Mitochondrial targeting function of norcantharidin TPP-PEG-PCL nanomicelles promotes apoptosis of liver tumor cells / 中草药

Objective: To prepare norcantharidin TPP-PEG-PCL nanomicelles and study its release in vitro, intracellular transport and promoting effect on hepatoma cell apoptosis. Methods: Thin film hydration method was used to prepare norcantharidin TPP-PEG-PCL nanomicelles, and the particle size, electric potential and microscopic electron microscopy morphological analysis were measured. At the same time, the nanomicelles were evaluated for stability, in vitro release, pharmacokinetics and critical micelle concentration. Coumarin-6 was used as a fluorescent probe to evaluate the uptake of TPP-PEG-PCL nanomicelles in liver tumor cells, lysosomal escape and mitochondrial targeting function; Under the same dosage conditions, the effect of norcantharidin TPP-PEG-PCL nanomicelles on promoting apoptosis of liver tumor cells was evaluated. Results: The cantharidin TPP-PEG-PCL nanomicelles had a particle size of (16.8 ± 0.2) nm, a Zeta potential of (14.3 ± 0.2) mV, and transmission electron microscopy images showed that nanomicelles had a regular spherical shape. The fluorescence test results showed that TPP-PEG-PCL nanomicelles can promote the cellular uptake of drugs, escape lysosomal capture, and finally target aggregation at the mitochondrial site; Cell survival rate and Hoechst staining results showed that cantharidin TPP-PEG-PCL nanomicelles had a good effect on promoting apoptosis of liver tumor cells. Norcantharidin TPP-PEG-PCL nanomicelles can significantly reduce mitochondrial membrane potential, increase intracellular ROS levels, increase pro-apoptotic protein Bcl-2, and reduce resistance. The expression of apoptotic proteins Bax and these pro-apoptotic related experimental results are significantly better than those of norcantharidin PEG-PCL nanomicelles and norcantharidin, which have statistical significance. Conclusion: Norcantharidin TPP-PEG-PCL nanomicelles have good liver tumor cell mitochondrial targeting and promote tumor cell apoptosis, and it is a potentially effective drug delivery system for targeting tumor cell mitochondria.

Molecular mechanism of indirubin-3'-monoxime and Matrine in the reversal of paclitaxel resistance in NCI-H520/TAX25 cell line / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Multidrug resistance (MDR) is a main reason for paclitaxel (TAX) treatment failure. Indirubin-3'-monoxime (IRO) and Matrine are traditional Chinese medicines, which may reverse the resistance of tumor cells to some chemotherapy drugs, but the relationship between paclitaxel resistance and Matrine is still unclear. The aim of this study was to explore the potential molecular mechanism of IRO and Matrine in reversal of TAX resistance.</p><p><b>METHODS</b>In this study, MTT assay was used to measure the non-cytotoxic dosage of IRO and Matrine on NCI-H520/TAX25 cells and determine the reversal extent of TAX resistance under non-toxic doses. In addition, RT-PCR and Western blotting were used to evaluate the mRNA expression and the protein level of survivin, Oct-4, and Sox-2 in NCI-H520/TAX25 cells using semi-quantitative methods.</p><p><b>RESULTS</b>There was no obvious inhibition on sensitive cell strains and drug-resistant strains, when the final concentration was at lest 4 µmol/L for IRO and 100 µmol/L for Matrine. So 4 µmol/L of IRO and 100 µmol/L of Matrine were considered as the reversal dosage. When 4 µmol/L of IRO or 100 µmol/L of Matrine were used together with TAX, the sensitivity to TAX increased evidently in NCI-H520/TAX2 cells; the reversal rate of IRO and Matrine was about 1.92 (43.56/22.6 nmol/L) and 1.74 (43.56/25.0 nmol/L), respectively. The mRNA expression and the protein level of survivin, Oct-4, and Sox-2 in NCI-H520/TAX25 decreased significantly (P < 0.05) after addition of IRO or Matrine in TAX treatment, compared to that of TAX treatment alone.</p><p><b>CONCLUSION</b>The decrease in both mRNA expression and protein level of survivin, Oct-4, and Sox-2 might be the molecular mechanism, by which IRO and Matrine mediate the reversal of TAX resistance.</p>

