As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Objective:To analyze the clinical characteristics, treatment, and outcomes of children with complete left bundle branch block (CLBBB) mediated by maternal autoantibodies.Methods:A retrospective analysis was conducted on nine children diagnosed with maternal autoantibody-mediated CLBBB, treated at Beijing Anzhen Hospital and Fujian Provincial Hospital from March 2015 to August 2023. Their clinical characteristics, electrocardiographic and echocardiographic findings before and after treatment were reviewed. Paired sample t-test was used for inter-group comparison. Results:Among the mothers, 6 had positive antinuclear antibodies (ANA), 5 had anti-Sjogren syndrome antigen A antibodies, and 3 had anti-Ro-52 antibodies. The cohort included one female and eight male children, diagnosed with CLBBB at the age of 1 (2, 13) months. The positive autoantibodies in the infants, consisted with maternal antibodies, were detected within the first 3 months of life among 3 cases. Treatments included anti-heart failure therapy, myocardial nutritional support, intravenous immunoglobulin (IVIG) and glucocorticoids. Before treatment, the levels of troponin I (0.175 (0.060, 10.270) μg/L) and N-terminal pro-B-type natriuretic peptide (420 (327, 12 865) ng/L) were elevated, which normalized in most cases after treatment. Post-treatment, the QRS duration significantly shortened compared to pre-treatment ((137±15) vs.(169±25) ms, t=3.76, P<0.001), and the QTc interval significantly decreased ((433±41) vs. (514±27) ms, t=4.95, P=0.001). Before treatment, varying degrees of mitral and tricuspid regurgitation and marked interventricular septal dyskinesia were observed in echocardiography. After treatment, valve regurgitation and ventricular septum motion significantly improved, with a marked increase in left ventricular ejection fraction ((51±13)% vs. (27±6)%, t=-6.66, P<0.001). Conclusions:Maternal autoantibody-mediated CLBBB in children presents with chronic heart failure in infancy. Early treatment with anti-heart failure medications, IVIG and glucocorticoids can improve clinical symptoms.

Objective:To investigate whether stress hyperglycemia (SH) is an independent risk factor for the occurrence and mortality of sepsis-associated encephalopathy (SAE).Methods:From August 2016 to October 2021, sepsis patients admitted to the ICU of Guangdong Provincial People's Hospital were selected as the study subjects. According to whether they developed to SH (RBG>11.1 mmol/L) within 7 days of enrollment, the pat ients were divided into the SH group and the non-SH group for analysis. Logistic regression was used to analyze whether SH was an independent risk factor for SAE occurrence, and ROC curve was used to analyze the predictive value of SH to SAE. Kaplan-Meier curve was used to compare the 90-day survival of SAE patients with or without SH. Cox regression analysis was used to analyze the risk factors of 28-day and 90-day death in SAE patients.Results:A total of 183 sepsis patients were included, including 62 patients in the SH group and 121 in the non-SH group. Logistic regression analysis demonstrated that SH was an independent risk factor for SAE ( OR=4.452, 95% CI: 2.021-9.808, P <0.001). ROC curve demonstrated that SH could accurately predict SAE (AUC=0.831; Sensitivity=78.4%; Specificity=76.8%; and Yoden index=0.553). Kaplan-Meier curve demonstrated that the 90-day survival of SAE patients with SH significantly declined (log-rank test: P<0.01). Cox regression analysis suggested that SH was a risk factor for death at day 28 and day 90 in SAE patients (28 d, HR=2.272, 95% CI: 1.212-4.260, P=0.010; 90 d, HR=2.456, 95% CI: 1.400-4.306, P<0.01). Conclusions:SH is an independent risk factor for SAE and can predict SAE occurrence. SH significantly reduces 90-day survival and increase mortality at 28 and 90 days in SAE patients.

OBJECTIVE: To explore the genetic basis for two children with sporadic neurofibromatosis type 1 (NF1) complicated with nephrotic syndrome (NS). METHODS: Clinical data of the children were collected. Both children were subjected to high-throughput sequencing, and candidate variants were verified by Sanger sequencing. RESULTS: Both children had café-au-lait macules, subaxillary freckle and Lisch nodules. Child 1 also had congenital tibiofibular pseudarthrosis on the left side. Genetic testing revealed that child 1 has harbored a heterozygous c.844C>T variant in the exon 8 of the NF1 gene, whilst child 2 has harbored a heterozygous c.1246C>T variant in the exon 11 of the NF1 gene. Both children were diagnosed with NF1 and have developed pronounced proteinuria, hypoalbuminemia, hypercholesterolemia and pitting edema at the ages of 3 and 10, respectively. Renal biopsy of child 2 has revealed minimal change nephropathy, and the diagnosis of nephrotic syndrome was established. Child 1 was treated with glucocorticoid, and child 2 was treated with glucocorticoid in combination with mycophenolate mofetil. The NS was relieved with no recurrence during 1 year's follow-up. CONCLUSION NF1 combined with NS is rare in the clinical settings. The prognosis of children with NF1 combined with minimal change nephropathy is relatively good. Detection of NF1 gene variant can facilitate early identification and diagnosis of NF1.
Child ; Humans ; Neurofibromatosis 1/genetics* ; Nephrotic Syndrome/genetics* ; Nephrosis, Lipoid ; Glucocorticoids ; Genetic Testing

