BACKGROUND:Multiple myeloma bone disease is a serious complication of multiple myeloma,and its pathogenesis is closely related to the dysregulation of the bone marrow microenvironment.Peripheral blood exosomes are secreted by various cell types and can reflect a variety of information such as the tumor microenvironment.Exosomal circular RNA is gradually becoming the focus of liquid biopsy due to its high stability,high abundance,high specificity,and high conservation.In multiple myeloma bone disease,there is still a lack of relevant research on the role of exosomal circular RNAs.With the development of single-cell RNA sequencing technology,clarifying the contribution of each cell type in the bone marrow microenvironment to multiple myeloma bone disease-related exosomal circular RNAs and the interaction between each cell type will help provide new biomarkers for the diagnosis and treatment of multiple myeloma bone disease.OBJECTIVE:To preliminarily determine which cells in the bone marrow microenvironment the multiple myeloma bone disease-related peripheral blood exosomal circular RNAs originated from,and explore the effects of cell interactions in the bone marrow microenvironment on multiple myeloma bone disease at the single-cell level.METHODS:Peripheral blood exosomes from six multiple myeloma bone disease patients and five healthy controls were collected for high-throughput sequencing,differently expressed circular RNAs were screened,and GO and KEGG enrichment analyses were performed.The bone marrow single-cell RNA sequencing dataset GSE271107 was obtained from the GEO database.The data of four multiple myeloma bone disease patients were integrated.After quality control and filtering,the batch effect was removed by Harmony method.Subgroup clustering was performed by UMAP,and cell groups were manually corrected after automatic annotation by SingleR.CellChat was used to infer and visualize the intercellular communication in single-cell RNA sequencing data,and analyze the interaction between ligands and receptors.RESULTS AND CONCLUSION:(1)Compared with healthy controls,the expression levels of 1 265 circular RNAs in peripheral blood exosomes of multiple myeloma bone disease patients were significantly upregulated.(2)GO and KEGG analyses suggested that the parent genes of differently expressed circular RNAs were mainly enriched in pathways in nervous system development,pathways in cancer,PI3K-Akt signaling pathway,Hippo signaling pathway,arrhythmogenic right ventricular cardiomyopathy,dilated cardiomyopathy,etc.,which were closely related to the proliferation,adhesion,migration,and homing of myeloma cells,and multiple myeloma-related complications(such as multiple myeloma bone disease,peripheral neuropathy,and cardiac events).(3)The parent genes of multiple myeloma bone disease-related differential circular RNAs were mainly derived from T cells/natural killer cells,B cells and monocytes/macrophages in the bone marrow microenvironment,which affected osteoclast function by regulating the secretion of multiple cytokines.(4)Monocytes/macrophages,as osteoclast precursor cells,interacted with tumor cells and other immune cells.The MIF pathway was the main pathway involved.The above data preliminarily identified the source cells of multiple myeloma bone disease-related peripheral blood exosomal circular RNA in the bone marrow microenvironment,and found that the ligand-receptor interaction of the MIF pathway between monocytes/macrophages and tumor cells and immune cells may be an important factor in the occurrence of multiple myeloma bone disease.

ObjectiveTo explore the academic characteristics of contemporary renowned Chinese medicine masters in treating diabetic kidney disease （DKD） from the perspectives of principles， methods， formulas， and medications. MethodsIn strict accordance with the Systematic Review of Text and Opinion （SrTO） process developed by the Joanna Briggs Institute （JBI）， an Australian evidence-based healthcare center， the databases including China National Knowledge Infrastructure （CNKI）， VIP Database， Wanfang Data， and China Biomedical Literature Service System （SinoMed） were searched. Based on predefined inclusion and exclusion criteria， text information extraction， quality evaluation， and text information synthesis were conducted sequentially. The data were analyzed and presented in the form of text and figures. ResultsA total of 215 articles related to 43 contemporary renowned experts in the fields of Chinese medicine nephrology and endocrinology were included. The study found that the academic thoughts of these masters in the treatment of DKD are extensive， involving multiple levels such as disease understanding， therapeutic strategies， formula application， and medication use. In terms of disease understanding， the primary pathogenesis is characterized by deficiency in the root and excess in the manifestation. It is emphasized that internal factors， such as congenital endowment deficiency， interact with external factors such as improper diet， emotional disturbances， invasion of exogenous pathogens， and delayed or inappropriate treatment， to jointly induce the disease. This further gives rise to various pathogenetic theories， including obstruction of renal collaterals by blood stasis， toxin-induced damage to renal collaterals， latent wind disturbing the kidney， and internal heat leading to mass formation. In terms of therapeutic strategies and medication use， the principal treatment method is to replenish Qi and nourish Yin. Stage-based and syndrome-differentiated treatments are advocated. Flexible use of insect-derived drugs and wind-dispelling drugs is emphasized， along with proficiency in applying classical formulas and drug pairs. Integrated internal and external treatments， as well as the combined application of multiple therapeutic approaches， are commonly employed for comprehensive management. Meanwhile， the concept of "preventive treatment of disease" is upheld， and individualized long-term management of patients is advocated. ConclusionThrough the SrTO process， the academic thoughts of contemporary renowned Chinese medicine masters in the treatment of DKD have been systematically and standardly synthesized， providing a scientific and standardized basis for future theoretical exploration.

