Causal role of immune cells in inflammatory bowel disease: A Mendelian randomization study.

Inflammatory bowel disease (IBD) is characterized by an inflammatory response closely related to the immune system, but the relationship between inflammation and IBD remains unclear. We performed a comprehensive 2-sample Mendelian randomization (MR) analysis to determine the causal relationship between immune cell characteristics and IBD. Using publicly available genetic data, we explored the relationship between 731 immune cell characteristics and IBD risk. Inverse-variance weighting was the primary analytical method. To test the robustness of the results, we used the weighted median-based, MR-Egger, simple mode, and mode-based methods. Finally, we performed a reverse MR analysis to assess the possibility of reverse causality. We identified suggestive associations between 2 immune cell traits and IBD risk (P = 4.18 × 10-5 for human leukocyte antigen-DR on CD14+ monocytes, OR: 0.902; 95% CI: 0.859-0.947; for CD39+ CD4+ T cells, P = 6.24 × 10-5; OR: 1.042; 95% CI: 1.021-1.063). Sensitivity analysis results of these immune cell traits were consistent. In reverse MR analysis, we found no statistically significant association between IBD and these 2 cell traits. Our study demonstrates the close connection between immune cells and IBD using MR, providing guidance for future clinical and basic research.

Risk prediction of hepatobiliary and pancreatic cancers in elderly Chinese: The Dongfeng-Tongji cohort.

AIM: Hepatobiliary and pancreatic (HBP) cancers are among the deadliest malignancies. The objective of the study is to build cost-effective models to identify high-risk individuals for early diagnosis and substantially to reduce the burden of HBP cancers. METHODS: Based on the prospective Dongfeng-Tongji cohort with ∼6 years follow-up, we identified 162 incident cases of hepatocellular carcinoma (HCC), 53 of biliary tract cancer (BTC), and 58 of pancreatic cancer (PC). We matched three controls to each case by age, sex, and hospital. We applied conditional logistic regression to identify predictive clinical variables, from which we constructed clinical risk scores (CRSs). We evaluated the utility of CRSs in stratifying high-risk individuals by 10-fold cross-validation. RESULTS: Among 50 variables we screened, 6 were independent predictors of HCC, with the top ones being hepatitis (OR = 8.51, 95% CI (3.83, 18.9)), plateletcrit (OR = 0.57, 95% CI (0.42, 0.78)), and alanine aminotransferase (OR = 2.06, 95% CI (1.39, 3.06)). Gallstone (OR = 2.70, 95% CI (1.17, 6.24)) and direct bilirubin (OR = 1.58, 95% CI (1.08, 2.31)) were predictive of BTC, while hyperlipidemia (OR = 2.56, 95% CI (1.12, 5.82)) and fasting blood glucose (OR = 2.00, 95% CI (1.26, 3.15)) were predictive of PC. The CRSs achieved AUCs of 0.784 for HCC, 0.648 for BTC, and 0.666 for PC, respectively. When applying to the full cohort with age and sex included as predictors, the AUCs were increased to 0.818, 0.704, and 0.699, respectively. CONCLUSIONS: Disease history and routine clinical variables are predictive of incident HBP cancers in elderly Chinese.

Mechanisms of Chinese Medicine in Gastroesophageal Reflux Disease Treatment: Data Mining and Systematic Pharmacology Study.

OBJECTIVE: To identify specific Chinese medicines (CMs) that may benefit patients with gastroesophageal reflux disease (GERD), and explore the action mechanism. METHODS: Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and PubMed from October 1, 2011 to October 1, 2021. Data from all eligible articles were extracted to establish the database of CMs for GERD. Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified. A system pharmacology approach was used to explore the action mechanism of these medicines. RESULTS: A total of 278 prescriptions for GERD were analyzed, including 192 CMs. Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination. A total of 32 active ingredients and 66 targets were screened for the treatment of GERD. Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer, fluid shear stress and atherosclerosis, advanced glycation end product (AGE), the receptor for AGE signaling pathway in diabetic complications, bladder cancer, and rheumatoid arthritis. CONCLUSION: Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways.

Evaluating Agricultural Sustainability and Green GDP in China: An Emergy Analysis.

