In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

In recent years, with the development of single-cell sequencing technology, spatial transcriptome technology and in vivo tracing technology, scientists have a deeper understanding of scientific issues about the in vivo development, functional regulation and ex vivo expansion of hematopoietic stem cells (HSCs). Among them, epigenetic modification plays an important role in the development and fate decisions, function maintenance and ex vivo expansion of HSCs, which has become a research hotspot in the field of stem cells in recent years. This article reviews the recent research progress of epigenetic modification in the development, functional regulation and expansion of HSCs.
Hematopoietic Stem Cells ; Epigenesis, Genetic ; Humans ; DNA Methylation

Objective To explore the long-term efficacy of percutaneous pulmonary valve implantation(PPVI)and the durability of the domestic self-expanding Venus P valve.Methods A total of 8 patients with post-surgical right ventricular outflow tract(RVOT)dysfunction,who were admitted to hospital from October 2014 to July 2016 and deemed anatomically suitable for PPVI with self-expanding valve,were included prospectively.Clinical,imaging,procedural and follow-up data were analyzed.The survival rates,perioperative and long-term complication rates,long-term efficacy of PPVI,and long-term function of Venus P in 8 patients were evaluated.The immediate procedural results were evaluated by clinical implant success rate,which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitation＜moderate and peak trans-pulmonary pressure gradient＜40 mmHg.Results A total of 8 patients were included,with 7 females,aged 14 to 36 years.The initial diagnosis included post-surgical Tetralogy of Fallot(5 cases),post-surgical Trilogy of Fallot(1 case),post-surgical Quadricuspid pulmonary valve stenosis(1 case)and post-surgical Double-Outlet Right Ventricle(1 case).The indications of PPVI included RVOT-pulmonary obstruction and regurgitation(1 case)and isolated regurgitation(7 cases).Clinical implant success was achieved in all of the 8 patients with firmly fixed valve,and there were no such complications as valve detachment,displacement or stent fracture.All patients experienced significant symptom relief after the procedure.The right ventricular end-diastolic volume index(RVEDVi)measured by CMR 6 months after PPVI showed a significant decrease compared to preprocedural values[(89.99±13.85)ml/m2 vs.(144.93±11.28)ml/m2,P=0.001].Postoperative pulmonary regurgitation were significantly improved or disappeared in all patients,and there was no statistically significant difference in the average peak pressure gradient measured by echocardiogram between preoperative and the latest follow-up[(23.25±8.39)mmHg vs.(18.75±6.28)mmHg,P=0.210].Over an average follow-up period of(9.25±0.71)years,1 case of infective endocarditis occurred 5 years after PPVI.During the follow-up,no death,deterioration of heart failure,malignant arrhythmia or other serious complications were observed.All patients completed 8-year follow-up,and 3 completed 10-year follow-up.All patients were graded as NYHA functional class one at the latest follow-up.Conclusions PPVI using the domestically produced self-expanding Venus P is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable anatomy.Our study confirms the long-term efficacy and durability of Venus P from multiple perspectives,and no severe stent fracture occurred without pre-stent implantation in the native RVOT.

Objective To explore the effects of alpha-mangostin(α-MG)on the in vitro osteoarthritis(OA)in rat chondrocytes induced by lipopolysaccharide(LPS)and the M1 polarization of macrophages.Methods An in vitro OA model of rat chondrocytes was induced by LPS.Both rat chondrocytes and macrophages were divided into the control group(normal culture),LPS group(stimulated with 1 μg/mL LPS for 24 hours),LPS+α-MG group(stimulated with 40 μmol/L α-MG combined with 1 μg/mL LPS for 24 hours),LPS+α-MG si-NC group(transfected with 70 μg/mL si-NC and stimulated with 40 μmol/L α-MG and 1 μg/mL LPS for 24 hours),and LPS+α-MG+si-BDNF group(transfected with 70 μg/mL si-BDNF and stimulated with 40 μmol/L α-MG and 1 μg/mL LPS for 24 hours).CCK-8 assay was used to detect the proliferative viability of chondrocytes and macrophages in each group,and flow cytometry was used to detect the apoptosis of chondrocytes and the polarization of macrophages.ELISA was used to detect the levels of interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α of chondrocytes in each group.Western blot was used to detect the expression of BDNF,PI3K,and Akt in chondrocytes and macrophages.Results In chondrocytes,compared with the control group,the LPS group had decreased cell proliferation rate,increased cell apoptosis rate,down-regulated expression of BDNF,PI3K and Akt proteins,and up-regulated levels of IL-1β,IL-6 and TNF-α(P<0.05);compared with the LPS group,the LPS+α-MG group showed increased cell proliferation rate,decreased cell apoptosis rate,up-regulated expression of BDNF,PI3K and Akt proteins,and down-regulated levels of IL-1β,IL-6 and TNF-α(P<0.05);compared with the LPS+α-MG+si-NC group,the LPS+α-MG si-BDNF group demonstrated decreased cell proliferation rate,increased cell apoptosis rate,down-regulated expression of BDNF,PI3K and Akt proteins,and increased levels of IL-1β,IL-6 and TNF-α(P<0.05).In macrophages,compared with the control group,the LPS group had decreased cell proliferation rate,increased proportion of M1 cells,and down-regulated expression of BDNF,PI3K and Akt proteins(P<0.05);compared with the LPS group,the LPS+α-MG group showed increased cell proliferation rate,decreased proportion of M1 cells,and up-regulated expression of BDNF,PI3K and Akt proteins(P<0.05);compared with the LPS+α-MG+si-NC group,the LPS+α-MG+si-BDNF group showed decreased cell proliferation rate,increased proportion of M1 cells,and down-regulated expression of BDNF,PI3K and Akt proteins(P<0.05).Conclusion α-MG inhibits the M1 polarization of macrophages to improve the apoptosis and inflammation of rat chondrocytes by activating the BDNF/PI3K/Akt signaling pathway.

