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.

The blood-brain barrier(BBB)is a semi-permeable biological barrier between brain tissue and plasma,however,its physical,enzymatic and immune properties,as well as its unique transport mechanism severely limit the entry of therapeutic drugs and diagnostic agents into the brain,which poses great challenges for the prevention and treatment of brain diseases.Hence,this review summarizes and discusses the complex structural components and various transport mechanisms of BBB,and interprets the difficulties and feasible ways of drug delivery across BBB.Furthermore,the latest research progress and future development trends of various delivery systems for brain drug delivery are introduced and discussed to provide references for further perfecting their design and driving their transformation.Finally,this review discusses the pathological changes of BBB in brain diseases and the design of drug delivery strategies for pathological BBB.Collectively,this review highlights the design and optimization of drug delivery strategies across the BBB based on nano-delivery system and provides accessible guide for current opportunities and challenges of intracerebral drug delivery.

Objective:To investigate the positive rate and isolate Bordetella pertussis in children with suspected whooping cough and their close family members in Zhejiang Province, and further explore the susceptibility and resistant mechanism of Bordetella pertussis to antibiotics. Methods:A total of 273 nasopharynx swabs specimens from children with suspected whooping cough in Hangzhou Children′s Hospital from May 2022 to October 2022 were collected. The strains were isolated and cultured using charcoal select agar plate. Pertussis target genes were detected by RT-PCR. E-test method was used to detect the sensitivity of Bordetella pertussis strains to different antibiotics. The mechanism of resistance of Bordetella pertussis to macrolides was analyzed by whole genome sequencing. The phylogenetic analysis of isolated strains was based on core genome multilocus sequence typing(cgMLST). Results:Among 273 clinical samples of children with suspected pertussis and their close family members, 168 samples were positive by fluorescence quantitative PCR, accounting for 61.54%, and 30 pertussis strains were successfully isolated with a positive rate of 10.98%. In addition, among the 143 samples of close family members, 54.55% (78/143) samples were positive by RT-PCR and 9.79% (14/143) samples were positive by culture, suggesting that the close family member are important in family transmission of pertussis. Besides, most of the positive samples were from mothers. The results of E-test showed that 96.67%(29/30) strains showed high resistance to azithromycin with MIC value>256 mg/L, and the resistant mechanism of azithromycin was A2047G mutation in 23S rRNA. The phylogenetic analysis based on the cgMSLT showed that the isolated strains were clustered into two new different clades.Conclusions:The positive rate of Bordetella pertussis in close family members is at a high level and the mother may be the main source of infection, which is of great significance for monitoring and laboratory detection of suspected children′s family members. Bordetella pertussis shows high resistance to macrolides in Zhejiang Province, so monitoring of the antimicrobial resistance should be further strengthened to provide theoretical basis for clinical treatment and drug guidance.

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Epitopes ; Humans ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics*

Background Preterm birth-related complications are the leading cause of death in newborns and children under the age of 5 years. Maternal heat exposure has been associated with both sleep status during pregnancy and the increased risk of preterm birth. However, whether sleep status could mediate the association between heat exposure and preterm birth remains unclear. Objective To evaluate the association between maternal heat exposure in early pregnancy and preterm birth, and to further explore potential mediation effect of sleep status on the association between heat exposure and preterm birth. Methods A birth cohort was established in Guangzhou Panyu Maternal Child Health Hospital (Guangzhou Panyu District He Xian Memorial Hospital) from 2017 until now. Pregnant women (with gestational age between 8 and 13 weeks) were included in this study when they presented to the hospital for their first prenatal care visit and signed an informed consent. Then they were followed up until delivery. A total of 3 268 pregnant women were included for the final analysis. Questionnaires were distributed to collect the demographic characteristics, lifestyles, and sleep status of pregnant women. Daily meteorological data during the study period were collected from meteorological monitoring stations in Guangzhou and the average ambient mean temperature of four weeks before the survey was calculated and assigned for each pregnancy. The 75th, 80th, 85th, 90th, and 95th percentiles (P₇₅, P₈₀, P₈₅, P₉₀, and P₉₅) of the average ambient temperature of all pregnant women were used as the thresholds to define heat exposure. Logistic regression was used to evaluate the effects of heat exposure in different definitions on preterm birth and sleep status (sleep duration, night sleep timing, and wake up timing). The mediation effects of sleep status on the relationship between heat exposure and preterm birth were also analyzed. Results Among all the included participants, 165 newborns were preterm births with an incidence rate of 5.0%. Heat exposures with thresholds of P₉₀ and P₉₅ increased the risk of preterm birth, with ORs (95%CIs) of 1.66 (1.04-2.57) and 1.90 (1.03-3.33), respectively (P<0.05). Heat exposures with thresholds of P₇₅, P₈₀, P₈₅, P₉₀, and P₉₅ decreased the sleep duration (<9 h vs. ≥9 h, control group: ≥9 h), and the ORs (95%CIs) were 1.51 (1.25-1.83), 1.44 (1.17-1.77), 1.35 (1.08-1.70), 1.43 (1.09-1.87), and 1.45 (1.00-2.13), respectively. Heat exposures with P₇₅ and P₈₀ thresholds resulted in earlier wake up timing (<8: 00 vs. ≥8: 00, control group: <8: 00), with ORs (95%CIs) of 0.77 (0.63-0.93) and 0.76(0.61-0.93), respectively. No significant association was observed between heat exposure and night sleep timing. The mediation analyses showed that under heat exposure with P₉₀ threshold, a statistically significant mediation effect was observed for sleep duration, and the proportion mediated was 6.07% (95%CI: 0.17%-25.00%) (P<0.05). No significant mediation effect was observed for night sleep timing and wake up timing. Conclusion An elevated risk of preterm birth after heat exposure in early pregnancy may be partly mediated through reducing sleep duration.

Atrial fibrillation (AF) is one of the most common arrhythmias, associated with high morbidity, mortality, and healthcare costs, and it places a significant burden on both individuals and society. Anti-arrhythmic drugs are the most commonly used strategy for treating AF. However, drug therapy faces challenges because of its limited efficacy and potential side effects. Catheter ablation is widely used as an alternative treatment for AF. Nevertheless, because the mechanism of AF is not fully understood, the recurrence rate after ablation remains high. In addition, the outcomes of ablation can vary significantly between medical institutions and patients, especially for persistent AF. Therefore, the issue of which ablation strategy is optimal is still far from settled. Computational modeling has the advantages of repeatable operation, low cost, freedom from risk, and complete control, and is a useful tool for not only predicting the results of different ablation strategies on the same model but also finding optimal personalized ablation targets for clinical reference and even guidance. This review summarizes three-dimensional computational modeling simulations of catheter ablation for AF, from the early-stage attempts such as Maze III or circumferential pulmonary vein isolation to the latest advances based on personalized substrate-guided ablation. Finally, we summarize current developments and challenges and provide our perspectives and suggestions for future directions.

The functionality of DNA biomacromolecules has been widely excavated, as therapeutic drugs, carriers, and functionalized modification derivatives. In this study, we developed a series of DNA tetrahedron nanocages (Td),

Based on the three delivery forms of CRISPR/Cas9 system at the levels of DNA, RNA and protein, this paper mainly approaches the development and new strategies of CRISPR/Cas9 delivery systems, as well as their application in the biomedical field and the clinical treatment of gene-related diseases. By summarizing and elaborating the CRISPR/Cas9 system delivery and gene therapy strategy, new ideas are provided for the discovery of innovative drugs and the development of gene therapy.