PURPOSE:This study evaluates phase-specific antiviral efficacy of tenofovir disoproxil fumarate (TDF) in pregnant women with hepatitis B virus (HBV) infection, comparing immune-tolerant (IT), inactive carrier (IC), and their corresponding gray zone (GZ-A, GZ-C). Perinatal outcomes and mother-to-child transmission (MTCT) risks were also assessed across these phases. METHODS:In this retrospective study, 717 pregnant women with HBV infection from Nanjing, China (2021-2023) were stratified into IT (n = 317), IC (n = 76), GZ-A (n = 98), and GZ-C (n = 226). Among them, 365 women received TDF antiviral therapy during mid-to-late pregnancy. Primary endpoints included complete virological response rate (CVR) and reductions in HBV DNA and HBsAg from baseline, measured at delivery and 6 months postpartum. RESULTS:TDF significantly reduced HBV DNA levels across all groups (p < .001), with the highest CVR rate observed in GZ-A (41.94% vs. 15.88% in IT at 6 months postpartum, p = .002). Despite higher rates of transient liver dysfunction in GZ-A (22.45% vs. 12.62% in IT, p = .007), no group exhibited increased MTCT or adverse pregnancy outcomes (APOs, p > .05). HBsAg decline was most pronounced in GZ-C at 6 months postpartum (Δ = 0.69 log10 IU/mL vs Δ = 0.47 log10 IU/mL in IC, p < .01). CONCLUSION:TDF effectively suppresses viral replication in pregnant women with HBV infection, including historically undertreated GZ subgroups, without compromising pregnancy safety. These findings provide a reference for phase-specific management strategies to optimize perinatal HBV care.

Background Intrahepatic cholestasis of pregnancy (ICP) is linked to negative outcomes in pregnancy, potentially due to placental autophagy dysfunction. Yinchenhao decoction (YCHD) may improve ICP outcomes, the object of this study was to examine the impact of YCHD on autophagy in the placenta of ICP rats and elucidate the underlying mechanisms. Methods The ICP rat model was induced with 17α-ethinyl estradiol and treated with intragastric YCHD. An ICP HTR-8/SVneo cell model was created using taurocholic acid and treated with YCHD drug-containing serum. The decoction's impact on ICP was evaluated using hematoxylin-eosin staining and serum biochemical markers. Assessment of cell viability was conducted by employing the CCK-8 assay. Immunohistochemistry and Western blotting analyzed autophagy markers LC3I and LC3II in placental tissues. Key proteins and genes related to the mTOR pathway were studied via Western blotting and quantitative real-time PCR. An electron microscope was used to observe an autolysosome. Results The damage induced by TCA in HTR-8/SVneo cells was notably alleviated by YCHD, which resulted in an upregulation of mTOR mRNA expression, a counteraction of rapamycin's mTOR pathway inhibition, and a decrease in LC3 expression. It improved survival and birth weight in ICP rats, restored liver function, and reduced bile acid. Additionally, YCHD lessened liver and placenta damage and decreased placental thrombosis. It activated p-mTOR/mTOR and p-PI3K/PI3K in the ICP rat placenta while inhibiting LC3II/LC3I, indicating mTOR pathway activation and autophagy inhibition. Conclusion YCHD alleviated symptoms and pathological damage in ICP rats and counteracted the damage induced by TCA. Its therapeutic mechanism involved activating the mTOR signaling pathway, thereby inhibiting aberrant placental autophagy. These findings hold significant importance in enhancing the clinical utility of YCHD.

Despite the clinical significance, data are limited on pregnancy outcomes and infant growth among women with chronic hepatitis B virus (HBV) infection treated with antiviral treatment before pregnancy (ATBP). This study aimed to evaluate the effects of ATBP on maternal pregnancy outcomes and infant growth parameters. A retrospective cohort study was conducted among 1031 women aged ≥20 years with singleton pregnancies and chronic HBV infection, recruited from January 2021 to January 2023. Propensity score matching was applied to balance baseline characteristics across 3 groups: 99 women receiving ATBP, 99 receiving antiviral treatment during pregnancy (ATDP), and 99 receiving no antiviral treatment. Pregnancy outcomes were analyzed using modified Poisson regression, while infant growth parameters were assessed by generalized linear regression, stratified by sex. After matching, mothers in the ATBP group exhibited a significantly lower risk of gestational abnormal alanine aminotransferase compared to those in the ATDP group. No significant differences were observed in maternal pregnancy outcomes (such as hypertensive disorders of pregnancy, gestational diabetes mellitus, and preterm birth) and in the growth parameters of their infants in the ATBP group versus the other 2 groups. Only 1 infant in this study, who was in the ATDP group and received antiviral treatment starting at 24 weeks of gestation, was diagnosed with chronic HBV infection. Our findings indicated that ATBP was associated with a lower risk of gestational alanine aminotransferase abnormalities in women with chronic HBV infection. However, we did not find a difference in maternal pregnancy outcomes or infant growth in the first year of life. These results provide insights for clinicians managing pregnancy in this population.

