Objective To study on a new generation of histone deacetylase inhibitor LBH589 on multiple myeloma (MM) resistant cells associated with changes in gene expression,and the mechanism of LBH589 reversal of MM cells' drug resistance.Methods By Western blot analysis,LBH589 (0,20,50 nmol/L) and 50 nmol/L LBH589 combined respectively with dexamethasone of 5 μmol/L at 24 h,expression of histone H4 acetylation and bcl-X gene on MMIR cells were detected.By real-time fluorescence quantitative PCR analysis,LBH589 (0,20,50 nmol/L) and 50 nmol/L LBH589 combined respectively with dexamethasone of 5 μmol/L at 24 h and 48 h,expression of TOSO on MM1R cells were detected.Results Western blot analysis showed that single LBH589 and combined with dexamethasone showed at 24 h the up-regulation on expression of the histone H4 acetylation[(0.205±0.008) ％,(0.346±0.009) ％,(0.580±0.053) ％,(0.986±0.012) ％,F =992.957,P =0.032],while down-regulation on expression of the bcl-X in MM1R cells in a dose-dependent manner[(1.210±0.160) ％,(0.930±0.036) ％,(0.730±0.017) ％,(0.488±0.029) ％,F =56.432,P =0.028].However,the group of single LBH589 was less effective than the combined group (all P ＜ 0.05).Real-time fluorescence quantitative PCR analysis showed single LBH589 and that combined with dexamethasone showed at 24 h and 48 h,the down-regulation on expression of the TOSO in MM1R cells in a dose-dependent manner,24 h specific numerical were (1.00±0.00) ％,(0.55±0.01) ％,(0.47±0.01) ％,(0.38±0.01) ％ (F =1006.344,P =0.041),48 h specific numerical were (1.00±0.00) ％,(0.39±0.04) ％,(0.05±0.01) ％,(0.03±0.00) ％ (F =2383.977,P =0.045),however,the group of single LBH589 was less effective than the combined group (all P ＜ 0.05).Conclusion Histone deacetylase inhibitor LBH589 can recover dexamethasone sensitivity of MM1R through effect the gene expression of bcl-X and TOSO,promot histone acetylation,and inducing cell apoptosis to treat tumor.

Objective To investigate the expression of DNA methylation related protein enhancer of zeste homolog 2 (EZH2) in multiple myeloma (MM) cell line U266 and enriched MM cells (MM-BMMNC) from 10 patients,and analyze the potential role of DNA methylation in the occurrence and development of MM.Methods Human MM cell line U266 and MM cells from 10 MM patients were studied.Enriched bone marrow mononuclear cells (N-BMMNC) from 10 healthy persons were used as the control.The expression of EZH2 were determined by Western blot using the ratio of target protein EZH2 and the internal reference β-actin expression as the final results.Results The preliminary in vitro results showed that EZH2 expression was higher in MM cell line U266 and patient MM-BMMNC (N-BMMNC 0.2277±0.1306,MM-BMMNC 0.9220±0.1301,U266 0.9730±0.1029),with statistically significant differences (P ＜ 0.05).Conclusion EZH2 is enriched in U266 and MM-BMMNC.DNA methylation may have a close correlation with the occurrence and development of MM.

Objective To study the inner diameter and hemodynamics of ophthalmic artery(OA)and central retinal artery(CRA)in hyperuricemia by Enhance-flow(eFlow)imaging and spectral Doppler.Methods One hundred and one patients with hyperuricemia and 30 volunteers were selected,the inner diameter in eFlow imaging and the peak systolic velocities(PSV),the end diastolic velocities(EDV),the resistive index(RI)were measured,and pulsatility index(PI)of OA and CRA were measured by spectral Doppler.The 101 patients were divided into two groups according to the time of diagnosing hyperuricemia,one group had a diagnosis of hyperuricemia for more than five years and the other had such a diagnosis for less than five years.The data were compared by t-test.Then,the patients were further divided into a group of hyperuricemia combined with hypertension and the other without hypertension.The differences between the experimental group and the group of volunteers were carried out by One-way ANOVA,the comparison between two groups were analyzed with SNK.Results The RI(0.68±0.09)and PI(1.3±0.4)of OA in patients who were diagnosed as hyperuricemia for more than 5 years was higher[RI:0.63±0.09,PI:1.1±0.3(t=3.504,P=0.001 ;t=3.164,P=0.002)],the EDV[(6±3)cm/s]of OA was lower than those patients with a diagnosis of hyperuricemia for less than 5 years[(8±5)cm/s,t=1.988,P=0.049].The PSV[(11.5±3.5)cm/s]and EDV[(3.7±1.1)cm/s]of CRA in hyperuricemia combination hypertension group was lower,and the RI (0.88±1.40)was higher than hyperuricemia without hypertension group[PSV:(13.5±4.0)cm/s,EDV:(4.1±1.2)cm/s,RI:0.67±0.08].Conclusion By eFlow and spectral Doppler,we have found that hyperu-ricemia could accelerate OA and CRA atherosclerosis.The eFlow and spectral Doppler are valuable methods to study the hemodynamics in ophthalmic artery of patients with hyperuricemia.

