[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].

Mother-to-child transmission of hepatitis B virus(HBV)is one of the primary causes of the high disease burden of chronic hepatitis B in China,and blocking this route of transmission has an important strategic significance for eliminating hepatitis B.While immediate combined immunoprophylaxis for neonates upon birth is the fundamental strategy to block the mother-to-child transmission of HBV,there is still a mother-to-child transmission rate of 9%in mothers with high viral loads.In recent years,breakthroughs have been made in the research on antiviral therapy during pregnancy for blocking mother-to-child transmission,which marks a pivotal milestone in eliminating the mother-to-child transmission of hepatitis B.Comprehensive prophylaxis of antiviral therapy during pregnancy and immunoprophylaxis for infants after birth has become the key strategy for eliminating the mother-to-child transmission of hepatitis B.This article summarizes the development and latest advances in antiviral therapy during pregnancy for blocking mother-to-child transmission,as well as related intervention strategies and indications,in order to provide a reference for clinicians and public health physicians.

Near-infrared (NIR)-light-triggered nanomedicine, including photodynamic therapy (PDT) and photothermal therapy (PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania (TiO_2-x ) for mild NIR-phototherapy. In tumor microenvironment, the overexpressed hyaluronidase (HAase) and glutathione (GSH) can readily destroy hyaluronic acid (HA) and disulfide bond and releases the Cas9/sgRNA from TiO_2-x to target the stress alleviating regulators, i.e., nuclear factor E2-related factor 2 (NRF2) and heat shock protein 90α (HSP90α), thereby reducing the stress tolerance of tumor cells. Under subsequent NIR light illumination, the TiO_2-x demonstrates a higher anticancer effect both in vitro and in vivo. This strategy not only provides a promising modality to kills cancer cells in a minimal side-effects manner by interrupting anti-stress pathways but also proposes a general approach to achieve controllable gene editing in tumor region without unwanted genetic mutation in normal environments.

Objective:To compare the efficacy and safety of telbivudine (LDT) and tenofovir disoproxil fumarate (TDF) treatment during the second and third trimester in pregnant women with high viral load of hepatitis B virus (HBV).Methods:Totally 506 pregnancy women with HBV infection who received antiviral therapy during the second and third trimester of pregnancy in the obstetrical clinic of The Affiliated Nanjing Hospital of Nanjing University of Chinese Medicine from January 1, 2016 to December 31, 2018 were retrospectively enrolled, and the anti-viral efficacy and safety in mothers and neonates were evaluated. Pregnancy women were divided into TDF group and LDT group according the medications. The efficacies including decline and negative rate of HBV DNA, the vertical transmission (VT) rate, the normalization rate of liver function in mothers between the two groups were compared. The safeties including birth weight of neonates, congenital deformities and the rates of preterm between the two groups were also compared. Chi-square test, independent sample t test or rank sum test were used for statistical analysis. Results:There were 239 pregnant women in the LDT group and 267 in the TDF group. The maternal HBV DNA levels before treatment in the LDT and TDF groups were (7.83±0.75) lg IU/mL and (7.82±0.66) lg IU/mL, respectively, while the maternal HBV DNA levels prior to delivery were 2.91(1.20) lg IU/mL and 2.83(1.01) lg IU/mL, respectively. The normalization rates of alanine aminotransferase (ALT) of chronic hepatitis B (CHB) pregnant women prior to delivery in TDF group and LDT group were 95.00%(38/40) and 98.18%(54/55), respectively. There were all no significant differences between the two groups ( t=0.097, U=1.040 and χ2=0.767, respectively, all P>0.05). For CHB pregnant women, the HBV DNA negative rate at one month postpartum in TDF group was 85.45%(47/55) and that in LDT group was 82.50%(33/40). The normalization rate of ALT in TDF group was 94.55%(52/55), and that in LDT group was 92.50%(37/40). There were no significant differences between the two groups ( χ2=0.152 and 0.164, respectively, P=0.697 and 0.687, respectively). The VT rates were 0(0/262) in TDF group and 0.43%(1/231) in LDT group, which had no significant difference between the two groups ( χ2=1.127, P=0.288). Two patients in LDT group who continued taking LDT 11 months postpartum switched to TDF because of HBV rt204 mutation, and no one had virus mutation in TDF group. No significant increased in creatine kinase in LDT group, and no significant abnormal calcium and phosphorus metabolism in the TDF group. The preterm rate was 7.87%(21/267) in TDF group and 4.18%(10/239) in LDT group, but there was no significant difference between the two groups ( χ2=2.970, P=0.085). However, the birth weight of neonates in TDF group ((3 204.72±490.50) g) was lower than that in LDT group ((3 374.31±467.50) g), and the difference was statistically significant ( t=3.780, P<0.01). During the course of treatment, no pregnant women discontinued treatment due to drug intolerance, and no infants presented with drug-related birth defects. Safeties for mothers and neonates were both good. Conclusions:Both LDT and TDF treatment could reduce the VT rate in pregnant women with high HBV viral load. The safety is good for both mothers and neonates. However, for CHB pregnant women who continue antiviral therapy postpartum, TDF is superior to LDT because of lower virus mutation, thus to reduce the risk of drug resistance.