Curzerenone is a major component of the traditional herbal medicine Curcumae Rhizoma with potential cancer-suppressing effects. This study aims to investigate the treatment effect of Curzerenone on cervical cancer cells and the underpinning mechanism. HeLa and SiHa cells were treated with Curzerenone. The 100 μM Curzerenone treatment repressed proliferation, migration, and invasion of the cells. The Curzerenone treatment also reduced cellular expression of programmed death ligand 1, which increased the proliferation and activity of CD8+ T cells in a co-culture system with cancer cells. Casein kinase 2 beta (CSNK2B), a predicted physiological target of Curzerenone, was found to be suppressed by Curzerenone. Further overexpression of CSNK2B blocked the treatment effects of Curzerenone. Curzerenone inhibited while CSNK2B triggered activation of the nuclear factor-kappa B (NF-κB) pathway. The oncogenic and immunosuppressive effects of CSNK2B were blocked by an NF-κB-specific inhibitor. In vivo, Curzerenone treatment inhibited the tumorigenic activity of cancer cells, and it increased the proportion of CD8+ T cells in the xenograft tumor tissues. However, these anti-tumor effects were diminished by the CSNK2B overexpression as well. In conclusion, this research suggests that Curzerenone targets CSNK2B and inactivates the NF-κB signaling to suppress malignancy and immune evasion in cervical cancer.

Hepatitis B virus (HBV) infection is a serious public health concern worldwide, especially during pregnancy due to the associated health risks for the mother and fetus. This study aimed to explore the relationship between alanine aminotransferase (ALT) levels, age and HBV DNA levels in pregnant women with chronic HBV infection. Our cohort study included 1743 pregnant women with HBV who gave birth from January 2021 to June 2024. Participants were divided into three groups based on HBV DNA levels (log IU/mL): low (≤ 3.3; n = 691), moderate (3.3-4.3; n = 398) and high (> 4.3; n = 654). We used modified Poisson regression models and linear trend tests to assess the relationships between HBV DNA levels and gestational minimally raised alanine aminotransferase (MRALT, 40-80 U/L) or raised alanine aminotransferase (RALT, > 80 U/L). Additionally, we evaluated the associations between MRALT/RALT and obstetric outcomes. In pregnant women of advanced maternal age (≥ 35 years), HBV DNA was independently linked to a higher incident RALT risk but not to MRALT risk. A gradient was evident between HBV DNA levels and RALT risk (p for trend < 0.001). Significant links between RALT and premature birth, as well as low birth weight, were found in both participants younger than 35 years and those older than 35 years, but without statistical significance in the latter group. Age significantly modified the association between elevated HBV DNA levels and RALT risk, highlighting the importance of age-stratified monitoring in pregnant women with chronic HBV infection. This highlights the importance of targeted management to prevent adverse outcomes.

