[Relationship between the HBsAg-positive infection status of mothers and the non/low-response to hepatitis B vaccine of their infants].

Objective: To explore the relationship between the status of HBsAg-positive infection of mothers and the non/low-response to hepatitis B vaccine of their infants. Methods: A total of 225 pairs of mothers and their infants were recruited in our cohort from June 2011 to July 2013. Infants were given three doses of hepatitis B vaccine at hour 24, first month and month 6(t)h respectively and were followed up for one year after birth. HBV serological markers and HBV DNA in the peripheral blood of both mothers and infants were detected by Electro-chemiluminescence immunoassay and fluorescence quantitative Polymerase Chain Reaction. Results: Six HBV infection models were detected in HBsAg-positive mothers, and "HBsAg (+), HBeAg (+), anti-HBc (+)" (model one) and "HBsAg (+), anti-HBe (+), anti-HBc (+)" (model two) accounted for 92.5%(208/225) of all the models. Rate of non/low-response to hepatitis B vaccine in infants born to mothers in model one was lower than those in model two, the differences are statistically significant (χ(2)=4.80, P=0.029). The rate of non/low-response to hepatitis B vaccine in infants showed a downward trend with the rising of HBeAg level in their mothers (χ(2)=4.86, P=0.028). Results from the unconditional logistic regression analysis showed that the HBeAg of the HBsAg-positive mothers was significantly correlated with the low risk of non/low-response to hepatitis B vaccine in infants (OR=0.598, 95%CI: 0.378-0.947). The positive rate of serum HBV DNA in HBsAg-positive mothers was 54.2%, while the rate of non/low-response to hepatitis B vaccine in infants born to HBV DNA positive mothers was similar to those infants born to HBV DNA negative mothers (χ(2)=0.22, P=0.640). Conclusions: "HBsAg (+), HBeAg (+), anti-HBc (+)" and "HBsAg (+), anti-HBe(+), anti-HBc (+)" were the common models seen in HBsAg-positive mothers, and the rate of non/low-response to hepatitis B vaccine was different between the two models. HBeAg of HBsAg-positive mothers might have positive effects on the immune response to hepatitis B vaccine in infants but the mechanisms remained not clear. HBV DNA of the HBsAg-positive mothers did not seem to be correlated with the immune response to hepatitis B vaccine in infants.

[Relationship between HBeAg from HBsAg positive mothers and regulatory T cells in neonates and its influence on HBV intrauterine transmission].

Objective: To explore the relationship between HBeAg in HBsAg positive mothers and CD(4)(+)CD(25)(+)Foxp3(+)regulatory T cells (Treg) in newborns, as well as how they would influence the increasing risk on HBV intrauterine transmission. Methods: We collected information on general demographic characteristics and delivery on 270 HBsAg positive mothers and their newborns from the Third People's Hospital of Taiyuan. Fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescence immunoassay (CLIA) were used to detect HBV DNA and HBV serological markers in peripheral blood from both mothers and neonates. The expression of Treg and other immune cells in peripheral blood of neonates were detected with flow cytometry (FCM). Results: Maternal HBeAg positive rates were associated with an increased risk of intrauterine transmission (OR=4.08, 95%CI: 1.89-8.82). Rates of Treg in newborns born to HBsAg-positive mothers were higher than that of the negative group (Z=2.29, P=0.022). Each pair of the subjects was assigned to five different groups according to the HBeAg titers of mothers. Frequencies of both Treg and HBeAg in newborns and HBV DNA in mothers between the above said 5 groups showed similar trends of changing patterns and the differences between groups were statistically significant(χ(2)=18.73, P<0.001; χ(2)=181.60, P<0.001; χ(2)=183.09, P<0.001). Results from partial correlation analysis showed that after adjusting for neonatal HBeAg and maternal HBV DNA, mother's HBeAg titers were positively related to the percentage of Treg in their newborns (r(s)=0.19, P=0.039). In addition, the frequencies of Treg were negatively correlated with pDC and CD(4)(+) T cell in their newborns (r(s)=-0.21, P=0.017; r(s)=-0.23, P=0.009). Conclusion: HBeAg from HBsAg positive mothers might have inhibited the function of neonatal DC cells and T cells to reduce the immune response to HBV by up-regulating the proportion of Treg and finally increased the risk of HBV intrauterine transmission.

