Trajectories of serum HBsAg during treatment and association with HBsAg loss in children with HBeAg-positive chronic hepatitis B: a latent class trajectory analysis.

BACKGROUND: The change of serum hepatitis B surface antigen (HBsAg) during treatment are associated with HBsAg loss. However, little is known about the trajectory patterns of HBsAg in early treatment and their relationship with subsequent HBsAg loss. This study aimed to identify trajectories of HBsAg in children with HBeAg-positive chronic hepatitis B (CHB) and investigate the association between trajectory patterns and HBsAg loss. METHODS: A retrospective study was conducted on 166 treatment-naive children with HBeAg-positive CHB. Latent class trajectory analysis was used to identify trajectory groups of serum HBsAg. Cox proportional hazard model was used to assess the association between HBsAg trajectory groups and HBsAg loss. RESULTS: The median follow-up time was 20.70 (12.54, 34.17) months, and HBsAg loss occurred in 70(42.17%) of all study participants. Using latent class trajectory analysis, HBeAg-positive CHB patients were classified into three trajectory groups: trajectory 1 (sustained stability, 24.70%), trajectory 2 (slow decline, 38.55%), and trajectory 3 (rapid decline, 36.75%), respectively. The median decline levels of HBsAg at the 3-month and 6-month follow-ups were the highest in trajectory 3 (1.08 and 3.28 log10 IU/ml), followed by trajectory 2 (0.27 and 1.26 log10 IU/ml), and no change in trajectory 1. The risk of achieving HBsAg loss was higher in both trajectory 2 (HR, 3.65 [95% CI, 1.70-7.83]) and trajectory 3 (HR, 7.27 [95% CI, 3.01-17.61]), respectively. CONCLUSION: Serum HBsAg levels during early treatment can be classified into distinct trajectory groups, which may serve as an additional predictive indicator for HBsAg loss in HBeAg-positive CHB children.

Characteristics and clinical treatment outcomes of chronic hepatitis B children with coexistence of hepatitis B surface antigen (HBsAg) and antibodies to HBsAg.

BACKGROUND: The coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) represents an uncommon serological pattern observed in patients with hepatitis B virus (HBV) infection, and its underlying mechanism and clinical significance have not been well established. The aim of this study was to investigate the association between this serological profile and clinical treatment outcomes in children with chronic hepatitis B (CHB). METHODS: This retrospective cohort study included 372 treatment-naïve CHB children from the Hunan Children's Hospital. The participants were categorized into HBsAb-positive group and HBsAb-negative group. The associations between HBsAb positive status to clinical outcomes were assessed using Cox proportional hazard regression. Receiver operating characteristic curve was conducted to evaluate the prediction ability in HBsAg loss. RESULTS: The coexistence of HBsAg and HBsAb accounted for 23.39% (87/372) of the participants. The crude incidence rates of HBsAg loss, hepatitis B e antigen (HBeAg) clearance, and HBV-DNA undetectability were higher in the HBsAb-positive group compared with the HBsAb-negative group (37.46 vs. 17.37, 49.51 vs. 28.66, 92.11 vs. 66.54 per 100 person-years, respectively, all P < 0.05). The Cox regression analysis revealed a significant association between this serological profile and an increased likelihood of HBsAg loss (HR = 1.78, P = 0.001), and HBeAg clearance (HR = 1.78, P = 0.001). In addition, a combination of HBsAb ≥ 0.84 log10 IU/L and age ≤ 5 years can help identify patients likely to achieve HBsAg loss after antiviral therapy, with an AUC of 0.71. CONCLUSIONS: Children who are positive for both HBsAg and HBsAb demonstrate a higher probability of favorable outcomes after antiviral treatment. Thus, children with HBsAb-positive CHB should be actively treated to achieve functional cure.

Predictive role of early treatment dynamics of HBV RNA and HBcrAg for HBeAg seroconversion in children with chronic hepatitis B.