BACKGROUND:The effectiveness of immunoprophylaxis for preterm infants delivered by hepatitis B virus(HBV)-infected mothers remains unclear. This study aimed to investigate the effectiveness of immunoprophylaxis in preterm infants. METHODS:Infants delivered by HBV-infected mothers between January 1, 2016 and December 31, 2018 were enrolled, Preterm infants received hepatitis B vaccine immediately after birth and at one, two and seven months while full-term infants received vaccine immediately after birth and at one and six months. All infants were followed utill 24 months. Effectiveness of immunoprophylaxis in preterm infants was analyzed by comparing the dynamics of HBV markers and responsible factors were investigated using multivariate regression analysis. RESULTS:During the study period (2016-2018), 2238 infants were enrolled, including 175 preterm infants and 2063 full-term infants. The differences in the HBsAb concentration between groups were not statistically significant at 7-12 and 24 months of age (P > 0.05), but the concentration in the preterm group were lower relative to the full-term group. Apgar score at 1 min was a predictor of medium-to-high response of HBsAb at 7-12 month (OR 2.687, P = 0.027). CONCLUSIONS:HBsAb concentration in preterm infants delivered by HBV-infected mothers who were vaccinated following the "0-1-2-7″ protocol were similar to those in full-term infants, thereby indicating good outcomes. One-minute Apgar score could be used to predict HBsAb levels in preterm infants at 7-12 months of age after completion of the immunoprophylaxis.

Objective: The objective is to explore the potential pathogenesis and therapeutic mechanism of Yinchenhao decoction (YCHD) in intrahepatic cholestasis of pregnancy (ICP) by focusing on the regulatory role of exosomal miR-370-3p on target genes TM9SF4 and KIT. Methods: Exosomes were isolated from the serum samples of normal pregnant women (control), patients with ICP, HTR-8/SVneo cells, and Sprague-Dawley (SD) pregnant rats via differential centrifugation. Characterization of these exosomes was performed using electron microscopy, nanoparticle tracking analysis (NTA), and western blotting. Quantitative reverse transcription PCR (qRT-PCR) and the bioinformatics tool starBase were used to identify miR-370-3p as a candidate miRNA. Dual-luciferase reporter assays were used to confirm that TM9SF4 and KIT are direct targets of miR-370-3p. An in vitro ICP cell model was established using HTR-8/SVneo cells to investigate the interactions between miR-370-3p and its targets. An animal model was established to validate the targeted regulation of miR-370-3p on TM9SF4 and KIT, as well as the therapeutic effect of YCHD in vivo. Results: The exosomal miR-370-3p expression was significantly upregulated, whereas the TM9SF4 and KIT expressions were downregulated as demonstrated by qRT-PCR and western blot analyses. RNA pull-down assays confirmed a direct negative regulatory relationship between miR-370-3p and both TM9SF4 and KIT at the molecular level. Finally, the therapeutic potential of YCHD was verified by its ability to reverse the altered expression patterns of miR-370-3p, TM9SF4, and KIT in the animal ICP model. Conclusion: Our study demonstrates that YCHD protects against ICP through the miR-370-3p/TM9SF4/KIT axis, suggesting miR-370-3p as a potential therapeutic target for ICP.

Abstract Background Shikonin (SK), a naphthoquinone with anti-tumor effects, has been found to decrease production of tumor-associated exosomes (exo). This study aims to verify the treatment effect of SK on ovarian cancer (OC) cells, especially on the production of exo and their subsequent effect on macrophage polarization. Methods OC cells SKOV3 and A2780 were treated with SK. The exo were isolated from OC cells with or without SK treatment, termed OC exo and SK OC exo, respectively. These exo were used to treat PMA-induced THP-1 cells (M0 macrophages). M2 polarization of macrophages was determined by measuring the M2 specific cell surface markers CD163 and CD206 as well as the secretion of M2 cytokine IL-10. The functions of galectin 3 (LGALS3/GAL3) and β-catenin in macrophage polarization were determined by gain- or loss-of-function assays. CB-17 SCID mice were subcutaneously injected with SKOV3 cells to generate xenograft tumors, followed by OC exo or SK OC exo treatment for in vivo experiments. Results SK suppressed viability, migration and invasion, and apoptosis resistance of OC cells in vitro. Compared to OC exo, SK OC exo reduced the M2 polarization of macrophages. Regarding the mechanism, SK reduced exo production in cancer cells, and it decreased the protein level of GAL3 in exo and recipient macrophages, leading to decreased β-catenin activation. M2 polarization of macrophages was restored by LGALS3 overexpression but decreased again by the β-catenin inhibitor FH535. Compared to OC exo, the SK OC exo treatment reduced the xenograft tumor growth in mice, and it decreased the M2 macrophage infiltration within tumor tissues. Conclusion This study suggests that SK reduces M2 macrophage population in OC by repressing exo production and blocking exosomal GAL3-mediated β-catenin activation.

