Development and application of bisphenol S electrochemical immunosensor and iridium oxide nanoparticle-based lateral flow immunoassay.

Bisphenol S (BPS) is a common pollutant in the environment and has posed a potential threat to aquatic animals and human health. To accurately assess the pollution level and ecological risk of BPS, there is an urgent need to establish simple and sensitive detection methods for BPS. In this study, BPS complete antigen was successfully prepared by introducing methyl 4-bromobutyrate and coupling bovine serum albumin (BSA). The monoclonal antibody against BPS (anti-BPS mAb) with high affinity (1: 256,000) was developed based on the BPS complete antigen, which showed low cross-reactivity with BPS structural analogues. Then, an electrochemical immunosensor was constructed to detect BPS using multi-walled carbon nanotubes and gold nanoflower composites as signal amplification elements and using anti-BPS mAb as the probe. The electrochemical immunosensor had a linear range from 1 to 250 ng⋅mL-1 and a limit of detection (LOD) down to 0.6 ng⋅mL-1. Additionally, a more stable and sensitive lateral flow immunoassay (LFIA) for BPS was developed based on iridium oxide nanoparticles, with a visual detection limit of 1 ng⋅mL-1, which was 10 times lower than that of classical Au-NPs LFIA. After evaluation of their stability and specificity, the reliability of these two methods were further validated by measuring BPS concentrations in the water and fish tissues. Thus, this study provides sensitive, robust and rapid methods for the detection of BPS in the environment and organisms, which can provide a methodological reference for monitoring environmental contaminants.

Combined healthy lifestyles and risk of depressive symptoms: A baseline survey in China.

BACKGROUND: Little evidence exists about whether a combination of healthy lifestyle factors is associated with a lower risk of depressive symptoms among Chinese population. We aimed to investigate the association between combined healthy lifestyle factors and risk of depressive symptoms. METHODS: We conducted a baseline survey from July 2021 to December 2023, including 53,642 Chinese adults from general population. A healthy lifestyle score was constructed based on six lifestyle factors (physical activity, smoking status, alcohol consumption, diet, sleep duration, and body mass index). Logistic regression models were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) adjusted for confounding variables. RESULTS: Each additional healthy lifestyle score was associated with a 20 % lower risk of having depressive symptoms (OR (95 % CI): 0.80 (0.78-0.81)). Compared with individuals with ≤2 healthy lifestyle factors, individuals with all the six healthy lifestyle factors had a 58 % reduced risk of having depressive symptoms (0.42 (0.37-0.47)). After stratification by gender, education and urbanization, the significant inverse association with healthy lifestyle score was stronger in women, individuals with high education, and urban residents. Besides, the significant negative association between healthy lifestyle score and depressive symptoms remained for different severity of depressive symptoms. LIMITATIONS: Given the cross-sectional nature of data, we cannot make causal inferences. CONCLUSIONS: Our study indicated that adherence to healthy lifestyle factors was associated with a reduced risk of having depressive symptoms among Chinese adults. The observed associations were modified by gender, education and urbanization. These findings warrant further verification in interventional studies.

Vitamin C Alleviates the Risk of Gestational Diabetes Mellitus Associated With Exposure to Metals.

Background: Exposure to heavy metals has been suggested to increase the risk of gestational diabetes mellitus (GDM) through the oxidative stress pathway. The study is aimed at examining whether vitamin C could modify the association between exposure to heavy metals and risk of GDM. Methods: We conducted a case-control study in Taiyuan, China, with 776 GDM cases and 776 controls. Data on vitamin C intake from diet and supplements were collected through questionnaires. Concentrations of metals in participants' blood were measured using inductively coupled plasma-mass spectrometry (ICP-MS). Unconditional logistic regression models were applied to estimate effect modification of vitamin C on the association between heavy metals and GDM. Results: Women with higher blood levels of mercury (Hg) (odds ratio (OR) = 2.36, 95% confidence interval (CI): 1.43, 3.92 and 2.04, 95% CI: 1.20, 3.46 for the second and third vs. the first tertile) and arsenic (As) (OR = 2.46, 95% CI: 1.37, 4.43 and 2.16, 95% CI: 1.12, 4.17 for the second and third vs. the first tertile) exposure were associated with increased risk of GDM among women without vitamin C supplement use and having dietary vitamin C intake < 85 mg/day. We found no significant association with metals among women who took vitamin C supplements and/or dietary vitamin C ≥ 85 mg/day. Significant interactions were observed between vitamin C and exposures to metals (i.e., Hg and As) on the risk of GDM (P interaction = 0.048 and 0.045, respectively). Conclusions: Our study, for the first time, suggests that vitamin C supplement use or higher dietary vitamin C intake during preconception and early pregnancy could alleviate the risk of GDM associated with exposure to As and Hg. The results warrant further investigation.

