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.

Functional cure (i.e., clinical cure) of chronic hepatitis B (CHB) is a core research objective in the field of hepatology. With the revision of the Expert opinions on the technical guiding Principles for clinical trials of drugs in the treatment of chronic hepatitis B virus infection, this article concisely reviews the evolving concept of functional cure for hepatitis B, research progress on the dynamic trajectories and threshold of key serological markers (such as HBsAg/anti-HBs), strategies for safety evaluation of treatment discontinuation, and the importance of building a collaborative innovation ecosystem involving scientific research, industry, healthcare, policy, and societal forces. Through multidimensional technological breakthroughs and interdisciplinary collaboration, the functional cure rate of chronic hepatitis B infection is expected to improve significantly over the next 5-10 years, laying the foundation for achieving the World Health Organization (WHO)'s goal of eliminating viral hepatitis as a public health threat by 2030.

Objective:To explore the predictive value of hepatitis B surface antibody (HBsAb) quantitative level for achieving hepatitis B surface antigen (HBsAg) seroclearance and serological conversion in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogs (NAs) or interferon (IFN).Methods:A two-center prospective cohort study was conducted, including CHB patients from Nanfang Hospital Southern Medical University and Eastern Theater General Hospital treated with NAs and IFN. All patients were followed up once every three to six months. Basic clinical information and test results were collected at each follow-up. The presence or absence of HBsAg seroclearance and serological conversion rate was evaluated. HBsAg serological conversion was defined as HBsAg quantification continuously below the detection limit (<0.05 IU/mL) at two detection time points at least six months apart. HBsAg serological conversion was defined as HBsAb positivity (≥10 IU/L) at the same time as the first HBsAg seroclearance. The Kruskal-Wallis test was used to compare the quantitative data of multiple groups, and the Wilcoxon rank-sum test was used to compare the data between groups. The chi-square test was used for the count data, and the Fisher exact test was used when the chi-square test was not met. Univariate and multivariate Cox analysis was used to determine the predictors of the study endpoints, and stepwise regression was used for variable screening.Results:A total of 2 266 CHB cases were included, of which 86.5% (1 959/2 266) were NA antiviral-received population. The median treatment duration before baseline was 10.5 (2.5, 37.6) months, and the baseline HBsAg quantification was 3.1 (2.6, 3.5) log 10 IU/mL. A total of 68 cases (3.0%) had HBsAg seroclearance, and 44 cases (1.9%) achieved serological conversion after 85.0 (62.7, 97.3) months of prospective follow-up. The level and positivity rate of HBsAb showed a progressive increase 36 months before and significantly after HBsAg seroclearance. Cox regression analysis results showed that baseline HBsAb level was an independent predictor of HBsAg serological conversion ( HR=2.26, P=0.002) in the overall population, especially in the subgroup with HBsAg between 100 and 1 000 IU/mL, suggesting HBsAb level had important predictive value. In addition, the serological conversion development rate was significantly higher in the GOLDEN model favourable patients than in the unfavourable patients (11.5% vs. 0, P<0.001). Conclusion:The baseline HBsAb quantitative level can predict HBsAg seroclearance and serological conversion for patients with CHB receiving antiviral treatment, which is of significant value in long-term treatment monitoring.

Functional cure (i.e., clinical cure) of chronic hepatitis B (CHB) is a core research objective in the field of hepatology. With the revision of the Expert opinions on the technical guiding Principles for clinical trials of drugs in the treatment of chronic hepatitis B virus infection, this article concisely reviews the evolving concept of functional cure for hepatitis B, research progress on the dynamic trajectories and threshold of key serological markers (such as HBsAg/anti-HBs), strategies for safety evaluation of treatment discontinuation, and the importance of building a collaborative innovation ecosystem involving scientific research, industry, healthcare, policy, and societal forces. Through multidimensional technological breakthroughs and interdisciplinary collaboration, the functional cure rate of chronic hepatitis B infection is expected to improve significantly over the next 5-10 years, laying the foundation for achieving the World Health Organization (WHO)'s goal of eliminating viral hepatitis as a public health threat by 2030.