Brain ; Humans ; Neoplasms ; Neurogenesis

OBJECTIVETo compare the various combined immunization schemes available for treatment of babies born to mothers with high-load hepatitis B virus (HBV) infection.

METHODSA total of 118 mothers with HBV infection status of hepatitis B surface antigen-positive (HBsAg+), hepatitis B e antigen-positive (HBeAg+) and HBV DNA load of more than 1.0 * 61og10 IU/mL were included in the study. All of the participants' babies received the main-passive immunization therapy according to the wishes of their families. For analysis,the infants were grouped according to the various dosages of the vaccine program (group A: hepatitis B immunoglobulin (HBIG) 200 IU and HBVac 20 mug intramuscular;group B:HBIG 200 IU and HBVac 10 mug intramuscular; group C HBIG 100 IU and HBVac 20 mug intramuscular injection) and times, and followed-up to 7 months of age.All results were statistically analyzed using SPSS software.

RESULTSAll of the infants produced anti-HBs after vaccination.After the HBIG injection schedule was completed in January, the mean concentrations of anti-HBs in groups A, B, and C were 263.56 ± 50.98,231.06 ± 74.07, and 99.23 ± 29.82 mIU/mL respectively;the concentrations were significantly different between groups A and C, and between groups B and C (P < 0.001). In July, the titers of anti-HBs in groups A, B, and C were 788.10 ± 281.96,428.39 ± 347.48, and 708.44 ± 315.69 mIU/mL respectively; the concentrations were significantly different between groups A and B, and between groups B and C (P < 0.05).

CONCLUSIONAdminisWation of the hepatitis B vaccine combined with HBIG at birth can achieve immune protection for babies born to highly viremic mothers. In January, the HBIG dosage of 200 IU was more reliable than 100 IU. The hepatitis B 20 tg dose vaccine was safe and effective.

Hepatitis B ; Hepatitis B Antibodies ; Hepatitis B Vaccines ; Hepatitis B e Antigens ; Hepatitis B virus ; Humans ; Immunization ; Immunoglobulins ; Infant ; Mothers ; Serologic Tests ; Vaccines, Combined ; Viral Load

OBJECTIVETo investigate whether cannabinoid receptor 1 (CB1R) is involved in nerve growth in endometriosis-associated ectopic cyst.

METHODSThe effect of CB1R agonist and antagonist on the expression of pan-neuronal marker protein gene product (PGP) 9.5 in ectopic cyst was examined by immunofluorescence and Western blot in endometriosis model of 18 rats.

RESULTSImmunofluorescence revealed that PGP 9.5 was expressed in the nerve fibers and was mainly distributed in the cyst hilum. Western blot revealed that the protein density of either PGP 9.5 (2 week: 0.38 ± 0.05; 4 week: 0.63 ± 0.03; 8 week: 0.80 ± 0.07, P < 0.01) or CB1R (2 week: 0.48 ± 0.04; 4 week: 0.68 ± 0.01; 8 week: 0.80 ± 0.03, P < 0.01) in the ectopic cyst increased with cyst size. In addition, compared to control group (0.75 ± 0.01), PGP 9.5 expression in the ectopic cyst was promoted by CB1R agonist ACPA (0.81 ± 0.01, P < 0.05), and inhibited by CB1R antagonist AM251 (0.67 ± 0.03, P < 0.01).

CONCLUSIONSCB1R was involved in the nerve growth of ectopic cyst associated with endometriosis.

Animals ; Blotting, Western ; Cysts ; metabolism ; Disease Models, Animal ; Endometriosis ; metabolism ; Female ; Peripheral Nerves ; growth & development ; metabolism ; Piperidines ; pharmacology ; Pyrazoles ; pharmacology ; Rats ; Receptor, Cannabinoid, CB1 ; antagonists & inhibitors ; physiology ; Ubiquitin Thiolesterase ; metabolism

OBJECTIVETo investigate the significance of NADPH quinine oxidoreductase 1 (NQO1) protein overexpression on prognostic evaluation of head and neck squamous cell carcinoma (HNSCC).

METHODSNQO1 protein was detected in 162 of HNSCC, 45 cases of adjacent nontumor tissues and 26 samples of normal head and neck epithelia using EnVision immunohistochemical. Correlation between NQO1 overexpression and patients prognosis was also analyzed.

RESULTSThe positive rate and strongly positive rate of NQO1 protein were 84.0% (136/162) and 69.8% (113/162) in HNSCC, respectively, and both of which were significantly higher than either those in adjacent nontumor tissues and normal head and neck epithelia (both P < 0.01). NQO1 expression was significantly correlated with the clinical stage, pT and chemoradiotherapy of HNSCC (P < 0.01). Kaplan-Meier survival analysis showed that overall survival and disease-free survival rates were significantly higher in HNSCC patients with high level NQO1 expression than that those with low level of NQO1 expression (Log-rank = 6.625 , P = 0.010;Log-rank = 6.234 , P = 0.013). Additional analysis by Cox proportional hazard regression model showed that high level of NQO1 expression was an independent hazard predictor for overall survival of patients with HNSCC (Wald = 6.626, P = 0.008).