Prevalence of hepatitis B in Chaoyang district, Beijing in 2010 / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the prevalence of hepatitis B infections and carrier status among general population in Chaoyang district, Beijing in 2010.</p><p><b>METHODS</b>From May to December 2010, 14 491 subjects over 12 months old were selected by multistage random cluster sampling method from residents in Chaoyang district, Beijing. Five millilitre venous blood specimens were collected from these subjects to test hepatitis B virus antigens and antibodies. Status of hepatitis B infections were analyzed in different age, sex and registered permanent residence groups.</p><p><b>RESULTS</b>The overall positive rate of surface antigen (HBsAg) was 2.66% (383/14 410). The lowest rate of 0.56% (9/1603) was found in the 1 to 14 years old group and the 35 to 44 years old group had the highest rate of 4.27% (92/2154). The rate in subjects younger than 24 years old was 1.03% (31/2986). The overall positive rate of surface antibody (anti-HBs) was 40.21% (5798/14 421). The highest positive rate of anti-HBs (80.59%, 407/505) was found in the 1 to 4 years old group. The overall positive rate of core antibody (anti-HBc) was 30.26% (4364/14 424). The overall hepatitis B virus infection rate was 30.32% (4364/14 393). For male and female groups, the positive rates of HBsAg were 2.93% (179/6108) and 2.44% (202/8287) respectively (χ² = 3.32, P > 0.05); anti-HBs were 41.93% (2563/6113) and 38.96% (3231/8293) respectively (χ² = 12.88, P < 0.01); and anti-HBc were 31.39% (1919/6114) and 29.39% (2438/8295) respectively (χ² = 6.65, P = 0.01). For local residents group and mobile population group, the positive rates of HBsAg were 2.46% (283/11 510) and 3.60% (98/2719) respectively (χ² = 11.08, P < 0.01); anti-HBs were 37.11% (4293/11 568) and 53.07% (1445/2723) respectively (χ² = 233.51, P < 0.01); and anti-HBc were 30.83% (3567/11 570), and 28.41% (774/2724) respectively (χ² = 6.08, P < 0.05).</p><p><b>CONCLUSION</b>The positive rate of HBsAg in population younger than 24 years old has reached a relatively low level. The mobile population has significantly higher positive rate of HBsAg than local residents, indicating the need for enhancing prevention and control measures for hepatitis B for the mobile population and local residents over 25 years old.</p>

Association between polymorphisms of insulin-like growth factor receptor gene and susceptibility to non-small-cell lung cancer in Fujian Chinese / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between polymorphisms of insulin-like growth factor receptor (IGF-1R and IGF-2R) and genetic susceptibility and non-small-cell lung cancer (NSCLC).</p><p><b>METHODS</b>A case-control study of 260 patients with NSCLC and 258 cancer-free subjects from Fujian was carried out. Genotypes of polymorphisms of IGF-1R +1013 and IGF-2R +1619 were determined by DNA sequencing and polymerase chain reaction-restrictive fragment length polymorphism.</p><p><b>RESULTS</b>(1) Significant differences in allele frequency and genotypes distribution of IGF-1R +1013 (G/A) were found between the two groups (P<0.05). On multivariate analysis after controlling age and gender, compared with GG genotype of the IGF-1R +1013 (G/A), the risk of lung cancer for individuals with GA genotype was increased by 0.80 times (95%CI: 1.24-2.59, P = 0.002), those with AA genotype was increased by 2.56 times (95%CI: 1.78-7.26, P = 0.000), and those with the polymorphic A variant (GA or AA) was increased by 0.98 times (95%CI: 1.39-2.83, P = 0.000). No significant differences in genotypic or allelic frequencies of IGF-2R +1619 (G/A) were found between the two groups (P> 0.05). (2) After stratification of the clinical status, the IGF-1R +1013 A allele increased the risk of lung squamous cell carcinoma (OR = 3.20, 95%CI: 1.75-5.84, P = 0.000), lung adenocarcinoma (OR = 1.55, 95%CI: 1.00-2.41, P = 0.049) and other types of lung cancer (OR = 1.96, 95% CI: 1.10-3.49, P = 0.023), but no association was found between the two SNPs and other clinical features. (3) IGF-1R +1013 (G/A) and IGF-2R +1619(G/A) polymorphisms showed a synergic effect (P = 0.003).</p><p><b>CONCLUSION</b>The common IGF-1R gene polymorphism G1013A may influence the risk of lung cancer. The polymorphisms of IGF-1R +1013 (G/A) and IGF-2R +1619 (G/A) have synergistic influence on the risk of lung cancer.</p>

