Objective To investigate the correlation between hepatitis B virus (HBV)drug -resistance gene mutations and hepatocellular carcinoma (HCC).Methods The clinical data of treatment -experienced patients,who underwent examination for HBV drug -resistance gene mutations in Beijing Ditan Hospital from January 1 to December 31,2013,and still had detectable HBV DNA after being treated with nucleos(t)ide analogues,were collected.All the patients were followed up,and the development of HCC was considered as the clinical out-come.The correlation between drug -resistance gene mutations and the development of HCC in patients with HBV infection was analyzed. The chi -square test was used for comparison of categorical between groups,the t -test was used for comparison of continuous data between two groups,and the log -rank test was used for comparison of the incidence of HCC between two groups.Results A total of 227 patients were enrolled in this study.According to the results of the detection of HBV drug -resistance gene mutations,103 patients (103 /227, 45.37%)had no drug -resistance gene mutations and 124 (124 /227,54.63%)had drug -resistance gene mutations.There were no sig-nificant differences between the mutation group and the non -mutation group in HBV DNA load (5.19 ±1.60 log10 IU /ml vs 5.44 ±1.75 log10 IU /ml,t =-1.134,P =0.258)and the percentage of patients with liver cirrhosis (24.19% (30 /124)vs 16.50% (17 /103),χ2 =2.026,P =0.155).The median follow -up was 28 months (range 4 -58 months),and the incidence of HCC was 7.49% (17 /227).A-mong the patients with HBV drug -resistance gene mutations,12 (12 /124,9.68%)developed HCC,and among those without HBV drug-resistance gene mutations,5 (5 /103,4.85%)developed HCC.Among the patients who developed HCC,70.59% (12 /17)had HBV drug -resistance gene mutations at baseline;among the patients who did not develop HCC,53.33% (112 /210)had HBV drug -resistance gene mutations at baseline.Conclusion The patients with poor control of HBV DNA during antiviral therapy have a comparable incidence of HCC to those not treated with antiviral therapy,with a relatively high risk of developing HCC;the treated patients with HBV drug -resist-ance gene mutations may have a higher risk of HCC than those without such mutations,which needs to be confirmed by the studies with a longer follow -up period and a larger sample size.

In the face of escalating problems with pathogen control, the development of proper formulations of existing antibiotics is as important as the development of novel antibiotics. Daptomycin is a lipopeptide antibiotic with potent activity against Gram-positive bacteria. Currently, only injectable solution of daptomycin has been approved for clinical use. In the present study, the formulation of PEGylated liposomal daptomycin (PLD) was prepared and optimized, and its efficacy against methicillin-resistant Staphylococcus aureus (MRSA252) strains was investigated. The obtained PLD had a mean vesicle diameter of (111.5 +/- 15.4) nm and a mean percent drug loading of (5.81 +/- 0.19) % with high storage stability. Potent activity of PLD against MRSA was demonstrated in vitro with a more sustained effect than that of conventional liposomal daptomycin and daptomycin solution. In addition, intravenous administration of a single dose (equal to human use) of PLD significantly increased the survival of mice in a MRSA252 systemic infection model compared with other formulations. Drug distribution in the lung was significantly enhanced following administration of PLD, and no measurable tissue lesions or pathological changes were detected during PLD treatment. Taken together, PEGylated liposomes loaded with daptomycin may represent a promising approach to reduce MRSA252 infections, especially those involving bloodstream dissemination, such as hematogenous pulmonary infection.
Animals ; Anti-Bacterial Agents ; pharmacology ; Daptomycin ; pharmacology ; Liposomes ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; Mice ; Staphylococcal Infections ; drug therapy

OBJECTIVETo investigate the effect of cinobufagin on the proliferation of lens epithelial cells (LECs) and the bcl-2 and bax mRNA expressions of rabbits.