Pollution level and ecological risk assessment of triazine herbicides in Laizhou Bay and derivation of seawater quality criteria.

Triazine herbicides are widely used in agriculture and have become common pollutants in marine environments. However, the spatiotemporal distribution characteristics and water quality criteria (WQC) of triazine herbicides are still unclear. This study found that triazine herbicides had a high detection rate of 100 % in surface seawater of Laizhou Bay, China, with average concentrations of 217.61, 225.13, 21.97, and 1296.72 ng/L in March, May, August, and October, respectively. Moreover, estuaries were important sources, and especially the Yellow River estuary exhibited the highest concentrations of 16,115.86 ng/L in October. The 10 triazine herbicides were detected in the sediments of Laizhou Bay, with a concentration ranging from 0.14-1.68 µg/kg. Atrazine and prometryn accounted for 33.41 %-59.10 % and 28.93 %-50.06 % of the total triazine herbicides in the seawater, and prometryn had the highest proportion (63.50 %) in the sediments. Correlation analysis revealed that triazine herbicides led to the loss of plankton biodiversity, which further decreased the dissolved oxygen. In addition, this study collected 45 acute toxicity data and 22 chronic toxicity data of atrazine, 16 acute toxicity data of prometryn, and supplemented with toxicity experiments of prometryn on marine organisms. Based on the toxicity database, the WQCs of atrazine and prometryn were derived using species sensitivity distribution. The overall risk probability of atrazine and prometryn were both less than 1.75 % in the Laizhou Bay, indicating an acceptable risk. This study not only clarified the pollution status and ecological risk of triazine herbicides, but also provided scientific basis for their environmental management standards.

Synthesis, Crystal Structure, and Photophysical Properties of Bromothiophene-Functionalized BF2-Curcuminoid as a Versatile Building Block.

A novel bromothiophene-functionalized BF2-curcuminoid (BTC-BF2) is synthesized by Knoevenagel condensation reaction. The structure of BTC-BF2 is determined by 1H-nuclear magnetic resonance (1H NMR), 13C-nuclear magnetic resonance (13C NMR), and high-resolution mass spectrometry (HRMS). Moreover, a nearly coplanar single crystal structure is successfully obtained and form a mesh structure through intermolecular multiple C─H···F hydrogen bond interactions. As expected, as-prepared BTC-BF2 exhibits solvent-dependent photophysical properties in solvents with different polarity and an intense red solid-state fluorescence. Density functional theory calculations further verify the relationships between its intrinsic electronic features and the photophysical properties. For its potential application aspect, BTC-BF2 shows a certain ability to generate singlet oxygen under irradiation with 530 nm green light. Moreover, BTC-BF2 can be utilized as versatile building block to construct novel far-red or NIR BF2-curcuminoid complexes for widely biological applications.

Occurrence and Reduction of Hepatitis B Vaccine Hesitancy Among Medical University Students - Shanxi Province, China, 2020.

What is already known about this topic?: Previous research has primarily examined the issue of hepatitis B vaccine hesitancy in migrant workers and other adult populations. However, there is a lack of studies that have specifically investigated the prevalence of hepatitis B vaccine hesitancy among university students. What is added by this report?: In this study, 19.84% of students expressed hesitancy towards receiving the hepatitis B immunization. A negative correlation was observed between hepatitis B vaccine hesitancy and knowledge, attitudes, and practices related to hepatitis B. Conversely, a positive relationship was identified between hepatitis B-related knowledge and attitudes and practices. What are the implications for public health practice?: This study examines the factors contributing to vaccine hesitancy towards hepatitis B at a medical university in China. The results have significant implications for developing strategies to improve hepatitis B vaccination rates.

Ecological risk assessment of heavy metals in desulfurized seawater discharged from a coal-fired power plant in Qingdao.