Inducing effect of total flavones in rhododendra on endothelium-derived hyperpolarizing factor responses in cerebral basilar artery of rats subjected to global cerebral ischemia reperfusion / 中草药

Objective: To study the effect of endothelium-derived hyperpolarizing factor (EDHF)-mediated responses of relaxation and hyperpolarization of vascular smooth muscle cell (VSMC) of rat cerebral basilar artery (CBA) subjected to cerebral ischemia/reperfusion (I/R) to total flavones in rhododendra (TFR). Methods: The model of global cerebral I/R in rats was made by 4-vessel occlusion (4-VO). The vasodilation and resting membrane potential (RMP) of VSMC of rat CBA were detected in vitro. Results: In the presence of 3×10-5 mol/L Nω-nitro-L-arginine-methyl-ester (L-NAME, an inhibitor of nitric oxide synthase) and 1×10-5 mol/L Indomethacin (Indo, an inhibitor of PGI2 synthesis), the global cerebral I/R markedly enhanced 1×10-7-1×10-5 mol/L acetylcholine (Ach)-elicited relaxation and hyperpolarization of RMP of VSMC in rat CBA. In the presence of L-NAME and Indo, 11-2 700 mg/L TFR induced significant and dose-dependent hyperpolarization of RMP of VSMC and relaxation of rat CBA subjected to global cerebral I/R. The hyperpolarization and relaxation were obviously inhibited by tetraethylammonium (an inhibitor IKCa at 1 mmol/L) and 1×10-4 mol/L dl-propargylglycine (PPG), an inhibitor of endogenous hydrogen sulfide (H2S) synthase. Conclusion: Global cerebral I/R could enhance the non-NO-non-PGI2-mediated responses of hyperpolarization and vasorelaxation in rat CAB. In rat CAB subjected to global cerebral I/R, TFR could significantly induce this non-NO-non-PGI2 hyperpolarization and relaxation, the so-called EDHF response that might be mediated by endogenous H2S.

Study on the cellular and humoral immunity effect of recombinant Chinese hamster ovary cell hepatitis B vaccine in adults / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the cellular and humoral immunity effect of 10 µg and 20 µg recombinant Chinese hamster ovary (CHO) cell hepatitis B vaccine in adults by randomized double-blind controlled trials.</p><p><b>METHOD</b>A total of 642 adults aged 18 - 45 years old, non-vaccinated against hepatitis B, and hepatitis B five blood indicators negative were selected as the study subjects. The study subjects were randomly divided into two groups and each group had 321 subjects. The subjects were given 10 µg and 20 µg recombinant CHO hepatitis B vaccination respectively by 0, 1st, 6th month schedule. Blood sample was collected from each study subject one month after the second dose vaccination. The anti-HBs level was detected by Abbott chemiluminescence detection method (I2000) to evaluate humoral immunity status. Of all the study objects, 153 cases were randomly selected by the Excel random function. Their blood samples were collected and Lymphocyte were separated to detect the IL-4 and IFN-γ levels in vitro by enzyme-linked immunospot (ELISPOT) method to evaluate the cellular immunity status.</p><p><b>RESULTS</b>The anti-HBs seroconversion rates in 10 µg and 20 µg dose group were 88.8% (285/321) and 95.3% (306/321) respectively, and 95%CI were 85.4% - 92.2% and 93.0% - 97.6% respectively. The spot forming cell (SFC) of IL-4 of the 20 µg-dose group (x(-) = 20.31) were significantly higher than the 10 µg-dose group (x(-) = 8.19, t = 3.27, P < 0.01). With the increasing of anti-HBs titer, the SFC of IL-4 also went up significantly. There was a positive correlation between SFC of IL-4 and anti-HBs (Spearman correlation coefficient = 0.538, P < 0.0001). No significant difference was found for IFN-γ SFC in two groups (10 µg group: x(-) = 1.49; 20 µg group: x(-) = 0.86; t = 1.83, P > 0.05).</p><p><b>CONCLUSION</b>The humoral and cellular immune effects of 20 µg recombinant CHO hepatitis B vaccine are better than that of the 10 µg recombinant CHO hepatitis B vaccine.20 µg recombinant CHO hepatitis B vaccine should be chosen as the adult's hepatitis B prevention vaccine.</p>

