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Objective To investigate the effects of indirubatin derivative E804 on proliferation and migration of non-small cell lung cancer(NSCLC)A549 cells,and to elucidate the possible mechanism of Nrf2-HO-1/GPX4 pathway.Methods Lung cancer A549 cells were used as the cell model.The proliferation and migration of differ-ent specific inhibitors(Nec-1,CQ,Z-VAD,DFO,Fer-1 and Lip-1)in 0,10 μmol/L E804 and 10 μmol/L E804+groups were observed by MTT and cell scratch assay.The contents of reactive oxygen species(ROS)were de-tected by DCFH-DA fluorescence probe method,the contents of Fe2+were detected by colorimetric method,the contents of reduced glutathione(GSH)were detected by spectrophotometry,and the contents of malondialdehyde(MDA)were detected by micromethod.The expression levels of SLC7A11,Transferrin,GPX4,SLC40A1,Nrf2 and HO-1 were detected by Western blot in cells of 0,2.5,5 and 10 μmol/L E804 groups.Results Compared with the control group(0 μmol/L E804),2.5,5 and 10 μmol/L E804 significantly increased intracellular ROS,Fe2+and MDA levels,and decreased intracellular GSH content(P＜0.01).Meanwhile,the expression levels of SLC7A11,GPX4,SLC40A1,Nrf2 and HO-1 significantly decreased(P＜0.01),and the expression level of Transferrin increased(P＜0.05).Compared with the 10 μmol/L E804 group alone,the apoptosis inhibitor(Z-VAD)group and the ferroptosis inhibitor(DFO,Fer-1 and Lip-1)group could significantly reverse the inhibition of proliferation and migration of A549 cells by 10 μmol/L E804(P＜0.01).Conclution E804 can induce ferrop-tosis and inhibit the proliferation and migration of A549 cells,which may be related to the inhibition of Nrf2-HO-1/GPX4 pathway.
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Objective @#To investigate the relevance between vitamin D receptor ( VDR) gene promoter methylation level and idiopathic hypocitraturia of the Bai nationality in Yunnan province．@*Methods @#Fifteen patients with idiopathic hypocitrouria of the Bai nationality in Yunnan province with double dominant expression (FF type) of single nucleotide polymorphism shot (SNP shot) rs2228570 (Fok Ⅰ ) genotype were selected as the experimental group. Fifteen people of the Bai nationality in Yunnan province with normal content of urinary citric acid were the control group．First，blood samples were taken from both groups．Next，the blood samples were treated with sulfites，RNA products of each sample were obtained by PCR amplification and in vitro transcription of T7 DNA polymerase．Then the corresponding RNA fragments were digested by base-specific enzymes．Finally the degree of methylation at each test site was obtained through the EpiTYPER procedure. @*Results@#In the statistical results of DNA methylation level，the methylation level of VDR Ⅰ fragment experimental group was 4. 136% ( 1. 655% ，5. 152% ) which was higher than 1. 261% (0. 827% ，1. 930% ) in the control group，and the difference was statistically significant (P ＜0. 001) ．Among the 33 CpG sites on VDR Ⅰ fragment，there were significant differences in DNA methylation levels of CPG-5 (F = 8. 831，P = 0. 008) and CpG-8 (F = 16. 155，P = 0. 001) between the experimental group and the control group．@*Conclusion@#The increased methylation level of VDR gene promoter is related with idiopathic hypocitric of the Bai nationality of Yunnan province．And compared with the normal Bai nationality people，the DNA methylation level of VDR gene promoter significantly increased in the Bai nationality patients with FF type of VDR gene SNP shot Fok Ⅰ .
