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.

Oromucosal drug delivery preparations offer advantages such as convenient administration,suitability for patients with dysphagia,rapid onset of action,and avoidance of first-pass metabolism in the liver.The 2020 edition of the Chinese Pharmacopoeia,EP11.0,BP2022,USP44-NF39,and JP18 all include relevant standards for the quality control of different oromucosal drug delivery systems.This article compares the differences in general re-quirements for oromucosal formulations among different countries and provides an overview of inspection items for marketed oral mucosal formulations and those documented in pharmacopoeias both domestically and internationally.Foreign pharmacopoeias include a wide range of oromucosal drug delivery formulations,with more refined quality control measures for systemic action.These findings can serve as a reference for the improvement and enhancement of standards for oromucosal drug delivery systems in China.

Objective:To evaluate the predictive value of stress+ rest gated myocardial perfusion imaging (G-MPI) in assessing all-cause mortality risk in patients with familial hypercholesterolemia (FH).Methods:From June 2010 to March 2022, 72 patients (39 males, 33 females; age (21.1±12.3) years) who diagnosed with FH clinically and genetically and underwent stress+ rest G-MPI in Beijing Anzhen Hospital, Capital Medical University were retrospectively followed up. Image analysis was performed using the 17-segment 5-point method to obtain left ventricular myocardial perfusion and functional parameters. Patients were followed for all-cause mortality events, and predictors associated with the risk of all-cause mortality were analyzed using Cox regression. The efficiencies of predictors were evaluated by ROC curve analysis, and the Kaplan-Meier method and log-rank test were used to compare the differences in the incidence of all-cause mortality in different groups of patients with FH. Independent-sample t test or Mann-Whitney U test was used to analyze the data. Results:The follow-up time of 72 patients was 7(4, 10) years, and all-cause death occurred in 16(22.2%) patients during the follow-up period. There were statistically significant differences in total cholesterol (TC), low density lipoprotein cholesterol (LDLC), summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), stress end-systolic volume (SESV), stress ejection fraction (SEF), rest end-diastolic volume (REDV), rest end-systolic volume (RESV) and rest ejection fraction (REF) between the death group and the survival group ( t values: from -2.65 to 4.47, z values: from -3.43 to -1.98, all P<0.05). Cox regression analysis showed that SDS (hazard ratio ( HR)=1.337, 95% CI: 1.114-1.604, P=0.002), SESV ( HR=1.019, 95% CI: 1.008-1.030, P<0.001) and LDLC ( HR=1.355, 95% CI: 1.049-1.749, P=0.020) were independent predictors associated with the risk of all-cause mortality in patients with FH. The optimal cut-off value of SESV for predicting mortality in patients with FH determined by ROC curve analysis was 35.5 ml, with the AUC of 0.701 (95% CI: 0.517-0.885). The incidence of all-cause mortality in the group with SESV≥35.5 ml was significantly higher than that in the group with SESV<35.5 ml (28.6% vs 6.9%; χ2=5.15, P=0.023). Conclusion:Stress+ rest G-MPI is an important imaging method for all-cause mortality risk assessment in patients with FH, and SDS, SESV and LDLC are important factors in predicting mortality in patients with FH.