Despite the prevalence of discharge of large volumes of heavy-metal-bearing seawater from coal-fired power plants into adjacent seas, studies on the associated ecological risks remain limited. This study continuously monitored concentrations of seven heavy metals (i.e. As, Cd, Cr, Cu, Hg, Pb, and Zn) in surface seawater near the outfall of a coal-fired power plant in Qingdao, China over three years. The results showed average concentrations of As, Cd, Cr, Cu, Hg, Pb, and Zn of 2.63, 0.33, 2.97, 4.63, 0.008, 0.85, and 25.00 µg/L, respectively. Given the lack of data on metal toxicity to local species, this study investigated species composition and biomass near discharge outfalls and constructed species sensitivity distribution (SSD) curves with biological flora characteristics. Hazardous concentrations for 5% of species (HC5) for As, Cd, Cr, Cu, Hg, Pb, and Zn derived from SSDs constructed from chronic toxicity data for native species were 3.23, 2.22, 0.06, 2.83, 0.66, 4.70, and 11.07 µg/L, respectively. This study further assessed ecological risk of heavy metals by applying the Hazard Quotient (HQ) and Joint Probability Curve (JPC) based on long-term heavy metal exposure data and chronic toxicity data for local species. The results revealed acceptable levels of ecological risk for As, Cd, Hg, and Pb, but unacceptable levels for Cr, Cu, and Zn. The order of studied heavy metals in terms of ecological risk was Cr > Cu ≈ Zn > As > Cd ≈ Pb > Hg. The results of this study can guide the assessment of ecological risk at heavy metal contaminated sites characterized by relatively low heavy metal concentrations and high discharge volumes, such as receiving waters of coal-fired power plant effluents.

Maternal A90V mutation in the PreS1 gene of sub-genotype C2 hepatitis B virus is associated with intrauterine transmission.

PreS/S gene mutations could impact virus secretion, infection and immune evasion. However, the relationship between PreS/S mutations and intrauterine transmission has not yet been clarified. Thus, we aimed to explore the associations between PreS/S gene mutations of HBV isolated from mothers and intrauterine transmission. We analyzed the mutations of PreS/S regions of the HBV genome in mothers with HBV DNA levels ≥ 106 IU/mL whose neonates experienced HBV intrauterine transmission (transmission group, GT) and those whose neonates did not experience intrauterine transmission (control group, GC) analyzed using clone-based sequencing. In total, 206 sequences were successfully amplified, including 98 sequences (from 21 mothers) from GT and 108 sequences (from 20 mothers) from GC of genotype C for mutational analysis. Among the 1203 nucleotides of PreS/S regions, there were 219 (18.20%) base substitutions, of which 103 (47.03%) base mutations caused amino acid changes. F80S, A90V and I68T were mutation hotspots. Mothers in GT had a higher mutation rate of A90V in the PreS1 gene than mothers in GC. The A90V mutation increased the risk of HBV intrauterine transmission after adjusting the maternal age and the mode of delivery (OR = 6.23, 95% CI: 1.18-32.97). Moreover, the area under the ROC curve (AUC) for intrauterine transmission due to A90V and a combination of A90V with the mode of delivery were 0.723 (95% CI: 0.575 to 0.891, P = 0.011) and 0.848 (95% CI: 0.723 to 0.972, P < 0.001), respectively. Mothers with the A90V mutation in the PreS1 gene may be a potential risk factor for HBV intrauterine transmission.

Predictors of immune persistence induced by two-dose BBIBP-CorV vaccine in high-risk occupational population.

BACKGROUND: The immune protection from infection may wane over time as neutralizing antibody levels decline. We aimed to develop a nomogram to predict long-term immune persistence induced by two-dose BBIBP-CorV vaccine and calculate the neutralizing antibody decline probability of individuals. METHODS: In the initial study, a total of 809 participants were recruited and randomly allocated (1:1:1) to vaccination group with three two-dose schedules on days 0 and 14, 0 and 21, or 0 and 28. The participants with neutralizing antibody titers of 16 or above on day 28 after the second dose were followed up at month 3, 6 and 10. Multivariable Cox proportional hazards regression model and nomogram model were used to identify predictors associated with maintaining of neutralizing antibody levels during 10 months after the second dose. RESULTS: A total of 744 participants followed up at day 28 after the second dose. The participants with age ≥ 50 (aHR = 3.556, 95 %CI: 1.141-4.884, P = 0.028) were associated with a high risk of response loss (titers < 16). The participants who were in 0-28 d group (aHR = 0.403, 95 %CI: 0.177-0.919, P = 0.031), had an influenza vaccination history (aHR = 0.468, 95 %CI: 0.267-0.921, P = 0.033) or were female (aHR = 0.542, 95 %CI: 0.269-0.935, P = 0.035) tended to maintain immune persistence during 10 months after the second dose. The nomogram was constructed and showed moderate discrimination[C-index:0.711 (95 %CI: 0.652-0.770); AUC: 0.731 (95 %CI: 0.663-0.792)] and good calibration. CONCLUSIONS: From 28 days to 10 months after receipt of the second dose of the BBIBP-CorV vaccine, neutralizing antibody levels were substantially decreased, especially among men, among persons 50 years of age or older, among persons with the 0-14 d group, and among persons without history of influenza vaccination. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100041705, ChiCTR2100041706.

