Objective To investigate maternal risk factors for fetal congenital heart diseases (CHD). Methods A case-control study was conducted on 16 645 pregnant women who underwent cardiovascular malformation screening for fetal cardiovascular system,whose pregnancy outcomes were recorded,and whose newborns were scanned by an echocardiography in Peking University People's Hospital,Haidian,Changping,Mentougou and Daxing Maternal and Child Health Hospital from Nov.2006 to Oct.2009.One hundred and twelve pregnant women whose babies were found to be CHD (40 severe CHD and 72 simple CHD) before or after delivery were taken as study group.Women in control group (n =304) were randomly selected from those pregnant women who had infants without CHD.Logistic regression analysis and x2 test were used to analyze the maternal risk factors for fetal CHD. Results (1) The average age of women whose infants had severe CHD was 28.3 years (21-40 years),and it was 29.9 years (22-39 years) for women whose infants had simple CHD.There were no significant differences between the control group (29.5 years,20-44 years) and the above two groups (t=1.511 and -0.826,P=0.138 and 0.410 respectively).(2) Single factor analysis:during first trimester,the rate of upper respiratory infection (18/39,46.2 ％) and exposure to certain chemicals (13/40,32.5％) of severe CHD group were higher than those of control group [(14.9％ (45/303) and 2.0％ (6/304)] (x2 =22.399 and 62.678,OR=4.895 and 23.753,95％CI:2.419-9.905 and 8.358-67.506,P =0.000 respectively).Compared with control group (0.0％,0/304),the rate of pregnant women with CHD family history in simple CHD group was significantly higher (4.2％,3/72)(Fisher exact test,P=0.007).(3) Logistic regression analysis:maternal upper respiratory infections (OR =5.120,95％CI:2.340-11.206,P =0.000) and exposure to certain chemicals (f)R=23.030,95％CI:7.506-70.665,P=0.000) during first trimester were risk factors for fetal severe CHD. Conclusions Upper respiratory infection and exposure to certain chemicals during first trimester might play important roles in the occurrence of fetal severe CHD.Maternal family history of CHD might associate with fetal simple CHD.

Objective To investigate the phenotypes and genotypes of a hereditary protein C(PC) deficiency pedigree.Methods Imrnunoassay(ELISA)was used for PC antigen and PS antigen; Immunoturbidimetry assay was used for measuring AT antigen;Chromogenic substrate assay was used for measuring the activity of PC,PS and AT in Sysmex 1500 automatic Blood Coagulation Analyzer.Polymerase chain reaction(PCR)for amplification of the fragment of each exon and side sequences of PC gene in 10 members of the 3 generations;Direct DNA sequencing was used to examine the mutation site.Results Among 10 members of the 3 generation pedigree,8 of them had a PC:Ag level of 1.06-1.92 mg/L(normal references 3.00-6.00 rag/L),the activity of PC was between 41% and 67%(normal references 70%- 140%),which was significantly lower than the normal references while the levels of PS:Ag,PS:A,AT:Ag and AT:A were all within normal range.DNA sequencing analysis showed that there was a G to T mutation in exon IX of the PC gene at 12 918 position in 8 members.This mutation resulted in the substitution of terminator TGA for TGG which encoding tryptophan at 372 amino acid.There was a polymorphism in 2 405C/ T,2 418A/G,2 583A/T in the promotor area.Conclusions This pedigree is a type I hereditary protein C deficiency.There is a G12 918T mutation in exon IX of PC gene.This mutation is reported for the first time and there is a polymorphism in 2 405C/T,2 418A/G,2 583A/T in the promotor area.

OBJECTIVETo investigate the regulatory effect of jianpi jiedu Recipe (JJR) on the microvessel density (MVD) and cyclooxygenase-2 (COX-2) in long-term infection of Helicobacter pylori induced gastric cancer of C57BL/6 mice, thus providing experimental bases for its treatment of the H. pylori correlated gastropathy.

METHODSC57BL/6 mouse gastric cancer model induced by H. pylori infection was established by gastrogavage of H. pylori standard strain SS1. Mice were divided into the control group, the model group, low dose JJR group, and the high dose JJR group, 40 in each group. Mice were sacrificed after 72-week medication. Changes of the gastric mucosa MVD of mice in each group were detected by immunohistochemical method. Expressions of COX-2 mRNA and protein were detected by Real-time fluorescent quantitative polymerase chain reaction and immunohistochemical method.