ObjectiveTo explore the academic characteristics of contemporary renowned Chinese medicine masters in treating diabetic kidney disease （DKD） from the perspectives of principles， methods， formulas， and medications. MethodsIn strict accordance with the Systematic Review of Text and Opinion （SrTO） process developed by the Joanna Briggs Institute （JBI）， an Australian evidence-based healthcare center， the databases including China National Knowledge Infrastructure （CNKI）， VIP Database， Wanfang Data， and China Biomedical Literature Service System （SinoMed） were searched. Based on predefined inclusion and exclusion criteria， text information extraction， quality evaluation， and text information synthesis were conducted sequentially. The data were analyzed and presented in the form of text and figures. ResultsA total of 215 articles related to 43 contemporary renowned experts in the fields of Chinese medicine nephrology and endocrinology were included. The study found that the academic thoughts of these masters in the treatment of DKD are extensive， involving multiple levels such as disease understanding， therapeutic strategies， formula application， and medication use. In terms of disease understanding， the primary pathogenesis is characterized by deficiency in the root and excess in the manifestation. It is emphasized that internal factors， such as congenital endowment deficiency， interact with external factors such as improper diet， emotional disturbances， invasion of exogenous pathogens， and delayed or inappropriate treatment， to jointly induce the disease. This further gives rise to various pathogenetic theories， including obstruction of renal collaterals by blood stasis， toxin-induced damage to renal collaterals， latent wind disturbing the kidney， and internal heat leading to mass formation. In terms of therapeutic strategies and medication use， the principal treatment method is to replenish Qi and nourish Yin. Stage-based and syndrome-differentiated treatments are advocated. Flexible use of insect-derived drugs and wind-dispelling drugs is emphasized， along with proficiency in applying classical formulas and drug pairs. Integrated internal and external treatments， as well as the combined application of multiple therapeutic approaches， are commonly employed for comprehensive management. Meanwhile， the concept of "preventive treatment of disease" is upheld， and individualized long-term management of patients is advocated. ConclusionThrough the SrTO process， the academic thoughts of contemporary renowned Chinese medicine masters in the treatment of DKD have been systematically and standardly synthesized， providing a scientific and standardized basis for future theoretical exploration.

BACKGROUND:Multiple myeloma bone disease is a serious complication of multiple myeloma,and its pathogenesis is closely related to the dysregulation of the bone marrow microenvironment.Peripheral blood exosomes are secreted by various cell types and can reflect a variety of information such as the tumor microenvironment.Exosomal circular RNA is gradually becoming the focus of liquid biopsy due to its high stability,high abundance,high specificity,and high conservation.In multiple myeloma bone disease,there is still a lack of relevant research on the role of exosomal circular RNAs.With the development of single-cell RNA sequencing technology,clarifying the contribution of each cell type in the bone marrow microenvironment to multiple myeloma bone disease-related exosomal circular RNAs and the interaction between each cell type will help provide new biomarkers for the diagnosis and treatment of multiple myeloma bone disease.OBJECTIVE:To preliminarily determine which cells in the bone marrow microenvironment the multiple myeloma bone disease-related peripheral blood exosomal circular RNAs originated from,and explore the effects of cell interactions in the bone marrow microenvironment on multiple myeloma bone disease at the single-cell level.METHODS:Peripheral blood exosomes from six multiple myeloma bone disease patients and five healthy controls were collected for high-throughput sequencing,differently expressed circular RNAs were screened,and GO and KEGG enrichment analyses were performed.The bone marrow single-cell RNA sequencing dataset GSE271107 was obtained from the GEO database.The data of four multiple myeloma bone disease patients were integrated.After quality control and filtering,the batch effect was removed by Harmony method.Subgroup clustering was performed by UMAP,and cell groups were manually corrected after automatic annotation by SingleR.CellChat was used to infer and visualize the intercellular communication in single-cell RNA sequencing data,and analyze the interaction between ligands and receptors.RESULTS AND CONCLUSION:(1)Compared with healthy controls,the expression levels of 1 265 circular RNAs in peripheral blood exosomes of multiple myeloma bone disease patients were significantly upregulated.(2)GO and KEGG analyses suggested that the parent genes of differently expressed circular RNAs were mainly enriched in pathways in nervous system development,pathways in cancer,PI3K-Akt signaling pathway,Hippo signaling pathway,arrhythmogenic right ventricular cardiomyopathy,dilated cardiomyopathy,etc.,which were closely related to the proliferation,adhesion,migration,and homing of myeloma cells,and multiple myeloma-related complications(such as multiple myeloma bone disease,peripheral neuropathy,and cardiac events).(3)The parent genes of multiple myeloma bone disease-related differential circular RNAs were mainly derived from T cells/natural killer cells,B cells and monocytes/macrophages in the bone marrow microenvironment,which affected osteoclast function by regulating the secretion of multiple cytokines.(4)Monocytes/macrophages,as osteoclast precursor cells,interacted with tumor cells and other immune cells.The MIF pathway was the main pathway involved.The above data preliminarily identified the source cells of multiple myeloma bone disease-related peripheral blood exosomal circular RNA in the bone marrow microenvironment,and found that the ligand-receptor interaction of the MIF pathway between monocytes/macrophages and tumor cells and immune cells may be an important factor in the occurrence of multiple myeloma bone disease.