Agricultural sustainability is the foundation and a guarantee of sustainable human reproduction. The scientific assessment of China's agricultural sustainability is a prerequisite for properly resolving the conflict between short-term economic interests and long-term ecological security. This paper uses the emergy analysis method to estimate agricultural sustainability in China and further calculates the agricultural environmental cost and green GDP. The results show that China's agricultural emergy yield rate (EYR) is generally greater than 1. This means that more emergy is obtained in relation to renewable and non-renewable inputs from human activity, which also indicates that China's agricultural agroecosystem is characteristic of a profound transition from a self-supporting tradition to a modern industry based on external economic resource consumption. In contrast, China's agricultural growth is mainly driven by the input of a large amount of non-renewable resources, which makes the environmental loading rate (ELR) increase year by year, resulting in the deterioration of China's agricultural emergy sustainability index (ESI). China's agricultural green GDP accounts for about 94.4% of traditional GDP, which means that the average agricultural environmental cost is about 5.6%, mainly from land loss, accounting for 48.23% of the environmental cost.

Rare variant association tests for ancestry-matched case-control data based on conditional logistic regression.

With the increasing volume of human sequencing data available, analysis incorporating external controls becomes a popular and cost-effective approach to boost statistical power in disease association studies. To prevent spurious association due to population stratification, it is important to match the ancestry backgrounds of cases and controls. However, rare variant association tests based on a standard logistic regression model are conservative when all ancestry-matched strata have the same case-control ratio and might become anti-conservative when case-control ratio varies across strata. Under the conditional logistic regression (CLR) model, we propose a weighted burden test (CLR-Burden), a variance component test (CLR-SKAT) and a hybrid test (CLR-MiST). We show that the CLR model coupled with ancestry matching is a general approach to control for population stratification, regardless of the spatial distribution of disease risks. Through extensive simulation studies, we demonstrate that the CLR-based tests robustly control type 1 errors under different matching schemes and are more powerful than the standard Burden, SKAT and MiST tests. Furthermore, because CLR-based tests allow for different case-control ratios across strata, a full-matching scheme can be employed to efficiently utilize all available cases and controls to accelerate the discovery of disease associated genes.

The use of restricted mean time lost under competing risks data.

BACKGROUND: Under competing risks, the commonly used sub-distribution hazard ratio (SHR) is not easy to interpret clinically and is valid only under the proportional sub-distribution hazard (SDH) assumption. This paper introduces an alternative statistical measure: the restricted mean time lost (RMTL). METHODS: First, the definition and estimation methods of the measures are introduced. Second, based on the differences in RMTLs, a basic difference test (Diff) and a supremum difference test (sDiff) are constructed. Then, the corresponding sample size estimation method is proposed. The statistical properties of the methods and the estimated sample size are evaluated using Monte Carlo simulations, and these methods are also applied to two real examples. RESULTS: The simulation results show that sDiff performs well and has relatively high test efficiency in most situations. Regarding sample size calculation, sDiff exhibits good performance in various situations. The methods are illustrated using two examples. CONCLUSIONS: RMTL can meaningfully summarize treatment effects for clinical decision making, which can then be reported with the SDH ratio for competing risks data. The proposed sDiff test and the two calculated sample size formulas have wide applicability and can be considered in real data analysis and trial design.

Comparison of two treatments in the presence of competing risks.

Competing risks data arise frequently in clinical trials, and a common problem encountered is the overall homogeneity between two groups. In competing risks analysis, when the proportional subdistribution hazard assumption is violated or two cumulative incidence function (CIF) curves cross; currently, the most commonly used testing methods, for example, the Gray test and the Pepe and Mori test, may lead to a significant loss of statistical testing power. In this article, we propose a testing method based on the area between the CIF curves (ABC). The ABC test captures the difference over the whole time interval for which survival information is available for both groups and is not based on any special assumptions regarding the underlying distributions. The ABC test was also extended to test short-term and long-term effects. We also consider a combined test and a two-stage procedure based on this new method, and a bootstrap resampling procedure is suggested in practice to approximate the limiting distribution of the combined test and two-stage test. An extensive series of Monte Carlo simulations is conducted to investigate the power and the type I error rate of the methods. In addition, based on our simulations, our proposed TS, Comb, and ABC tests have a relatively high power in most situations. In addition, the methods are illustrated using two different datasets with different CIF situations.

Dynamic prediction and prognostic analysis of patients with cervical cancer: a landmarking analysis approach.

PURPOSE: Providing up-to-date information on patient prognosis is important in determining the optimal treatment strategies. The currently available prediction models, such as the Cox model, are limited to making predictions from baseline and do not consider the time-varying effects of covariates. METHODS: A total of 1501 cervical cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database were included. We introduced three landmark dynamic prediction models (models 1-3) that explore the dynamic effects of prognostic factors to obtain 5-year dynamic survival rate predictions at different prediction times. The performances of these models were evaluated by Harrell's C-index and the Brier score using cross-validation. RESULTS: Some variables did not meet the proportional hazards assumption, indicating that the constant hazard ratios were unreliable. Model 3, which showed the best performance for prediction, was selected as the final model. Significant time-varying effects were observed for age at diagnosis, International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and histological subtypes. Three patients were as examples used to illustrate how the predicted probabilities change at different prediction times during follow-up. CONCLUSIONS: Model 3 can effectively incorporate covariates with time-varying effects and update the probability of surviving an additional 5 years at different prediction times. The use of the landmark approach may provide evidence for clinical decision making by updating personalized information for patients.