RESULTSThe occurrence rate of gastric cancer in the control group, the model group, the low dose JJR group, and the high dose JJR group was 0, 22.2%, 11.1%, and 10.0%, respectively. The gastric mucosa MVD (number/cm2) of mice in each group was 2.50 +/- 1.54, 18.56 +/- 2.62, 14.61 +/- 3.60, and 7.39 +/- 1.75, respectively. The gastric mucosa MVD in the model group increased more obviously than that in the control group (P < 0.01). The gastric mucosa MVD significantly decreased in the low dose JJR group and the high dose JJR group (P < 0.01). Expressions of COX-2 mRNA and protein in the model group increased more obviously than those in the control group (P < 0.01). Low dose JJR and high dose JJR could decrease their expressions in a dose dependent manner.

CONCLUSIONSH. pylori infection could increase the gastric mucosa MVD of C57BL/6 mice and promote COX-2 expressions, which might play a promoting effect in the incidence of H. pylori induced gastric cancer. JJR could decrease the gastric mucosa MVD and inhibit COX-2 expressions, which might be one of its important mechanisms of preventing and treating gastric cancer.

Animals ; Cyclooxygenase 2 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Gastric Mucosa ; blood supply ; drug effects ; metabolism ; Helicobacter Infections ; metabolism ; Helicobacter pylori ; Mice ; Mice, Inbred C57BL ; Microvessels ; pathology ; Stomach Neoplasms ; blood supply ; metabolism ; microbiology

Adult ; Aldosterone ; blood ; Angiotensin II ; blood ; Diet, Sodium-Restricted ; Female ; Humans ; Kidney ; physiopathology ; Kidney Function Tests ; Liver Cirrhosis ; blood ; physiopathology ; Male ; Middle Aged ; Renin ; blood ; Sodium ; administration & dosage

OBJECTIVETo explore the effect of compound qizhu granule (CQG) on cellular immunity of chronic hepatitis B (CHB) patients.

METHODSTotally 103 CHB patients treated with lamivudin (LAM) for 6 months, who had partial virological response (HBeAg positive) were randomly assigned to two groups, 50 in the treatment group and 53 in the control group. All patients took LAM 100 mg (once a day) plus ADV 10 mg (once a day). Patients in the treatment group additionally took CQG, one dose per day. After one-year treatment hepatitis B virus (HBV) DNA negative rates, HBeAg seroconversion, levels of HBV specific cytotoxic T lymphocyte (CTL), non-specific CTL and natural killing (NK) cells were compared between the two groups.

RESULTSAfter 1-year treatment, HBV DNA negative rate of the treatment group was 88: 0% in 44 cases, slightly higher than that of the control group (41 cases, 77.4%), but with no statistical difference (P >0.05). HBeAg seroconversion of the treatment group was 32.0% in 16 cases, higher than that of the control group (8 cases, 15.1%), with statistical difference (P <0.05). Levels of HBV specific CTL (0.79%±0. 07%), non-specific CTL (19.4%±1.8%) and NK cells (14. 1%± 1.5%) of the treatment group were higher than those of the control group (0.58% ± 0.08%, 17.5% ± 1.7%, and 11.1%±1.5%, respectively; allP <0.01).

CONCLUSIONTreating CHB patients with partial virological response by ADV plus CQG could improve specific and non-specific cellular immunity, thereby elevating HBeAg seroconversion rate.

Drugs, Chinese Herbal ; therapeutic use ; Hepatitis B e Antigens ; immunology ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Immunity, Cellular ; immunology ; T-Lymphocytes, Cytotoxic ; drug effects