Objective:To explore the expression of bone marrow stromal antigen 2(BST2)in advanced non-small cell lung cancer(NSCLC)tissues and its impact on the prognosis of cisplatin chemotherapy.Methods:This study was a prospective study,127 advanced NSCLC patients who received treatment at Shangrao People's Hospital from January 2022 to December 2023 were prospective selected,all patients received cisplatin+gemcitabine chemotherapy regimen.They were divided into survival group(n=85)and death group(n=42)according to the prognosis.The relationship between expression of BST2 and clinicopathological characteristics was analyzed.The survival situation was analyzed by Kaplan-Meier method.Influencing factors of prognosis after cisplatin chemotherapy were discussed by univariate and multivariate COX regression analyses.Results:The positive expression rate of BST2 in cancer tissues(34.65％)in advanced NSCLC tissues was significantly higher than that in adjacent tissues(7.09％)(P＜0.05).Expression of BST2 was associated with tumor TNM staging,lymph node metastasis and differentiation degree(P＜0.05).The 1-year survival rate of patients with high expression of BST2(56.98％)was significantly lower than that of patients with low expression(87.80％)(P＜0.05).High expression of BST2 and TNM stage Ⅳ were independent prognostic risk factors for cisplatin chemotherapy in patients with advanced NSCLC(P＜0.05).Conclusion:The expressed of BST2 is highly in patients with advanced NSCLC tissues and closely related to cisplatin chemotherapy poor prognosis,suggesting its potential as a prognostic biomarker.

Objective To explore the long-term efficacy of percutaneous pulmonary valve implantation(PPVI)and the durability of the domestic self-expanding Venus P valve.Methods A total of 8 patients with post-surgical right ventricular outflow tract(RVOT)dysfunction,who were admitted to hospital from October 2014 to July 2016 and deemed anatomically suitable for PPVI with self-expanding valve,were included prospectively.Clinical,imaging,procedural and follow-up data were analyzed.The survival rates,perioperative and long-term complication rates,long-term efficacy of PPVI,and long-term function of Venus P in 8 patients were evaluated.The immediate procedural results were evaluated by clinical implant success rate,which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitation＜moderate and peak trans-pulmonary pressure gradient＜40 mmHg.Results A total of 8 patients were included,with 7 females,aged 14 to 36 years.The initial diagnosis included post-surgical Tetralogy of Fallot(5 cases),post-surgical Trilogy of Fallot(1 case),post-surgical Quadricuspid pulmonary valve stenosis(1 case)and post-surgical Double-Outlet Right Ventricle(1 case).The indications of PPVI included RVOT-pulmonary obstruction and regurgitation(1 case)and isolated regurgitation(7 cases).Clinical implant success was achieved in all of the 8 patients with firmly fixed valve,and there were no such complications as valve detachment,displacement or stent fracture.All patients experienced significant symptom relief after the procedure.The right ventricular end-diastolic volume index(RVEDVi)measured by CMR 6 months after PPVI showed a significant decrease compared to preprocedural values[(89.99±13.85)ml/m2 vs.(144.93±11.28)ml/m2,P=0.001].Postoperative pulmonary regurgitation were significantly improved or disappeared in all patients,and there was no statistically significant difference in the average peak pressure gradient measured by echocardiogram between preoperative and the latest follow-up[(23.25±8.39)mmHg vs.(18.75±6.28)mmHg,P=0.210].Over an average follow-up period of(9.25±0.71)years,1 case of infective endocarditis occurred 5 years after PPVI.During the follow-up,no death,deterioration of heart failure,malignant arrhythmia or other serious complications were observed.All patients completed 8-year follow-up,and 3 completed 10-year follow-up.All patients were graded as NYHA functional class one at the latest follow-up.Conclusions PPVI using the domestically produced self-expanding Venus P is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable anatomy.Our study confirms the long-term efficacy and durability of Venus P from multiple perspectives,and no severe stent fracture occurred without pre-stent implantation in the native RVOT.