Aims/Background The relationship between drug exposure and pregnancy outcomes is still unclear. The study was designed to characterise the overall condition of drug exposure during pregnancy and uncover related pregnancy outcomes. Methods Pregnant women were enrolled in the study from 1 October 2019 to 31 April 2022, at a tertiary hospital in Jiangsu Province, China. Basic maternal information and data regarding drug exposure during different pregnancy trimesters were gathered using the `Eugenic Baby' platform. Based on drug use data and the pregnancy and lactation labelling rule, pregnant women were divided into three groups to explore the relationship between drug exposure and pregnancy outcomes. Results Analysis revealed that fetal protection drugs were used in 43.99% of early pregnancy cases. Pregnant women utilised more unrecommended drugs (according to the pregnancy and lactation labelling rule) in the first trimester than in the following trimesters. Regarding pregnancy outcomes, 56 of the 837 live infants had a malformation, and congenital heart disease was the main type. Gestational age, mode of delivery, birth weight, height, and head circumference were significantly different (p < 0.05) among the three groups. According to multivariate logistic regression analysis, preterm birth (odds ratio=3.226, 95% confidence intervals: 1.447-7.194, p=0.004) and predicted increased risk of maternal drug exposure after adjusting for covariates. Conclusion Drug exposure of various types is common during pregnancy. Compared to the second and third trimester, unrecommended drugs are used more frequently in the first trimester. Drug exposure is associated with adverse pregnancy outcomes and these associations need to be further confirmed. It is vital to fully consider treatment benefits and potential risks before medication initiation during pregnancy.

Tenofovir alafenamide fumarate (TAF) has been endorsed by guidelines for blockade of mother-to-child transmission of hepatitis B virus (HBV), given that its efficacy and safety are comparable to tenofovir disoproxil fumarate (TDF). However, there is a lack of comparative studies regarding the treatment efficacy in patients with diverse viral loads. This study retrospectively analyzed 96 hepatitis B e antigen (HBeAg)-positive pregnant women with HBV DNA levels of >= 2 x 10(5) IU/mL. Based on viral loads (HBV DNA levels), participants in the TAF and TDF groups were stratified into three subgroups, namely, the High-G (titer >= 8 log(10) IU/mL), Middle-G (7 log(10) IU/mL <= titer < 8 log(10) IU/mL) and Low-G (titer <7 log(10) IU/mL) subgroups. The primary endpoint was effectiveness of TAF and TDF in patients with varying viral loads, whereas secondary endpoints were hepatitis B surface antigen (HBsAg) positivity in infants at 7 to 12 months and the safety profile for mothers and children. Compared with baseline levels, median HBV DNA levels in mothers were decreased by 4.51 and 4.09 log(10) IU/mL in the TAF and TDF groups (P = 0.04) predelivery, respectively. In the High-G subgroup, the titers were significantly lower in the TAF group (P = 0.045). A higher proportion of patients experienced a virus decline of >= 4 log(10) IU/mL in the TAF group compared with the TDF group, with rates of 78.26% versus 58% (P = 0.034), respectively. Moreover, the median serum phosphate levels significantly decreased from baseline to predelivery in the TDF group (P = 0.04). Finally, infants in both cohorts tested negative for HBsAg at 7-12 months after delivery. Overall, our findings indicate that TAF can be considered the preferred option for the treatment of HBeAg-positive pregnant women with HBV DNA levels of >= 8 log(10) IU/mL.

Abstract Background Little research has been conducted to investigate whether age can modify the impact of hepatitis B virus (HBV) replication on alanine aminotransferase (ALT) levels during pregnancy in women with chronic hepatitis B (CHB). We initially hypothesized that maternal age might modify the relationship between HBV DNA levels and gestational ALT levels. Methods In a retrospective cohort study, 1205 pregnant women with CHB delivered at the Second Hospital of Nanjing between January 2021 and January 2023. Our objective was to analyze the association between different levels of HBV DNA and the risk of gestational abnormal ALT levels, adjusting for age using modified Poisson regression. Results Our research indicated that individuals with high HBV DNA levels of 2000 IU/ml or higher were more probable to experience abnormal ALT with a relative risk of 2.64 (P < 0.01) and a high ALT level (RR = 1.25, P < 0.01) after adjusting for covariates. Considering the age, women with high HBV DNA aged 35 and above had an even higher risk of gestational abnormal ALT (RR = 3.70, P < 0.01) and a high level of ALT (RR = 1.44, P < 0.01). However, the risk of ALT abnormality in women with low HBV DNA would not modify by age. Conclusion Women with CHB may experience significant gestational ALT abnormalities, so they should frequently monitor ALT during pregnancy and receive timely treatment.