OBJECTIVE Despite the status of cisplatin (DDP) as a classical chemotherapeutic agent in the treatment of cancer, the development of multidrug resistance often leads to a failure of DDP therapy.Traditional Chinese medicine(TCM)as adjuvant chemotherapy of cancer drugs in China has been widely used in cancer treatment.ZuoJin WAN (ZJW),a TCM formula,was proved reversing drug resistance in gastric cancer,but its exact mechanism was still unclear. METHODS CCK-8 assay was used to detect the cell viability. The levels of proteins and mRNA were evaluated using Western blot and q-PCR. Mitochondrial membrane potential was measured by fl ow cytometry. Depolymerisa-tion of F-actin and translocation of G-actin(gamma-actin)from the cytoplasm to the mitochondria was detected using an immuno fl uorescence assay. RESULTS phosphorylated coflin-1 (p-coflin-1) was overexpressed in the DDP-resistant human gastric cancer cell lines SGC7901/DDP and BGC823/DDP, relative to the respective parent cell lines(SGC7901 and BGC823),and DDP induced the dephosphory-lation of p-coflin-1 in both parent lines but not in the DDP-resistant lines. However, ZJW could induce the dephosphorylation of pcoflin-1 and promote coflin-1 translocation from the cytoplasm into the mito-chondria in both SGC7901/DDP and BGC823/DDP cells. This mitochondrial translocation of coflin-1 was found to induce the conversion of flamentous actin to globular-actin, activate mitochondrial dam-age and calcium overloading, and induce the mitochondrial apoptosis pathway. These effects of ZJW on DDP-resistant human gastric cancer cell lines could be reversed via transfection with coflin-1-specifc siRNA,or treatment with a PP1 and PP2A inhibitor.CONCLUSION ZJW can be used as an inhibitor of chemoresistance in gastric cancer, which may partly be due to dephosphorylation of p-coflin-1 via the activation of PP1 and PP2A.

BACKGROUNDOxymatrine has certain antiviral effects in the treatment of chronic hepatitis B (CHB), but its exact mechanism is unclear. The objective of the present study was to explore oxymatrine's antiviral mechanism by studying its effect on the hepatitis B virus (HBV) specific cytotoxic T lymphocyte (CTL) surface programmed death receptor-1 (PD-1) expression in CHB patients.

METHODSSixty-five CHB patients who had HBV DNA(3)10(4) copies/ml, positive HBeAg, positive human leukocyte antigen (HLA)-A2, alanine aminotransferase (ALT) > 2 x upper limit of normal value (ULN) were randomly divided into two groups: treatment group (n = 33), treated with an intravenous infusion of 600 mg oxymatrine in glucose solution once a day for a month, then with a 200 mg oxymatrine oral capsule three times a day, and a 200 mg silibin meglumine tablet three times a day; control group (n = 32) patients were treated only with silibin meglumine tablet, method and dosage were the same as those of treatment group. Three months later, peripheral blood HBV-specific CTL surface PD-1 expression, HBV-specific CTL level, HBV DNA, HBeAg, and results of liver function tests were analyzed and compared.

RESULTSThree months post-treatment, in the treatment group, peripheral blood HBV-specific CTL surface PD-1 expression ((19.42 ± 15.94)%) decreased significantly compared to the pretreatment level ((31.30 ± 24.06)%; P < 0.05), and decreased significantly compared to that of control group three months after treatment ((29.45 ± 21.62)%; P < 0.05). HBV-specific CTL level ((0.42 ± 0.07)%) significantly increased compared with the pretreatment ((0.29 ± 0.15)%; P < 0.01), and the control group posttreatment level was (0.31 ± 0.15)% (P < 0.05). HBV DNA level in 11 cases became negative (HBV DNA < 500 copies/ml, 33.33%), which was higher than that of the control group after treatment (two cases, 6.25%; χ(2) = 7.45, P < 0.01), HBeAg of nine cases turned negative (27.27%), which was higher than that of the control group after treatment (one case, 3.13%; χ(2) = 7.27, P < 0.01).

CONCLUSIONOxymatrine could downregulate peripheral blood HBV-specific CTL surface PD-1 expression in CHB patients, increase HBV-specific CTL level, which may be one of the possible mechanisms by which oxymatrine clears or inhibits HBV in CHB patients.

Adult ; Alkaloids ; therapeutic use ; Antiviral Agents ; therapeutic use ; DNA, Viral ; blood ; Female ; Hepatitis B virus ; immunology ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Male ; Middle Aged ; Programmed Cell Death 1 Receptor ; analysis ; Quinolizines ; therapeutic use ; T-Lymphocytes, Cytotoxic ; chemistry

OBJECTIVETo explore the anti-viral mechanism of kurarinol through studying its influence on cytotoxic T lymphocyte (CTL) surface program death receptor-1 (PD-1) expression of patients with chronic hepatitis B (CHB).

