Objective To investigate the mechanism of hearing loss caused by tympanic membrane(TM)per-foration.Methods We constructed a full ear finite element model,and the personalized finite element model of TM perforation was constructed to simulate hearing loss caused by TM perforation.The difference between the displace-ment response of the basement membrane and the baseline was applied to simulate hearing loss,and the contribution of various components of the middle ear to hearing loss was analyzed to study the mechanism of hearing loss caused by TM perforation.Results If the coupling of the round window membrane and the middle ear air was removed,the hearing loss at the low frequency was about 40 dB,while the high-frequency was the same as the baseline.Re-moval of the coupling between the inner side of the eardrum and the middle ear cavity resulted in a reduction in par-tial low-frequency hearing and an increase in high-frequency hearing loss.The continuous disconnection between the air in the external auditory canal and the air in the middle ear cavity increased the low-frequency hearing loss.How-ever,after the removal of the coupling between the round window membrane and the middle ear air and the connec-tion between the middle ear air and the lateral side of the TM,the original hearing loss of 40 dB at low-frequency dropped to 10 dB.While the removal of the coupling between the middle ear cavity air and the ossicular chain had no significant impact on hearing loss.Conclusion TM perforation may cause hearing loss by both the reduction of sound transmission and the reduction of sound pressure difference between the two sides of TM.The round window membrane can counteract the influence of the hearing loss caused by TM perforation.

OBJECTIVETo access the antibody persistence 24-month after revaccination with 3-dose of hepatitis B vaccine (HepB) among non-response adults.

METHODSA total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling methods. Each group was vaccinated with one of the following four types of HepB at 0-, 1-, 6-months schedule: 20 µg HepB derived in Saccharomyces Cerevisiae (HepB-SC), 20 µg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 µg HepB-SC and 10 µg HepB derived in Hansenula Polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). The non-responders were revaccinated with three doses of HepB at 0-, 1-, 6-months schedule and the type of HepB was the same as which was used for primary immunization. Blood samples were collected one month (T1) and two years (T24) after revaccination and anti-HBs, antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface angtigen (HBsAg) (if anti-HBs < 10 mU/ml) were detected by CMIA. χ(2) test was used to compared age, gender and body mass index (BMI) between different groups and the anti-HBs positive rate at T1 and T24; analysis of variance (ANOVA) was used to compare the geometric mean concentration (GMC) of anti-HBs between difference groups. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis respectively.

RESULTSA total of 900 non-responders were identified and 71.7% (645/900) of them completed three-dose revaccination and blood collection after revaccination. 467 (72.4%) non-responsive adults were followed up at T24. The anti-HBs positive rate decreased from 85.65% (95% CI: 82.14%-88.71%) at T1 to 60.60% (95% CI: 56.01%-65.06%) at T24 and the corresponding GMC decreased from 175.62 (95% CI: 139.03-221.84) mU/ml to 21.43 (95% CI: 17.62-26.06) mU/ml. Multivariate analysis showed that positive rate of anti-HBs at T24 was associated with gender, HepB type for revaccination and anti-HBs level at T1, but only anti-HBs level at T1 was associated with the anti-HBs titer at T24. No subject showed HBsAg seroconversion and anti-HBc conversion rate was 3.64% (17/467) at T24.

CONCLUSIONAnti-HBs titer decreases rapidly two years after HepB revaccination among non-responsive adults, but more than half non-responderd still kept anti-HBs above protective level. The immunity durability after revaccination was associated with gender, HepB type for revaccination and anti-HBs titer one month after revaccination.

Adolescent ; Adult ; Animals ; Body Mass Index ; CHO Cells ; China ; Cricetinae ; Cricetulus ; Enzyme-Linked Immunosorbent Assay ; Female ; Follow-Up Studies ; Hepatitis B ; prevention & control ; Hepatitis B Antibodies ; blood ; Hepatitis B Core Antigens ; immunology ; Hepatitis B Surface Antigens ; immunology ; Hepatitis B Vaccines ; administration & dosage ; classification ; Humans ; Immunization, Secondary ; Male ; Middle Aged ; Multivariate Analysis ; Pichia ; Risk Factors ; Saccharomyces cerevisiae ; Seroconversion ; Vaccination ; Young Adult

OBJECTIVETo assess the 24-month efficacy after booster vaccination with 3 doses of hepatitis B vaccine among low-response adults in Zhangqiu county of Shandong province.

