Hepatitis E is a globally distributed infection that varies in seroprevalence between developed and developing regions.In the less developed regions of Asia and Africa,a high seropositivity rate has been reported for hepatitis E virus(HEV)antibodies.Although acute hepatitis E is often self-limited and has a favorable prognosis,some populations experience severe manifestations,which may progress to liver failure.Moreover,some immunocompromised patients are at risk of developing chronic HEV infection and cirrhosis.Proactive screening,reducing misdiagnosis,improving patient management,timely anti-viral therapy for severe and chronic cases,and vaccination of high-risk groups are important measures to reduce the morbidity of hepatitis E.This review focused on the clinical presentation,management,and prevention of hepatitis E.

Objective:To investigate effects of capecitabine metronomic chemotherapy combined with exemestane on the proliferation of breast cancer MCF-7 cells and PI3-K/AKT signaling pathway.Methods:MCF-7 cells cultured in vitro were divided into the control group (adding DMEM without drugs), 30 μmol/L exemestane group, capecitabine metronomic chemotherapy combined drugs group [30 μmol/L exemestane combined with different concentrations (50, 33, 17 μmol/L) of capecitabine]. CCK-8 assay was used to detect the cell proliferation inhibition rate, the half-maximal inhibitory concentration ( IC50) was calculated, and the changes of cell cycle and apoptosis rate of MCF-7 in different drug groups were assessed by using flow cytometry. The related-protein expression of PI3K-AKT signaling pathway of MCF-7 cells was detected by using Western blot. Results:The IC50 of capecitabine and exemestane on MCF-7 cells for 72 h was 101.2 μmol/L and 60.6 μmol/L, respectively. The proliferation inhibition rate of MCF-7 cells in 30 μmol/L exemestane for 24 h and 48 h combined with 50, 33 and 17 μmol/L capecitabine group was higher than that in 30 μmol/L exemestane group (all P<0.01). The apoptosis rates were (18.1±2.6)%, (34.6±3.0)%, (27.6±1.3)%, (23.1±1.6)%, respectively in 30 μmol/L exemestane group, 30 μmol/L exemestane + 50 μmol/L capecitabine group, 30 μmol/L exemestane + 33 μmol/L capecitabine group, 30 μmol/L exemestane + 17 μmol/L capecitabine group, and the difference was statistically significant ( F = 23.652, P<0.01). Compared with the control group, the proportion of MCF-7 cells in phase G 2 of 30 μmol/L exemestane group was increased [(16.7±2.6)% vs. (10.6±2.2)%], while that in phase G 1 was decreased [(53.3±4.0)% vs. (56.3±3.2)%]. The proportion of MCF-7 cells in phase S of 30 μmol/L exemestane + 50 μmol/L capecitabine group was increased [(39.0±3.6)% vs. (33.1±2.0)%]. MCF-7 cells of 30 μmol/L of exemestane + 33 μmol/L capecitabine group were more blocked in phase S [(51.7±4.1)%], and cells in phase G 2 were nearly disappeared [(1.2±0.5)%]; the cell proportion MCF-7 cells in phase G 2 of 30 μmol/L exemestane plus 17 μmol/L capecitabine group was increased [(26.2±3.1)%]. Western blot analysis showed that low dose capecitabine metronomic chemotherapy promoted exemestane to inhibit the expression of PI3K, motivated AKT serine phosphorylated at protein 473 [the increased expression of p-AKT (473)], promoted S6 protein expression at downstream of signaling pathway and increased its phosphorylation level (the increased expression of p-S6), thereby activating apoptosis signal. Conclusion:Capecitabine metronomic chemotherapy combined with exemestane can synergistically inhibit the proliferation of breast cancer MCF-7 cells and activate apoptosis mechanisms of MCF-7 cells through affecting PI3K-AKT signaling pathway.

Objective To explore the early predictors of macrolide-unresponsive Mycoplasma pneumoniae pneumonia(MUMPP)and construct a nomogram prediction model.Methods The clinical data of 159 chil-dren with Mycoplasma pneumoniae pneumonia(MPP)admitted to the hospital from January 2023 to Februar-y 2024 were retrospectively collected.According to the time of admission,they were divided into modeling group(112 cases)and validation group(47 cases).The modeling group was further divided into MUMPP group(51 cases)and MPP group(61 cases)according to the drug response.The clinical data and laboratory indexes of each group were compared.The independent predictors of MUMPP were analyzed by univariate and multivariate analysis,and a nomogram prediction model was constructed.Receiver operating characteristic(ROC)curve,area under the curve(AUC),decision curve,calibration curve and Hosmer-Lemeshow goodness of fit test were used to evaluate the discrimination,clinical practicability and calibration of the model.Results The systemic immune inflammation index(SII),C-reactive protein(CRP)/albumin(ALB)and D-dimer were independent influencing factors of MUMPP(P＜0.05).The AUC was 0.938(95％CI 0.890-0.986)in the modeling group and 0.912(95％CI 0.832-0.992)in the validation group.x2 was 3.768 and P was 0.877 in Hosmer-Lemeshow goodness-of-fit test,threshold probability between 5％and 99％had high net clinical benefit.Conclusion The nomogram prediction model established by SII,CRP/ALB and D-dimer has good prediction accuracy and high clinical application value for children with MUMPP.