[Influencing factors for non/low-response to hepatitis-B vaccine in infants of HBsAg positive mothers].

Objective: To investigate the influencing factors for non/low-response to hepatitis B vaccine in infants of HBsAg-positive mothers. Methods: A total of 286 HBsAg-positive pregnant women and their infants were recruited from the Third People's Hospital of Taiyuan during July 2011 to January 2013. The infants were immunized with hepatitis B vaccine according to the 0-1-6 month vaccination schedule and followed up for 12 months. The serum HBV DNA level of mothers, neonates and infants were detected by electro chemilum inescence immunoassay kits and fluorescene quantiative polymerase chain rection. Results: Among 286 infants, the rate of non/low-response to hepatitis B vaccine was 18.53% (53/286). Non-conditional logistic regression analysis indicated that the mother's HBV DNA level ≥1×10(7) copies/ml (OR=2.592, 95%CI: 1.121-5.996) and natural birth (OR=1.932, 95%CI: 1.021-3.654) were the risk factors for non/low-response to hepatitis B vaccine, the risks were 2.592 times and 1.932 times higher compared with the infants whose mothers were HBV DNA negative and the infants whose mothers had cesarean delivery. There was no multiplicative or additive interaction between high HBV DNA load and natural birth (OR=1.055, 95%CI: 0.209-5.321), (RERI=1.617, 95%CI: -4.038-7.272; AP=0.364, 95%CI: -0.527-1.225; SI=1.195, 95%CI: 0.270-13.135). After stratified analysis of mother's HBV DNA level, delivery mode of mothers was not associated with non/low-response of their infants. Conclusion: The mother's load of HBV DNA≥1×10(7) copies/ml might be the factor for non/low-response to hepatitis B vaccine in infants of HBsAg positive mothers.

[Effect of interleukin-6 and interleukin-12 on immune response to hepatitis B vaccination in infants of HBsAg-positive mothers].

Objective: To explore the effect of interleukin-6 (IL-6) and Interleukin-12 (IL-12) on immune response to hepatitis B vaccination in infants of HBsAg-positive mothers. Methods: A total of 91 neonates whose mothers were HBsAg-positive were included and followed up for 12 months. HBV DNA and HBV serological markers in the peripheral blood of the neonates and infants were detected with fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescence immunoassay (CLIA), and the levels of IL-6 and IL-12 in the peripheral blood of the neonates and infants were detected with enzyme-linked immunosorbent assay (ELISA). Results: The non-/hypo-response rate to hepatitis B vaccination was 35.16% (32/91) in the 91 infants. In the neonatal period and infantile period, the level of IL-6 in non-/hypo-response group was lower than that in high-response group, while the level of IL-12 was higher than that in high-response group, and there was significant difference (P<0.01). From the neonatal period to the infantile period, the level of IL-6 increased, while the level of IL-12 descended in both groups, and there was significant difference (P<0.01). Furthermore, the level of anti-HBs of infants was positively correlated with the level of IL-6 (r(s)=0.70, 0.79, P<0.01), and was negatively correlated with the level of IL-12 (r(s)=-0.71, -0.72, P<0.01) in the neonatal period and the infantile period. From the neonatal period to the infantile period, the increased level of IL-6 was positively associated with the level of anti-HBs (r(s)= -0.74, P<0.01), while the decreased level of IL-12 was negatively associated with the level of anti-HBs (r(s)=-0.42, P<0.01). The level of IL-6 was negatively correlated with the level of IL-12 in the neonatal period and the infantile period (r(s)=-0.68, -0.70, P<0.01). Conclusions: IL-6 might promote the immune response to hepatitis B vaccination in infants whose mothers were HBsAg-positive, while IL-12 might inhibit the immune response. IL-6 and IL-12 would affect the immune response to hepatitis B vaccination in infants of HBsAg-positive mothers at the same time.

[Correlative factors on prevalence rate of dislipidemia among 1 337 coal miners in Shanxi province].