Objective:To explore the expression of bone marrow stromal antigen 2(BST2)in advanced non-small cell lung cancer(NSCLC)tissues and its impact on the prognosis of cisplatin chemotherapy.Methods:This study was a prospective study,127 advanced NSCLC patients who received treatment at Shangrao People's Hospital from January 2022 to December 2023 were prospective selected,all patients received cisplatin+gemcitabine chemotherapy regimen.They were divided into survival group(n=85)and death group(n=42)according to the prognosis.The relationship between expression of BST2 and clinicopathological characteristics was analyzed.The survival situation was analyzed by Kaplan-Meier method.Influencing factors of prognosis after cisplatin chemotherapy were discussed by univariate and multivariate COX regression analyses.Results:The positive expression rate of BST2 in cancer tissues(34.65％)in advanced NSCLC tissues was significantly higher than that in adjacent tissues(7.09％)(P＜0.05).Expression of BST2 was associated with tumor TNM staging,lymph node metastasis and differentiation degree(P＜0.05).The 1-year survival rate of patients with high expression of BST2(56.98％)was significantly lower than that of patients with low expression(87.80％)(P＜0.05).High expression of BST2 and TNM stage Ⅳ were independent prognostic risk factors for cisplatin chemotherapy in patients with advanced NSCLC(P＜0.05).Conclusion:The expressed of BST2 is highly in patients with advanced NSCLC tissues and closely related to cisplatin chemotherapy poor prognosis,suggesting its potential as a prognostic biomarker.

Objective To explore the effects of alpha-mangostin(α-MG)on the in vitro osteoarthritis(OA)in rat chondrocytes induced by lipopolysaccharide(LPS)and the M1 polarization of macrophages.Methods An in vitro OA model of rat chondrocytes was induced by LPS.Both rat chondrocytes and macrophages were divided into the control group(normal culture),LPS group(stimulated with 1 μg/mL LPS for 24 hours),LPS+α-MG group(stimulated with 40 μmol/L α-MG combined with 1 μg/mL LPS for 24 hours),LPS+α-MG si-NC group(transfected with 70 μg/mL si-NC and stimulated with 40 μmol/L α-MG and 1 μg/mL LPS for 24 hours),and LPS+α-MG+si-BDNF group(transfected with 70 μg/mL si-BDNF and stimulated with 40 μmol/L α-MG and 1 μg/mL LPS for 24 hours).CCK-8 assay was used to detect the proliferative viability of chondrocytes and macrophages in each group,and flow cytometry was used to detect the apoptosis of chondrocytes and the polarization of macrophages.ELISA was used to detect the levels of interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α of chondrocytes in each group.Western blot was used to detect the expression of BDNF,PI3K,and Akt in chondrocytes and macrophages.Results In chondrocytes,compared with the control group,the LPS group had decreased cell proliferation rate,increased cell apoptosis rate,down-regulated expression of BDNF,PI3K and Akt proteins,and up-regulated levels of IL-1β,IL-6 and TNF-α(P<0.05);compared with the LPS group,the LPS+α-MG group showed increased cell proliferation rate,decreased cell apoptosis rate,up-regulated expression of BDNF,PI3K and Akt proteins,and down-regulated levels of IL-1β,IL-6 and TNF-α(P<0.05);compared with the LPS+α-MG+si-NC group,the LPS+α-MG si-BDNF group demonstrated decreased cell proliferation rate,increased cell apoptosis rate,down-regulated expression of BDNF,PI3K and Akt proteins,and increased levels of IL-1β,IL-6 and TNF-α(P<0.05).In macrophages,compared with the control group,the LPS group had decreased cell proliferation rate,increased proportion of M1 cells,and down-regulated expression of BDNF,PI3K and Akt proteins(P<0.05);compared with the LPS group,the LPS+α-MG group showed increased cell proliferation rate,decreased proportion of M1 cells,and up-regulated expression of BDNF,PI3K and Akt proteins(P<0.05);compared with the LPS+α-MG+si-NC group,the LPS+α-MG+si-BDNF group showed decreased cell proliferation rate,increased proportion of M1 cells,and down-regulated expression of BDNF,PI3K and Akt proteins(P<0.05).Conclusion α-MG inhibits the M1 polarization of macrophages to improve the apoptosis and inflammation of rat chondrocytes by activating the BDNF/PI3K/Akt signaling pathway.