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OBJECTIVE: To investigate the effects of Enalapril maleate folic acid tablets on carotid atherosclerosis in H type hypertension patients with type 2 diabetes mellitus (T2DM) and its potential mechanism.METHODS: In prospective control study, 182 H type hypertension patients with T2DM were selected from Chongqing People's Hospital during Jan. 2014-Jan. 2016, and then randomly divided into observation group and control group, with 91 cases in each group. All patients received basic or hypoglycemic treatment of premixed insulin; observation group was additionally given Enalapril maleate folic acid tablets (containing enalapril maleate 10 mg, folic acid 0. 8 mg in each tablet) orally, one tablet, qd; control group was additionally given Enalapril maleate tablets (containing enalapril maleate 10 mg in each tablet) orally, one tablet, qd. Treatment course lasted for 12 months. The levels of blood pressure, plasma homocysteine (Hcy), fasting blood glucose (FBG), C-reactive protein (CRP) and carotid plaque score were detected in 2 groups before treatment, 12 months after treatment. RESULTS: Compared to before treatment, SBP and DBP of 2 groups were decreased significantly in 2 groups after 12 months of treatment (P<0. 05); there was no statistical significance between 2 groups (P>0. 05). The levels of plasma Hcy, FBG and CRP, carotid intima-media thickness and carotid plaque integral in observation group were significantly lower than control group (P<0. 05). CONCLUSIONS: Enalapril maleate folic acid tablets can relieve inflammation by reducing plasma Hcy, FBG and CRP so as to treat carotid atherosclerosis in H type hypertension patients with T2DM.
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Objective To investigate the association of rs523349(V89L),rs9282858(A49T)and TA repeat polymorphisms in testosterone 5-alpha-reductase Ⅱ(SRD5A2) gene with prostate cancer(PCa) in the population of Yi nationality in Yunnan Province. Methods Sanger sequence detection technique was used to detect rs523349(V89L),rs9282858(A49T)and TA repeat polymorphisms of SRD5A2 gene in 122 subjects with confirmed PCa and 135 age-matched healthy controls in the Yunnan Yi population,then the association of these polymorphisms with prostate cancer was analyzed. Results The AA genotype of rs9282858 site in SRD5A2 gene was not found between the Pca patients and the healthy controls in the Yunnan Yi population. The genotypic and allelic frequency distributions of rs523349 and rs9282858 were not significantly varied between the Pca patients and the controls(P>0.05). But the genotypic and allelic frequency distributions of TA repeat site were significantly varied(P < 0.05). The genotype containing(TA)9 allele was more common in the Pca patients than the healthy controls(P=0.033). Compared with(TA)0 allele subjects,(TA)9 allele subjects had a higher PCa risk(OR=2.181, 95% CI :1.111~4.281,P=0.021). Conclusion The TA repeat polymorphisms of SRD5A2 gene was associated with PCa risk in the Yunnan Yi population,which could be used as a risk factor to screen the high-risk individuals.
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Objective To investigate the efficacy and safety of different strategy of antithrombotic therapy in elderly patients with atrial fibrillation (AF) and coronary disease.Methods 224 inpatients and outpatients with AF and coronary disease whose mean follow-up time was 2 years,were divided into warfarin group,warfarin combined with antiplatelet drug(aspirin or clopidogrel) group,antiplatelet drug(aspirin or clopidogrel) group and control group.The thromboembolic event rate and adverse events incidence were observed in different groups.Results The risk of thromboembolic events,particular emerging risk of cerebral infarction in the control group(12.50 ％) was significantly higher than other groups (P＜ 0.05).Thrombotic event rates in warfarin + single joint group(2.78％) was lower than other groups(warfarin group 4.29 ％,single joint group 5.81％),but there was no significant statistical difference.The overall risk of bleeding in the control group (3.13 ％) was significantly lower than other antithrombotic group (P＜0.05).The incidence of skin bruising in single joint group was lower than other antithrombotic groups,the overall bleeding risk,especially gasfrointestinal bleeding in warfarin+ single joint group was significantly higher than other groups (P＜ 0.05).Conclusion Elderly patients with coronary heart disease and atrial fibrillation need antithrombotic therapy to prevent thrombotic events.Using warfarin alone or warfarin combined antiplatelet drug does not lead to serious bleeding events,but generally bleeding risk should be attracted more attention.