Objective: To understand the prevalence rate and correlative factors of dislipidemia among Shanxi coal miners and to provide evidence for the development of programs on dislipidemia prevention. Methods: We investigated 1 337 mine workers from a Coal Group in April 2016 and collected data related to their blood biochemistry. We then classified the types in accordance with the diagnostic criteria of " Guidelines for prevention and treatment of dyslipidemia in Chinese adults (2007)" , using χ(2) test and unconditional logistic regression model for analysis. Results: The overall prevalence rate of Dislipidemia was 59.1% (790/1 337), with males as 60.4% (708/1 173) and females as 50.0%(82/164) while males appeared higher (χ(2)=6.386, P<0.05). Among the 20-34, 35-49, 50 and above year-old groups, the rates were 68.8%, 58.7%, 49.5%, respectively. Results from the χ(2) test showed that gender, age and body mass index were the influencing factors on dislipidemia (χ(2)=7.117, P<0.01; χ(2)=37.135, P<0.01; χ(2)=7.009, P<0.05), while logistic regression analysis showed that sex, age, body mass index level, systolic blood pressure were significantly associated with dislipidemia (P<0.05). Male miners appeared 1.501 times (OR=1.501, 95%CI: 1.895-2.516) higher than female miners in suffering from the risk of dyslipidemia. In different age groups, risks of dyslipidemia in the 35-49, 20-34 year-old groups were 1.672 (OR=1.672, 95%CI: 1.501-2.392) and 2.369 times (OR= 2.369, 95% CI: 1.275-3.469) higher than the 50 year-old. Group that with high BMI, the risk of dyslipidemia was 1.443 times (OR=1.443, 95%CI: 1.139-1.828) higher than the normal BMI group. Group with abnormal systolic pressure was 1.829 times (OR=1.829, 95%CI: 1.152-2.906) higher than normal systolic pressure group. However, diastolic blood pressure, blood sugar, uric acid, and electrocardiogram findings did not seem to show statistically significant meanings on dislipidemia. Conclusion: Among the coal mine workers, those who were males, aged from 20 to 34, having high blood pressure (systolic blood pressure abnormalities) or with high BMI (≥24.0 kg/m(2)) need to be taken special attention on care and prevention of dislipidemia.

[Effect of telbivudine on infants born to HBsAg-positive mothers with non-/hypo-response to hepatitis B vaccine during their second and third trimesters of pregnancy].

Objective: To explore the effect of telbivudine treatment in a prevention program on infants born to HBsAg-positive mothers with non-/hypo-responsiveness to hepatitis B vaccine. Methods: A retrospective cohort study with a total of 321 HBsAg-positive pregnant women and their infants enrolled, was conducted. The mothers were recruited from the Third People' s Hospital of Taiyuan, from July 2011 to January 2013. According to the situation of telbivudine intake in second and third trimesters of pregnancy, the participants were divided into two groups: with telbivudine-treated or as control. The neonates were followed up till the age of 12 months. Maternal, neonatal and infantile HBV-M together with HBV DNA in serum were measured using the electro-chemiluminescence immuno-assay (ECLIA) kits and fluorescence quantitative polymerase chain reaction (FQ-PCR) assay, respectively. Results: The rate of non-/hypo-response was 17.99%. After adjusting the potential confounding factors, the telbivudine treatment on HBsAg-positive mothers in the second and third trimesters of pregnancy seemed as the protective factor for non-/hypo-response to hepatitis B vaccine in infants (aRR=0.119, 95% CI: 0.014-0.974). Levels of IFN-γ and IL-10 in telbivudine-treated group were higher than those in the controls (aRR=8.684, 95%CI: 1.977-38.140; aRR=5.330, 95% CI: 1.278-22.236). When the serum levels of IFN-γ and IL-10 in neonatal peripheral blood were higher than 228.47 pg/ml and 174.05 pg/ml respectively, the infants were less likely to be non-/hypo-responsive to the hepatitis B vaccine (aRR=0.300, 95%CI: 0.105-0.857) (aRR= 0.104, 95% CI: 0.030-0.354). Conclusion: Telbivudine treatment provided for the HBsAg-positive mothers in second and third trimesters of pregnancy were less likely to develop non-/low-responsive to hepatitis B vaccine in infants since IFN-γ and IL-10 might have played a vital role in this process.

