Objective:To screen broadly neutralizing antibodies in human immunodeficiency virus-1（HIV-1）chronically infected individuals and characterize their molecular features and to provide new strategies for rational vaccine development and antibody-based therapeutics.Methods:A total of 34 treatment-na?ve individuals with chronic HIV-1 infection were enrolled. Plasma antibody binding levels were measured against two HIV-1 envelope proteins. Single antigen-specific memory B cells were sorted from high-binding samples，and antibody variable region genes were amplified by PCR for paired expression. The monoclonal antibodies were evaluated for neutralizing activity using pseudovirus assays，and their structural features were analyzed by integrating AlphaFold 3 prediction with Discovery Studio molecular docking.Results:Plasma samples showed strong binding to DU422-GP140 and BG505-GP140. Eight monoclonal antibodies were isolated from two donors. Among them，antibodies 0919-A4，0919-A9 and 0808-A2 could cross-react with GP140 from HIV-1 subtypes AE，BC and B. The monoclonal antibody 0919-A9 demonstrated potent neutralizing activity against SF162（Tier 1）and CH181（Tier 2）pseudoviruses，with somatic hypermutation rates of 13.27%（heavy chain）and 15.58%（light chain）. Structural modeling revealed its specific targeting of the V1V2 region on GP120.Conclusion:The isolated antibody 0919-A9 effectively neutralizes Tier 2 pseudoviruses. Its high somatic mutation frequency and V1V2-targeting property underlie its neutralizing activity，providing both a promising candidate and mechanistic insights for HIV vaccine development and antibody-based therapeutic strategies.

To address issues such as loss of detailed information, blurred target boundaries, and unclear structural hierarchy in medical image fusion, this paper proposes an adaptive feature medical image fusion network based on a full-scale diffusion model. First, a region-level feature map is generated using a kernel-based saliency map to enhance local features and boundary details. Then, a full-scale diffusion feature extraction network is employed for global feature extraction, alongside a multi-scale denoising U-shaped network designed to fully capture cross-layer information. A multi-scale feature integration module is introduced to reinforce texture details and structural information extracted by the encoder. Finally, an adaptive fusion scheme is applied to progressively fuse region-level features, global features, and source images layer by layer, enhancing the preservation of detail information. To validate the effectiveness of the proposed method, this paper validates the proposed model on the publicly available Harvard dataset and an abdominal dataset. By comparing with nine other representative image fusion methods, the proposed approach achieved improvements across seven evaluation metrics. The results demonstrate that the proposed method effectively extracts both global and local features of medical images, enhances texture details and target boundary clarity, and generates fusion image with high contrast and rich information, providing more reliable support for subsequent clinical diagnosis.
Humans ; Image Processing, Computer-Assisted/methods* ; Algorithms ; Neural Networks, Computer ; Diagnostic Imaging/methods* ; Image Interpretation, Computer-Assisted/methods*

Objective:To analyze and discuss the current status, hotspots and development dynamics of self-management in chronic heart failure (CHF) patients at home and abroad based on China National Knowledge Infrastructure and Web of Science databases.Methods:Literature on self-management of CHF patients was searched in China National Knowledge Infrastructure and Web of Science. The search period was from January 1, 2014 to May 31, 2024. Keyword cluster analysis was performed using Cite Space 6.3.R1 software.Results:A total of 411 articles in Chinese and 878 articles in English were included. In the past ten years, the annual publication volume of English literature was generally even, and the distribution trend of annual publication volume of Chinese literature showed an upward and then a downward trend. The hotspots of self-management of CHF patients in the Chinese literature mainly focused on health education, self-efficacy, and disease prognosis, and the hotspots of self-management of CHF patients in the English literature mainly focused on quality of life, disease management, and self-care.Conclusions:Analyzing the current status, hotspots and developmental dynamics of self-management in CHF patients can provide a reference for how to effectively promote self-management in CHF patients and conduct related research in the future.

Objective:To analyze and discuss the current status, hotspots and development dynamics of self-management in chronic heart failure (CHF) patients at home and abroad based on China National Knowledge Infrastructure and Web of Science databases.Methods:Literature on self-management of CHF patients was searched in China National Knowledge Infrastructure and Web of Science. The search period was from January 1, 2014 to May 31, 2024. Keyword cluster analysis was performed using Cite Space 6.3.R1 software.Results:A total of 411 articles in Chinese and 878 articles in English were included. In the past ten years, the annual publication volume of English literature was generally even, and the distribution trend of annual publication volume of Chinese literature showed an upward and then a downward trend. The hotspots of self-management of CHF patients in the Chinese literature mainly focused on health education, self-efficacy, and disease prognosis, and the hotspots of self-management of CHF patients in the English literature mainly focused on quality of life, disease management, and self-care.Conclusions:Analyzing the current status, hotspots and developmental dynamics of self-management in CHF patients can provide a reference for how to effectively promote self-management in CHF patients and conduct related research in the future.

