Human Respiratory Stem Cells (RSCs) play a crucial role in the maintenance, repair and regeneration of the respiratory system. As a novel therapeutic method, stem cell therapy is a popular research direction in the medical field. And with the in-depth research on the mechanism of pneumonia caused by respiratory infections in recent years, the use of RSCs to explore pneumonia caused by respiratory infections and its therapeutic strategies has become a hot topic. In this paper, we firstly outlined the types of RSCs, summarized the mechanism of pneumonia caused by respiratory tract infections, discussed the advantages of RSCs application and the progress of culture differentiation, and elaborated the therapeutic exploration of RSCs in pneumonia caused by respiratory tract infections.

This article reports a case of membranous nephropathy in an adolescent accompanied by monoclonal IgG1-κ deposition. The 16-year-old female patient was hospitalized for experiencing proteinuria and hematuria for more than 20 days. The patient had a history of mycoplasma infection and acute kidney injury, and renal pathology revealed glomerular membrane lesions accompanied by crescent formation. Electron microscopy showed electron dense deposits in the subepithelial and mesangial regions, and immunofluorescence demonstrated monotypic IgG1-κ deposits in the glomerulus. Bone marrow examination did not find any abnormal plasma cells, nor were there significant abnormalities in serum or urine free light chain κ/λ ratio. The diagnosis was proliferative glomerulonephritis characterized by membranous lesions with monoclonal IgG1-κ deposits. This disease is rare in children and adolescents, and currently there is limited understanding of its mechanism, with limited clinical treatment experience. This article aims to provide clinical insights through case analysis and literature review.

Tacrolimus is an immunosuppressant that was clinically used for organ transplantation in the 1990s. In the early 2000s, tacrolimus began to be used to treat pediatric kidney diseases in China. This article reviews the therapeutic effects, clinical dosages, and treatment methods of tacrolimus in the treatment of steroid-resistant, steroid-dependent, frequently relapsing, different pathological types, and monogenic mutation-related childhood nephrotic syndrome. It explores the clinical guiding role of machine learning in tacrolimus treatment for childhood nephrotic syndrome, aiming to provide references for the clinical research and application of tacrolimus in pediatric kidney diseases.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective:To investigate the relationship among iron content, volume and drainage venous oxygen saturation (SvO 2) in deep gray matter nuclei of healthy people using quantitative susceptibility mapping (QSM). Methods:The study was a cross-sectional study. A total of 126 healthy volunteers were prospectively enrolled in the community in Tianjin from June 2019 to December 2023, and 57 males and 69 females, aged 48±15 years. All healthy volunteers underwent MRI examinations to get STrategically Acquired Gradient Echo images, then it was post-processed to obtain T 1 weighted enhanced images, QSM maps and the maximum intensity projection images. In QSM maps, caudate nucleus (CN), putamen (PUT), globus pallidus (GP), thalamus (THU), subthalamic nucleus (STN), substantia nigra (SN) and red nucleus (RN) were semi-automatically segmented to calculate the iron content and volume using SPIN software. Four bilateral deep cerebral veins regions of interest, including septum pellucidum veins, thalamostriate veins, internal cerebral veins and basilar veins, were manually delineated on the maximum intensity projection images of QSM to obtain venous magnetic sensitivity. The venous magnetic sensitivity was calculated as SvO 2. To observe the age-related trend of SvO 2, iron content and volume, the partial correlation analysis was conducted. The relationships between iron content, volume and SvO 2 were explored using the partial correlation analysis. To explore the potential effects of SvO 2 between iron content and volume in deep gray matter, the mediation analysis was utilized. Results:The relationships between the SvO 2 of thalamostriate veins ( r=0.23, P=0.018), basilar veins ( r=0.27, P=0.004) and age were positive. The relationships between the SvO 2 of internal cerebral veins and the iron contents of CN ( r=?0.25, P=0.042) and PUT ( r=?0.33, P<0.001) were negative. The relationships between the SvO 2 of basilar veins and the iron contents of STN ( r=?0.25, P=0.042) and SN ( r=?0.24, P=0.045) were negative. The relationships between iron content and volume including CN ( r=0.46, P<0.001), PUT ( r=0.20, P=0.027), GP ( r=0.76, P<0.001), STN ( r=0.87, P<0.001), SN ( r=0.90, P<0.001), RN ( r=0.79, P<0.001) were positive. The mediation analysis showed that the SvO 2 of internal cerebral veins indirectly mediated the relationship between iron content and volume of CN, PUT, GP and THU. Conclusions:The process of iron deposition required the participation of oxygen in deep gray matter nuclei. Volume shows positive correlation with iron content in deep gray matter nuclei, with individual variations. The SvO 2 of internal cerebral veins mediate the relationship between iron content and volume of deep gray matter nuclei.