[Effect of Huazhuo Jiedu formula on HIF-1α, VEGF, and PTEN in chronic erosive gastritis patients with syndrome of accumulation of turbidity and toxicity].

To observe the clinical efficacy of Huazhuo Jiedu formula in treating chronic erosive gastritis (CEG) patients with syndrome of accumulation of turbidity and toxicity, explore its mechanism by observing the changes in expression levels of hypoxia inducible factor (HIF-1α), vascular endothelial growth factor (VEGF) in serum and gastric mucosa tissues after treatment, and provide theoretical basis for the clinical application of Huazhuo Jiedu formula in treating chronic erosive gastritis. All 70 patient of CEG were randomly divided into control group and treatment group, 35 cases in each group. The patients in control group received Alatan Wuwei Wan, bid, 1 bag/time; while the patients in treatment group were given with Huazhuo Jiedu formula, 1 dose/day. The course of the treatment was 6 months in both groups. The changes in clinical symptoms, gastroscopic signs, pathology and the expression levels of HIF-1α, VEGF, and phosphatase and tensin homolog deleted on chromosome ten (PTEN) in serum and gastric mucosa tissues were observed in both groups. The results showed that treatment group was better than control group in clinical efficacy, gastroscopic efficacy and pathological effect after treatment (P<0.05); the levels of HIF-1α and VEGF in serum of treatment group were lower than those in the control group after treatment (P<0.05), while the level of PTEN in serum of treatment group was higher than that in the control group after treatment (P<0.05); the levels of HIF-1α and VEGF in gastric mucosa tissues in the treatment group were lower than those in the control group after treatment, while the level of PTEN in gastric mucosa tissues in treatment group was higher than that in the control group after treatment (P<0.05), with statistically significant differences between these two groups (P<0.05). Huazhuo Jiedu formula can improve the clinical symptoms, gastroscopic signs and pathological conditions in CEG patients with syndrome of accumulation of turbidity and toxicity, and the mechanism may be associated with decreasing the expression level of HIF-1α, VEGF and increasing the expression level of PTEN.

[Influence of three booster doses hepatitis B vaccine on the persistence of immune-protection among infants with normal and high antibody response to primary vaccination: a matched case-control study].

OBJECTIVE: To examine the influence of three-booster-doses hepatitis B vaccines on children with normal and high antibody response to primary vaccination. METHODS: Antibody against hepatitis B surface antigen (anti-HBs) were detected after primary vaccination and children with normal or high response to hepatitis B primary vaccination at infancy, were identified. Children who were given three booster doses were selected to form the booster group and who were given no booster dose were 1∶1 matched with the same gender and residence to form the control group. Blood samples were obtained from all the participants and tested for anti-HBs and anti-HBc, 5 years after the primary vaccination. RESULTS: The positive rates of anti-HBs response to primary vaccination were 97.39% (224/230, 95% CI: 94.41%-99.04%) in the booster group and 53.91% (124/230, 95% CI: 47.24%-60.48%) in the control group (P<0.05), 5 years after the primary vaccination. Geometric mean concentration (GMC) of anti-HBs were 1 140.02 (887.46-1 464.46) mIU/ml in the booster group and 11.53 (8.73-15.23) mIU/ml in the control group (P<0.05). The prevalence rates of breakthrough HBV infection were 0.87% (2/230) in the booster group and 2.17%(5/230) in the control group (P>0.05). RESULTS from the multivariable analysis showed that the booster doses (OR=38.75, 95%CI: 16.23-92.54) and the level of anti-HBs after the primary vaccination (OR =3.06, 95%CI:1.51-6.17) were independently associated with the positive rates of anti-HBs, 5 years after the primary vaccination (P<0.05). CONCLUSION: Programs with three booster doses to children that showing normal and high antibody response to primary vaccination could improve the persistence of anti-HBs but possibly would not be able to prevent the HBV infection.

[Persistence of immune memory to hepatitis B vaccine among infants with normal or high antibody response to primary vaccination: a five-year following-up study].