DNA methylation analysis reveals the effect of arsenic on gestational diabetes mellitus.

BACKGROUND: Arsenic (As) exposure is one of the risk factors for gestational diabetes mellitus (GDM). This study aimed to explore the effect of As-exposure on DNA methylation in GDM and to establish a risk assessment model of GDM in As exposed pregnant women. METHOD: We collected elbow vein blood of pregnant women before delivery to measure As concentration and DNA methylation data. Then compared the DNA methylation data and established a nomogram. RESULT: We identified a total of 10 key differentially methylated CpGs (DMCs) and found 6 corresponding genes. Functions were enriched in Hippo signaling pathway, cell tight junction, prophetic acid metabolism, ketone body metabolic process, and antigen processing and presentation. A nomogram was established that can predict GDM risks (c-index = 0.595, s:p = 0.973). CONCLUSION: We found 6 genes associated with GDM with high As exposure. The prediction of the nomograms has been proven to be effective.

Prenatal polymetallic exposure and small for gestational age: A case-control study in Taiyuan, China.

BACKGROUND: Studies focused on independent effects of metals on small for gestational age, failing to account for potential interdependence among metals. METHODS: In this case-control study, we selected 187 pregnant women and 187 matched controls from the First Hospital of Shanxi Medical University. Determination of 12 elements in the venous blood of pregnant women before delivery by ICP-MS. Logistic regression, weighted quantile sum regression (WQSR) and Bayesian kernel machine regression (BKMR) were used to estimate the overall effect and identify important mixture components that drive the associations with SGA. RESULTS: An increased risk of SGA was associated with As (OR= 1.06,95%CI: 1.01,1.12), Cd (OR= 1.24,95%CI: 1.04,1.47) and Pb (OR= 1.05,95%CI: 1.02,1.08), while Zn (OR= 0.58,95%CI: 0.45,0.76) and Mn (OR= 0.97,95%CI: 0.94,0.99) were protective factors for SGA. In the WQSR positive model, the mixture of heavy metals has a positive combined effect on SGA (OR= 1.74,95%CI: 1.15, 2.62), with Sb and Cd having the highest weights. The BKMR models confirmed that the metal mixture was associated with decreased risk of SGA when the concentration of 12 metals was between the 30th percentile and the 65th percentile, and Zn and Cd had the greatest independent effect. Zn and SGA may not be linearly correlated, higher Zn level may reduce the effect of Cd on the risk of SGA. CONCLUSIONS: Our study suggested that exposure to multiple metals was associated with risk of SGA, and the observed association with multiple metals was dominated by Zn, Cd. Sb exposure during pregnancy may also increase the risk of SGA.

Decreased placental TLR3 is associated with hepatitis B virus vaccine responsiveness in infants born to HBsAg-positive mothers.

