Objective To evaluate the clinical efficacy of oral Sarpogrelate hydrochloride in the treatment of chronic arterial ischemia of the lower extremities.Methods In this study 892 patients,who suffered from arteriosclerosis (ASO) or thromboangiitis obliterans ( TAO ) or diabetic foot ( DF ),with symptoms of intermittent claudication, sensation of cold, pain, ulcer, and without a history of vasotransplantation or bypass grafting or interventional therapy, were treated by taking Sarpogrelate hydrochloride tablets 100 mg tid for consecutive 8 weeks.The improvement rate of concomitant symptoms and the total effective rate of ASO, TAO, DF were evaluated.Drug adverse reaction were recorded.Results The improvement rate of intermittent claudication,sensation of cold,pain and ulcer were 96.9％,97.1％,89.0％ and 86.9％ respectively.The total effective rate for ASO,TAO,DF was 83.5％.A total of 81 cases (9.1％) reported mild side effects,including 7 patients with mild rash after 2- 5 days' medication,21 patients with mild nausea and 53 patients with stomach discomfort after 1 - 2 days' medication.Symptoms were managed conservatively without discontinuing taking sarpogrelate hydrochloride.Conclusions Sarpogrelate hydrochloride oral is a safe and effective therapy for chronic arterial ischemia diseases of the lower extremities.

BackgroundWith the increasing prevalence of dry eye and the continuous improvement of living standards,the problem of dry eye more and more get the attention of people.At present,China still lacks the large population-based epidemiological data of dry eye. Objective To investigate the prevalence and possible risk factors of dry eye in a community of Huidong County of population aged 14 and over.Methods From September 2010 to January 2011,using questionnaires and examination of dry eye related,2800 people were selected randomly for cross-sectional survey.Those suspected as dry eye were examed by the SchirmerⅠtest ( S Ⅱ T),tear-film breakup time(BUT),corneal fluorescein staining(F1).Results In the 2475 questionnaire effectively,154 persons were diagnosed as dry eye,and the prevalence rate of dry eye was 6.22％,8.06％in females,4.14％in males.The prevalence rate increases with age.The S Ⅰ T and BUT decreased with increasing age.S Ⅰ T and BUT in females are less than males.Foreign body sensation is the primary complaints of patients.Logistic analysis showed that the most common risk factors in dry eye are age and gender.The system disease and eye diseases,eye fatigue and long exposure to dust are also main determinants.ConclusionsThe population prevalence rate of dry eye increased with age,the prevalence rate of dry eye in females is higher than that in males.The key factors associated with dry eye are age,gender,systemic disease and eye diseases,occupation,working environment.

Objective To investigate the mRNA and protein expression levels of interferon(IFN)-?in the peripheral blood of patients with systemic lupus erythematosus(SLE),to analyze the relationship between IFN-?and disease activity,and to evaluate the role of IFN-?in the pathogenesis of lupus.Methods SYBR green dyeⅠbased real-time quantatives PCR method was used to compare the mRNA expression levels of IFN-?in the peripheral blood leucocyte of SLE patients and healthy controls.Surum levels of IFN-?were measured with ELISA method.Results IFNA1 mRNA expression level in SLE patients(2.8?3.5)was signifi- cantly lower than that of normal controls(12.7?10.7,P=0.000).There was no significant difference between patients treated with glucocorticoid and those without in the expression level of IFNA1(P=0.549).Serum levels of IFN-?in SLE patients was significantly higher than that of normal controls(P=0.003).The SLEDAI score and anti-dsDNA antibody correlated positively,and complement components C3,C4 and leukocytes correlated negatively with serum concentration of IFN-?.IFN-?level correlated with the presence of fever and rash. Conclusion The close relationship between IFN-?serum level and disease activity in SLE patients suggests that IFN-?might be of importance in the disease process.

OBJECTIVETo localize susceptibility loci in Chinese systemic lupus erythematosus (SLE) cohort by linkage disequilibrium mapping the genomic interval in human chromosome 16 so as to understand whether the pathogenesis of human SLE is related to chromosome 16.