This study aimed to assess the predictive capacity of emerging serological markers, serum HBV RNA and HBcrAg, for HBeAg seroconversion in children with HBeAg-positive chronic hepatitis B (CHB). Treatment-naïve HBeAg-positive CHB children who admitted to the Liver Disease Center of Hunan Children's Hospital between April 2021 and September 2022 and received treatment with the combined entecavir and interferon-alpha treatment were recruited. Serum HBV RNA and HBcrAg were measured at baseline and Weeks 12, 24, and 48 of treatment. Our study showed that serum HBV RNA (HR = 0.71, 95% CI: 0.56-0.91, p = 0.006), HBcrAg (HR = 0.60, 95% CI: 0.43-0.84, p = 0.003), and HBsAg (HR = 0.49, 95%CI: 0.36-0.69, p < 0.001) at Week 12 were independent predictors of HBeAg seroconversion. ROC curve analysis presented that serum HBV RNA decline value (ΔHBV RNA) at Week 36 and HBcrAg decline value (ΔHBcrAg) at Week 12 (AUC = 0.871, p = 0.003 and AUC = 0.810, p = 0.003, respectively) could effectively predict HBeAg seroconversion. Furthermore, the optimal critical values were determined and the children with ΔHBV RNA > 3.759 log10 copies/mL at Week 36 or ΔHBcrAg >0.350 log10 U/mL at Week 12 more likely to achieve HBeAg seroconversion. The serum HBV RNA and HBcrAg provide new insights into the treatment of CHB in children. Early assessment of serum HBV RNA and HBcrAg during treatment can assist clinical decision-making and optimize individualized therapeutic approaches.

Incidence and Predictors of HBsAg Loss in Paediatric Patients With Chronic Hepatitis B Undergoing Antiviral Treatment.

BACKGROUND AND AIMS: Achieving HBsAg loss is a critical clinical milestone in the management of chronic hepatitis B (CHB) towards the eradication of hepatitis B. However, there are limited researches on the incidence and determinants of HBsAg loss in paediatric CHB patients undergoing antiviral treatment. Therefore, we aimed to analyse the incidence and potential determinants of HBsAg loss in children who suffered from CHB and received antiviral treatment. METHODS: This retrospective cohort study was performed on paediatric patients with progressive CHB who initiated either monotherapy or combination therapy using interferon/peg-interferon and entecavir. We utilised Cox regression models to evaluate the relationships between HBsAg loss and various determining factors. RESULTS: In total of 306 subjects with an average age of 4.99 years (range 1-15) were identified in this study, of whom 200 (65.4%) were male. After a median follow-up of 26 months, HBsAg loss occurred in 135 participants. The accumulated rate of HBsAg loss was 67.8% at the end of the follow-up evaluation. Multivariate Cox regression analysis revealed that older age (HR = 0.84, 95% CI: 0.79-0.90), female sex (HR = 1.61, 95% CI: 1.13-2.30), baseline HBsAg levels (HR = 0.72, 95% CI: 0.62-0.84), HBsAb positivity (HR = 1.77, 95% CI: 1.20-2.59) and serum bilirubin levels (HR = 0.96, 95% CI: 0.92-0.99) were statistically significant predictors of HBsAg loss. CONCLUSION: The incidence of HBsAg loss continues to increase in paediatric patients with CHB after antiviral treatment. Age, sex, baseline HBsAg and bilirubin levels and HBsAb positivity are found to be associated with sustained HBsAg loss.