Background: Although hepatitis B vaccination has a significant impact on the reduction hepatitis B virus (HBV) infection, babies born to hepatitis B surface antigen (HBsAg) positive mothers bear a high risk of being poor responsive to the vaccine with unilluminated mechanism. Toll-like receptor 3 (TLR3) plays a vital role in placental immunity, which affects the immune response of these babies. This study investigated the role of placental TLR3 in the immune responses of babies born to HBsAg-positive mothers to the HBV vaccine. Methods: One hundred pairs of HBsAg-positive mothers and their newborns were recruited. Maternal blood samples were collected before delivery, and placental tissues were collected after delivery. Newborns were administered standard passive and active immunoprophylaxis and followed up until the age of 1. Infant blood samples were collected at 1 year of age. Mothers and infants were tested for HBV serological markers and HBV DNA by electrochemiluminescence immunoassay and fluorescence quantitative polymerase chain reaction. respectively. Placental TLR3 was detected by immunohistochemistry and score in a semi-quantitative fashion, circulating cytokines in infants were detected by enzyme-linked immunosorbent assay. Infants with anti-HBs ≥100 and <100 mIU/mL were classified into the high-responsiveness group and the non- or hypo-responsiveness group. Results: The TLR3 protein was expressed in all placentas. Compared with the high-responsiveness group, the expression of TLR3 in the non- or hypo-responsiveness group was significantly decreased (χ2=10.39, P=0.001). A non-conditional logistic regression model showed that the increased expression of placental TLR3 protein decreased the odds of HBV vaccine non- or hypo-responsiveness in the babies of HBsAg-positive mothers [OR =0.25 (95% CI: 0.11-0.58)], and this association remained significant after accounting for maternal factors, such as HBeAg and HBV DNA, as well as infant cytokines, including IL-6, IL-12, TNF-α, IFN-α, and IFN-γ [OR =0.15 (95% CI: 0.05-0.44)]. Conclusions: Decreased placental TLR3 expression is associated with impaired responsiveness to HBV vaccination in babies born to HBsAg-positive mothers.

Elevated HMGB1 and sRAGE levels in cerebrospinal fluid of aneurysmal subarachnoid hemorrhage patients.

BACKGROUND: Neuroinflammation after aneurysmal subarachnoid hemorrhage (aSAH) leads to poor outcome of patients. High mobility group box 1 (HMGB1) contributes to inflammation through binding to receptors for advanced glycation end-products (RAGE) in various diseases. We aimed to determine the production of these two factors after aSAH and their relationship with clinical features. METHODS: HMGB1 and soluble RAGE (sRAGE) levels in cerebrospinal fluid (CSF) of aSAH patients and controls were measured, and their temporal courses were observed. The correlation between early concentrations (days 1-3) and clinical symptoms assessed by disease severity scores, neuroinflammation estimated by CSF IL-6 levels, as well as prognosis evidenced by delayed cerebral ischemia (DCI) and 6-month adverse outcome was investigated. Finally, combined analysis of early levels for predicting prognosis was confirmed. RESULTS: CSF HMGB1 and sRAGE levels were higher in aSAH patients than in controls (P < 0.05), and the levels decreased from higher early to lower over time. Their early concentrations were positively associated with disease severity scores, IL-6 levels, DCI and 6-month poor outcome (P < 0.05). HMGB1 ≥ 6045.5 pg/ml (OR = 14.291, P = 0.046) and sRAGE ≥ 572.0 pg/ml (OR = 13.988, P = 0.043) emerged as independent predictors for DCI, while HMGB1 ≥ 5163.2 pg/ml (OR = 7.483, P = 0.043) and sRAGE ≥ 537.3 pg/ml (OR = 12.653, P = 0.042) were predictors for 6-month poor outcome. Combined analysis of them improved predictive values of adverse prognosis. CONCLUSION: CSF HMGB1 and sRAGE levels of aSAH patients were increased early and then varied dynamically, which might act as potential biomarkers for poor outcome, especially when co-analyzed.

The top 100 most cited articles on COVID-19 vaccine: a bibliometric analysis.

This study aimed to uncover the current major topics regarding COVID-19 vaccine, and systematically evaluate the development trends for future research. The top 100 most cited original articles on COVID-19 vaccine from January 2020 to October 2022 were identified from Web of Science Core Collection database. CiteSpace (v6.1.R3) was adopted for bibliometric analysis with statistical and visual analysis. The number of citations ranged from 206 to 5881, with a median of 349.5. The USA (n = 56), England (n = 33), and China (n = 16) ranked the top three countries/regions in terms of the number of publications. Harvard Medical School (centrality = 0.71), Boston Children's Hospital (centrality = 0.67), and Public Health England (centrality = 0.57) were the top three institutions leading the way on COVID-19 vaccine research. The New England of medicine journal dominated with 22 articles in the 32 high-quality journals. The three most frequent keywords were immunization (centrality = 0.25), influenza vaccination (centrality = 0.21), and coronavirus (centrality = 0.18). Cluster analysis of keywords showed that the top four categories were protection efficacy, vaccine hesitancy, spike protein, and second vaccine dose (Q value = 0.535, S value = 0.879). Cluster analysis of cited references showed that top eight largest categories were Cov-2 variant, clinical trial, large integrated health system, COV-2 rhesus macaque, mRNA vaccine, vaccination intent, phase II study, and Cov-2 omicron variant (Q value = 0.672, S value = 0.794). The research on COVID-19 vaccine is currently the hottest topic in academic community. At present, COVID-19 vaccines researches have focused on vaccine efficacy, vaccine hesitancy, and the efficacy of current vaccines on omicron variants. However, how to increase vaccine uptake, focus on mutations in the spike protein, evaluate of the efficacy of booster vaccine, and how effective new vaccines under pre- and clinical development against omicron will be spotlight in the future.

