Existing nucleos（t）ide analogues and pegylated interferon exhibit limited efficacy in the functional cure of hepatitis B. Recently， small nucleic acid drugs， such as antisense oligonucleotides and small interfering RNAs， have brought unprecedented breakthroughs in the functional cure of hepatitis B with their brand-new mechanisms of action and remarkable efficacy in early clinical studies. Small nucleic acid drugs， such as antisense oligonucleotides and small interfering RNAs， can reduce the level of HBsAg and strive to achieve HBsAg seroclearance. The reduction in HBsAg may restore the hepatitis B-specific immune function of the body to some extent and may further transform the simple clearance of HBsAg into hard endpoints with clinical value， such as reducing hepatitis B-related liver events. By meticulously analyzing the dynamic trajectory of HBsAg alterations within the context of new drug applications and further optimizing combined treatment strategies and regimens， it is expected to transform the functional cure of hepatitis B into the ultimate goal of improving survival rates and quality of life.

Abstract: This study aims to find out the causes for the dissolution of unqualified samples found during evaluation sampling of lansoprazole enteric-coated preparations by the laser infrared imaging system and orbitrap high resolution mass spectrometry, with suggestions for improvement. Lansoprazole enteric-coated preparations were tested by current standard, the dissolution of a batch of samples was below the limit and other items were in line with the standard. Considering that this product is unstable to acid and alkali, the following exploratory experiments were designed from different dimensions, based on the conclusion of the unannounced inspection of the company, to explore the reasons for the unqualified batch, including the influence of high-temperature and high-humidity storage environment on the key quality properties of the sample, the influence of 2-hour acid resistance test on dissolution result, the imaging of the core and the measure of coating layer thickness, the optimization of chromatographic conditions of related substances, and the analysis of the source of impurities. It was found that improper storage in circulation and poor coating process caused the low dissolution of this batch: the high-temperature and high-humidity storage environment possible in the circulation process led to the decreasing efficacy of disintegrating agent in the samples and thus the difficulty to release the active pharmaceutical ingredient fully; the coating solution could not be uniformly sprayed on the core, resulting in thin isolation layer and different thickness, which then affected the protection of the main drug against acid degradation. The above two reasons together resulted in unqualified dissolution of this batch. The overall quality of lansoprazole enteric-soluble preparation is good, but the formulation and process in some companies need to be optimized; and the temperature and humidity in the circulation process need to be controlled in strict accordance with the regulations.

Objective: To analyze the trend of the burden of leukemia among people under 35 years in China from 1990 to 2019. Methods: Incidence, mortality and disability-adjusted life years (DALY) of leukemia among people under 35 years in China from 1990 to 2019 were collected by using the Global Burden of Disease (GBD) Study Database 2019. The trends in leukemia incidence, mortality and DALY rates were analyzed using the average annual percent change (AAPC) and age-period-cohort model. Results: From 1990 to 2019, the incidence, mortality and DALY rates of leukemia among people under 35 years in China showed a downward trend (AAPC=-2.336%, -3.604% and -3.589%, all P<0.05), with more pronounced downward trends in females (AAPC=-3.209%, -3.787% and -3.818%, all P<0.05) than in males (AAPC=-2.521%, -3.292% and -3.306%, all P<0.05). According to the age-period-cohort model, the risks of leukemia incidence, mortality and DALY rates decreased with increasing age. Among them, the children under 5 years had the highest risks of leukemia incidence, mortality and DALY rates (RR=4.697, 2.718 and 3.059). Over time, the risks of leukemia incidence, mortality and DALY rates also decreased from 1990-1994 (RR=1.217, 1.264 and 1.296) to 2015-2019 (RR=0.901, 0.696 and 0.691). With regard to birth cohorts, the risks of leukemia incidence, mortality and DALY rates first increased and then decreased, peaking in the 1986-1990 birth cohort (RR=1.335, 1.192 and 1.231). Conclusions The incidence, mortality and DALY rates of leukemia among people under 35 years in China from 1990 to 2019 showed a downward trend. Males and children under 5 years were the key populations for leukemia prevention and control.