Association of whole blood copper, zinc, calcium, magnesium, and iron with non-alcoholic fatty liver disease in overweight and obese children. / å ¨è¡€é“œã€é”Œã€é’™ã€é•ã€é“ä¸Žè¶ é‡è‚¥èƒ–å„¿ç«¥éžé ’ç²¾æ€§è„‚è‚ªè‚ç— çš„å ³è”.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder in overweight and obese children, and its etiology and pathogenesis remain unclear, lacking effective preventive and therapeutic measures. This study aims to explore the association between whole blood copper, zinc, calcium, magnesium and iron levels and NAFLD in overweight and obese children aged 6 to 17 years, providing a scientific basis for the prevention and intervention of early NAFLD in overweight and obese children. METHODS: A cross-sectional study design was used to collect relevant data from overweight and obese children who visited the Hunan Children's Hospital from January 2019 to December 2021 through questionnaire surveys. Fasting blood samples were collected from the subjects, and various indicators such as blood glucose, blood lipid, and mineral elements were detected. All children were divided into an overweight group (n=400) and a NAFLD group (n=202). The NAFLD group was divided into 2 subgroups according to the ALT level: A non-alcoholic fatty liver (NAFL) group and a non-alcoholic steatohepatitis (NASH) group. Logistic regression analysis was used to analyze the association between minerals (copper, zinc, calcium, magnesium, and iron) and NAFLD, NAFL and NASH. RESULTS: A total of 602 subjects were included, of whom 73.6% were male, with a median age of 10 (9, 11) years, and a body mass index (BMI) of 24.9 (22.7, 27.4) kg/m2. The intergroup comparison results showed that compared with the overweight group, the NAFLD group had higher levels of age, BMI, diastolic blood pressure (DBP), systolic blood pressure (SBP), triglyceride (TG), low density lipoprotein (LDL), alanine transaminase (ALT) and aspartate aminotransferase (AST), and lower level of high density lipoprotein (HDL). The NAFL group had higher levels of age, BMI, DBP, SBP, ALT, and AST, and lower levels of HDL compared with the overweight group. The levels of age, BMI, DBP, SBP, TG, LDL, ALT, and AST of NASH were higher than those in the overweight group, while the level of HDL was lower than that in overweight group (all P<0.017). After adjusting for a variety of confounders, the OR of NAFLD for the highest quantile of iron was 1.79 (95% CI 1.07 to 3.00) compared to the lowest quantile, and no significant association was observed between copper, zinc, calcium, and magnesium, and NAFLD. The subgroup analysis of NAFLD showed that the OR for the highest quantile of iron in children with NAFL was 2.21 (95% CI 1.26 to 3.88), while no significant association was observed between iron level and NASH. In addition, no significant associations were observed between copper, zinc, calcium, and magnesium levels and NAFL or NASH. CONCLUSIONS: High iron level increases the risk of NAFLD (more likely NAFL) in overweight and obese children, while copper, zinc, calcium, magnesium, and other elements are not associated with the risk of NAFLD in overweight and obese children.

Distribution properties of ultraviolet absorbents in different species of biodegradable plastics.

Ultraviolet absorbents (UVAs) in the environment have been of increasing concern because of their potential toxicity. However, data on UVAs in the biodegradable plastics are still limited. In this work, we determined the concentrations of 13 UVAs in 6 different types of biodegradable plastic products from Beijing, China, by an ultra-high-performance liquid chromatography with mass spectrometry and found the total concentrations in the range of 37.21-1,138,526 ng g-1. These target UVAs, BP (benzophenone), BP-3, BP-12, UV-328, UV-234, UV-326, UV-329, UV-360 and UV-P are prevalent in the plastic bags, garbage bags, food packaging bags, plastic lunch boxes and tableware, product packing bags and mulch films, except for BP-1, UV-320, UV-327 and UV-PS. This finding showed that the total concentrations of the 13 UVAs in biodegradable mulch films (mean: 1,138,527 ng g-1) were several orders of magnitude higher than those in the other 5 categories of samples (mean: 37.21-186.9 ng g-1). And the UV-328 and BP-1 were the most important components of UVAs in the biodegradable mulch films, with the levels ranging of 726,568-1,062,687 ng g-1 and 317,470-506,178 ng g-1, respectively. As the majority of UVAs were detected in biodegradable plastics, the potential risk of UVAs exposure may exist in the environment with the large-scale use of biodegradable plastics.

Comparison of hospital delivery costs between cesarean section and natural delivery and analysis of influencing factors. / å‰–å®«äº§ä¸Žè‡ªç„¶åˆ†å¨©è€ ä½é™¢è´¹ç”¨çš„æ¯”è¾ƒä¸Žç›¸å ³å› ç´ åˆ†æž.