Objective:To explore the predictive value of hepatitis B surface antibody (HBsAb) quantitative level for achieving hepatitis B surface antigen (HBsAg) seroclearance and serological conversion in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogs (NAs) or interferon (IFN).Methods:A two-center prospective cohort study was conducted, including CHB patients from Nanfang Hospital Southern Medical University and Eastern Theater General Hospital treated with NAs and IFN. All patients were followed up once every three to six months. Basic clinical information and test results were collected at each follow-up. The presence or absence of HBsAg seroclearance and serological conversion rate was evaluated. HBsAg serological conversion was defined as HBsAg quantification continuously below the detection limit (<0.05 IU/mL) at two detection time points at least six months apart. HBsAg serological conversion was defined as HBsAb positivity (≥10 IU/L) at the same time as the first HBsAg seroclearance. The Kruskal-Wallis test was used to compare the quantitative data of multiple groups, and the Wilcoxon rank-sum test was used to compare the data between groups. The chi-square test was used for the count data, and the Fisher exact test was used when the chi-square test was not met. Univariate and multivariate Cox analysis was used to determine the predictors of the study endpoints, and stepwise regression was used for variable screening.Results:A total of 2 266 CHB cases were included, of which 86.5% (1 959/2 266) were NA antiviral-received population. The median treatment duration before baseline was 10.5 (2.5, 37.6) months, and the baseline HBsAg quantification was 3.1 (2.6, 3.5) log 10 IU/mL. A total of 68 cases (3.0%) had HBsAg seroclearance, and 44 cases (1.9%) achieved serological conversion after 85.0 (62.7, 97.3) months of prospective follow-up. The level and positivity rate of HBsAb showed a progressive increase 36 months before and significantly after HBsAg seroclearance. Cox regression analysis results showed that baseline HBsAb level was an independent predictor of HBsAg serological conversion ( HR=2.26, P=0.002) in the overall population, especially in the subgroup with HBsAg between 100 and 1 000 IU/mL, suggesting HBsAb level had important predictive value. In addition, the serological conversion development rate was significantly higher in the GOLDEN model favourable patients than in the unfavourable patients (11.5% vs. 0, P<0.001). Conclusion:The baseline HBsAb quantitative level can predict HBsAg seroclearance and serological conversion for patients with CHB receiving antiviral treatment, which is of significant value in long-term treatment monitoring.

Objective To investigate the application value of the global myocardial work parameters in the non-invasive pressure-strain loop (PSL) technology for early assessment of left ventricular systolic function in patients with chronic kidney disease (CKD). Methods A retrospective analysis was performed on 74 patients with normal left ventricular ejection fraction (LVEF) who were hospitalized in the Nephrology Department of Zhongshan Hospital (Xiamen Branch), Fudan University, from August 2021 to December 2021. Based on CKD stages, patients were divided into early group (CKD stages 1-3) and advanced group (CKD stages 4-5). Additionally, 30 healthy volunteers matched for age and gender were selected as the control group. General clinical data, routine left ventricular ultrasound indicators, myocardial strain, and global myocardial work parameters were collected and compared among the three groups. Correlation analysis and multiple linear regression were used to assess the influencing factors of myocardial work. Results There were no statistically significant differences in global work index (GWI) and global constructive work (GCW) among the three groups. Compared to the control group, both CKD groups showed significantly reduced global work efficiency (GWE), along with significantly increased global waste work (GWW, P＜0.05). The absolute value of global longitudinal strain (GLS) in the advanced CKD group (n＝42) was significantly lower than that in the early CKD group (n＝32; [﹣17.09±0.82]% vs [﹣18.33±0.90]%, P＜0.05), and GWE was also significantly lower (93.00%[90.00%, 95.00%] vs 96.00%[92.25%, 96.75%], P＜0.05), while GWW was significantly higher than that in the early CKD group (150.00 mmHg%[105.25 mmHg%, 215.00 mmHg%] vs 88.00 mmHg%[64.25 mmHg%, 144.50 mmHg%], P＜0.05). Correlation analysis showed that GWE was negatively correlated with the absolute value of GLS and peak strain dispersion (PSD; r＝﹣0.396, ﹣0.558, P＜0.05), GWW was positively correlated with absolute value of GLS, and PSD (r＝0.341, 0.610, P＜0.01). Multiple linear regression results indicated that PSD was an independent influencing factor for GWE (β＝﹣0.558, P＜0.001) and GWW (β＝0.538, P＜0.001). Conclusions The myocardial work parameters GWE and GWW in non-invasive left ventricular PSL technology can identify subclinical left ventricular systolic dysfunction in patients with CKD early and quantitatively.

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.

BACKGROUND:Shikonin contributes to the promotion of bone defect repair and the treatment of osteoporosis. OBJECTIVE:To summarize the application potential of shikonin and its derivatives in oral soft and hard tissue regeneration. METHODS:A literature review was conducted in databases such as PubMed,Web of Science,Wanfang,China National Knowledge Infrastructure(CNKI),and VIP,spanning articles from 2002 to 2023.The search terms were"shikonin,oral cavity,periodontitis,antibacterial,bone formation,osteoclast,osteoporosis,toxicology"in Chinese and English. RESULTS AND CONCLUSION:Shikonin and its derivatives possess anti-inflammatory effects,inhibit periodontal pathogens such as Porphyromonas gingivalis,promote periodontal wound healing,and regenerate alveolar bone tissue.Shikonin formulations can be used to treat oral diseases such as aphthous ulcers and oral candidiasis.These findings suggest a promising future for shikonin and its derivatives in treating periodontal diseases,preventing oral ailments,and promoting the regeneration of both soft and hard periodontal tissues.Further research is needed to explore how to combine shikonin with tissue engineering to achieve quicker healing of oral soft and hard tissues.