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Objective To studythe efficacy of levosimendan in treating refractory heart failure complicating severe renal in sufficiency.Methods Sixty-seven cases of refractory heart failure complicating severe renal insufficiency in the internal medicine department of our hospital were randomly divided into the levosimendan treatment group(L group,n=33)and dopamine treatment group(D group,n=34).The changes of N-terminal pro-B-type natriuretic peptide(NT-pro-BNP),left ventricular ejection fraction (LVEF)and glomerular filtration rate(GFR)before treatment and on 1,3,7,30 d after treatment were compared between the two groups and analyzed.Results Before the treatment,there were no statistically significant differences in the baseline indicators between the two groups(P＞0.05).The group L:the NT-pro-BNP level on 1,3,7 d after treatment was decreased significantly(P＜ 0.05),LVEF on 3,7 d was significantly increased compared with th baseline(P＜0.05)and GFR on 1,3,7,30 d was significantly increased compared with the baseline(P＜0.05).The group D:the NT-pro-BNP level on 7 d of treatment was significantly decreased(P＜0.05),LVEF on 7 d of treatment was significantly increased compared with the baseline(P＜0.05),and no statistically significant changes were observed in GFR on 1,3,7,30 d(P＞0.05).After treatment,NT-pro-BNP,LVEF and GFR significant level values in the group L were better than those in the group D.Conclusion Levosimendan is superior to dopamine in improving heart and renal function for the patients with refractory heart failure complicating severe renal insufficiency.
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From November 2003 to May 2010, intrathecal drug delivery system (IDDS) was implanted in 18 patients with chronic intractable pain. Analgesia was provided with morphine. Thirteen patients suffered from late stage cancer and 5 from diseases other than cancer. VAS score was used to measure intensity of pain in all 18patients. QLQ-C30 score was used to evaluate quality of life in cancer patients. The patients were followed up for 3-62 months in 5 non-cancer patients. All 13 cancer patients died at 57 days-10 months after operation. VAS scores were significantly decreased and QLQ-C30 scores increased by intrathecal administration of morphine. Side effects developed in all patients to some extent including nausea, vomiting, constipation, urinary retention, pruritus and over-sedation and vanished in a week. Intrathecal catheter was cut while being pulled out of the needle in 1 patient. Two patients developed low intracranial pressure after operation. Cerebrospinal fluid leakage occurred in 1 patient. One patient developed neuropathic pain in the posterolateral side of right leg.
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Seventy-four patients aged 26-63 yr who had suffered cervicogenic headache for 3 months-21 yr were treated with puked radiofrequency applied to C2 dorsal root ganglion, which is located in the middle of the posterior side of lateral atlantoaxial joint. A trochar was introduced percutaneously under the guidance of X-ray aiming at the target point. As it was inserted through the deep fascia, the stylet was withdrawn and a 10 cm long 22 gauge curved blunt electrode was inserted into the trochar and advanced until the patients felt radiating pain from the point of puncture to occiput. Lateral radiograph was obtained to verify the placement of electrode. The tip of the electrode was usually located in front of spinal canal at the atlantoaxial joint level. Sensory stimulation was performed with 50 Hz and 0.1-0.5 V and the patients could feel radiating pain at occiput. Motor stimulation was performed with 2 Hz and 0.4-1.0 V and regular pulsation of the patient's muscle of occiput could occur. Pulsed radiofrequency was applied at 42 ℃7 for 240 s and was performed twice on each side. VAS scores and disturbances of daily activity, mood and sleep were recorded before operation and at 1 week and 1, 3, 6, 12 and 18 months after pulsed radiofrequency treatment. Complications and recurrence within 12 and 18 months were recorded. Follow-up was lost in 22 patients. VAS scores and disturbances of daily activity, mood and sleep significantly decreased after procedure. All of the patients responded without complications like infection, spinal cord and vertebral artery injury. Some patients had transient occipital neuralgia which was usually relieved within 24 h. The recurrence rate in 12 and 18 months after operation was 19% and 31% respectively.
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OBJECTIVE:To observe the effect of intravenous administration of amiodarone on postoperative heart failure and ventricular arrhythmia.METHODS:A total of 42 postoperative heart failure patients with ventricular tachycardia and multi-source ventricular premature beat were treated with lidocaine,but clinical efficacy was not obtained.Those patients received intravenous administration of diluted amiodarome 150 mg.After 30 minutes the dose of amiodarone was kept at 0.5～1.0 mg?min-1,and the total dosage ranged from 1 000 mg to 1 200 mg within 24 h.Clinical symptoms were recorded in every hour,such as cardiac rhythm,heart rate,blood pressure,heart failure.RESULTS:After 24 h of treatment,17 cases of ventricular arrhythmia had apparent effect(40%),20 cases of partial effect(47%),5 cases of no effect(12%),there were statistical significance in difference before and after treatment(P