OBJECTIVES: The increasing costs of hospital delivery have increased the economic burden of pregnant women, and the mode of delivery is the main factor affecting the costs of hospital delivery. This study aims to explore the difference in costs between cesarean section and natural delivery, and to provide reference for controlling the increase of hospital delivery costs. METHODS: The data of inpatient delivery in the Hunan Maternal and Child Health Care Hospital from January 2016 to December 2020 were selected to compare the total inpatient costs and average daily costs of cesarean section and natural delivery. The linear trend model was used to analyze the trend change of inpatient delivery costs and the generalized linear model was used to analyze the influential factors for inpatient delivery costs. RESULTS: The average hospitalization costs of cesarean section (10 447.25 yuan) were higher than that of natural delivery (5 567.95 yuan), and the average daily costs of cesarean section (1 902.57 yuan) were higher than those of natural delivery (1 666.40 yuan). There was no significant increase or decrease in trend for cesarean section, while the average annual growth rate of the costs of natural delivery was 11.79%. The main factors affecting the hospitalization costs of cesarean section and natural delivery included age, occupation, medical insurance, route of admission, length of stay, premature delivery and complications (all P<0.05). CONCLUSIONS: The total hospitalization costs and average daily costs of cesarean section are higher than those of natural delivery, but the costs of natural delivery show a faster growth trend, and the hospitalization costs of cesarean section and natural delivery should be controlled by targeted measures.

[A cross-sectional study on the prevalence rate and influencing factors of non-alcoholic fatty liver disease in overweight/obese children]. / è¶ é‡/è‚¥èƒ–å„¿ç«¥éžé ’ç²¾æ€§è„‚è‚ªè‚ç— æ‚£ç— çŽ‡åŠå ¶å½±å“å› ç´ çš„æ¨ªæ–­é¢ç ”ç©¶.

OBJECTIVES: To investigate the prevalence rate of non-alcoholic fatty liver disease (NAFLD) in overweight/obese children who visit a hospital, and to explore the influencing factors of NAFLD, in order to provide a basis for the prevention of NAFLD in overweight/obese children. METHODS: Overweight/obese children who visited Hunan Children's Hospital from June 2019 to September 2021 were recruited. The prevalence rate of NAFLD was examined. Logistic regression analysis was used to explore the factors influencing the development of NAFLD [non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH)]. Receiver operating characteristic curve analysis was used to evaluate the predictive value of the influencing factors for NAFL and NASH. RESULTS: A total of 844 overweight/obese children aged 6-17 years were enrolled. The prevalence rate of NAFLD in overweight/obese children was 38.2% (322/844), among which the prevalence rates of NAFL and NASH were 28.8% (243/844) and 9.4% (79/844), respectively. Multivariate logistic regression analysis showed that the increase of waist-to-hip ratio (WHR) and low high-density lipoprotein cholesterol (HDL-C) were associated with the development of NAFL and NASH (P<0.05). The receiver operating characteristic curve analysis showed that the combined measurement of WHR and HDL-C had a predictive value for NAFL (area under the curve: 0.653, 95%CI: 0.613-0.694), and for NASH (area under the curve: 0.771, 95%CI: 0.723-0.819). CONCLUSIONS: The prevalence rate of NAFLD in overweight/obese children who visit a hospital is high. WHR and HDL-C are associated with the development of NAFLD and the combined measurement of WHR and HDL-C has a certain value for predicating the development of NAFLD.

Postpartum hemorrhage and postpartum depressive symptoms: A retrospective cohort study.

BACKGROUND: Many psychological and obstetrical factors contribute to the development of postpartum depression. However, little is known about how postpartum hemorrhage (PPH) influences postpartum depressive symptoms. This study explored the relationship between PPH and postpartum depressive symptoms in the Chinese population. METHODS: A retrospective cohort study was conducted at the Baoan Maternal and Child Health Hospital in Shenzhen, China, from January 2016 to June 2020. The Edinburgh Postnatal Depression Scale was used to assess postpartum depressive symptoms. A multivariate logistic regression model was used to estimate the odds ratios (ORs) with 95% confidence intervals (95% CIs) between PPH and risk of postpartum depressive symptoms. RESULTS: Of the 7734 respondents, 293 (3.8%) and 7441 were in the PPH and control groups, respectively. Puerperal women with PPH were more likely to screen positive for postpartum depressive symptoms than those without PPH (16.4% vs. 11.7%, p = .016). Adjusting for other covariates, women with PPH still had higher risk of postpartum depressive symptoms (OR = 1.68, 95% CI: 1.16-2.42). Stratification analyses revealed no interaction between PPH and maternal age, prepregnancy body mass index, mode of delivery, and fetal sex in developing depressive symptoms (p for interaction > .05). CONCLUSIONS: PPH may increase the risk of postpartum depressive symptoms. Therefore, women with PPH should be actively screened for depressive symptoms in the immediate postpartum period.