Reducing hepatitis B virus (HBV) mother-to-child transmission (MTCT) is a fundamental step toward the HBV elimination goal. The multicentred, multilevel SHIELD program aimed to use an intense intervention package to reduce HBV MTCT in China. This study was conducted in diverse health settings across China, encompassing 30,109 pregnant women from 178 hospitals, part of the interim analysis of stage II of the SHIELD program, and 8,642 pregnant women from 160 community-level health facilities in stage III of the SHIELD program. The study found that the overall MTCT rate was 0.23% (39 of 16,908; 95% confidence interval (CI): 0.16–0.32%) in stage II and 0.23% (12 of 5,290; 95% CI: 0.12–0.40%) in stage III. The MTCT rate was lower among participants who were compliant with the interventions (stage II: 0.16% (95% CI: 0.10–0.26%); stage III: 0.03% (95% CI: 0.00–0.19%)) than among those who were noncompliant (3.16% (95% CI: 1.94–4.85%); 1.91% (95% CI: 0.83–3.73%); P < 0.001). Our findings demonstrate that the comprehensive interventions among HBV-infected pregnant women were feasible and effective in dramatically reducing MTCT.

Goals: The study is to evaluate the efficacy and long-term safety of telbivudine (LdT) usage for hepatitis B surface antigen (HBsAg) positive pregnant women with high viral load. Background: The efficacy and safety of LdT during pregnancy were not assessed from a long-term perspective. Study: HBsAg-positive pregnant women were enrolled and grouped according to antiviral initiation time. Group A (n=100) and group B (n=100) were treated with LdT initiated in the second or third trimester. Group C (n=90) received no antiviral treatment. The efficacy and safety of LdT treatment were compared and infants were followed-up at 1, 5, and 10 years. Denver developmental screening test was conducted at 5 years. Results: Viral loads before delivery in LdT-treated groups were lower than that in group C and group A was lower than that in group B (P<0.001). No infants in LdT-treated groups were infected whereas 8.8% (8/90) infants in group C had positive HBsAg (χ2=23.20, P<0.001). All LdT-treated mothers were well tolerated and no LdT-related adverse events in infants were reported. Part of the physical growth index of infants was higher than Chinese standard values (SV) and showed significant differences. In groups A and B, the developmental screening test qualified rate of 100% (48/48) and 97.96% (48/49) showed no significant difference compared with 92% in normal Chinese children (χ2=5.72, P=0.06). Conclusions: Treatment initiated during the second trimester could strengthen the success of mother-to-child transmission blockage. LdT treatment during pregnancy is safe for both mothers and infants in the long term.

以多种代谢异常为特征的代谢综合征(metabolic syndrome,MS)常表现为超重或肥胖、脂代谢异常、糖代谢异常、血压升高等,其患病率逐年升高.妊娠期代谢综合征(gestational metabolic syndrome,GMS)是妊娠期间特殊的MS类型,目前尚缺乏统一的定义和诊断标准.GMS对育龄期女性及其子代产生的短期和长期影响不容忽视.本文就MS不同组分对育龄期女性的影响及全生育周期管理做一述评.

Recently，the European Association for the Study of the Liver organized the development of the clinical practice guidelines for the management of liver diseases in pregnancy，which include 105 recommendations for the clinical management of liver diseases in pregnancy. This article gives an excerpt of the main contents of the guidelines.