METHODSA total of 24 237 adults aged 18-49 years old, never received HepB vaccination, without HBV infection history, and had been living at 3 towns of Zhangqiu county in Shandong province for more than half a year in september, 2009, were collected blood samples of 3-5 ml. A total of 11 590 adults who were negative for hepatitis B virus (HBV) surface antigen (HBsAg) , antibody to HBsAg (Anti-HBs) and antibody to HBV core antigen (Anti-HBc), were divided into four groups randomly and were vaccinated following the schedule of 0-1-6 with 20 µg hepatitis B vaccine made by recombinant deoxyribonucleic acid techniques in Saccharomyces cerevisiae (HepB-SC), 20 µg hepatitis B vaccine made by Chinese hamster ovary cell (HepB-CHO), 10 µg HepB-SC and 10 µg hepatitis B vaccine made by recombinant deoxyribonucleic acid techniques in Hansenula Polymorpha (HepB-HP), respectively. The adults who were low-response to the primary hepatitis B vaccination (10 mU/ml ≤ anti-HBs<100 mU/ml) were divided into four groups by cluster random sampling. These groups were revaccinated with 3-dose of above-mentioned four kinds of HepB respectively. Blood samples were drawn from 1 month (T1) and 24 month (T24) after the 3 dose revaccination, respectively. Anti-HBs and anti-HBc was detected by Chemiluminescence Microparticle Imunoassay (CMIA).

RESULTSOut of the 8 592 adults who have accepted the primary vaccination of hepatitis B and been collected the blood samples, 1 306 subjects showed low-response. A total of 718 low-response subjects were collected blood samples after T1 and T24 following 3 doses of booster vaccination. The proportion of the four groups was 32.3% (232/718), 25.8% (185/718) , 19.3% (139/718) , 22.6% (162/718) , respectively. The average proportion of anti-HBs ≥ 100 mIU/ml were decreased from 77.58% after T1 to 35.63% after T24 (χ² = 256.87, P < 0.01). The proportion of anti-HBs ≥ 100 mIU/ml in T24 were 38.8% (90/177), 39.5% (73/185), 25.2% (35/139) and 35.8% (58/162) in four groups, respectively. The proportion of anti-HBs>100 mIU/ml in T24 was significantly different among groups (χ² = 8.81, P = 0.032). The average geometric mean concentration (GMC) was significantly reduced from 443.53 mIU/ml after T1 to 48.98 mIU/ml after T24 (F = 439.41, P < 0.01). The GMC was 60.26 (45.71-77.62), 1.29 (38.90-69.18) , 35.48 (25.70-48.98) and 46.77 (33.88-6.07) mIU/ml in four groups, respectively (F = 1.97, P = 0.117) . Compared with vaccinated 20 µg HepB-SC, the proportion of anti-HBs ≥ 100 mIU/ml and GMC was 0.56 (0.35-0.91) and -0.20 (-0.39--0.02) times. The positive of HBsAg was not found and the positive rate of anti-HBc was 2.6% (18/692) in T24.

CONCLUSIONProtective antibody following booster vaccination with three doses of hepatitis B vaccines among low-response adults after 2 years fade faster. Antibody level of anti-HBs in T24 was corrected with the booster vaccine type and age. 20 µgHepB-SC seemed better than 10 µg HepB-SC.

Adult ; Animals ; CHO Cells ; Cricetulus ; Follow-Up Studies ; Hepatitis B ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens ; Hepatitis B Vaccines ; Hepatitis B virus ; Humans ; Immunization, Secondary ; Pichia ; Vaccination

Targeted protein degradation(TPD)has rapidly emerged as a therapeutic modality to eliminate previously undruggable proteins by repurposing the cell's endogenous protein degrada-tion machinery.However,the susceptibility of proteins for targeting by TPD approaches,termed"degradability",is largely unknown.Here,we developed a machine learning model,model-free anal-ysis of protein degradability(MAPD),to predict degradability from features intrinsic to protein tar-gets.MAPD shows accurate performance in predicting kinases that are degradable by TPD compounds[with an area under the precision-recall curve(AUPRC)of 0.759 and an area under the receiver operating characteristic curve(AUROC)of 0.775]and is likely generalizable to inde-pendent non-kinase proteins.We found five features with statistical significance to achieve optimal prediction,with ubiquitination potential being the most predictive.By structural modeling,we found that E2-accessible ubiquitination sites,but not lysine residues in general,are particularly associated with kinase degradability.Finally,we extended MAPD predictions to the entire proteome to find 964 disease-causing proteins(including proteins encoded by 278 cancer genes)that may be tractable to TPD drug development.