Automated Intact Glycopeptide Enrichment Method Facilitating Highly Reproducible Analysis of Serum Site-Specific N-Glycoproteome.

Bottom-up proteomics has been increasingly applied in clinical research to study the disease pathophysiology and to discover disease biomarkers. However, glycoproteomic analysis always requires tedious experimental steps for intact glycopeptide enrichment, which has been the technique bottleneck for large-scale analysis of clinical samples. Herein, we developed an automated glycopeptide enrichment method for the analysis of serum site-specific N-glycoproteome. This automated method allowed for processing one sample within 20 min. It showed higher enrichment specificity, more intact glycopeptide identifications, and better quantitative reproducibility than the traditional manual method using microtip enrichment devices. We further applied this method to investigate the serum site-specific N-glycosylation changes between four patients with pancreatic cancer and seven healthy controls. The principal component analysis of intact N-glycopeptides showed good clustering across cancer and normal groups. Furthermore, we found that the site-specific glycoforms, monofucosylated and nonsialylated oligosaccharides, on IgG1 site 180 expressed a significant decrease in pancreatic cancer patients compared to healthy controls. Together, the automated method is a powerful tool for site-specific N-glycoproteomic analysis of complex biological samples, and it has great potential for clinical utilities.

Development of urinary pseudotargeted LC-MS-based metabolomics method and its application in hepatocellular carcinoma biomarker discovery.

Hepatocellular carcinoma (HCC) is one of the pestilent malignancies leading to cancer-related death. Discovering effective biomarkers for HCC diagnosis is an urgent demand. To identify potential metabolite biomarkers, we developed a urinary pseudotargeted method based on liquid chromatography-hybrid triple quadrupole linear ion trap mass spectrometry (LC-QTRAP MS). Compared with nontargeted method, the pseudotargeted method can achieve better data quality, which benefits differential metabolites discovery. The established method was applied to cirrhosis (CIR) and HCC investigation. It was found that urinary nucleosides, bile acids, citric acid, and several amino acids were significantly changed in liver disease groups compared with the controls, featuring the dysregulation of purine metabolism, energy metabolism, and amino metabolism in liver diseases. Furthermore, some metabolites such as cyclic adenosine monophosphate, glutamine, and short- and medium-chain acylcarnitines were the differential metabolites of HCC and CIR. On the basis of binary logistic regression, butyrylcarnitine (carnitine C4:0) and hydantoin-5-propionic acid were defined as combinational markers to distinguish HCC from CIR. The area under curve was 0.786 and 0.773 for discovery stage and validation stage samples, respectively. These data show that the established pseudotargeted method is a complementary one of targeted and nontargeted methods for metabolomics study.

Uptake, accumulation and metabolism of UV-320 in vegetables and its impact on growth and quality.

UV-320 is classified as a Substance of Very High Concern (SVHC) by the European Chemicals Agency and has attracted significant attention due to its presence in the environment. Understanding the uptake, translocation and metabolic patterns of UV-320 in vegetables is essential for assessing their ability to bioaccumulate and potential risks to human health. In this study, we investigated the uptake and translocation of UV-320 in lettuce and radish by hydroponic experiments. The results showed that the root concentration factors (Croot/Csolution, RCF) of lettuce and radish were in the range of 47.9 to 464 mL/g and 194 to 787 mL/g, respectively. The transfer factors (Cshoot/Croot, TF) were observed to be 0.001-0.012 for lettuce and 0.02-0.05 for radish. Additionally, non-targeted screening identified twelve phase I and one phase II metabolites of UV-320 in vegetables, which were confirmed based on their molecular formulas and structures. The metabolic pathways involving oxidation, ketonylation and deamination were proposed in vegetables. Also, we have observed that UV-320 inhibits the growth of vegetables. Meanwhile, we evaluated the health risk of UV-320 in lettuce and radish and found that the consumption of lettuce is relatively safe, while the consumption of radish has a risk of HQ >1 for both adults and children, which should be seriously considered. This study provides valuable insights into the behavior and ecological risks of UV-320 in the environment.

