜0.01)[(25±20)pg/ml vs(38±25)pg/ml][(73±10)pg/ml vs(80±15)pg/ml].② Eight weeks after trans-plantation,the mice in the treatment group had lower percentages of marginal zone B cells[(15±4)% vs (21±5)%],and the numbers of marginal zone B cells were significantly decreased in the treatment group as compared with the control group[(9±6)×10~6 vs(19±10)×10~6,P＜0.05].③ Eight weeks after transplantation,the mice in the treatment group had lower percentages of T1 and T2 B cells[(3.4±2.1)% vs(7.3±4.0)%][(2.6+1.4)%vs(4.8±2.7)%],and the numbers of T1[(2.7±1.7)×10~6 vs(5.1±2.0)×10~6,P＜0.05]and T2 B cells[(2.0±1.2)×10~6 vs(3.7±1.7)×10~6,P＜0.05]were both significantly decreased in the treatment group as compared with the control group.Conclusion BM-MSCs transplantation decreases the expression of BAFF in association with the diminished production of the pathogenic cytokines IFN-γ and IL-10.Inhibition of BAFF also results in decreased numbers of T1 and T2 B cells and MZ B cells.
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AIM: To explore the role of NO/ inducible nitric oxide synthase (iNOS) in the metabotromi glutamate receptor 2/3C (mGluR2/3) mediated-brain ischemic tolerance induced by cerebral ischemic preconditioning (CIP), and to observe the influences of α-methyl- (4-tetrazolyl- phenyl) glycine (MTPG), an antagonist of mGluR2/3, on the expression of iNOS during the induction of brain ischemic tolerance. METHODS: Thirty-six Sprague-Dawley rats were subjected to four vessel occluding global brain ischemic model. Thionin staining and immunohistochemistry were used for neuropathological evaluation and assay of iNOS expression in the hippocampal CA1 subregion of the rats. RESULTS: In the sham group, weak expression of iNOS was detected. The expression of iNOS in the CIP and CIP+ischemic insult groups were increased significantly compared with that in the sham group. Administration of MTPG via lateral cerebral ventricle 20 min before CIP blocked the up-regulation of iNOS induced by CIP, but had no influence on the pyramidal neuron survival. However, in the MTPG+CIP+ischemic insult group, the expression of iNOS was extremely intensive compared to that in CIP and MTPG+CIP groups. Importantly, this up-regulation was accompanied with obvious delayed neuronal death. CONCLUSION: NO/iNOS pathway plays an important role in the process of mGluR2/3 mediated-brain ischemic tolerance induced by CIP.
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Objective To observe the effects of nose-stuffy continuous positive airway pressure(CPAP)combined with large-dose Mucosolvan on the hyaline membrane disease of newborn(NHMD). Methods Third),divided into three equal parts,by intravenous drop infusion]. According to the results of SpO2 and blood gas analysis,the CPAP setting was adjusted. Before and after the treatment,the SpO2、RR、PaO2、PaCO2、SaO2 of all the children were analyzed. Results Ten children of all(76.9%) were cured,two died,one quitThe SpO2 of the total,at one hour after the treatment,improved significantly(P＜0.001);the RR、PaO2、SaO2 at 24 hours later also improved(P＜0.05). Conclusion The method of nose-stuffy continuous positive airway pressure(CPAP) combined with large-dose Mucosolvan,which had good effects on ameliorating the symptom and improving the gas exchange,is worth used in primary hospitals widely.
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The aim of this study is to investigate the effect and mechanism of angiotensin (Ang) II on E-selectin and vascular cell adhesion molecule-1 (VCAM-1) expression in rat brain microvascular endothelial cells (BMEC) and evaluate the effect of compound EXP-2528, a novel Ang Ⅱ type 1 (AT1) receptor antagonist. The experiment was performed in cultured BMEC of rat. The mRNA and protein expression of E-selectin and VCAM-1 in BMEC was analyzed by RT-PCR and Western blotting, respectively. The results showed that the mRNA and protein expression of E-selectin and VCAM-1 in BMEC were significantly upregulated by 4 h or 18 h exposure to 1×10-7 mol·L-1 Ang Ⅱ. These effects were abolished by pretreatment with the selective AT1 receptor antagonists losartan and compound EXP-2528, but not with the AT2 selective antagonist PD123319. Combining losartan with PD123319 also significantly inhibited Ang Ⅱ-induced E-selectin and VCAM-1 expression in BMEC, but there was no significant difference compared with losartan group. These findings indicated that Ang Ⅱ upregulated E-selectin and VCAM-1 in BMEC by activating AT1 receptor and then involved in the development of cerebrovascular disease.