[Effects related to HBeAg status and mode of delivery as well as the interactions on intrauterine transmission among HBsAg-positive mothers].

OBJECTIVE: To investigate the relationship between HBeAg status, mode of delivery and intrauterine transmission of the HBsAg-positive mothers as well as their interactions. METHODS: A total of 344 HBsAg-positive pregnant women and their infants were enrolled in this study. The mothers were recruited from the Third People's Hospital of Taiyuan, from July 2011 to January 2013. Serum HBV-M and HBV DNA were measured using the electro-chemiluminescence immune-assay (ECLIA) kits and fluorescene quantitative polymerase chain reaction (FQ-PCR) assay, respectively. Univariate analysis and unconditional logistic regression analysis were used to explore the risk factors on intrauterine transmission. RESULTS: Among 344 neonates born to HBsAg-positive mothers, 42 were validated as HBV intrauterine transmitted, with the rate of intrauterine transmission as 12.21% (42/344). The rates of intrauterine transmission among HBeAg-positive and HBeAg-negative mothers were 18.52% (30/162) and 6.59% (12/182), respectively. The rates of intrauterine transmission were 22.22% (34/153) and 4.19% (8/191) in the groups of vaginal birth or caesarean delivery, respectively. RESULTS from unconditional logistic regression analysis showed that after adjusting the confounding factors, HBeAg-positive mothers (OR=3.003, 95% CI: 1.368-6.593) and vaginal birth (OR=7.333, 95% CI: 3.108-17.302) might serve as the risk factors for the HBV intrauterine transmission. Data from the interaction analysis showed that there were additive interactions [relative excess risk due to interaction (RERI) as 14.229; the attributable proportion (AP) due to interaction as 0.587; the synergy index (SI) as 2.579] and multiplicative interaction (OR=1.084, 95%CI: 0.720-1.632) between HBeAg status and the modes of delivery. CONCLUSION: Vaginal birth and HBeAg-positive might serve as the risk factors for HBV intrauterine transmission. There also appeared additive interactions between HBeAg status and the mode of delivery.

New class of plastic bulk metallic glass.

An intrinsic plastic Cu(45)Zr(46)Al(7)Ti(2) bulk metallic glass (BMG) with high strength and superior compressive plastic strain of up to 32.5% was successfully fabricated by copper mold casting. The superior compressive plastic strain was attributed to a large amount of randomly distributed free volume induced by Ti minor alloying, which results in extensive shear band formation, branching, interaction and self-healing of minor cracks. The mechanism of plasticity presented here suggests that the creation of a large amount of free volume in BMGs by minor alloying or other methods might be a promising new way to enhance the plasticity of BMGs.

[Studies on the anti-tumorpromotion activities of dehydroepiandrosterone and its mechanism of action].

AIM: To investigate the anti-tumorpromoting activity of dehydroepiandrosterone (DHEA) and its mechanism of action. METHODS: Using croton oil-induced ear edema model and applying confocal laser scanning microscopy, flow cytometry, immuno-fluorescent techniques to investigate the inhibitory effect of DHEA on tumor promotion. RESULTS: DHEA 25 mg.kg-1 was shown to inhibit croton oil induced ear edema in mice by 51%. DHEA at dose of 40 mg.kg-1 and 10 mg.kg-1 exhibited inhibitory effects on croton oil-induced ornithine decarboxylase (ODC) activity by 64% and 53%, respectively. These results revealed that DHEA can block the change of cell cycle and the percentage of S phase was decreased to 17% at concentration of 10(-7) mol.L-1. The increase of[Ca2+]i and pH as well as PKC-activation induced by TPA stimulation were significantly inhibited by DHEA pretreatment. CONCLUSION: The present experiments demonstrate that DHEA appears to be an attractive candidate as an anti-tumorpromotion agent for tumor chemoprevention. The mechanism of its action might be related to its inhibitory effects on ODC activity and Ca(2+)-DG-PKC signal pathway.

[Studies of antitumor and chemopreventive agents against neoplasm: synthesis of coumarin 3-glyoxal derivatives and relationship between structure and antimutagenic activity].