Objective:To construct a value evaluation framework for high-value medical consumables,providing a guidance for medical insurance access and hospital access management scenarios in China.Methods:It conducted literature review,qualitative in-terviews and quantitative surveys.A total of 12 experts were invited for qualitative interviews,while 100 experts from four fields of health technology assessment,medical insurance,hospital management,and clinical practice participated in the quantitative survey.Through those process,it generated the composition of the value framework and the scoring of each item.Differences in ratings be-tween different scenarios and experts were analyzed through chi-square tests.The recommendation level for each item was graded.Re-sults:A comprehensive value evaluation framework for high-value medical consumables was established,which included 6 core dimen-sions,comprised 16 items for secondary dimensions and 50 items for tertiary dimensions.It showed significant differences between the medical insurance access and hospital access scenarios,as well as among different fields of experts in the same scenario.furthermore,grading the items in two scenarios.The medical insurance access scenario had 8 highly recommended items,and the hospital access scenario had 24 highly recommended items.Conclusion:Value evaluation should encourage multi-dimensional assessments and inter-disciplinary participation,continually improving the management of high-value medical consumables in medical insurance and hospital access.

Objective To assess the 24-month efficacy after booster vaccination with 3 doses of hepatitis B vaccine among low-response adults in Zhangqiu county of Shandong province.Methods A total of 24 237 adults aged 18-49 years old, never received HepB vaccination,without HBV infection history,and had been living at 3 towns of Zhangqiu county in Shandong province for more than half a year in september, 2009,were collected blood samples of 3-5 ml.A total of 11 590 adults who were negative for hepatitis B virus (HBV)surface antigen(HBsAg),antibody to HBsAg(Anti-HBs)and antibody to HBV core antigen(Anti-HBc),were divided into four groups randomly and were vaccinated following the schedule of 0-1-6 with 20 μg hepatitis B vaccine made by recombinant deoxyribonucleic acid techniques in Saccharomyces cerevisiae ( HepB-SC) , 20μg hepatitis B vaccine made by Chinese hamster ovary cell ( HepB-CHO) , 10μg HepB-SC and 10 μg hepatitis B vaccine made by recombinant deoxyribonucleic acid techniques in Hansenula Polymorpha ( HepB-HP ) , respectively. The adults who were low-response to the primary hepatitis B vaccination ( 10 mU/ml≤anti-HBs <100 mU/ml ) were divided into four groups by cluster random sampling.These groups were revaccinated with 3-dose of above-mentioned four kinds of HepB respectively.Blood samples were drawn from 1month( T1 ) and 24 month( T24 ) after the 3 dose revaccination, respectively.Anti-HBs and anti-HBc was detected by Chemiluminescence Microparticle Imunoassay( CMIA) . Results Out of the 8 592 adults who have accepted the primary vaccination of hepatitis B and been collected the blood samples,1 306 subjects showed low-response.A total of 718 low-response subjects were collected blood samples after T1 and T24 following 3 doses of booster vaccination.The proportion of the four groups was 32.3% ( 232/718 ) , 25.8% ( 185/718 ) , 19.3% ( 139/718 ) , 22.6% ( 162/718 ) , respectively.The average proportion of anti-HBs≥100 mIU/ml were decreased from 77.58% after T1 to 35.63%after T24(χ2 =256.87,P<0.01).The proportion of anti-HBs≥100 mIU/ml in T24 were 38.8%(90/177),39.5%(73/185),25.2%(35/139) and 35.8%(58/162) in four groups,respectively.The proportion of anti-HBs >100 mIU/ml in T24 was significantly different among groups (χ2 =8.81, P =0.032).The average geometric mean concentration(GMC) was significantly reduced from 443.53 mIU/ml after T1 to 48.98 mIU/ml after T24 (F =439.41,P<0.01).The GMC was 60.26(45.71-77.62),1.29 (38.90-69.18),35.48(25.70-48.98) and 46.77(33.88-6.07) mIU/ml in four groups,respectively(F=1.97,P=0.117).Compared with vaccinated 20 μg HepB-SC, the proportion of anti-HBs≥100 mIU/ml and GMC was 0.56(0.35-0.91) and -0.20(-0.39--0.02)times.The positive of HBsAg was not found and the positive rate of anti-HBc was 2.6% ( 18/692 ) in T24 .Conclusion Protective antibody following booster vaccination with three doses of hepatitis B vaccines among low-response adults after 2 years fade faster.Antibody level of anti-HBs in T24 was corrected with the booster vaccine type and age.20μgHepB-SC seemed better than 10 μg HepB-SC.