METHODSCultured LECs were treated for 72 h with cinobufagin of different concentrations, the end titer was 0.1 mg/L for low, 0.2 mg/L for moderate and 0.3 mg/L for high concentration, respectively. The inhibitory rate of cinobufagin on LECs' proliferation was detected using MTT method; the mRNA expressions of bcl-2 and bax genes in LECs were examined using reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSProliferation of LECs was inhibited significantly by cinobufagin in a concentration dependent manner, the inhibitory rate was 24.65%, 30.13% and 36.98% respectively for low, moderate and high concentration. With the drug concentration increasing, the mRNA expression levels of the pro-apoptotic bax were increased, whereas those of the anti-apoptotic bcl-2 decreased.

CONCLUSIONCinobufagin can remarkably inhibit the proliferation and induce the apoptosis of LECs in vitro, it might be taken as one of the drugs for the prevention and treatment of after-cataract.

Animals ; Apoptosis ; drug effects ; Bufanolides ; pharmacology ; Cell Proliferation ; drug effects ; Epithelial Cells ; drug effects ; metabolism ; Lens, Crystalline ; cytology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA, Messenger ; genetics ; Rabbits ; bcl-2-Associated X Protein ; metabolism

In this study, we developed a novel liposome-silica hybrid nano-carrier for tumor combination therapy via oral route, using paclitaxel and cyclosporine as a model drug pair. Optimization of the preparation of the drug-loading formulation and characterization of its physicochemical parameters and drug release profile were performed in vitro. Then in vivo pharmacodynamics and pharmacokinetics studies were performed. The results showed that the obtained formulation has a small particle size (mean diameter of 100.2 +/- 15.2 nm), a homogeneous distribution [the polydispersity index was (0.251 +/- 0.018)] and high encapsulation efficiency (90.15 +/- 2.47) % and (80.64 +/- 3.52) % for paclitaxel and cyclosporine respectively with a mild and easy preparation process. A sequential drug release trend of cyclosporine prior to palictaxel was observed. The liposome-silica hybrid nano-carrier showed good biocompatibility in vivo and co-delivery of cyclosporine and paclitaxel significantly enhanced the oral absorption of paclitaxel with improved anti-tumor efficacy, suggesting a promising approach for multi-drug therapy against tumor and other serious diseases via oral route.
ATP-Binding Cassette, Sub-Family B, Member 1 ; antagonists & inhibitors ; Administration, Oral ; Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacokinetics ; pharmacology ; Biological Availability ; Cyclosporine ; administration & dosage ; pharmacokinetics ; pharmacology ; Drug Carriers ; chemistry ; Female ; Liposomes ; chemistry ; Male ; Mice ; Nanoparticles ; Neoplasm Transplantation ; Paclitaxel ; administration & dosage ; pharmacokinetics ; pharmacology ; Particle Size ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sarcoma 180 ; pathology ; Silicon Dioxide ; chemistry ; Tumor Burden ; drug effects

Abstract: Objective　This study aims to explore the prevalence and risk factors of metabolic syndrome (MS) among the adults in Hainan Province, and to provide scientific basis for MS prevention and control. Methods　A multi-stage cluster random sampling method was applied to select 3 690 permanent residents aged 18 years and above in Hainan Province. The survey was conducted by trained investigators using household appointments and centralized surveys. A questionnaire survey, physical measurement, and laboratory examination were conducted after the collection of blood samples. The processed samples were then tested by a quality-controlled laboratory. Finally, we analysed the prevalence of metabolic syndrome (MS) and its relationship with population characteristics and health-related behaviors. Results　The crude prevalence of MS in the population aged 18 and above in Hainan province was 19.46% and the standardized prevalence was 13.21%, with a higher rate in urban areas (22.21%) than in rural areas (18.13%). The prevalence of MS increased with age (P<0.001), and there were significant differences in MS prevalence among different marital and occupational statuses (P<0.01). Logistic regression results indicated that the age groups of 40-<50 years (OR=2.986, 95%CI:1.355-6.580), 50-<60 years (OR=3.739, 95%CI: 1.715-8.151), 60-<70 years (OR=3.890, 95%CI: 1.769-8.556), 70 years and above (OR=3.927, 95%CI: 1.758-8.771), technical, transportation and production personnel (OR=1.579, 95%CI: 1.033-2.412), retired (OR=1.788, 95%CI: 1.415-2.259), unemployed (OR=1.503, 95%CI: 1.044-2.165), smoking cessation (OR=1.582, 95%CI: 1.162-2.154), insufficient intake of fruits and vegetables (OR=1.196, 95%CI: 1.005-1.422), and insufficient physical activity (OR=1.437, 95%CI: 1.155-1.787) were all associated with the prevalence of MS. Among the investigated subjects, 30.22% of them had one abnormal component, with hyperglycemia being the highest (54.44%); 24.25% of them had two abnormal components, with "hyperglycemia + hypertension" being the highest (33.30%); and 19.46% had three or more components, with "overweight/obesity + hyperglycemia + hypertension" being the highest (24.79%). Conclusions　The prevalence of MS in Hainan Province is on the rise, and effective lifestyle intervention measures are needed to reduce the risk of MS.