Objective:To screen broadly neutralizing antibodies in human immunodeficiency virus-1（HIV-1）chronically infected individuals and characterize their molecular features and to provide new strategies for rational vaccine development and antibody-based therapeutics.Methods:A total of 34 treatment-na?ve individuals with chronic HIV-1 infection were enrolled. Plasma antibody binding levels were measured against two HIV-1 envelope proteins. Single antigen-specific memory B cells were sorted from high-binding samples，and antibody variable region genes were amplified by PCR for paired expression. The monoclonal antibodies were evaluated for neutralizing activity using pseudovirus assays，and their structural features were analyzed by integrating AlphaFold 3 prediction with Discovery Studio molecular docking.Results:Plasma samples showed strong binding to DU422-GP140 and BG505-GP140. Eight monoclonal antibodies were isolated from two donors. Among them，antibodies 0919-A4，0919-A9 and 0808-A2 could cross-react with GP140 from HIV-1 subtypes AE，BC and B. The monoclonal antibody 0919-A9 demonstrated potent neutralizing activity against SF162（Tier 1）and CH181（Tier 2）pseudoviruses，with somatic hypermutation rates of 13.27%（heavy chain）and 15.58%（light chain）. Structural modeling revealed its specific targeting of the V1V2 region on GP120.Conclusion:The isolated antibody 0919-A9 effectively neutralizes Tier 2 pseudoviruses. Its high somatic mutation frequency and V1V2-targeting property underlie its neutralizing activity，providing both a promising candidate and mechanistic insights for HIV vaccine development and antibody-based therapeutic strategies.

Clinical researches including the Mayo Anesthesia Safety in Kids (MASK) study have found that children undergoing multiple anesthesia may have a higher risk of fine motor control difficulties. However, the underlying mechanisms remain elusive. Here, we report that erythropoietin receptor (EPOR), a microglial receptor associated with phagocytic activity, was significantly downregulated in the medial prefrontal cortex of young mice after multiple sevoflurane anesthesia exposure. Importantly, we found that the inhibited erythropoietin (EPO)/EPOR signaling axis led to microglial polarization, excessive excitatory synaptic pruning, and abnormal fine motor control skills in mice with multiple anesthesia exposure, and those above-mentioned situations were fully reversed by supplementing EPO-derived peptide ARA290 by intraperitoneal injection. Together, the microglial EPOR was identified as a key mediator regulating early synaptic development in this study, which impacted sevoflurane-induced fine motor dysfunction. Moreover, ARA290 might serve as a new treatment against neurotoxicity induced by general anesthesia in clinical practice by targeting the EPO/EPOR signaling pathway.
Animals ; Sevoflurane/toxicity* ; Microglia/drug effects* ; Anesthetics, Inhalation/adverse effects* ; Mice ; Mice, Inbred C57BL ; Receptors, Erythropoietin/metabolism* ; Neuronal Plasticity/drug effects* ; Male ; Prefrontal Cortex/drug effects* ; Erythropoietin/pharmacology* ; Signal Transduction/drug effects*