Objective To access the antibody persistence 24-month after revaccination with 3-dose of hepatitis B vaccine (HepB) among non-response adults. Methods A total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling methods. Each group was vaccinated with one of the following four types of HepB at 0-, 1-, 6- months schedule: 20 μg HepB derived in Saccharomyces Cerevisiae (HepB-SC), 20 μg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 μg HepB-SC and 10 μg HepB derived in Hansenula Polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). The non-responders were revaccinated with three doses of HepB at 0-, 1-, 6-months schedule and the type of HepB was the same as which was used for primary immunization. Blood samples were collected one month (T1) and two years (T24) after revaccination and anti-HBs, antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface angtigen (HBsAg) (if anti-HBs<10 mU/ml) were detected by CMIA.χ2 test was used to compared age, gender and body mass index (BMI) between different groups and the anti-HBs positive rate at T1 and T24; analysis of variance (ANOVA) was used to compare the geometric mean concentration (GMC) of anti-HBs between difference groups. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis respectively. Results A total of 900 non-responders were identified and 71.7%(645/900) of them completed three-dose revaccination and blood collection after revaccination. 467 (72.4%) non-responsive adults were followed up at T24. The anti-HBs positive rate decreased from 85.65%(95%CI:82.14%-88.71%) at T1 to 60.60%(95%CI:56.01%-65.06%) at T24 and the corresponding GMC decreased from 175.62 (95%CI: 139.03-221.84)mU/ml to 21.43 (95%CI:17.62-26.06)mU/ml. Multivariate analysis showed that positive rate of anti-HBs at T24 was associated with gender, HepB type for revaccination and anti-HBs level at T1, but only anti-HBs level at T1 was associated with the anti-HBs titer at T24. No subject showed HBsAg seroconversion and anti-HBc conversion rate was 3.64%(17/467) at T24. Conclusion Anti-HBs titer decreases rapidly two years after HepB revaccination among non-responsive adults, but more than half non-responderd still kept anti-HBs above protective level. The immunity durability after revaccination was associated with gender, HepB type for revaccination and anti-HBs titer one month after revaccination.