Background and aim:Few studies have reported hepatitis B surface antigen(HBsAg)kinetics after nucleos(t)ide analog(NA)discontinuation in patients with noncirrhotic chronic hepatitis B(CHB).The study specifically investigated long-term HBsAg kinetics after NA discontinuation. Methods:Between January 2014 to January 2024,this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation treatment.Demographic,clinical,and laboratory data were collected and analyzed after NA discontinuation. Results:Ninety-six patients who finished 5 years of follow-up were included.HBsAg remained unde-tectable in 29 patients with end of treatment(EOT)HBsAg negativity.Among 67 patients with EOT HBsAg positivity,HBsAg seroclearance occurred in 12(17.9％)patients with an estimated annual inci-dence of HBsAg seroclearance of 3.6％.Patients with EOT HBsAg levels of ≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of＞1000 IU/mL(33.3％vs.5.4％).The pro-portion of patients with HBsAg ≤1000 IU/mL increased during follow-up.Logistic regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL.The optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/mL. Conclusions:Patients with EOT HBsAg negativity experienced no relapse and maintained HBsAg sero-clearance during 5 years of follow-up after NA discontinuation.A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of ≤1000 IU/mL during 5 years of follow-up after NA discontinuation.Close monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation.

Objective To investigate short-term efficacy and security of telbivudine as a sequential therapy in the HBeAg positive chronic hepatitis B (CHB) patients with pegylated IFNα-2a treatment failure.Methods 27 CHB patients with HBeAg positive and HBV DNA detectable after a 48-week pegylated IFNα-2a therapy were enrolled into this study,and were assigned to group A,with telbivudine as a sequential therapy.54 CHB patients with HBeAg positive were assigned to group B,with telbivudine as a naive treatment.To assessment the efficacy and security of telbivudine at week 48.Results At week 12,the rates of aminotransferases normalization,HBeAg seroconversion and HBV DNA undetectable (＜ 100 IU/ ml) among the two groups were 59.3％,14.8％,66.7％ vs 75.9％,5.6％,46.3％ respectively.At week 24,the rates among the two groups were 92.6％,25.9％,70.3％ vs 92.6％,7.4％,85.2％,respectively.At week 48,the rates among the two groups were 88.9％,29.6％,81.5％ vs 98.1％,28.0％,83.3％ respectively.All these were not statistically significant.But the rate of HBeAg seroconversion in group A is higher than that in group B.The virological breakthrough rate of group B at week 48 is 14.8％,no virological breakthrough was observed in group A.During the treatment,38.3％ of patients had creatine kinase(CK) elevation,but there was no case stopping treatment for severe adverse effect.Conclusion CHB patients with HBeAg positive after a 48-week pegylated IFNα-2a treatment failure can also achieve the same efficacy and security as the na(i)ve treatment,after receiving telbivudine as a sequential therapy.

Objective:To investigate the clinical features and prognosis of hypertrophic cardiomyopathy（HCM）in children.Methods:The clinical data of 184 children diagnosed as HCM,who visited Beijing Children's Hospital of Capital Medical University from January 1，2006 to August 31，2022 were retrospectively analyzed.The children were divided into primary HCM group and secondary HCM group according to the etiology of HCM，and their clinical characteristics and prognosis were compared.Results:A total of 184 children[115（62.50%）males and 69(37.50%) females] with HCM were included.The median age at first diagnosis was 4.54（0.50，10.25）years.Among the participants，141（76.63%）cases had primary HCM，and 43（23.37%）cases had secondary HCM.Compared with the patients in primary HCM group，the patients in secondary HCM group had lower age of onset，with a higher proportion of the children under 1 year of age.Most cases had atypical symptoms，including a higher proportion of first-onset heart failure，higher proportion of enlarged cardiac shadow on chest radiograph，and lower left ventricular ejection fraction in the secondary HCM group（ P<0.05）.The proportion of older children，ratio of ventricular septal thickness to left ventricular posterior wall thickness，and the detection rate of left ventricular outflow tract obstruction in the primary HCM group was higher than those in patients with secondary HCM group（ P<0.05）.The survival curve for two groups showed that the secondary HCM group had significantly lower 1-year，2-year，3-year，5-year，and 10-year survival rates than those in the primary HCM group（ P<0.05）. Conclusion:The clinical manifestations of HCM in children are heterogenous due to different etiology，and it is necessary to actively clarify the etiology，improve risk assessment，and provide personalized management and treatment method.