Distribution characteristics and sources of ultraviolet absorbents in facility agricultural soils in China.

The environmental contamination of ultraviolet absorbents (UVAs) has attracted global attention for the persistence, bioaccumulation and ecotoxicity. However, little is known about the content and distribution characteristics of UVAs in agricultural soils, especially in facility agricultural soils. In this study, the contents and distribution characteristics of 16 UVAs were surveyed in agricultural facility soils (N = 61) and field soil samples (N = 61) from 27 provinces in China. The total content of 16 UVAs (Σ16UVAs) in facility soils (mean 64.2 ± 55.4 ng/g) was higher than that in field soils (mean 9.66 ± 7.66 ng/g), suggesting that UVAs in facility soils are associated with mulch film. The Σ16UVAs content in the soil mulched with biodegradable (PBAT) film was higher than that in the soil mulched with polyethylene (PE) film, which indicated that the UVA pollution in the soil mulched with biodegradable film was more serious. With the continuous promotion of the use of biodegradable films may pose a threat to soil and ecological health. Therefore, studies on the content and distribution characteristics of UVAs in facility soils are needed to provide scientific basis for the controlling and monitoring of novel pollutants.

Occurrence of organic ultraviolet absorbers in the particle and gas samples from plastic greenhouses: Human inhalation intake risk assessment.

The environmental pollution of organic ultraviolet absorbers (UVAs) has attracted global attention. However, the distribution, sources and risk assessment of UVAs in air from plastic greenhouses are rarely reported. This study was the first to investigate the concentrations of ten UVAs in the air samples from plastic greenhouses. The total concentrations of ten UVAs (∑10UVAs) in the air samples ranged from 5.7 × 103 ng/m3 to 6.3 × 103 ng/m3 (median 5.7 × 103 ng/m3) in greenhouses covered with biodegradable mulch film, 288.2 ng/m3 to 376.4 ng/m3 (median 333.9 ng/m3) in greenhouses covered with PE mulch film, and 97.9 ng/m3 to 142.6 ng/m3 (median 114.9 ng/m3) in greenhouses covered without mulch film. The concentrations of ten UVAs in 65 commercial agricultural films were simultaneously analyzed. Additionally, the potential health risks for greenhouse workers exposed to UVAs were estimated. And the migration simulations showed that the health risk in greenhouses may be higher even if only one UVA is added to the biodegradable mulch film. Therefore, the exposure risk of UVAs in plastic greenhouses needs to be highly prioritized.

Insights into the uptake, accumulation, and metabolism of UV-328 in lettuce (Lactuca sativa L.) and radish (Raphanus sativus L.).

2-(2H-benzotriazole-2yl)-4,6-di-t-pentylphenol (UV-328), a newly listed persistent organic pollutant (POP) under the Stockholm Convention, has garnered significant attention. It is imperative to understand the uptake, translocation and metabolic pathways of UV-328 in plants to assess its bioaccumulation capacity and potential human health risks. In this study, the absorption, accumulation, and metabolic characteristics of UV-328 in lettuce (Lactuca sativa L.) and radish (Raphanus sativus L.) were assessed by hydroponic experiments. In the hydroponics experiment, UV-328 was significantly absorbed by the roots of the plants, with average root concentration factors (RCFs) ranging from 58.5 to 400 mL/g for lettuce and 84.4-154 mL/g for radish. However, UV-328 was poorly translocated from roots to shoots, with a translocation factor (TF) below 0.055. Furthermore, UV-328 underwent transformation and metabolism within the plant. Utilizing a nontarget screening strategy, fourteen phase I metabolites of UV-328 were firstly identified. The metabolic pathways of UV-328 in plants including hydroxylation, demethylation, oxidation, acetylation and deoxygenation were also suggested. It was worth noting that UV-328 has a significant adverse impact on plant growth and quality. The concentration of chlorophyll in plants exposed to UV-328 was significantly reduced, as were the concentrations of water, flavonoids, vitamin C and amino acids.

Clinical and virological characteristics of coexistent hepatitis B surface antigen and antibody in treatment-naive children with chronic hepatitis B virus infection.