Aim: To investigate the immune status of Chinese chronic hepatitis B (CHB) pregnant women and their clinical characteristics.Methods: About 1544 CHB pregnant women without antiviral therapy from 2013 to 2018 were selected from the hospital records. The definition of immune status is based on American Association for the Study of Liver Diseases (AASLD) 2018 Hepatitis B Guidance, and those who did not meet any criteria of the immune status were referred to in the gray zones (GZ).Results: There were 284 patients in the immune-tolerance phase, 72 patients in the HBeAg-positive immune active phase, 553 patients in the inactive phase, 61 patients in the HBeAg-negative immune active phase. Of note, 574 (37.18%) patients did not fit into any of the above phases were defined as the GZ. Patients with elevated ALT had a higher rate of intrahepatic cholestasis of pregnancy (ICP). Mother to child HBV transmission was rare (only two cases) and occurred in mothers in the immune-tolerant phase.Conclusions: Our data showed that more than one-third of CHB pregnant women were classified into the GZ. In standard stages, advanced age is associated with HBeAg-negative and a higher cesarean rate in the inactive phase. The incidence of ICP was higher in immune active phases, including GB and GD. The probability of mother-to-child transmission in gray zones is low.

目的:分析阿昔洛韦联合静注人免疫球蛋白对妊娠晚期并发水痘孕妇的疗效,以及该方案对患者妊娠结局的影响.方法:收集2018年1月至2020年12月我院妊娠晚期合并水痘的孕妇48例,将其分为对照组(n=24)与观察组(n=24),对照组仅用阿昔洛韦治疗,观察组采用阿昔洛韦联合静注人免疫球蛋白治疗,应用单因素和多重线性回归的方法对数据进行分析.结果:观察组的疗效显著优于对照组.单因素分析结果显示,两组患者在疱疹结痂时间、热程、并发症发生率比较差异有统计学意义(P＜0.05),而年龄、发病孕周和分娩孕周比较差异无统计学意义(P＞0.05).多重线性回归分析结果显示,疱疹结痂时间与治疗方法呈负相关(B=-1.159,P＜0.05),与热程呈正相关(B=0.648,P＜0.05);热程与疱疹结痂时间呈正相关(B=0.304,P＜0.05),与治疗方法呈负相关(B=-1.285,P＜0.05).结论:阿昔洛韦联合静注人免疫球蛋白治疗可提升抗病毒作用,缩短热程和疱疹结痂时间,并降低并发症发生率,减轻临床症状.在确保母婴安全的情况下,应尽量推迟分娩,以预防新生儿水痘的发生.

Background The relationship of maternal HBeAg and infants’ response to hepatitis B vaccine remains controversial. This study aims to observe the dynamic changes in infant birth HBV markers and study the time-varying effects of maternal HBeAg on vaccination response of infants born to women with chronic HBV infection. Methods 3163 infants born to HBsAg positive mothers including 1737 with maternal HBeAg positive in group A and 1426 negative in group B were enrolled eventually. Demographic information and laboratory tests were collected at birth, 7-12th and 24th month. The dynamic changes of infant HBV markers and HBsAb titers at different time points were compared between the two groups. Results The infant HBV markers at birth displayed different modes. During the follow-up, we observed a significant downward trend in the positive rates of HBsAg, HBeAg, HBeAb and HBcAb. The HBsAg of two groups switched to negative at 7–12 months and HBeAg in Group A became negative at 24 months. The HBsAb titers of the infants in the two groups were 576.91(192.8–1000.0) vs 719.67(208.1–1000.0) at 7–12 months (Z = -3.049, P = 0.002) and 783.5(227.8–1000.0) vs 891.4(234.0–1000.0) at 24 months (Z = -0.853, P = 0.394). High HBV DNA viral load (OR 1.260, 95% CI 1.139–1.395, P < 0.001) and maternal HBeAg level (OR 1.003, 95% CI 1.002–1.003, P < 0.001) were associated with the higher HBeAg positive rate of infants. Conclusions Maternal HBeAg did affect the infants’ immune response to vaccination and reduce the anti-response at 7-12th month temporarily, but these influences were negligible by 24th months after birth, which proved that the maternal HBeAg would not induce immune tolerance of infants from a long-term perspective.

The World Health Organization (WHO) has set the goal of eliminating hepatitis as a threat to public health by 2030. Blocking mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is not only the key to eliminating viral hepatitis, but also a hot issue in the field of hepatitis B prevention and treatment. To standardize the clinical management of preventing MTCT of HBV and achieve zero HBV infection among infants, the Chinese Foundation for Hepatitis Prevention and Control organized experts to compile a management algorithm for prevention of MTCT of HBV based on the latest research progress and guidelines, including 10 steps of pregnancy management and postpartum follow-up, among which screening, antiviral treatment, and infant immunization are its core components.