OBJECTIVETo explore the impact of a new generation of histone deacetylase inhibitor LBH589 alone or in combination with proteasome inhibitor bortezomib on multiple myeloma (MM) cells proliferation and its mechanism.

METHODSMM cell line U266 and dexamethasone resistant cell line MM1R cells were treated with different concentrations of LBH589 alone or in combination with bortezomib, the inhibition of cells proliferation was detected by MTT, the cell cycle and apoptosis by flow cytometry. The expression level of histone H4 acetylation and PARP, Bcl-X protein was analyzed by western blot, expression level of caspase-3, APAF-1 and TOSO gene by real-time fluorescence quantitative PCR.

RESULTSU266 and MM1R cell proliferation were inhibited by different concentrations of LBH589 (0, 10, 20, 50 nmol/L) alone or 50 nmol/L of LBH589 in combination with bortezomib (10, 20 nmol/L) in a dose- and time-dependent manner. Inhibition effect was significantly higher in all combinative groups than in single agent groups (all P < 0.05). The percentage of G(0)/G(1) phase in MM1R cells were 36.60%, 46.50%, 51.40%, 57.10%, 75.48%, 79.73%, respectively, and the apoptosis rate were 5.27%, 31.41%, 39.78%, 44.07%, 73.60%, 83.27%, respectively. The effects appeared to occur in a dose-dependent manner, and being significantly higher in all combinative groups than in single agent groups (all P < 0.05). The expression of the caspase-3 and APAF-1 gene up-regulated gradually, while TOSO gene expression in MM1R cells down-regulated gradually in a dose- and time-dependent manner (all P < 0.05).

CONCLUSIONSLBH589 can inhibit the growth of MM cells, block the cell cycle and induce cell apoptosis, which has anti-resistant effect on multidrug resistant cell. At the same time LBH589 in combination with bortezomib on myeloma cell has a synergistic effect, its mechanism and reversal of drug resistance mechanism involves in multiple changes in gene expression.

Acetylation ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Line, Tumor ; Cell Proliferation ; Drug Resistance, Neoplasm ; drug effects ; Drug Synergism ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; Hydroxamic Acids ; pharmacology ; Indoles ; pharmacology ; Multiple Myeloma ; pathology ; Pyrazines ; pharmacology

OBJECTIVETo study topiramate's new functions according to the medicinal property combinations, in order to apply the traditional Chinese medicinal theory in discovering new purposes of old drugs.

METHODAccording to New Traditional Chinese Medicinal Families--Chemical Traditional Chinese Medicines, the authors found out topiramate's property. Then based on the therapeutic principle of diabetes, hypertension, epilepsy and lung cancer, as well as the relations of efficacies and medicinal property combinations, they summarized the corresponding medicinal property combination modes, compared topiramate's medicinal property combination mode with corresponding medicinal property combination modes of these diseases, and predict topiramate's new functions.

RESULTAccording to the comparison, the corresponding medicinal property combinations were consistent with topiramate's medicinal property combinations as evidenced by corresponding literatures, whereas other medicinal property combinations were not.

CONCLUSIONBased on medicinal property combination modes, the authors screened topiramate's new functions according to e of TCM clinical experience, discovered topiramate's therapeutic effects on diabetes, hypertension and lung cancer in addition to epilepsy, and explore new drug function according to medicinal property combination modes, which could help greatly shorten the new drug R&D period.

Diabetes Mellitus ; drug therapy ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; chemistry ; therapeutic use ; Fructose ; analogs & derivatives ; chemistry ; therapeutic use ; Humans ; Hypertension ; drug therapy ; Lung Neoplasms ; drug therapy ; Phytotherapy

OBJECTIVE:To systematically review the efficacy of agomelatine in the treatment of depression in acute phase, and provide evidence-based reference for the clinical treatment. METHODS:Retrieved from Cochrane Library,Medline,EMBase, CJFD,VIP,CBM,Wanfang Database,WHO Clinical Trials Registry Platform and American Clinical Trials Registry Platform, the randomized controlled trials (RCT) about agomelatine versus placebo in the depression patients in acute phase. After quality evaluation and data extraction,Meta-analysis was conducted by using Rev Man 5.2 statistics software. RESULTS:A total of 7 RCT were included,involving 2 378 patients. Results of Meta-analysis showed the effective rate in agomelatine group was obviously bet-ter than placebo group [RR=1.43 ,95%CI(1.29 ,1.59),P<0.001] ,remission rate was obviously better than placebo group [RR=1.27 ,95%CI(1.03 ,1.57),P=0.02] ,and the endpoint score of depression scales was obviously lower than placebo group [MD=-2.92,95%CI(-3.65,-2.20),P<0.001],there was statistically significance. CONCLUSIONS:Agomelatine is effective in the treatment of depression patients in acute phase. However,due to the limit of methodological quality and sample size,it remains to be further verified with more rigorously designed and long-term follow-up of large-scale RCT.