Objective To investigate the neurobehavioral development of young children aged 24 to 60 months in Shunde and explore the factors influencing the development of young children and provide reference for the interven-tion of neurobehavioral development delays in young children.Methods A retrospective cohort study was used to enroll the young children who were initially screened by the Pediatric Neuropsychological Developmental Scale(Pe-diatric Heart Scale)with a score of ≤85 was included in the study.With a score of ≤85,the young children might be at risk of developmental delays,and needed to be further diagnosed by the GESELL Developmental Diagnostic Scale,the basic information of the young children and their mothers at the time of birth were investigated,as well as basic information about the young children at the time of completing the GESELL Developmental Diagnostic Scale was collected.Results A total of 271 young children were included,196 males and 75 females.Young children had the lowest developmental quotient(DQ)in the language domain among the five domains(P＜0.001).Multiple lin-ear regression models showed:compared with girls,the language domain DQ of boys decreased by 5.321 points(P=0.049,95％CI:-10.620--0.021),and the personal-social domain DQ decreased by 4.474 points(P=0.023,95％CI:-8.316--0.631).Compared with young children via natural vaginal delivery(NVD),the gross motor domain DQ of young children via caesarean section(CS)decreased by 4.890 points(P=0.008,95％CI:-8.499--1.281),the fine motor domain DQ decreased by 3.373 points(P=0.037,95％CI:-6.532--0.213),the language domain DQ decreased by 7.621 points(P=0.004,95％CI:-12.826--2.416),per-sonal-social domain DQ decreased by 6.232 points(P=0.001,95％CI:-10.006--2.457).The results of bi-nary logistic regression models showed,compared with young children via NVD,the risk of gross motor domain retar-dation in young children increased(OR=1.763,95％CI:1.003-3.100),the risk of fine motor domain retardation increased(OR=2.217,95％CI:1.235-3.980),the risk of language domain retardation increased(OR=3.306,95％CI:1.080-10.124).Conclusion Young children with suspected neurobehavioral delays were more likely to have delayed development in language domain than in other domains,boys had lower DQ in language domain and personal-social domain than girls,and the development of young children via CS was slower than that via NVD.Fo-cus should be on the language development of young children especially on the language and personal-social devel-opment of boys.Carefully chose delivery way.Focus should be placed on assessment of young children's comprehen-sive neurobehavioral development in early time.

Mother-to-child transmission is the major route of transmission for hepatitis B virus(HBV),and prevention of the mother-to-child transmission of HBV is the key link in the prevention and control of hepatitis B and one of the five essential core strategies for achieving the global elimination of hepatitis B by 2030.Combined immunization for neonates born to HBV-infected mothers and maternal antiviral intervention during pregnancy are important measures for blocking mother-to-child transmission,and thereby,the implementation of the comprehensive strategy of combined immunization and maternal antiviral intervention will help to accelerate the process of eliminating mother-to-child transmission.Chinese scholars have put forward the concept of"zero mother-to-child transmission of hepatitis B"and launched"Shield Program"in China,aiming to promote the implementation of the preventive strategy for mother-to-child transmission and lay a solid foundation for eliminating viral hepatitis in China.The Shield Program has provided detailed implementation strategies,successful practice experience,and reliable data for blocking the mother-to-child transmission of hepatitis B,fostering the consensus on the zero mother-to-child transmission of HBV in the academic community,and it also has an important reference value for eliminating the mother-to-child transmission of HBV in China and globally.

Chronic hepatitis B virus(HBV)infection remains a major public health challenge in China,affecting over 70 million people and posing great challenges to the prevention and control of the disease.At present,both the government and sectors of the society are making efforts to achieve the goal of eliminating viral hepatitis as a public health threat by 2030.Mother-to-child transmission is the main route of transmission of HBV,and therefore,blocking the mother-to-child transmission of HBV is the key link in eliminating viral hepatitis.At present,several critical issues still remain unresolved,including the long-term safety of tenofovir alafenamide fumarate during pregnancy,the safety of antiviral therapy in early pregnancy,the effectiveness of immunoglobulin-free strategy,and the risk of HBV transmission through germ cells.Addressing these challenges is important for promoting the blocking of the mother-to-child transmission of HBV and accelerating the progress toward the 2030 goals.

Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

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).

Chronic hepatitis B virus (HBV) infection remains a pivotal global public health concern. Attaining a functional cure for hepatitis B continues to be a hot and difficult issue that requires immediate attention in clinical practice. There are currently nucleos(t)ide analogues (NAs) that can persistently suppress HBV DNA; however, the functional cure rate of pegylated interferon alfa (PEG-IFN-α) alone or in combination with NAs has not yet met clinical needs. The research and development on novel mechanisms for HBV antiviral drugs, especially small nucleic acid drugs, has brought breakthroughs to the functional cure of hepatitis B. The functional cure trajectory mapping and its prediction model can guide the selection of clinical treatment strategies based on the longitudinal data for HBsAg at various time intervals. The personalized management of hepatitis B patients can be optimized by utilizing varying HBsAg levels as a key watershed to aid in the screening of subjects in clinical trials.