CONCLUSIONSNQO1 expression level is closely correlated with the progression and prognosis of patients with HNSCC. High level of NQO1 expression may be used as an important indicator for patients with poor prognostic HNSCC.

Breast ; enzymology ; Carcinoma, Squamous Cell ; enzymology ; mortality ; pathology ; Disease-Free Survival ; Female ; Head and Neck Neoplasms ; enzymology ; mortality ; pathology ; Humans ; Kaplan-Meier Estimate ; NAD(P)H Dehydrogenase (Quinone) ; metabolism ; NADH, NADPH Oxidoreductases ; metabolism ; Prognosis ; Proportional Hazards Models

OBJECTIVETo detect the expression of pan-neuronal marker protein gene product (PGP)9.5 and its clinicopathologic significance in breast cancer.

METHODSThe expression of PGP9.5 was examined by immunohistochemistry EnVision method in 196 cases during 2007 to 2011, including 20 normal tissues, 14 cases of fibroadenoma, 18 cases of ductal carcinoma in situ (DCIS) and 144 cases of invasive ductal carcinoma (IDC) of the breast. The relationship between PGP9.5 expression and clinicopathologic characteristics of IDC was assessed.

RESULTSPGP9.5 expression was localized in the stroma of all normal breast tissues, but there was no expression observed in all fibroadenomas and DCIS. Overall, the expression rate of PGP9.5 in IDC was 61.8% (89/144). PGP9.5 expression increased from grade 1 tumors (29.4%, 10/34) to grade 2-3 tumors (71.8%, 79/110; P = 0.000). In addition, patients with less than 3 years disease-free survival tended to show higher PGP9.5 expression (64.8%, 35/54), compared to patients with equal to and/or more than 3 years disease-free survival (46.7%, 42/90; P = 0.035). However, there was no correlation between PGP9.5 expression and tumor size, tumor stage, lymph metastasis, hormone receptor expression.

CONCLUSIONPGP9.5 expression is correlated with tumor grade and prognosis in IDC of the breast.

Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; metabolism ; pathology ; Disease-Free Survival ; Female ; Fibroadenoma ; metabolism ; pathology ; Humans ; Middle Aged ; Neoplasm Grading ; Ubiquitin Thiolesterase ; metabolism

Objective To evaluate the efficacy and safety of telbivudine for pregnant women with hepatitis Be antigen (HBeAg)negative chronic hepatitis B(CHB). Methods Sixty-two cases of HBeAg negative CHB pregnant women were collected from May 2007 to May 2012,and they were divided into telbivudine group (n=31 ,600 mg per day by oral administration)and compound glycyrrhizin group (n=31 ,120 mg per day by intravenous administration).All neonates were given intramuscular injection of 200 IU hepatitis Bimmune globalin at birth immediately and 15 days after birth,and 20 μg genetically engineered hepatitis B vaccine at 0,1 and 6 months after birth.The serum alanine aminotransferase (ALT)level and hepatitis B virus (HBV)DNA titer were monitored.The HBV DNA negative conversion rate,the rate of intrauterine infection,duration of pregnancy,delivery mode,neonate weight and disability rate were compared between groups.All categorical data were analyzed using the chi-square test and comparison between groups was analyzed by t test.Results In telbivudine group,the HBV DNA level before delivery ([0.20±0.11]lg copy/mL)and 6 weeks after delivery ([0.22±0.13]lg copy/mL) were lower than that before treatment [(6.24±0.75 )lg copy/mL]and the differences were statistically significant (t=303.128 and 301 .321 ,respectively;both P <0.01).The negative conversion rate of HBV DNA in telbivudine group was 28 cases before delivery,while in compound glycyrrhizin group,no one had HBV DNA negative conversion.And statistical significant differences were achieved between these two groups before delivery and 6 weeks after delivery (t = -20.285 and -8.721 ,respectively;both P <0.01).In telbivudine group,the ALT levels before delivery and 6 weeks after delivery were (13.08±5.87) U/L and (25.97 ± 17.48)U/L,respectively,which were significantly decreased compared with that before treatment (205.95± 95.69 )U/L.The differences were statistically significant (t = 93.128 and 81.321, respectively;both P <0.01).In compound glycyrrhizin group,the ALT level before delivery ([104.15 ± 69.15]U/L)was lower than that before treatment ([209.60 ± 102.24]U/L)and the difference was statistically significant (t = 9.281 ,P =0.032).However,the ALT level was fluctuant 6 weeks after delivery (150.26± 86.43)U/L,which was not significantly different from that before treatment (t =2.821 ,P =0.122).The ALT levels before delivery and 6 month after delivery were significantly different in both two groups (t=-2.559 and -3.158,respectively;both P <0.05 ).There were no statistically significant differences between these two groups in the rate of intrauterine infection, duration of pregnancy,delivery mode,neonate weight and disability rate.Conclusion The using of telbivudine for pregnant women with HBeAg negative CHB can effectively control the hepatitis activation and reduce the virus titer.