METHODSFive microsatellite markers in chromosome 16 spanning from 57.79 cM to 65.1 cM were used for fluorescence based genotyping in 157 SLE families. Evidence for linkage disequilibrium was assessed using the extended transmission disequilibrium test (ETDT) program and Genehunter software. Susceptibility gene was searched in the positive locus, and real-time PCR method was used to detect gene expression.

RESULTSWith the ETDT, evidence for linkage disequilibrium of the marker D16S409 (P=0.0278) and D16S517 (P<0.0001) with SLE were found. It was observed that 271 bp allele of D16S517 was much in evidence for preferential transmission, while 277 bp allele was found to be transmitted less often than expected. Genehunter analysis is concordant with ETDT. By real-time PCR, OAZ(OLF1/ EBF-associated zinc finger protein) gene which is located in the positive locus showed higher expression in SLE patients than in normal controls.

CONCLUSIONResults reveal that 16q12 (58.46 cM) is associated with Chinese SLE. OAZ is a likely susceptibility gene in this locus for SLE.

Adolescent ; Adult ; Alleles ; China ; Chromosomes, Human, Pair 16 ; genetics ; Cohort Studies ; DNA ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; genetics ; Humans ; Linkage Disequilibrium ; Lupus Erythematosus, Systemic ; genetics ; Male ; Microsatellite Repeats ; Middle Aged

Animals ; Antibodies, Bacterial ; blood ; Bacterial Proteins ; genetics ; immunology ; Brucella Vaccine ; immunology ; Brucella abortus ; immunology ; Female ; Immunization ; Interferon-gamma ; biosynthesis ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C ; Periplasmic Binding Proteins ; genetics ; immunology ; Ribosomal Proteins ; genetics ; immunology ; Vaccines, DNA ; immunology

To research the effect of Ginseng Radix et Rhizoma and Aconiti Lateralis Radix Praeparata compatibility on cardiac toxicity in rats by UPLC-Q-TOF/MS, and explore the endogenous markers and molecule mechanism. Different compatibility of Shenfu decoction were given to male Wistar rats at dosage of 20 g · kg(-1) for 7 days, collected the serum, and analyze the endogenous metabolites effected by Shenfu formulation by principal component analysis and partial least-squares analysis. Results showed that content of glutathione, phosphatidylcholine and citric acid decreased in mixed-decoction group, while ascorbic acid, uric acid, D-galactose, tryptophan, L-phenylalanine increased. The results showed cardiac toxicity of Aconiti Lateralis Radix Praeparata in Shenfu mixed-decoction. Shenfu co-decoction group showed a similar or weaker trend compared with control group, but most of them do not have a statistically significant. The results indicated the scientific basis of Shenfu compatibility by comparison of co-decoction group with mixed-decoction group. Shenfu compatibility can reduce cardiac toxicity induced by Aconiti Lateralis Radix Praeparata, and citric acid, glutathione, phosphatidyl choline, uric acid might be regarded as potential markers of cardiotoxicity.
Animals ; Biomarkers ; Cardiotoxicity ; Drugs, Chinese Herbal ; toxicity ; Glutathione ; blood ; Least-Squares Analysis ; Male ; Metabolomics ; methods ; Principal Component Analysis ; Rats ; Rats, Wistar