Objective To study adverse drug events(ADEs)of busulfan the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS),and to mine the potential ADE signals,so as to provide reference for the safe drug use in clinical practice.Methods Data from the first quarter of 2004 to the first quarter of 2023 were retrieved from the FAERS database,and ADE records for busulfan as a primary suspect drug were obtained through data cleaning and standardization of target drug names.Risk signals for busulfan ADEs were mined based on the reporting odds ratio method,the proportional reporting ratio method,and Medicines and Healthcare Products Regulatory Agency method.The information component method was used to assess the intense of the risk signals.The ADEs were systematically classified according to Medical Dictionary for Regulatory Activities(MedDRA),and two ranking sequence of busulfan ADEs were generated by signal occurrence frequency and signal intense,respectively.Results A total of 20 326 ADE records were collected,involving 5 615 patients with 556 related ADE signals,of which 117 were newly reported as compared to those in the drug instruction of busulfan.Male patients accounted for a higher proportion than female patients(40.71％vs.30.74％).The main population of patients were younger than 18 years old(31.56％).The reports were most reported by physicians(33.71％)and other health professionals(24.35％)as well as pharmacists(23.86％),mainly from the United States(29.69％),Japan(15.78％),and France(11.79％).The top five ADEs in terms of occurrence frequency were busulfan use in unapproved indications,hepatic veno-occlusive disease(HVOD),mucosal inflammation,cytomegalovirus infection,and graft versus host disease.The top five ADEs in terms of signal intense were HVOD,acute graft versus host disease,veno-occlusive disease,graft versus host disease,and chronic graft versus host disease.The ADE signals involves 23 system organ classes.The top three SOCs in terms of the number of ADE signals were infections/infestations,investigations and neoplasms benign/malignant/unspecified(include cysts and polyps).Conclusion When busulfan is used in clinic,attention should be paid to its adverse events in hepatic veno-occlusive disease,infections,graft versus host disease,neurotoxicity,and venous thromboembolism,which are likely to cause serious consequences.The clinical pharmacists can assist clinicians to make prevention plans in case of busulfan ADEs,so as to improve the safety of busulfan use in clinic.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective:To evaluate the prognostic significance of inflammatory biomarkers,prognostic nutritional index and clinicopathological characteristics in tongue squamous cell carcinoma(TSCC)patients who underwent cervical dissection.Methods:The retrospective cohort study consisted of 297 patients undergoing tumor resection for TSCC between January 2017 and July 2018.The study population was divided into the training set and validation set by 7:3 randomly.The peripheral blood indices of interest were preoperative neutrophil-to-lymphocyte ratio(NLR),lymphocyte-to-monocyte ratio(LMR),platelet-to-lymphocyte ratio(PLR),systemic immune-inflammation index(SII),systemic inflammation score(SIS)and prognostic nutritional index(PNI).Kaplan-Meier survival analysis and multivariable Cox regression analysis were used to evaluate independent prognostic factors for overall survival(OS)and disease-specific survival(DSS).The nomogram's accuracy was internally validated using concordance index,receiver operating characteristic(ROC)curve,area under the curve(AUC),calibration plot and decision curve analysis.Results:According to the univariate Cox regression analysis,clinical TNM stage,clinical T category,clinical N category,differentiation grade,depth of invasion(DOI),tumor size and pre-treatment PNI were the prognostic factors of TSCC.Multivariate Cox regression analysis revealed that pre-treatment PNI,clinical N category,DOI and tumor size were independent prognostic factors for OS or DSS(P＜0.05).Positive neck nodal status(N≥1),PNI≤50.65 and DOI＞2.4 cm were associated with the poorer 5-year OS,while a positive neck nodal status(N≥1),PNI≤50.65 and tumor size＞3.4 cm were associated with poorer 5-year DSS.The concordance index of the nomograms based on independent prognostic factors was 0.708(95％CI,0.625-0.791)for OS and 0.717(95％CI,0.600-0.834)for DSS.The C-indexes for external validation of OS and DSS were 0.659(95％CI,0.550-0.767)and 0.780(95％CI,0.669-0.890),respectively.The 1-,3-and 5-year time-dependent ROC analyses(AUC=0.66,0.71 and 0.72,and AUC=0.68,0.77 and 0.79,respec-tively)of the nomogram for the OS and DSS pronounced robust discriminative ability of the model.The calibration curves showed good agreement between the predicted and actual observations of OS and DSS,while the decision curve confirmed its pronounced application value.Conclusion:Pre-treatment PNI,clinical N category,DOI and tumor size can potentially be used to predict OS and DSS of patients with TSCC.The prognostic nomogram based on these variables exhibited good accurary in predicting OS and DSS in patients with TSCC who underwent cervical dissection.They are effective tools for predicting sur-vival and helps to choose appropriate treatment strategies to improve the prognosis.

Objective:To evaluate the current situation of interventional treatment for children with tic disorder and family needs for interventions and to analyze the factors influencing intervention needs.Methods:This cross-sectional study encompassed 362 children and their families who sought medical attention at Children′s Hospital of Chongqing Medical University, from October 2022 to January 2023.Factors influencing their intervention needs were analyzed.Results:A total of 362 children were surveyed.The main therapies of family concern included medication and behavioral intervention.Currently, the predominant therapy employed in the care of these children was medication (102/126, 80.9%), not with standing the fact that 77.8% of parents expressed discontent with its efficacy.Of the children and families included in the survey, 276 (76.2%) gave responses delineating their specific intervention needs.The paramount among these was the need for social support, with the score of (2.69±0.96) points.Multiple linear regression analysis revealed the notable influence of the duration of the ailment, the presence of comorbidities, the gravity of the disorder, the monthly household income, parental anxiety levels, and concerns germane to the therapeutic regimen on the family needs for interventions (all P<0.05). Conclusions:The extant therapeutic approaches applied in tic disorder exhibit a discernable constraint in terms of efficacy.Parents evince a pronounced yearning for interventions.These needs are contingent upon a spectrum of determinants.Clinicians are advised to consider the family needs for interventions when formulating therapeutic strategies, so that they can propound bespoke intervention plans to ameliorate therapeutic outcomes.