Objective:To investigate the influence and mechanism of stromal interaction molecule 1 (STIM1) in microglia/macrophages M1 activation after cerebral ischemia-reperfusion injury.Methods:(1) Animal experiment: 20 male C57BL/6J mice were randomly divided into sham-operated (Sham) group, middle cerebral artery occlusion and reperfusion (MCAO/R) group, MCAO/R+si-Ctrl group, and MCAO/R+si-STIM1 group ( n=5); MCAO/R models were established in mice of the latter 3 groups; empty vector control virus and STIM1 gene knockout lentivirus were transfected into mice in the MCAO/R+si-Ctrl group and MCAO/R+si-STIM1 group. The transfection efficiency of STIM1 and the expression of microglia/macrophages M1 activation marker cluster of differentiation 86 (CD86) in each group were observed. (2) Cell experiment: primary microglia were divided into Ctrl group, oxygen-glucose deprivation/re-oxygenation (OGD/R) group, OGD/R+si-Ctrl group, OGD/R+si-STIM1 group, OGD/R+solvent group, and OGD/R+4-phenylbutyric acid (4-PBA) group; OGD/R models were established in the later 5 groups; empty vector control virus and STIM1 gene knockout lentivirus were transfected into mice in the OGD/R+si-Ctrl group and OGD/R+si-STIM1 group; cells in the OGD/R+4-PBA group were pre-treated with 1 mmol/L 4-PBA for 1 h at 24 h before OGD/R modelling to inhibit endoplasmic reticulum stress (ERS), and cells in the OGD/R+solvent group were pre-treated with 0.5% dimethyl sulfoxide (DMSO) for 1 h at the same time. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), ELISA, Western blotting and other methods were used to detect the levels of CD86, tumour necrosis factor-α ( TNF-α) mRNA, interleukin (IL)-1β, and ERS-related proteins (transcription factor C/EBP homologous protein [CHOP], activated transcription factor 4 [ATF4]) in these cells. Results:(1) Animal experiment: the STIM1 expression in MCAO/R+si-STIM1 group was significantly lower than that in Sham group, MACO/R group and MCAO/R+si-Ctrl group ( P<0.05); as compared with that in the MACO/R group and MCAO/R+si-Ctrl group, the number of microglia/macrophages co-expressing CD86 and Iba-1 around the ischemic foci of mice in the MCAO/R+si-STIM1 group was significantly decreased ( P<0.05). (2) Cell experiment: as compared with those in the OGD/R group and OGD/R+si-Ctrl group, the expression levels of STIM1, CD86, and TNF-α mRNA, and supernatant IL-1β content in the OGD/R+si-STIM1 group were significantly decreased ( P<0.05); as compared with those in the OGD/R group and OGD/R+si-CTRL group, the ATF4 and CHOP expression levels in OGD/R+si-STIM1 group were significantly decreased ( P<0.05); as compared with those in the OGD/R group and OGD/R+solvent group, the CD86 level, TNF-α mRNA expression level and IL-1β content in the OGD/R+4-PBA group were significantly decreased ( P<0.05). Conclusion:STIM1 affects microglia/macrophages M1 activation after ischemia-reperfusion injury by regulating ERS level.

Objective:To analyze and evaluate caring experience of caregivers of patients undergoing tracheotomy.Methods:PubMed, Web of Science, Cochrane Library, EBSCO, Embase, Chinese National Knowledge Infrastructure (CNKI) , Wanfang Database, VIP Database and SinoMed were searched by computer, and literature on quality studies on caring experience of caregivers of patients undergoing tracheostomy were searched. The time limit for retrieval was from the establishment of the database to November 30, 2020. The quality of literature was evaluated by using the quality evaluation standards of Australia Joanna Briggs Institute (JBI) Evidence-based Health Care Center. The results were analyzed by the collective integration method.Results:A total of 7 articles were included, including 5 English articles and 2 Chinese articles. Among them, 6 articles were phenomenological studies and 1 article was grounded theory research. In the end, it was summarized into 10 categories and integrated into 3 integrated results. The first integration result was psychological overload of caregivers, difficulties in role adaptation and social interaction and negative state. The second integrated result was that the caregivers' ability to care for was insufficient and they were exhausted. For them, the transition period after discharge was difficult to adapt and they were eager for support. The third integrated result was that caregivers gradually adapted, actively faced reality, changed their concepts and learned to be grateful while achieving self-growth.Conclusions:The status of caregivers of patients undergoing tracheotomy has both negative and positive aspects, and there are many psychological, social and family problems as well as nursing guidance needs. Medical staff should pay attention to the psychological pressure of caregivers of patients undergoing tracheotomy, provide them with disease care guidance, help caregivers strengthen the social and family support system, reduce the caregiver burden and improve the quality of care.

Objective:To evaluate the therapeutic efficacy and side effects of P-Gemox regimen combined with intensity modulated radiotherapy in the treatment of extranodal NK/T cell lymphoma, nasal type (ENKTL).Methods:The data of 60 patients with ENKTL confirmed by pathomorphology and immunohistochemistry in Guizhou Cancer Hospital from July 2014 to October 2019 were retrospectively analyzed. All patients received P-Gemox chemotherapy combined with intensity modulated radiotherapy (at least 2 cycles), and the efficacy and adverse reactions were evaluated.Results:The complete remission rate of 60 patients was 65.0% (39/60), the partial remission rate was 25.0% (15/60), and the total effective rate was 90.0% (54/60). The main side reactions were myelosuppression, transaminase elevation and radiation mucositis; most of them were mild to moderate, which were relieved after treatment or the withdrawal of radiotherapy and chemotherapy. No treatment-related death cases were found. The overall survival rate of 1-year, 2-year, 3-year was 91%, 75% and 69%; the progression-free survival rate of 1-year, 2-year, 3-year was 86%, 68% and 62%. During the treatment, 3 cases died due to the progress of the disease and infection. Multivariate analysis showed that with and without hemophagocytic syndrome and radiotherapy dose were related to prognosis (all P < 0.05). Conclusion:P-Gemox, as the first-line induction chemotherapy regimen combined with intensity modulated radiotherapy has good short-term efficacy and safety for patients with ENKTL.