Objective To explore the effects and mechanism of gambogic acid ( GA) on lipopolysaccharide ( LPS)-induced acute lung injury ( ALI) .Methods ALI model was established by the injection of lipopolysaccharide into the tail vein of mice(4mg/kg, iv).The mice were randomly divided into control group (control), model group (model), GA group(GA), and pretreatment with GA of ALI group (GA+LPS).After six hours, the wet/dry weight ratio ( W/D) of the lung, myeloperoxidase ( MPO) activity in lung tissue , total proteins and number of white blood cells in bronchoalveolar lavage fluid ( BALF) were determined .Tumor necrosis factor-α( TNF-α) and interleukin-1β( IL-1β) were measured by the enzyme-linked immunosorbent assay methods .Results Compared with control group, the wet/dry weight ratio (W/D) of the lung, MPO activity in lung tissue, levels of total pro-teins and number of white blood cells in BALF of LPS group obviously increased , in addition the level of lung tissue TNF-αand IL-1βin LPS group were significantly higher (all P<0.01), while in GA pretreatment groups alleviated all the changes in ALI mice .Conclusions GA pre-treatment attenuated LPS-induced ALI , possibly by inhibiting inflammatory cytokines production so as to decrease the recruitment of neutrophils , reduce pulmonary edema .

BACKGROUNDLiver targeting drug delivery systems can improve the curative effects and relieve the cytotoxicity of the chemotherapy drugs in the treatment of liver diseases. Nanoparticles carrying therapeutic drugs are currently under hot investigation with great clinical significance. This study was aimed to investigate the different tissue distribution of the adriamycin polybutylcyanoacrylate nanoparticle (ADM-PBCA-NP) in the mice body after an injection via lateral tail vein, and to study the liver targeting effects of ADM-PBCA-NP in different diameters on normal mice liver.

METHODSOne hundred and eighty Kunming mice were randomly divided into 6 groups with 30 mice in each group (5 treatment groups of ADM-PBCA-NP in the different diameter ranges, non-conjugated free adriamycin injection was employed as the control group). A single dose of either conjugated or free adriamycin equaled 2 mg/kg of body weight was delivered via the tail vein. Five mice in each trail were sacrificed at 5, 15, 30 minutes, 1, 5 and 12 hours postinjection, respectively. The adriamycin concentrations in the respectively collected liver, kidney, spleen, heart, lung and plasma were demonstrated using a high performance liquid chromatography with fluorescence detector.

RESULTSCompared with the control group, adriamycin was hardly detected in the heart muscle of the treatment groups (P < 0.05). The nanoparticle-conjugated adriamycin was cleaned up quickly from the kidney tissue. The adriamycin concentrations of the mice liver and spleen in the experimental groups were significantly higher than that in the control group, except for the group with the nanoparticles diameters of (22.3 +/- 6.2) nm (P < 0.05). The ADM-PBCA-NP in (101.0 +/- 20.3) nm diameter had the highest liver distribution, and the second highest adriamycin distribution in liver was the group of (143.0 +/- 23.5) nm diameter (P < 0.05). Moreover, adriamycin was released slowly in the liver during the detection period in the experimental groups. ADM-PBCA-NP in (22.3 +/- 6.2) nm diameter was not distributed in the tissue of the liver, kidney, heart, spleen, and lung.

CONCLUSIONSADM-PBCA-NP in 100 - 150 nm diameter range has the best liver targeting with a characteristic of slow medicine release. It also decreases the medicine distribution in the heart, kidney and lung. In the treatment of liver cancer, the polybutylcyanoacrylate nanoparticles system has a good liver targeting ability, which increases the anticancer activity and markedly decreases the toxicity of adriamycin.

Animals ; Antineoplastic Agents ; administration & dosage ; Doxorubicin ; administration & dosage ; Drug Delivery Systems ; Enbucrilate ; administration & dosage ; Liver ; metabolism ; Mice ; Nanostructures ; Tissue Distribution

OBJECTIVESTo investigate role of hypoxia inducible factor 1 (HIF-1) in the transcriptional activation of heat shock protein 70-2 (HSP70-2) in hepatocellular carcinoma (HCC) cells under hypoxic conditions.

METHODSHCC cells were exposed to reduced oxygen atmosphere (1% O2), or treated with YC-1 or HIF-1 alpha siRNA, the expression of HIF-1 alpha and HSP70-2 were detected by Western blot analysis. Serial deletions of the HSPA2 promoter were cloned in the reporter pGL3-Basic plasmid. These reporter plasmids were co-transfected with HIF-1 alpha siRNA, and the promoter activities were detected with the dual luciferase assay.