Study on the immuno-effects and influencing factors of Chinese Hamster Ovary (CHO) cell hepatitis B vaccine among adults, under different dosages / 中华流行病学杂志

Objective To evaluate the immuno-effect and related influencing factors on 10 μg and 20 μg Chinese hamster ovary (CHO) cell hepatitis B vaccine, using the randomized double-blind controlled trials in adult population. Methods A total of 642 adults aged 18-45 years old, non-vaccinated against hepatitis B, and negative on five blood indicators for hepatitis B, were selected as the study objects from four districts in Beijing. The study objects were randomly divided into two groups, and then accepted 10 tg and 20 μg recombinant CHO hepatitis B vaccination by 0-1-6 month schedule. Influencing factors were investigated by means of questionnaire. Blood samples were collected one month after the third dose of vaccination. Anti-HBs level was detected by Abott chemiluminescence detection method. For the anti-HBs negative person, fluorescent quantitative PCR method was used to find out if the person had been infected with HBV. Logistic regression analysis was used to find out the influencing factors of anti-HBs seroconversion on every studied subject. Results The anti-HBs seroconversion rates on 10 μg and 20 μg dose groups were 88.8%(95%CI: 85.4%-92.2%) and 95.3%(95%CI: 93.0%-97.6%)respectively. Taking the anti-HBs level＜100 mIU/ml as the low/non-response standard, the low response and non-response rates were 34.3% and 17.4% respectively. The geometric mean titers(GMT)of anti-HBs were 173.42 mIU/ml for the 10 μg dose group and 588.51 mIU/ml for the 20 μg dose group. Data from the Multivariate analysis showed that: diabetes, spouses infected with hepatitis B virus and old age were unfavorable factors for anti-HBs Seroconversion. 20 μg dose of the vaccine was conducive to seroconversion.Conclusion 20 μg CHO hepatitis B vaccine seemed better than 10 μg CHO hepatitis B vaccine while many factors need to be taken into account for evaluation on hepatitis B vaccines.

Analysis on the proportion of reported hepatitis B cases through pilot surveillance in China during 2006 / 中华流行病学杂志

<p><b>OBJECTIVE</b>To better understand the proportions of reported hepatitis B cases in pilot surveillance cites through investigation and laboratory testing.</p><p><b>METHODS</b>To confirm the reported cases of hepatitis B by collecting blood specimen and laboratory testing on HBsAg, IgM of Anti-HBc, Anti-HAV in 18 pilot surveillance counties.</p><p><b>RESULTS</b>Among 2858 cases of hepatitis B reported in 2006, 23.97% of them were reported as suspected acute cases, 14.87% as acute cases, 20.33% as suspected chronic cases, 34.67% as chronic cases, 4.09% as cirrhosis and 2.06% as HCC. Among 1681 reported hepatitis B cases confirmed by laboratory testing, results showed that 24.16% of them were diagnosed as acute hepatitis B, but only 15.37% were confirmed as acute hepatitis B. Although the proportion confirmed as hepatitis B kept consistent as before, misclassification was found.</p><p><b>CONCLUSION</b>In current surveillance system, reported hepatitis B cases were mainly chronic, only up to one third belonged to acute hepatitis B. The reported incidence of hepatitis B did not reflect the real incidence due to misclassification. To better define the burden on hepatitis B disease, it was necessary and urgent to revise the diagnostic criteria and to conduct surveillance on hepatitis B, under separate reporting categories which including acute and chronic cases of the disease.</p>