Exploration of Risk Factors for Pancreatic Cancer and Development of a Clinical High-Risk Group Rating Scale.

(1) Background: There are few studies on people at high risk for clinical pancreatic cancer (PC). We aimed to explore the risk factors of PC and establish a scale for identifying high-risk populations of clinical PC. (2) Methods: We conducted a matched case-control study, retrospectively collecting demographic data and common clinical indicators from all subjects. Logistic regression was used to explore the risk factors of PC. Based on these factors, we created a high-risk population rating scale, which showed a higher diagnostic value. (3) Results: 385 cases and 428 controls were finally enrolled in our study. Multivariate analysis showed that body mass index (BMI) below 18.5 kg/m2 (OR 5.944, 95%CI: 1.759~20.084), smoking (OR 2.745, 95%CI: 1.555~4.844), new-onset diabetes (OR 5.239, 95%CI: 2.091~13.125), low high-density lipoprotein cholesterol (HDL-C) levels (OR 1.790, 95%CI: 1.044~3.069), and carbohydrate antigen 19-9 (CA19-9) levels no less than 35 U/mL (OR 160.328, 95%CI: 83.392~308.243) were associated with an increased risk of PC, whereas high total cholesterol (TC) levels were related to a lower risk of PC (OR 0.392, 95%CI: 0.211~0.730). The high-risk population scale, whose area under the receiver operating curve reached 0.948 (p < 0.001), showed a greater clinical diagnostic value. (4) Conclusions: Smoking history, new-onset diabetes, BMI, TC, HDL-C, and CA19-9 levels were associated with the risk of PC. The high-risk population rating scale might be used for early clinical PC screening.

Folic acid supplementation in pregnant women with hepatitis B surface antigen improves infant hepatitis B surface antibody mediated by infant IL-4.

Immunoprophylaxis has not completely eliminated hepatitis B virus (HBV) infection due to hyporesponsiveness to hepatitis B vaccine (HepB). We explored the impact of folic acid supplementation (FAS) in pregnant women with positive hepatitis B surface antigen (HBsAg) on their infant hepatitis B surface antibody (anti-HBs) and the mediation effect of infant interleukin-4 (IL-4). We recruited HBsAg-positive mothers and their neonates at baseline. Maternal FAS was obtained via a questionnaire, and neonatal anti-HBs and IL-4 were detected. Follow-up was performed at 11-13 months of age of infants, when anti-HBs and IL-4 were measured. We applied univariate and multivariate analyses. A mediation effect model was performed to explore the mediating role of IL-4. A total of 399 mother-neonate pairs were enrolled and 195 mother-infant pairs were eligible for this analysis. The infant anti-HBs geometric mean concentrations in the maternal FAS group were significnatly higher than those in the no-FAS group (383·8 mIU/ml, 95 % CI: 294·2 mIU/ml to 500·7 mIU/ml v. 217·0 mIU/ml, 95 % CI: 147·0 mIU/ml to 320·4 mIU/ml, z = -3·2, P = 0·001). Infants born to women who took folic acid (FA) within the first trimester were more likely to have high anti-HBs titres (adjusted ß-value = 194·1, P = 0·003). The fold change in IL-4 from neonates to infants partially mediated the beneficial influence of maternal FAS on infant anti-HBs (24·7 % mediation effect) after adjusting for confounding factors. FAS during the first trimester to HBsAg-positive mothers could facilitate higher anti-HBs levels in infants aged 11-13 months partly by upregulating IL-4 in infants.