BACKGROUND: The protective effect of mesenchymal stem cells (MSCs) on cardiac ischemia-reperfusion (I/R) injury has been widely reported. Dental pulp-derived mesenchymal stem cells (DP-MSCs) have therapeutic effects on various diseases, including diabetes and cirrhosis. This study aimed to determine the therapeutic effects of DP-MSCs on I/R injury and elucidate the underlying mechanism. METHODS: Myocardial I/R injury model mice were treated with DP-MSCs or a miR-19a-3p mimic. The infarct volume, fibrotic area, pyroptosis, inflammation level, and cardiac function were measured. Cardiomyocytes exposed to hypoxia-reoxygenation were transfected with the miR-19a-3p mimic, miR-19a-3p inhibitor, or negative control. Pyroptosis and protein expression in the interferon regulatory factor 8/mitogen-activated protein kinase (IRF-8/MAPK) pathway were measured. RESULTS: DP-MSCs protected cardiac function in cardiac I/R-injured mice and inhibited cardiomyocyte pyroptosis. The upregulation of miR-19a-3p protected cardiac function, inhibited cardiomyocyte pyroptosis, and inhibited IRF-8/MAPK signaling in cardiac I/R-injured mice. DP-MSCs inhibited cardiomyocyte pyroptosis and the IRF-8/MAPK signaling by upregulating the miR-19a-3p levels in cardiomyocytes injured by I/R. CONCLUSION DP-MSCs protected cardiac function by inhibiting cardiomyocyte pyroptosis through miR-19a-3p under I/R conditions.
Animals ; MicroRNAs/metabolism* ; Pyroptosis/genetics* ; Mesenchymal Stem Cells/metabolism* ; Myocytes, Cardiac/cytology* ; Mice ; Male ; Mice, Inbred C57BL ; Dental Pulp/cytology* ; Myocardial Reperfusion Injury/therapy* ; MAP Kinase Signaling System/physiology*

This article reports a case of membranous nephropathy in an adolescent accompanied by monoclonal IgG1-κ deposition. The 16-year-old female patient was hospitalized for experiencing proteinuria and hematuria for more than 20 days. The patient had a history of mycoplasma infection and acute kidney injury, and renal pathology revealed glomerular membrane lesions accompanied by crescent formation. Electron microscopy showed electron dense deposits in the subepithelial and mesangial regions, and immunofluorescence demonstrated monotypic IgG1-κ deposits in the glomerulus. Bone marrow examination did not find any abnormal plasma cells, nor were there significant abnormalities in serum or urine free light chain κ/λ ratio. The diagnosis was proliferative glomerulonephritis characterized by membranous lesions with monoclonal IgG1-κ deposits. This disease is rare in children and adolescents, and currently there is limited understanding of its mechanism, with limited clinical treatment experience. This article aims to provide clinical insights through case analysis and literature review.

Tacrolimus is an immunosuppressant that was clinically used for organ transplantation in the 1990s. In the early 2000s, tacrolimus began to be used to treat pediatric kidney diseases in China. This article reviews the therapeutic effects, clinical dosages, and treatment methods of tacrolimus in the treatment of steroid-resistant, steroid-dependent, frequently relapsing, different pathological types, and monogenic mutation-related childhood nephrotic syndrome. It explores the clinical guiding role of machine learning in tacrolimus treatment for childhood nephrotic syndrome, aiming to provide references for the clinical research and application of tacrolimus in pediatric kidney diseases.

Objective:To investigate the relationship among iron content, volume and drainage venous oxygen saturation (SvO 2) in deep gray matter nuclei of healthy people using quantitative susceptibility mapping (QSM). Methods:The study was a cross-sectional study. A total of 126 healthy volunteers were prospectively enrolled in the community in Tianjin from June 2019 to December 2023, and 57 males and 69 females, aged 48±15 years. All healthy volunteers underwent MRI examinations to get STrategically Acquired Gradient Echo images, then it was post-processed to obtain T 1 weighted enhanced images, QSM maps and the maximum intensity projection images. In QSM maps, caudate nucleus (CN), putamen (PUT), globus pallidus (GP), thalamus (THU), subthalamic nucleus (STN), substantia nigra (SN) and red nucleus (RN) were semi-automatically segmented to calculate the iron content and volume using SPIN software. Four bilateral deep cerebral veins regions of interest, including septum pellucidum veins, thalamostriate veins, internal cerebral veins and basilar veins, were manually delineated on the maximum intensity projection images of QSM to obtain venous magnetic sensitivity. The venous magnetic sensitivity was calculated as SvO 2. To observe the age-related trend of SvO 2, iron content and volume, the partial correlation analysis was conducted. The relationships between iron content, volume and SvO 2 were explored using the partial correlation analysis. To explore the potential effects of SvO 2 between iron content and volume in deep gray matter, the mediation analysis was utilized. Results:The relationships between the SvO 2 of thalamostriate veins ( r=0.23, P=0.018), basilar veins ( r=0.27, P=0.004) and age were positive. The relationships between the SvO 2 of internal cerebral veins and the iron contents of CN ( r=?0.25, P=0.042) and PUT ( r=?0.33, P<0.001) were negative. The relationships between the SvO 2 of basilar veins and the iron contents of STN ( r=?0.25, P=0.042) and SN ( r=?0.24, P=0.045) were negative. The relationships between iron content and volume including CN ( r=0.46, P<0.001), PUT ( r=0.20, P=0.027), GP ( r=0.76, P<0.001), STN ( r=0.87, P<0.001), SN ( r=0.90, P<0.001), RN ( r=0.79, P<0.001) were positive. The mediation analysis showed that the SvO 2 of internal cerebral veins indirectly mediated the relationship between iron content and volume of CN, PUT, GP and THU. Conclusions:The process of iron deposition required the participation of oxygen in deep gray matter nuclei. Volume shows positive correlation with iron content in deep gray matter nuclei, with individual variations. The SvO 2 of internal cerebral veins mediate the relationship between iron content and volume of deep gray matter nuclei.

Human Respiratory Stem Cells (RSCs) play a crucial role in the maintenance, repair and regeneration of the respiratory system. As a novel therapeutic method, stem cell therapy is a popular research direction in the medical field. And with the in-depth research on the mechanism of pneumonia caused by respiratory infections in recent years, the use of RSCs to explore pneumonia caused by respiratory infections and its therapeutic strategies has become a hot topic. In this paper, we firstly outlined the types of RSCs, summarized the mechanism of pneumonia caused by respiratory tract infections, discussed the advantages of RSCs application and the progress of culture differentiation, and elaborated the therapeutic exploration of RSCs in pneumonia caused by respiratory tract infections.