METHODS69 cases of CHB, HBV DNA > or = 10(4) copies/ml, HBeAg positive, human leukocyte antigen (HLA)-A2 positive, alanine aminotransferase (ALT) > 2 x upper limit of normal value(ULN).69 cases were randomly divided into two groups:34 cases in treatment group,600 mg of kurarinol glucose injection was used for intravenous dripping, once a day, one month later, 200 mg of kurarinol capsule was used orally,three times a day and 200 mg of silybin meglumine tablet was used orally, three times a day. 35 cases in control group, only silibin meglumine tablet was used, method and dosage were the same as those of treatment group. Three months later, their peripheral blood HBV specific CTL surface PD-1 expression, non-specific CTL surface PD-1 expression and level of HBV specific CTL,HBV DNA and HBeAg negative rate and liver functions were analyzed and compared.

RESULTS3 months after treatment, peripheral blood HBV specific CTL surface PD-1 expression of the treatment group decreased compared with that before treatment (t = 2.39, P < 0.05), it also decreased compared with that of the control group 3 months after treatment (t = 2.26, P < 0.05), HBV specific CTL increased compared with that before treatment( t = 3.01, P < 0.01), it also increased compared with that of the control group after treatment (t = 2.65, P < 0.05). There was no significant difference of non-specific CTL surface PD-1 expression compared with that before treatment (P > 0.05), and there was no significant difference compared with that of the control group after treatment (P > 0.05). HBV DNA of 11 cases (32.5%) turned negative ( HBV DNA < 500 copies/ ml), higher than that of the control group after treatment (2 cases, 5.71%) chi2 = 7.99, P < 0.01, HBeAg of 9 cases (26.47%) turned negative, higher than that of the control group after treatment (1 case, 2.86%), chi2 = 7.75, P < 0.01.

CONCLUSIONKurarinol can increase level of HBV specific CTL by down-regulating peripheral blood HBV specific CTL surface PD-1 expression of CHB patients, which may be one of the possible mechanisms that kurarinol can remove or inhibit HBV of CHB patients.

Adult ; Drugs, Chinese Herbal ; administration & dosage ; Flavonoids ; administration & dosage ; Gene Expression ; drug effects ; Hepatitis B virus ; physiology ; Hepatitis B, Chronic ; drug therapy ; genetics ; immunology ; virology ; Humans ; Male ; Middle Aged ; Programmed Cell Death 1 Receptor ; genetics ; immunology ; T-Lymphocytes, Cytotoxic ; drug effects ; immunology ; Treatment Outcome ; Young Adult

Bile Ducts, Intrahepatic ; metabolism ; Humans ; Interleukin-2 Receptor alpha Subunit ; metabolism ; Liver ; metabolism

OBJECTIVEIn order to investigate whether or not thrombopoietin (TPO) could promote the fibrogenesis of bone marrow stromal cells in absence of megakaryocytes (MKs).

METHODSImproved dexter culture system with various TPO concentrations was used for ex vivo culture of bone marrow stromal cells. Relative proliferation index, the expressions of fibronectin, laminin and type IV collagen, and the systhesis of type III procollagen were detected at different time points during culture process.

RESULTSTPO stimulated the proliferation of bone marrow stromal cells. Relative proliferation index of the stromal cells increased with the TPO concentration increasing, and was not related to the exposure time. The expressions of fibronectin, laminin, and type IV collagen appeared stronger in the TPO groups than those in the control group. But the expressions of these molecules were not dependent upon the culture time. TPO could accelerate the synthesis of type III procollagen in bone marrow stromal cells, and this acceleration was unrelated to the TPO concentration.

CONCLUSIONThese findings suggested that TPO could stimulate the stromal cells with a consequence of increased syntheses and secretions of the extracellular matrix and collagen in absence of MKs. In other words, TPO could promote the fibrogenesis of bone marrow stromal cells without the existence of MKs.

Cells, Cultured ; Collagen Type III ; metabolism ; Collagen Type IV ; metabolism ; Extracellular Matrix ; metabolism ; Fibronectins ; metabolism ; Fibrosis ; pathology ; Humans ; Laminin ; metabolism ; Megakaryocytes ; cytology ; Mesenchymal Stromal Cells ; cytology ; metabolism ; pathology ; Thrombopoietin ; pharmacology