Serological pattern of simultaneous positivity for hepatitis B surface antigen (HBsAg) and antibody against HBsAg (anti-HBs) is considered a specific and atypical phenomenon among patients with chronic hepatitis B virus (HBV) infection, especially in pediatric patients. Unfortunately, there is limited understanding of the clinical and virological characteristics among children having chronic HBV infection and the coexistence of HBsAg and anti-HBs. Hence, our objective was to determine the prevalence of coexistent HBsAg and anti-HBs and to explore the associated clinical and virological features in this patient population. The researchers conducted a retrospective cohort study on the 413 pediatric patients with chronic HBV infection from December 2011 to June 2022. The patients were stratified into two groups based on their anti-HBs status. Demographic, serum biochemical and virological parameters of two group were compared. Of the total 413 enrolled subjects, 94 (22.8%) were tested positive for both HBsAg and anti-HBs. Patients with anti-HBs were younger and demonstrated significantly higher ratio of albumin to globulin (A/G), elevated serum levels of alanine transaminase (ALT), lower ratio of aspartate transaminase (AST)/ALT (AST/ALT) and reduced serum levels of globulin, HBsAg and HBV DNA, Additionally, these patients were more likely to show coexistent HBeAg and anti-HBe when compared to patients without anti-HBs. The results of multivariate logistical analysis revealed that AST/ALT, serum levels of globulin and HBsAg were negatively associated with coexistence of HBsAg and anti-HBs. Our data demonstrated a considerable prevalence of coexisting HBsAg and anti-HBs in pediatric patients. Children with this specific serological pattern were commonly of a younger age, seemly predisposing them to early liver impairment and lower HBV replication activity.

Integrative metabolomics highlights gut microbiota metabolites as novel NAFLD-related candidate biomarkers in children.

Altered gut microbiota and metabolites are important for non-alcoholic fatty liver disease (NAFLD) in children. We aimed to comprehensively examine the effects of gut metabolites on NAFLD progression. We performed integrative metabolomics (untargeted discovery and targeted validation) analysis of non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), and obesity in children. Fecal samples were collected from 75 subjects in the discovery cohort (25 NAFL, 25 NASH, and 25 obese control children) and 145 subjects in an independent validation cohort (53 NAFL, 39 NASH, and 53 obese control children). Among 2,491 metabolites, untargeted metabolomics revealed a complete NAFLD metabolic map containing 318 increased and 123 decreased metabolites. Then, machine learning selected 65 important metabolites that can distinguish the severity of the NAFLD. Furthermore, precision-targeted metabolomics selected 5 novel gut metabolites from 20 typical metabolites. The functionality of candidate metabolites was validated in hepatocyte cell lines. In the end, this study annotated two novel elevated pathogenic metabolites (dodecanoic acid and creatinine) and a relationship between depleted protective gut microbiota (Butyricicoccus and Alistipes), increased inflammation (IL-1ß), lipid metabolism (TG), and liver function (ALT and AST). This study demonstrates the role of novel gut metabolites (dodecanoic acid and creatinine), as the fatty acid metabolism regulator contributing to NAFLD development through its influence on inflammation and liver function. IMPORTANCE: Altered gut microbiota and metabolites are a major cause of non-alcoholic fatty liver disease (NAFLD) in children. This study demonstrated a complete gut metabolic map of children with NAFLD, containing 318 increased and 123 decreased metabolites by untargeted metabolomic. Multiple validation approaches (machine learning and targeted metabolomic) selected five novel gut metabolites for targeted metabolomics, which can distinguish NAFLD status and severity. The gut microbiota (Butyricicoccus and Alistipes) and metabolites (creatinine and dodecanoic acid) were novel biomarkers associated with impaired liver function and inflammation and validated by experiments of hepatocyte cell lines. The data provide a better understanding of the importance of gut microbiota and metabolite alterations in NAFLD, which implies that the altered gut microbiota and metabolites may represent a potential target to prevent NAFLD development.

Cultivated Enterococcus faecium B6 from children with obesity promotes nonalcoholic fatty liver disease by the bioactive metabolite tyramine.