A sero-epidemiologiecal study on hepatitis B among general population in Beijing / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the serological infection rate of hepatitis B virus (HBV) in general population aged over one year old in Beijing and to provide information for control and prevention of the disease.</p><p><b>METHODS</b>A multistage randomized cluster sampling was carried out in general population of Beijing, aged over one year old. Every study subject's hepatitis B immunization history and main risk factors were investigated through questionnaire. Venous blood samples were collected and then tested for five hepatitis B serological antigens and antibodies by means of Abbott Microparticle Enzyme Immunoassy method.</p><p><b>RESULTS</b>The prevalence rates of HBsAg, anti-HBs, anti-HBc and total HBV infection rate were 3.49% (95% CI:2.99-3.99), 37.79% (95% CI: 36.46-39.12), 35.04% (95% CI: 33.72-36.35) and 35.09% (33.78-36.40) respectively. The age standardized rates were 3.02% ,42.47% ,26.86% and 26.90% respectively.</p><p><b>CONCLUSION</b>Achievement in hepatitis B control and prevention was made in Beijing since the prevalence rate of hepatitis B surface antigen had been below 1% for children aged less than 5 years old. As for the general population, the prevalence rate of hepatitis B surface antigen had reduced to</p>

Diagnostic value of ischemia-modified albumin in patients with acute coronary syndrome / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the diagnostic value of ischemia-modified albumin (IMA) for patients with acute coronary syndrome (ACS).</p><p><b>METHODS</b>We detected the IMA levels by albumin cobalt-binding (ACB) test and observed its dynamic changes in 492 patients with ACS, 74 patients with high blood pressure, 78 patients with viral myocarditis (VMC), 395 patients with acute chest pain (133 patients with acute ACS and 262 follow-up patients due to chest pain), 68 patients underwent percutaneous coronary intervention (PCI) and 830 healthy controls. Cardiac troponin I (cTnI) levels were assayed and electrocardiogram (ECG) recorded in patients with ACS.</p><p><b>RESULTS</b>The optimal diagnostic cutoff point for IMA in this study population was found to be 0.45 ABSU by ROC analysis. The IMA level (ABSU) in ACS group (0.55 +/- 0.11) was significantly higher than that in VMC group (0.38 +/- 0.11) and IMA levels in ACS and VMC groups were both higher than that in control and high blood pressure groups (0.34 +/- 0.08 and 0.35 +/- 0.08, all P < 0.05). IMA levels and the positive rates in patients with ACS were significantly higher (0.54 +/- 0.12 vs 0.44 +/- 0.12, 77.4% vs 39.3%, all P < 0.01) than those in chest pain follow-up group. In 133 patients with ACS, positive rate for IMA was significantly higher than that for cTnI within 1 h of admission (82.0% vs 40.6%, P < 0.01), and was similar at 6 - 24 h after admission (96.2% vs. 95.5%, P > 0.05). In 72 patients presenting to the emergency center within 3 h of acute chest pain and with negative cTnI, positive rate for IMA was 86.1% and for ECG 72.2%, the sensitivity for ACS diagnosis rised to 93.1% with both methods. The IMA leve was higher immediately after PCI than that before PCI (P < 0.05). IMA levels peaked 1d after hospitalization, then decreased gradually and returned to normal 14 days later.</p><p><b>CONCLUSIONS</b>IMA was a useful biochemical marker for the early diagnosis of ACS.</p>

Effect of Exogenous Hydrogen Sulfide on Expression of Lung Muc5ac and Cytokines in Ovalbumin-Induced Asthma Rats / 实用儿科临床杂志

Objective To explore the effect of gaseous signal molecule hydrogen sulfide(H2S)on the expression of lung Muc5ac and Th1/Th2 cytokines in ovalbumin(OVA)-induced asthma rats and explore the effect of H2S on asthma.Methods Twenty-six healthy SD rats were randomly divided into 3 groups:control group(Group A,n=8),asthma group(Group B,OVA induced,n=9)and NaHS group(Group C,OVA induced rats treated with NaHS,n=9).Twenty-four hours after treatment,rats were anatomized to measure serum interleukin(IL)-4,interferon-? and the levels of infiltration into inflammatory cells around bronchus were observed,which were scored with the optical microscope.The expression of lung Muc5ac was determined by immunohistochemical staining.Results The score of the levels of infiltration into inflammatory cells around bronchus expressed by median was 1 score in group A,4 score in group B and 2 score in group C.There were dramatically statistics significance among the 3 groups(H=13.75 P