Objective To assess the 3-year anti-HBs persistence after primary vaccination with three-dose of hepatitis B vaccine (HepB) among normal and high-responder adults. Methods A total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in local areas for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling method. Each group was vaccinated with one of the following four types of HepB at 0-1-6 months schedule: 20 μg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20μg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10μg HepB-SC and 10 μg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). During the follow-up to normal and high-responders, the following information was collected: the demographic characteristic (including age and gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases. Blood samples were collected one month (T1) and three years after primary vaccination (T2) and anti-HBs, anti-HBc and HBsAg (if anti-HBs<10 mU/ml) were detected by CMIA. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis, respectively. Results A total of 4 677 normal and high-responders were identified. Among 4 677 participants, 2 014 (43.06%) were males and 2 663 (56.94%) were females. The positive rate was 100%at T1 and it decreased to 80.99% (3 788/4 677) three years after vaccination. The corresponding GMC was decreased from 1 413.48 (95%CI:1 358.86-1 470.30) mU/ml to 60.33 (95%CI:56.97-63.90) mU/ml. When comparing with those vaccinated 20 μg HepB-CHO, the significantly lower positive rate of anti-HBs three years after vaccination was observed in those vaccinated 20 μg HepB-SC, 10 μg HepB-SC and 10 μg HepB-HP. The OR (95%CI) was 0.65 (0.50-0.84), 0.52 (0.41-0.67) and 0.31 (0.28-0.45), respectively. The GMC of anti-HBs was also significantly lower among those vaccinated 20μg HepB-SC, 10μg HepB-SC and 10 μg HepB-HP. The b (95%CI) was -0.33 (-0.47- -0.20), -0.41 (-0.55- -0.28) and -0.78 (-0.92--0.65), respectively. The GMC of anti-HBs in those aged 30-39 years old and 40-49 years old were lower than that in 18-29 years. The b (95%CI) was-0.31 (-0.47--0.15) and-0.24 (-0.39--0.09), respectively. When comparing with those whose anti-HBs titer was less than 999 mU/ml at T1, the significantly higher positive rate of anti-HBs three years after vaccination was observed in those whose anti-HBs titer was 1 000-1 999 mU/ml, those whose anti-HBs titer was 2 000-9 999 mU/ml and those whose anti-HBs titer was ≥10 000 mU/ml. The OR (95%CI) was 4.97 (3.80-6.49), 7.87 (16.19-10.01) and 9.67 (6.47-14.44), respectively. When comparing with those whose anti-HBs titer was ≤999 mU/ml at T1, the GMC of anti-HBs three years after vaccination was also significantly higher among those whose anti-HBs titer at T1 was 1 000-1 999 mU/ml, those whose anti-HBs titer at T1 was 2 000-2 999 mU/ml and those whose anti-HBs titer at T1 was≥10 000 mU/ml. The b (95%CI) was 1.00 (0.87-1.14), 1.85 (1.74-1.97) and 3.28 (3.12-3.44), respectively. Four subjects showed HBsAg seroconversion and anti-HBc conversion rate was 4.68% at T2. Conclusions Anti-HBs GMC decreased rapidly three years after primary vaccination among normal and high-responder adults, while the positive rate of anti-HBs still kept at a high level. The anti-HBs persistence after primary vaccination was associated with HepB type, age and GMC of anti-HBs one month after vaccination.

Objective To evaluate the 5-year antibody persistence and the risk factors associated with the persistence after primary vaccination of hepatitis B vaccine (HepB) among normal or high-response adults. Methods A total of 24 237 healthy adults who had no histories of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and were aged 18-49 years were selected from 79 villages in north of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling methods. Each group was vaccinated with one of the following four types of HepB at 0-1-6 months schedule: 20 μg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20 μg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10 μg HepB-SC and 10 μg HepB derived in Hansenula polymorpha (HepB-HP). The normal and high-responder was followed up and their demographic characteristic (including age, gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases were investigated. Blood samples were collected one month (T1) and five years (T2) and anti-HBs, anti-HBc and HBsAg (if anti-HBs<10 mU/ml) were detected by CMIA. A total of 1 902 participants were followed up and the risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis, respectively. Results Among 1 902 adults, 824 (43.32%) were male and 1 078 (56.68%) were female. The anti-HBs positive rate was 100% at T1 and it decreased to 73.29% (1 394 cases) at T2. The corresponding GMC was decreased from 1 527.15 (95%CI:1 437.84-1 622.01) mU/ml at T1 to 35.07 (95%CI:32.20-38.19) mU/ml at T2. When comparing with those vaccinated 20μg HepB-SC, the significantly lower positive rate at T2 was observed in those vaccinated 10 μg HepB-SC group and 10 μg HepB-HP group. The OR (95%CI) was 0.41 (0.28-0.61) and 0.27 (0.18-0.39), respectively. The GMC of anti-HBs was also significantly lower among those vaccinated 10 μ g HepB-SC and 10 μ g HepB-HP. The b ( 95%CI ) was -0.20 ( -0.28- -0.12)and-0.36(-0.44--0.29), respectively. When comparing with those occasionally drinking, the significantly lower positive rate at T2 was observed in those regular drinking. The OR(95%CI) was 0.51(0.30-0.87). The GMC of anti-HBs in age group of 18-29 was significantly higher than those in 40-49 age group;the b (95%CI) was-0.10(-0.18--0.01). When comparing with those whose anti-HBs titer was less than 999 mU/ml at T1, the significantly higher positive rate of anti-HBs at T2 was observed in those whose anti-HBs titer was 1 000-1 999 mU/ml, those whose anti-HBs titer was 2 000-2 999 mU/ml and those whose anti-HBs titer was ≥10 000 mU/ml. The OR (95%CI) was 10.11 (6.90-14.82), 20.42 (13.98-29.82) and 54.58 (22.08-134.92), respectively. When comparing with those whose anti-HBs titer was ≤999 mU/ml at T1, the GMC of anti-HBs at T2 was also significantly higher among those whose anti-HBs titer at T1 was 1 000-1 999 mU/ml, those whose anti-HBs titer at T1 was 2 000-2 999 mU/ml and those whose anti-HBs titer at T1 was≥10 000 mU/ml. The b (95%CI) was 0.55 (0.47-0.62), 0.94 (0.88-1.00) and 1.63 (1.54-1.72), respectively. Nobody was found positive to HBsAg at T2 and the conversion rate of anti-HBc was 3.89% (74/1 902) at T2. Conclusion Anti-HBs GMC decreased rapidly at T2 among normal and high-responder adults, while the positive rate of anti-HBs still kept at a high level. The antibody persistence among normal and high-responder adults at T2 was associated with HepB type, age, history of drinking and GMC of anti-HBs at T1.