Objective:To investigate the diagnostic and early-warning value of laboratory test indicators for sepsis-induced myocardial injury (SIMD).Methods:The clinical data of 183 patients with sepsis admitted to the Department of Emergency and Critical Care Medicine of Guangdong Provincial People's Hospital from August 2016 to October 2020 were collected. The patient's age, gender, past medical history, vital signs and pathogen culture results were extracted. Cardiac function, blood routine, liver function, renal function, inflammatory factors, coagulation function, APACHE Ⅱ and SOFA scores were recorded at enrollment and 72 h after admission. SIMD was defined as cTnT ≥300 pg/mL and NT-proBNP ≥1243 pg/mL twice in 72 h intervals between enrolled cases, and the early-warning factors of patients with SIMD were analyzed. The differences in various indicators between the two groups were compared, and Logistic regression analysis was used to explore the diagnostic efficacy of cTnT and NT-proBNP combined for SIMD, and the correlation between PCT/PLT ratio and the occurrence of SIMD.Results:Among 250 patients, 67 patients were excluded for lack of the main indicators, and 183 patients (including 62 patients with history of cardiac disease) were enrolled finally. Among 183 patients with sepsis, 105 patients (57.38%) with cTNT ≥300 pg/mL and NT-proBNP ≥1 243 pg/mL, were diagnosed as myocardial injury; after excluding 62 patients with history of cardiac disease, 59 patients (48.76%) with cTNT ≥300 pg/mL and NT-proBNP ≥1 243 pg/mL were diagnosed as myocardial injury. Logistic regression analysis showed that increased PCT/PLT ratio ( OR=1.585, 95% CI: 1.124-2.237, P=0.009) was an independent risk factor for early-warning of SIMD. The PCT/PLT ratio ( OR= 1.850, 95% CI: 1.103-3.102, P=0.020) could stably predict the occurrence of SIMD in patients without previous history of heart disease. ROC curve analysis showed that PCT/PLT ratio could effectively predict the occurrence of SIMD (AUC=0.693, 95% CI: 0.617-0.769, P<0.001), the optimal cut-off value was 0.177 (sensitivity: 65.7%, specificity: 66.7%). The PCT/PLT ratio was still effective in predicting the occurrence of SIMD after excluding patients with previous history of heart disease (AUC=0.733, 95% CI: 0.643-0.823, P<0.001), and the optimal cut-off value was 0.429 (sensitivity: 55.9%, specificity: 83.9%). Conclusions:The combination of cTnT and NT-proBNP has certain diagnostic value for SIMD, and the PCT/PLT ratio could warn the occurrence of SIMD.

Objective:To investigate the short-term and medium-term changes of the left ventricular ejection fraction (LVEF) and the predictive value of relevant electrocardiogram (ECG) indexes in children with dilated cardiomyopathy (DCM) complicated with complete left bundle branch block (CLBBB).Methods:Children clinically diagnosed with DCM in the Department of Heart Center, Women and Children′s Hospital, Qingdao University and Beijing Anzhen Hospital, Capital Medical University between November 2011 and August 2020 were retrospectively recruited.According to the combination of CLBBB, they were divided into CLBBB group and non-CLBBB group.Echocardiogram and ECG were regularly performed.Short-term and medium-term changes of LVEF based on the 1-5-year follow-up data were compared between groups.COX proportional hazards model and Kaplan-Meier multiplicative limit method were used to analyze the predictive value of ECG indexes of LVEF changes in children with DCM combined with CLBBB.Results:Ninety-four children with DCM were enrolled, including 35 cases in CLBBB group and 59 cases in non-CLBBB group.There was no difference in baseline LVEF between groups.However, significant differences were found in QRS duration, corre-cted QT interval(QTc), R peak time in lead V 5 (T V5R) and QRS notching or slurring between groups ( P<0.05). LVEF of all children showed an upward trend within one year after onset, while the Z value of eft ventricular end diastolic diameter(LVEDd) showed a downward trend, and the two indexes tended to be stable within 1 - 5 years.The Z value of LVEDd in CLBBB group was significantly higher than that of non-CLBBB group, while LVEF was significantly lower (all P<0.05). The mean LVEF of CLBBB group slightly fluctuated around 50%, that of LVEF in non-CLBBB group was 60%.The multivariate COX regression analysis showed that QRS duration ( HR=0.979; 95% CI: 0.960-0.999, P<0.05) and QTc ( HR=0.988; 95% CI: 0.979-0.998, P<0.05) were independent predictors of LVEF recovery in children with DCM.Kaplan-Meier method showed a significant difference of LVEF normalization between DCM children with different QRS durations ( P<0.05), which was also detected in those with QTc interval ( P<0.05). Conclusions:LVEF of children with DCM combined with CLBBB increases in the short term after standard treatment, and then being stable.CLBBB can affect the recovery of left ventricular systolic function in children with DCM.Moreover, QRS duration and QTc interval are independent predictors of LVEF recovery in DCM children.