Cell Line ; Embryonic Stem Cells ; Genetic Vectors ; Green Fluorescent Proteins ; genetics ; Humans ; Lentivirus ; genetics ; Transfection

Objective To compare the efficacy and safety of vitrectomy combined with internal limiting membrane flap and vitrectomy combined with internal limiting membrane peeling for the treatment of idiopathic macular hole with different sizes.Methods A total of 127 consective patients (127 eyes)were divided into two groups according to the size of the hole diameter of the smallest split points by less than or equal to 500 μm (small diameter macular hole group) and more than 500 μm (huge diameter macular hole group).According to different surgical methods the patients were divided into non ILM flap coverage group (peeling 1 group and peeling 2 group) and ILM flap cover group (covering 1 group and covering 2 group).All the patients underwent vitrectomy combined with internal limiting membrane peeling or vitrectomy combined with limiting membrane flap.Preoperative and postoperative best correct visual acuity,closure ratio of macular hole and postoperative major complications were observed and followed up.Results The postoperative best correct visual acuity improved in all the groups,there was no significance difference between small diameter macular hole group and huge diameter macuiar hole group (t =0.112 2,0.750 8;all P ＞0.05).The closure ratio of peeling 1 group and covering 2 group at postoperative 6 months were all 100％,there was no statistical difference (P ＞ 0.05),which in peeling 2 group and covering 2 group were 84.85％ and 100.00％,there was statistical difference (x2 =13.292,P ＜ 0.05).There was no statistical difference in preoperative defect diameter of the inner and outer junction between peeling 2 group and covering 2 groups (P ＞0.05),there was also no statistical difference between peeling 2 group and covering 2 groups at postoperative 1 months (P ＞ 0.05),but there were statistical differences at postoperative 3 months,6 months and 12 months (all P ＜ 0.05),the covering 2 group were less than the peeling 2 group.Conclusion ILM flap coverage helps to heal macular holes greater than 500 μm diameter,and has no extra effect on healing of diameter less than 500 μm.

Adjuvants, Immunologic ; chemistry ; pharmacology ; Anti-Inflammatory Agents, Non-Steroidal ; chemistry ; pharmacology ; Clerodendrum ; chemistry ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Phytotherapy ; Urinary Tract Infections ; drug therapy

AIM: To investigate the effect of Thymosin ? 1 on the development and matutation of thymocytes. METHODS: The proportion of CD4+CD8+ thymocytes and the expression of smoothened (Smo) of the hedgehog (Hh)-signaling in CD4-CD8-thymocytes were examined to observe the effect of thymosin ? 1 on thymocyte development and matutation. RESULTS: Flowcytometric analysis showed that thymosin ? 1 showed activity at a low dose of 30 ?g/kg, and 30 ?g/kg thymosin ? 1 accelerated the replenishment and maturation of thymocytes according to the expression of Smo of the Hh-signaling in CD4-CD8-thymocytes, the potent negative regulator of proliferative responses. CONCLUSION: Thymosin ? 1 can accelerate thymocyte development from CD4-CD8- to CD4+CD8+.

Phthalate esters belong to the group of environmental hormones,which are ubiquitous environmental pollutants and they can damage the human health through breathing to get into the body.The recent researches on the analysis of phthalate esters in the air such as sampling,pretreatment and determination were reviewed and some related issues were discussed in the paper.It would be reference for the further study of phthalate esters.