Objective To assess the 4-year anti-HBs persistence after revaccination with 3-dose of hepatitis B vaccine (HepB) among low-responsive adults. Methods A total of 24 237 healthy adults who had no history of hepatitis B infection and hepatitis B vaccination, resided in the local area for more than six months and were aged 18-49 years were selected from 79 villages of Zhangqiu county, Shandong province, China in 2009. Blood samples were obtained and hepatitis B surface antigen (HBsAg), antibody against hepatitis B surface antigen (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were detected using ELISA method. A total of 11 590 persons who were negative for all of these indicators were divided into four groups by cluster sampling method. Each group was vaccinated with one of the following four types of HepB at 0-1-6 months schedule:20μg HepB derived in Saccharomyces cerevisiae (HepB-SC), 20μg HepB derived in Chinese hamster ovary cell (HepB-CHO), 10μg HepB-SC and 10μg HepB derived in Hansenula polymorpha (HepB-HP). Blood samples were collected one month after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). The 892 low-responders were revaccinated with three doses of HepB at 0-1-6 months schedule and the type of HepB was the same as which was used for primary immunization. During the follow-up to low-responders, the following informations were collected: the demographic characteristics (including age, gender), histories of hepatitis B infection, hepatitis B vaccination, smoking, drinking and chronic diseases. Blood samples were collected one month (T1) and four years after revaccination and anti-HBs, anti-HBc and HBsAg (if anti-HBs <10 mU/ml) were detected by CMIA. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple logistic regression analysis and multifactor linear regression model analysis respectively. Anti-HBs titer at T1 was grouped according to the level and was considered as the independent variable in the model analysis. Results A total of 529 participants were identified from 892 low-responders. Among 529 participants, 276 (52.2%) were males and 253 (47.8%) were females. The positive rate was 82.6% (437/529) at T1 and it decreased to 28.2% (149/529) four years after revaccination. The corresponding GMC decreased from 542.06 (95%CI: 466.72-629.56) mU/ml to 27.69 (95%CI: 23.08-33.23) mU/ml. Multivariable analysis showed the positive rate of anti-HBs 4 years after revaccination was independently associated with anti-HBs titer at T1. The positive rate among those whose anti-HBs titer more than 1 000 mU/ml at T1 was significantly higher than those whose anti-HBs titer less than 100 mU/ml. The OR (95%CI) was 39.67 (13.81-114.01). The GMC was associated with HepB type for revaccination and anti-HBs titer at T1. The GMC among those revaccinated 20 μg HepB was significantly higher than those revaccinated 20 μg HepB-CHO, 10 μg HepB-SC and 10 μg HepB-HP. The b (95%CI) was-0.40 (-0.78--0.02),-0.57 (-1.01--0.15) and-0.63 (-1.03--0.23), respectively. The GMC among those whose anti-HBs titer 100-999 mU/ml and those whose anti-HBs titer≥1 000 mU/ml at T1 were higher than those whose anti-HBs titer <100 mU/ml. The b (95%CI) was 0.93 (0.53-1.33) and 3.31 (2.88-3.73) respectively. Conclusion Anti-HBs GMC decreased rapidly 4 years after revaccination among low-responsive adults, but still kept good protecion. The anti-HBs persistence after revaccination was associated with HepB type for revaccination and anti-HBs level of titer one month after revaccination.