OBJECTIVE: To examine the immune memory status to hepatitis B vaccine among infants with normal or high antibody response to primary vaccination, 5 years after the primary vaccination and the risk factors associated with the immune memory. METHODS: Titers of the antibody against hepatitis B surface antigen (anti-HBs) were detected, five years after the primary vaccination among children who appeared normal or high response to hepatitis B primary vaccination in infancy. Those whose anti-HBs titers were low than protective level (10 mIU/ml) were given a challenge dose of hepatitis B vaccine and titers of anti-HBs were detected 14 days after the challenge. Positive rate and geometric mean titer (GMT) of anti-HBs were calculated. Level of the anti-HBs titers after primary vaccination, at following-up and after the challenge periods were divided into different levels, respectively. Risk factors associated with the levels of anti-HBs titer after the challenge were examined by univariate analysis that and multivariable analysis. RESULTS: Anti-HBs waned to the level below protective standard among 37.98% of the children with normal or high antibody response to hepatitis B primary vaccination; among those children whose anti-HBs were below the protection standard. The seroconversion rate and GMT of anti-HBs after the challenge dose were 98.95% (757/765) and 2 811.69 mIU/ml [95% Confidence Interval (CI) :2 513.55-3 145.19 mIU/ml] , respectively. Titers and levels of anti-HBs after the challenge, appeared an increase with anti-HBs after primary vaccination and the anti-HBs in the following-up (F=5.46, 10.23 respectively; P<0.000 1 for both) periods. Results from the multivariable analysis showed that gender, premature birth and birth weight were factors insignificantly associated with the anti-HBs titers after the dose of challenge, while the anti-HBs levels were independently associated with the levels of anti-HBs titer after the challenge [OR = 1.001 (95%CI: 1.000-1.002) , P<0.001; OR=1.28 (95%CI: 1.81-1.39) , P<0.001]at the following-up periods. CONCLUSIONS: Strong immune memory could be found among those children with normal or high responses to hepatitis B vaccination, 5 years after the primary vaccination. The intensity of immune memory might be associated with the anti-HBs titer after primary vaccination as well as the anti-HBs titers before the challenge dose was given.

[Anti-HBs persistence after revaccination with three doses of hepatitis B vaccines among non-responsive adults: 24-month of follow-up].

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. 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. 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.

[Matching study on immune response between single anti-HBc positivity and healthy adults after primary immunization and revaccination of hepatitis B vaccine].

OBJECTIVE: To compare the antibody response between adults with hepatitis B virus (HBV) core antibody (anti-HBc) single positivity and healthy adults after primary immunization and revaccination of hepatitis B vaccine(HepB). METHODS: Adults aged from 18 to 49 who were both negative for HBV surface antigen (HBsAg) and antibody to HBsAg (anti-HBs), but positive for anti-HBc and narrated no history of HepB immunization by themselves, were selected as single anti-HBc positive group ('anti-HBc alone'). Adults who were negative for HBsAg, anti-HBs and anti-HBc, with age differences within 2 years, and same gender under the 1 : 1 matching program, were selected to form the control group. Both groups were vaccinated on 0-1-6 schedule with the same HepB. Those who were non-response to HepB at primary immunization were revaccination on 0-1-6 schedule. Response rates and geometric mean concentrations (GMC) between the two groups were compared. RESULTS: In total, the number of anticipants were 228 pairs. Rates on non-response, low-response, normal-response and high-response after the primary immunization were 8.77% , 11.84%, 31.14% and 48.25% in the control group respectively. The corresponding rates were 8.33%, 30.70%, 35.96% and 25.00% in the 'anti-HBc alone'. The rate of low-response in the control group was lower than that in the 'anti-HBc alone' (χ(2) = 22.28, P < 0.01), while the rate of high-response was higher than that in the control group (χ(2) = 24.43, P < 0.01). GMC of anti-HBs in the control group (534.07 mIU/ml) was higher than that in the 'anti-HBc alone' (183.99 mIU/ml) (u = 4.42, P < 0.01). The anti-HBs conversion rates were 82.35% and 41.18% in the control group and in the 'anti-HBc alone' respectively after the first-dose revaccination, but increased to 90.00% and 82.35% after the third-dose revaccination. The anti-HBs conversion rates in the control group were higher than that in the 'anti-HBc alone' after the first-dose revaccination (P < 0.05), while there was no difference seen between the two groups after the third-dose revaccination (P > 0.05). CONCLUSION: Immune response in the anti-HBc positive adults after primary immunization was weaker than that in common adults. However, immune response induced by HepB was enough to prevent them from infecting HBV. The rates of response showed an obvious increase after revaccination, hence the same HepB immunization strategy could be used.

[Antibody persistence following booster vaccination with three doses of hepatitis B vaccines among low-response adults in Zhangqiu county of Shandong province: 24-month of follow-up from 2009].

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), 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). 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. 20 µgHepB-SC seemed better than 10 µg HepB-SC.