Gut microbiota plays an essential role in nonalcoholic fatty liver disease (NAFLD). However, the contribution of individual bacterial strains and their metabolites to childhood NAFLD pathogenesis remains poorly understood. Herein, the critical bacteria in children with obesity accompanied by NAFLD were identified by microbiome analysis. Bacteria abundant in the NAFLD group were systematically assessed for their lipogenic effects. The underlying mechanisms and microbial-derived metabolites in NAFLD pathogenesis were investigated using multi-omics and LC-MS/MS analysis. The roles of the crucial metabolite in NAFLD were validated in vitro and in vivo as well as in an additional cohort. The results showed that Enterococcus spp. was enriched in children with obesity and NAFLD. The patient-derived Enterococcus faecium B6 (E. faecium B6) significantly contributed to NAFLD symptoms in mice. E. faecium B6 produced a crucial bioactive metabolite, tyramine, which probably activated PPAR-γ, leading to lipid accumulation, inflammation, and fibrosis in the liver. Moreover, these findings were successfully validated in an additional cohort. This pioneering study elucidated the important functions of cultivated E. faecium B6 and its bioactive metabolite (tyramine) in exacerbating NAFLD. These findings advance the comprehensive understanding of NAFLD pathogenesis and provide new insights for the development of microbe/metabolite-based therapeutic strategies.

Development of glycoprotein capture-based label-free method for the high-throughput screening of differential glycoproteins in hepatocellular carcinoma.

A robust, reproducible, and high throughput method was developed for the relative quantitative analysis of glycoprotein abundances in human serum. Instead of quantifying glycoproteins by glycopeptides in conventional quantitative glycoproteomics, glycoproteins were quantified by nonglycosylated peptides derived from the glycoprotein digest, which consists of the capture of glycoproteins in serum samples and the release of nonglycopeptides by trypsin digestion of captured glycoproteins followed by two-dimensional liquid chromatography-tandem MS analysis of released peptides. Protein quantification was achieved by comparing the spectrum counts of identified nonglycosylated peptides of glycoproteins between different samples. This method was demonstrated to have almost the same specificity and sensitivity in glycoproteins quantification as capture at glycopeptides level. The differential abundance of proteins present at as low as nanogram per milliliter levels was quantified with high confidence. The established method was applied to the analysis of human serum samples from healthy people and patients with hepatocellular carcinoma (HCC) to screen differential glycoproteins in HCC. Thirty eight glycoproteins were found with substantial concentration changes between normal and HCC serum samples, including α-fetoprotein, the only clinically used marker for HCC diagnosis. The abundance changes of three glycoproteins, i.e. galectin-3 binding protein, insulin-like growth factor binding protein 3, and thrombospondin 1, which were associated with the development of HCC, were further confirmed by enzyme-linked immunosorbent assay. In conclusion, the developed method was an effective approach to quantitatively analyze glycoproteins in human serum and could be further applied in the biomarker discovery for HCC and other cancers.

Mulch film: An overlooked diffuse source of organic ultraviolet absorbers in agricultural soil.

Ultraviolet absorbers (UVAs) are emerging pollutants of concern owing to their environmental persistence and endocrine-disrupting effects. UVAs are added to agricultural films to prevent UV-induced degradation, potentially leading to the release of UVAs into the soil. In this study, the occurrence of four frequently used UVAs (UV-324, UV-326, UV-328, and UV-531) in film-mulched agricultural soils (using conventional polyethylene films and biodegradable films) was investigated. Results showed that the UVA concentrations were several orders of magnitude higher in film-mulched soil (mean 91.4 µg/kg) than in unmulched soil (mean 0.08 µg/kg), indicating that mulch films are important sources of UVAs released into agricultural soil. Notably, the mean UVA concentration was up to 10 times higher in biodegradable-film-mulched soils than in polyethylene (PE) film-mulched soils; this result is consistent with our finding that the mean UVA concentration was 448 times higher in commercial biodegradable films than in PE films. In simulated migration experiments, UVAs migrated more readily into the soil from the biodegradable film than from the PE film. To our knowledge, this is the first report demonstrating that the use of mulch films may cause the accumulation of UVAs in agricultural soils as non-point sources. In particular, biodegradable plastic mulches can release more UVAs into soils.