Maternal A90V mutation in the PreS1 gene of sub-genotype C2 hepatitis B virus is associated with intrauterine transmission

ABSTRACT PreS/S gene mutations could impact virus secretion, infection and immune evasion. However, the relationship between PreS/S mutations and intrauterine transmission has not yet been clarified. Thus, we aimed to explore the associations between PreS/S gene mutations of HBV isolated from mothers and intrauterine transmission. We analyzed the mutations of PreS/S regions of the HBV genome in mothers with HBV DNA levels ≥ 106 IU/mL whose neonates experienced HBV intrauterine transmission (transmission group, GT) and those whose neonates did not experience intrauterine transmission (control group, GC) analyzed using clone-based sequencing. In total, 206 sequences were successfully amplified, including 98 sequences (from 21 mothers) from GT and 108 sequences (from 20 mothers) from GC of genotype C for mutational analysis. Among the 1203 nucleotides of PreS/S regions, there were 219 (18.20%) base substitutions, of which 103 (47.03%) base mutations caused amino acid changes. F80S, A90V and I68T were mutation hotspots. Mothers in GT had a higher mutation rate of A90V in the PreS1 gene than mothers in GC. The A90V mutation increased the risk of HBV intrauterine transmission after adjusting the maternal age and the mode of delivery (OR = 6.23, 95% CI: 1.18-32.97). Moreover, the area under the ROC curve (AUC) for intrauterine transmission due to A90V and a combination of A90V with the mode of delivery were 0.723 (95% CI: 0.575 to 0.891, P = 0.011) and 0.848 (95% CI: 0.723 to 0.972, P < 0.001), respectively. Mothers with the A90V mutation in the PreS1 gene may be a potential risk factor for HBV intrauterine transmission.

Immune persistence induced by two-dose BBIBP-CorV vaccine with different intervals, and immunogenicity and safety of a homologous booster dose in high-risk occupational population.

BACKGROUND: The immune persistence of neutralizing antibodies elicited by BBIBP-CorV vaccines on day 0-14, 0-21 and 0-28 schedule, and the immunogenicity and safety of a homologous booster dose after different priming vaccination regimens is scarcely reported. METHODS: : Responders (GMT≥16) at day 28, after priming with the two-dose vaccine, were followed up at 3, 6, and 10 months. Eligible participants received a homologous booster dose at month 10 and were followed-up 28 days post-booster. RESULTS: The GMT of neutralizing antibodies in 0-28d-10 m and 0-21d-10 m group were significantly higher than 0-14d-10 m group from month 3 (71.6 & 64.2 vs 46.4, p < 0.001) to month 10 (32.4 & 28.8 vs 20.3, p < 0.001) after the second dose. On day 28 post-booster, a remarkable rebound in neutralizing antibodies (246.2, 277.5, and 288.6, respectively) was observed in the three groups. All adverse reactions were mild after booster injection. CONCLUSIONS: The priming two-dose BBIBP-CorV vaccine with 0-28 days and 0-21 days schedule could lead to a longer persistence of neutralizing antibody than the 0-14 days schedule. Regardless of the priming vaccination regimens, a homologous booster dose led to a strong rebound in neutralizing antibodies and might persist for at least 18 months.

Duration of immunogenicity of high-dose and prolonged-schedule hepatitis B vaccine among patients with chronic kidney disease: A one year follow-up study in China.

BACKGROUND: Patients with chronic kidney disease (CKD) have immunological defects that result in reduced production and faster decay of anti-HBs after hepatitis B vaccination. We assessed the duration of the immunogenicity after four-standard-dose and four-triple-dose regimens among patients with CKD. METHODS: A randomized controlled trial was conducted between May 2019 and February 2020. Patients were randomly allocated to receive three or four doses of 20 µg    , or four doses of 60 µg   of hepatitis B vaccine. Immunogenicity was assessed for 18 months till February 2021. RESULTS: Between months 7 and 18, the seroconversion rate decreased from 81.7% (58/71) to 64.3% (36/56) in IM20 × 3 group, from 93.0% (66/71) to 77.4% (41/53) in IM20 × 4 group, and from 93.2% (68/73) to 90.7% (49/54) in IM60 × 4 group. Seroconversion was higher in IM60 × 4 group than in IM20 × 3 group at month 18 (P < 0.05). In multivariate analysis, CKD patients without immune suppression or hormone therapy or patients with IM60 × 4 were more likely to have durable immunogenicity at month 18. CONCLUSIONS: Patients receiving four-triple-dose regimen of hepatitis B vaccine showed improved duration of immunogenicity at the one-year follow-up. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03962881).