It has been shown that alpha-glyoxal and its derivatives possess antivirus and antitumor activities. Eighteen new coumarin 3-glyoxal derivatives were synthesized in our laboratory. The fragmentation pattern of MS and the characteristic signals of 1HNMR of these compounds have also been studied. In pharmacological test in vitro most of these analogues showed antimutagenic activities, among them, compound 9 exhibited very strong antimutagenic activity and eight compounds showed strong effects. The struture-activity relationship and the possible active substructure responsible for the activity of these compounds were discussed. As expected, coumarin 3-glyoxals showed higher antimutagenic activities than their 3-acetyl coumarin counterparts. We also found that alkylation or esterification of 7-hydroxy were favorable to their activities.

[Studies of chemopreventive agents against neoplasma: synthesis of 3-acetyl coumarin derivatives and relationship between antimutagenic activity and structure].

Twenty-five 3-acetylcoumarin derivatives were synthesized among which twenty-two were not reported before. Antimutagenic activity screen in vitro has shown that some of these compounds have various activities. The structure and activity relationship for 5-, 7-, 8-substituents has been studied. Pharmacological data showed that: the substituent on position 8 has important effect on its activity. When there is only a hydroxy group on position 7, its activity is the highest among those with other substituents, but when a methyl is on position 8, the order of the activity is reversed. Other trends have also been found which provided some clues for further structural modification.

The influence of the extent of target organs on sensitivities of methods for screening rodent carcinogens.

Two hundred and thirty-three rodent carcinogens from the Carcinogenic Potency Database (CPDB) were analyzed with CASE (Computer Automated Structure Evaluation), and a comparison of the extents of target organs with the sensitivities for long-term carcinogenic bioassays in rats and mice, Salmonella assay (Sty), electrophilic substructure alert analysis (ESAA) and CASE was made. The carcinogenicity of 233 chemicals was evaluated in both rat and mouse bioassays. The present study showed that the sensitivities of the five methods for screening carcinogens were related to the extents of target organs of carcinogens. Among the carcinogens that did not induce tumors (extent = 0) in rats, the sensitivities of Sty and ESAA were 46 and 53, respectively. Among the carcinogens which induced tumors at a single organ (extent = 1) in rats, the sensitivities were 57 and 64 respectively; and 71 and 80 at multiple organs (extent > 1) respectively. The sensitivities of CASE were 76, 82, and 89 respectively at these three different extents. Similar results were obtained with these carcinogens in mice. The results indicate that mutagenic or electrophilic carcinogens are more likely to induce tumors at multiple target organs; in contrast, most carcinogens which induced tumors at only a single target organ in one species are rarely mutagenic or electrophilic. The sensitivities of Sty and ESAA were lower than that of the CASE method in these carcinogens. CASE analyzed chemical structures of many carcinogens and non-carcinogens and then established a database of key fragments, and its parameters are not only based on mutagenicity or electrophilicity of chemicals, and this resulted in a more exact detection of the carcinogenicity of chemicals with the CASE method.

[Structural basis of mutagenicity of heterocyclic amines].

The CASE (computer-automated structure evaluation) was used to gain an understanding of the basis of mutagenicity of heterocyclic amines. It was found that the activity of these molecules was dependent upon the amino connected with the carbon in the benzene cycle, and the position of nitrogens in the heterocycle was also important. Both the sensitivity and specificity of the CASE system established in my laboratory approached 1.00.

[A computer system of automated evaluation of structure-activity relationship of chemical mutagens].

A computer automated structure evaluation (CASE) system has been established. The data base of the system consists of more than 2000 chemicals and hundreds of biophores and biophobes identified by CASE. All programs can be run in micro-computer. Thus, entry of a chemical unknown genetoxity will result in the generation of all the possible fragments. On the basis of the presence and/or absence of these descriptors, CASE can predict activity or lack of it. In addition, and independently of the above, CASE also performs spell out, please and comparison program of genetic toxicology. The CASE program can be used to predict the mutagenicity and carcinogenicity of the many untested chemicals in the ambient environment. The sensitivity and specificity of this system all exceeds 90% and therefore the system has a very good-prospect of being used for forecasting.