RESULTSWestern blot analysis showed that both HIF-1 alpha and HSP70-2 proteins were strongly increased after HCC cells were exposed to hypoxic conditions (1% O2) for 6 h, and the expression level of HSP70-2 was increased in a time-dependent manner. Treatment of HepG2 cells with YC-1 or HIF-1 alpha siRNA significantly inhibited the expression of HIF-1 alpha and HSP70-2. In silico analysis of the HSP70-2 promoter using the Gene2 Promoter software revealed the presence of two putative hypoxic response element (HRE) consensus at -446bp (HRE1) and -238bp (HRE2). Depletion of promoter sequence between -653 and -385 led to a dramatic reduction of promoter activity, whereas further deletion to position -201 did not reduce the activity further. These data suggested that HRE1 plays an important role in hypoxia-induced activation of the HSPA2 promoter. Site-directed mutagenesis further confirmed these results. Mutation of HRE1 but not of HRE2 abrogated the sensitivity of the HSP70-2 promoter to hypoxia.

CONCLUSIONSHSP70-2 expression is up-regulated in response to hypoxia and a HIF-1 binding site (HRE1) in the HSP70-2 promoter is involved in this response.

Base Sequence ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Hypoxia ; Gene Expression Regulation, Neoplastic ; HSP70 Heat-Shock Proteins ; genetics ; metabolism ; Hep G2 Cells ; Humans ; Hypoxia-Inducible Factor 1 ; genetics ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; antagonists & inhibitors ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; Molecular Sequence Data ; Plasmids ; genetics ; Promoter Regions, Genetic ; RNA, Small Interfering ; genetics ; Transfection ; Up-Regulation

OBJECTIVEThis study aimed to assess the clinical significance of intrahepatic hepatitis B core antigen (HBcAg) (+) in patients with chronic hepatitis B (CHB).

METHODS200 CHB patients were prospectively studied using fluorescence quantitative PCR (FQ-PCR), combined PCR with fluorescence probe hybridization technique, to determine serum HBV DNA. Serum HBeAg was measured quantitatively. Liver biopsies were performed and immunohistochemistry stained liver slides were examined in all the cases. Correlation analyses were performed.

RESULTSBased on the HBV DNA levels, the patients were divided into 5 groups: group A (<3 log10 copies/ml) n=20, group B (>or=3 log10 copies/ml-<5 log10 copies/ml) n=13, group C (>or=5 log10 copies/ml-<6 log10 copies/ml) n=24, group D (>or=6 log10 copies/ml-<8 log10 copies/ml) n=116, and group E (>or=8 log10 copies/ml) n=27, and 87.5% of the CHB patients were intrahepatic HBcAg (+). The rate of HBcAg (+) was 55.0% (11/20) in group A, 53.8% (7/13) in group B, 75.0% (19/24) in group C, 96.6% (112/116) in group D, and 100% (27/27) in group E. A strong correlation was found between the rate of HBcAg (+) and the level of serum HBV DNA (r=0.80). This type of association also appeared between serum HBV DNA levels and HBeAg (+) (r=0.47). Of 20 CHB patients who were serum HBV DNA negative, 25% (5) were HBeAg (+), and 55% (11) were HBcAg (+), whereas 15 patients were both HBV DNA (-) and HBeAg (-), and 46.7% (7) were HBcAg (+).

CONCLUSIONSIntrahepatic HBcAg (+) in CHB patients might be more reliable in reflecting HBV replication. Determination of HBcAg (+) may have clinical significance for evaluating the efficacy of antiviral therapy and for predicting the therapeutic responses to different antiviral agents.

Adult ; DNA, Viral ; blood ; Female ; Hepatitis B Core Antigens ; analysis ; Hepatitis B virus ; immunology ; physiology ; Hepatitis B, Chronic ; immunology ; virology ; Humans ; Liver ; virology ; Male ; Virus Replication ; Young Adult