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Aim To observe the damages induced by hydrogen peroxide in cultured bovine cerebral microvascular endothelial cells (BCMEC) and evaluate the protective effects of hydroxyethylpuerarin on hydrogen peroxide-injured BCMEC. Methods BCMEC were cultured and transferred into modified Eagle medium (MEM). The viability of cells was detected by MTT assay. Cell injury was determined by lactate dehydrogenase (LDH) activity in the extracellular medium. Flow cytometry was employed to observe the occurrence of apoptosis. Morphologic changes of cells were visualized under phase contrast and electron occurrence of apoptosis. Hydroxyethylpuerarin was shown to increase the survival rate and decrease the activity of LDH of BCMEC damaged by hydrogen peroxide. Hydroxyethylpuerarin was also found to protect BCMEC against apoptosis induced by hydrogen peroxide. Conclusion Hydrogen peroxide induces BCMEC injury either by apoptosis or through necrosis. Hydroxyethylpuerarin protects BCMEC against hydrogen peroxide-induced injury in a concentration-dependent manner. Its antioxidant effects might be involved as the mechanism protection.
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BACKGROUND: Metabotropic glutamate receptor(mGluR) is G-protein coupled membrane receptors, which participate in various physiology or pathology process in brain, but how it induce brain ischemic tolerance(BIT)is unclear.OBJECTIVE: To study roles of mGluR2/3 and mGluR1/5 in the BIT induction.DESIGN: Randomized controlled study based on experimental animals.SETTING: Neurological department of provincial hospital and pathophysiological department of basic institute in a university.MATERIALS: The study was conducted at the Pathophysiological Department, Institute of Basic Medicine, Hebei Medical University from May 2002 to May 2003. Totally 64 healthy male SD rats were selected from the Experimental Animal Center of Hebei Medical University. Glial fibrillary acidic protein (GFAP) antibody, MTPG and(s)-4C3HPG were got from Sigma Company.INTERVENTIONS: 4 vessel occlusion(4VO) brain ischemic models in rats stained with thionine staining and GFAP immunohistochemistry staining. were used. Sixty-four rats, of which bilateral vertebral arteries were occluded permanently by electrocautery, were divided into the following 8groups: sham operation group, cerebral ischemic preconditioning(CIP)group, ischemic insult group; BIT group; MTPG + sham operation group;MTPG+BIT group; MTPG+ischemia group and(s) -4C3HPG+BIT coup. All the rats were killed 7 days after the operation or the final ischemic treatment. Cerebral sections were selected and stained with thionine staining and GFAP immunohistochemistry staining.MAIN OUTCOME MEASURE: The changes of the morphologic hippocampal pyramidal cell and GFAP expression of astrocyte.RESULTS: ① The 8 minutes ischemic insult increased the histological grade(HG) in CA1 area, decreased the pyramidal neuronal density(ND)and increased the expression of GFAP significantly( P ＜ 0.05) . ② The above changes were not observed in the BIT group, indicating that the CIP could protect pyramidal neurons against the 8-minute ischemic insult. ③The protective effects of the CIP were blocked by MTPG or(s)-4C3HPG, as manifested by significant increases in HG and decreases in ND in the groups of MTPG + BIT, MTPG + ischemia and(s)-4C3HPG + BIT( P ＜ 0.05).CONCLUSION: MTPG or (s) -4C3HPG could block the induction of BIT induced by CIP, but mGluR2/3 or mGluR1/5 could participate in the induction of BIT by which protect effect of mGluR is further induced.
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OBJECTIVE:To discuss the pathways to enhance core competitiveness by the implementation of the Good Supply Practice(GSP)management in Medicine Chain Drug Stores.METHODS:To analysis from sequentiae several aspects: consummate the quality system,create the brand value and conversion the management philosophy in drug retail trade.RESULTS & CONCLUSIONS:Through the implementation of the GSP to create efficiency with management,create brands with quality and offer best after-sale service and customer service so as to enhance enterprises' core competitiveness.
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AIM: To explore the role of NO in the induction of brain ischemic tolerance (BIT) by observing changes of NOS activity and NO_2-/NO_3- content following a transient cerebral ischemia. METHODS: The rat 4-vessel occluding brain ischemic model was used. 140 male Wistar rats were divided into sham, cerebral ischemic preconditioning (CIP), ischemic insult and CIP+ischemic insult groups. An occlusion of the 4 vessels for 3 min was normally used as CIP, and a relative long one for 10 min was used as ischemic insult. When CIP was followed by ischemic insult, the interval between them was 3 d. The CA1 region of the hippocampus of rats was dissected out at 0 h, 2 h, 16 h, 24 h, 36 h, 72 h and 7 d after the last time of ischemia to assay its NOS activity and NO_2-/NO_3- content. RESULTS: The NOS activity and NO_2-/NO_3- content began to increase at 16 h, peaked at 24 h and decreased to basal level at 36 h of reperfusion after CIP. The duration of the up-regulation of NOS activity and NO_2-/NO_3- content was much shorter than that of BIT, which usually takes place 1-7 d after CIP. The pattern of upregulation of the NOS activity and NO_2-/NO_3- content was similar to the CIP group, but the maximum (24 h) was much more than that in CIP group (P