Objective:To explore the relationship between cardiac discomfort symptoms, fear of disease progress and post-traumatic stress disorder (PTSD) in patients with acute myocardial infarction(AMI) after discharge, and to clarify main intervention direction of PTSD in patients with AMI.Methods:Patients with AMI who were discharged from Tangshan Gongren Hospital between 1 month and 1 year were selected from November 2019 to November 2020.The cardiac discomfort symptoms scale, fear of progress questionnaire(FoP-Q-SF) and post-traumatic stress disorder self-rating scale(PTSD-SS) were used to investigate cardiac discomfort symptoms, fear of disease progress level and post-traumatic stress disorder status.Spearman rank correlation analysis was used to analyze the relationship between cardiac discomfort symptoms, fear of disease progress and post-traumatic stress disorder by SPSS 24.0 software. The mediating effect of fear of disease progress was analyzed by AMOS 24.0 software.Results:The PTSD score was (32.78±12.38) of patients with AMI discharged from hospital for 1 month to 1 year and the incidence of PTSD was 12.3%.Spearman correlation test showed cardiac discomfort symptoms and fear of disease progress were positively correlated with PTSD( r=0.530, 0.723, both P<0.01) and cardiac discomfort symptoms was positively correlated with fear of disease progress( r=0.518, P<0.01). Mediating effect test showed that fear of disease progress was a complete mediator between cardiac discomfort symptoms and PTSD. Conclusion:Cardiac discomfort symptoms can affect PTSD through a complete mediator of fear of disease progress.

Objective:To investigate the levels of periphreal blood free carnitine and amino acids in healthy pregnant women in the third trimester and their association with maternal, fetal, and neonatal cardiac function and structure.Methods:This prospective descriptive study included healthy singleton pregnancies who underwent routine obstetric examination and delivered in two district maternal and child health hospitals (one in the urban and one in the suburb an area) in Beijing from June 2017 to February 2018. All recruiters had serology Down's syndrome screening test at (18±1) gestational weeks. Besides measurement of amino acids and free carnitine levels in whole blood and urine samples by liquid chromatography-tandem mass spectrometry, all cases underwent maternal and fetal echocardiography at (35±1) weeks of gestation. And neonatal echocardiography was performed after delivery to assess the heart function and structure. Antenatal factors were also collected, including maternal education background, age at first marriage and conception, gravidity, and folic acid supplement in early pregnancy. Statistical analysis was performed using t-test, ANOVA, Chi-square test, Pearson correlation coefficient, and Kappa test. Results:A total of 493 mother-neonate dyads were enrolled in this study. Blood free carnitine levels in the healthy pregnant women in the third trimester ranged from 5.09 to 59.17 μmol/L (reference value: 10.00-50.00 μmol/L) with an average value of (13.03±3.87) μmol/L. None was found with structural abnormalities by cardiac ultrasound, showing an average left ventricular end diastolic diameter (LVEDD) and end systolic diameter (LVESD) of (45.70±3.08) mm and (29.17±3.12) mm, respectively, and left ventricular ejection fraction (LVEF) of all cases were over 55%. No cardiac malformation was detected by the third-trimester fetal echocardiography. The average birth weight of the 493 newborns was (3 340±313) g. Those whose birth weight <2 500 g and >4 000 g were accounted for 1.0% (5 cases) and 3.0% (15 cases) with the average maternal blood free carnitine level of (13.25±2.17) μmol/L (10.46-19.21 μmol/L) and (12.64±2.50) μmol/L (8.78-17.73 μmol/L) ( t=0.42, P>0.05). The average LVEDD and LVESD of the 493 newborns were (17.21±1.27) mm and (11.03±1.30) mm, respectively. For the 64 newborns (13.0%) whose LVEF<60%, the maternal blood free carnitine level was (12.93±2.78) μmol/L (7.34-22.13 μmol/L), showing no statistical difference ( t=-0.29, P>0.05) with those 59 neonates (12.0%) whose LVEF over 75% and maternal carnitine level of (13.09±3.24) μmol/L (8.66-27.49 μmol/L). All cases were divided into four groups based on the quartiles of maternal blood free carnitine level and no significant difference in maternal or neonatal LVEDD or LVEF was observed among these groups (all P>0.05). Conclusions:Blood free carnitine concentration in healthy pregnant women in the third trimester is at the lower limit of normal range, and no significant effect on maternal cardiac function and fetal cardiac structure is seen. However, the effect of low maternal carnitine level in the third trimester on children's myocardial function and whether carnitine should be supplemented in the third trimester are worthy of further investigation with larger sample size.