This article introduces the definition, classification, premarket admission and other administering specialities about In-Vitro Diagnostic Reagents in the U.S.A. and China. And by analyzing manufacture and administration of In-Vitro Diagnostic Reagents in our country, It is pointed out that a suitable administering model in accordance with the characteristics of In-Vitro Diagnostic Reagents should be adopted to perfect the administration.
China ; Device Approval ; Indicators and Reagents ; classification ; standards ; Quality Control ; Reagent Kits, Diagnostic ; classification ; standards ; United States ; United States Food and Drug Administration

This article makes a pilot study on the key points of the quality management system of in-vitro diagnostic reagents by analyzing the technical characteristics and production methods of these products as well as the status in quo, and problems the in-vitro diagnostic reagent industry in China is facing nowadays. It can serve as a reference to the supervision departments and the manufacturers in this field which are establishing and running the quality management system.
China ; Equipment and Supplies ; standards ; Humans ; Indicators and Reagents ; chemistry ; standards ; Pilot Projects ; Quality Assurance, Health Care ; organization & administration ; Quality Control ; Reagent Kits, Diagnostic ; standards ; Safety Management ; Technology, Pharmaceutical ; organization & administration ; standards ; Total Quality Management

OBJECTIVETo investigate the prevalence rate and risk factors for asthma in children from the Futian District of Shenzhen, China who were aged from 0-14 years between 2010 and 2011, and to provide scientific evidence for the prevention and treatment of childhood asthma.

METHODSA multistage stratified cluster sampling survey of 7168 children aged 0-14 years from the Futian District of Shenzhen was conducted using the Third National Childhood Asthma Epidemiological Questionnaire 2010, to investigate the prevalence rate of childhood asthma. A case-control study (1∶1) and logistic regression analysis were used to investigate the risk factors for childhood asthma.

RESULTSOf the 7168 children surveyed, 169 were diagnosed with asthma, with a total prevalence rate of 2.36%. The prevalence rate was higher in males than in females (3.06% vs 1.55%, P<0.01). Of the 169 cases, 115 (68.1%) had their first asthma attack before the age of 3 years, 95 (56.2%) had moderate attacks, 159 (94.1%) had sudden attacks, 86 (50.9%) suffered from asthma during periods of seasonal change, 97 (57.4%) had attacks before going to bed, 157 (92.9%) suffered from asthma caused by respiratory infection, and 159 (94.1%) had sneezing as the sign of oncoming attack. The case-control study (including the 169 asthma cases and 169 healthy children) and logistic regression analysis both showed that the independent risk factors for asthma in children were a personal history of drug allergy (OR=3.431, 95%CI: 1.240-9.496, P=0.018), a history of food allergy (OR=4.043, 95%CI: 1.669-9.795, P= 0.002), allergic rhinitis (OR=9.686, 95%CI: 5.137-18.263, P<0.001), and a family history of allergy (OR=4.059, 95%CI: 2.054-8.018, P<0.001).

CONCLUSIONSThe prevalence rate of asthma was 2.36% in children aged 0-14 years in the Futian District of Shenzhen between 2010 and 2011. The prevalence rate had not increased when compared with the rate in this region 10 years earlier (2.39%). The prevalence rate of childhood asthma is higher in males than in females. Personal history of drug allergy, food allergy, allergic rhinitis and a family history of allergy are the independent risk factors for childhood asthma in this region.

Adolescent ; Asthma ; epidemiology ; etiology ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Infant, Newborn ; Logistic Models ; Male ; Prevalence ; Risk Factors ; Seasons

OBJECTIVETo observe the clinical efficacy of shensong yangxin capsule (SYC) on ventricular premature beat (VPB) differentiated in TCM as palpitation of Qi-yin deficiency syndrome or Xin collateral stagnation syndrome, and cardiovascular autonomic nervous function in patients with coronary heart disease (CHD).

METHODSThe randomized, double-blind, parallel contrast method was adopted, patients were randomly assigned by 3:1 ratio into two groups. One hundred and sixty-five patients in SYC treated group and 56 in the control group (treated with Xinlvning tablet), and the therapeutic course for both groups was 4 weeks.

RESULTSThe clinical efficacy on VPB and in improving TCM syndromes was better in SYC group than that in the control group (P < 0.01). After treatment, the heart rate variability (HRV) and QT dispersion in the two groups were improved in a certain degree. The changes of SDNN, SDANN, SDNN Index and PNN50 in the two groups were significantly different (P < 0.05, P < 0.01), the efficacy in the treated group was superior to that in the control group.

CONCLUSIONSYC has definite effect on VPB and TCM Syndromes, it can obviously meliorate the activity of cardiovascular autonomic nervous system in the patients with CHD.

Adult ; Aged ; Autonomic Nervous System ; drug effects ; physiopathology ; Capsules ; Coronary Disease ; complications ; drug therapy ; Double-Blind Method ; Drug Administration Schedule ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Heart ; innervation ; Humans ; Male ; Middle Aged ; Phytotherapy ; Ventricular Premature Complexes ; drug therapy ; etiology