ObjectiveOxygen partial pressure (pO₂) is a critical indicator of the tumor microenvironment and plays an essential role in regulating tumor progression and therapeutic response, particularly for oxygen-dependent treatments such as photodynamic therapy (PDT). Although photoacoustic imaging (PAI) has shown great potential for functional and molecular imaging, conventional oxygenation imaging approaches based on hemoglobin absorption mainly provide relative oxygen saturation information and cannot directly quantify tissue oxygen partial pressure. Therefore, this study aimed to develop a fast laser sequence-based pump-probe photoacoustic tomography (PP-PAT) system for quantitative, non-invasive, and dynamic monitoring of oxygen partial pressure in tumor tissues. MethodsThe proposed PP-PAT system was developed based on the oxygen-sensitive triplet-state lifetime characteristics of methylene blue (MB). Upon optical excitation, MB molecules undergo transitions from the ground state to an excited state and subsequently form metastable triplet states through intersystem crossing. The lifetime of the triplet state is strongly affected by surrounding oxygen concentration due to dynamic oxygen quenching, providing a direct correlation between triplet-state kinetics and local oxygen partial pressure. A dual-wavelength pump-probe excitation scheme was implemented to selectively interrogate MB triplet-state dynamics. The pump pulse was used to initiate the triplet-state population, while the delayed probe pulse was applied to detect the transient triplet-state response. By optimizing the temporal interval between the pump and probe pulses, transient triplet-state differential (TTD) signals were extracted to enhance the specificity of oxygen-dependent molecular information and suppress background interference from conventional photoacoustic signals. The performance of the PP-PAT system was systematically evaluated through phantom and in vivo experiments. First, a single-tube phantom containing MB solution was used to investigate signal stability, reproducibility, and the influence of signal averaging on imaging quality. Subsequently, a dual-tube phantom model was established to simulate oxygen consumption during PDT, where one MB-containing tube was exposed to laser irradiation and the other served as a control. Finally, in vivo experiments were performed using a subcutaneous tumor model in nude mice. MB was locally injected into the tumor region before imaging to evaluate the feasibility of tumor oxygen partial pressure mapping using the proposed PP-PAT system. ResultsPhantom experiments demonstrated that the extracted TTD signals exhibited high stability and effectively reflected MB triplet-state dynamics while reducing non-specific background contributions. Signal averaging significantly improved the signal-to-noise ratio, and 50 repeated acquisitions provided an optimal compromise between image quality and acquisition efficiency. In the dual-tube phantom experiments, continuous PDT irradiation induced progressive oxygen depletion in the treated sample. The corresponding TTD decay rate gradually decreased, accompanied by an increase in the calculated triplet-state lifetime, indicating reduced oxygen quenching and decreased oxygen partial pressure. In contrast, the control sample showed relatively stable TTD kinetics and oxygenation levels during the same period. These results demonstrated that PP-PAT could quantitatively characterize oxygen consumption dynamics associated with photochemical reactions. In vivo experiments further demonstrated the capability of PP-PAT for spatially resolved oxygen partial pressure imaging in MB-injected tumor tissues. The reconstructed pO₂ maps revealed heterogeneous oxygen distributions within tumors, showing relatively hypoxic regions in the tumor core and higher oxygenation levels near the tumor boundary. This spatial oxygen distribution pattern was consistent with the typical physiological characteristics of solid tumors, where abnormal vascular structures and limited oxygen diffusion result in intratumoral oxygen gradients. ConclusionThis study presents a fast laser sequence-based PP-PAT system capable of quantitative and non-invasive imaging of tissue oxygen partial pressure. By utilizing the oxygen-dependent triplet-state lifetime of MB and extracting TTD signals, the proposed method provides molecularly specific information related to oxygen dynamics beyond conventional photoacoustic oxygenation imaging. The system enables dynamic monitoring of oxygen consumption during PDT and reveals spatial oxygen heterogeneity within tumors. This technique provides a promising imaging approach for tumor hypoxia characterization, evaluation of oxygen-dependent therapeutic responses, and precision-guided cancer treatment.

BACKGROUND:Intestinal acute graft-versus-host disease is one of the most aggressive complications after allogeneic hematopoietic stem cell transplantation with high lethality.How to improve intestinal inflammation and regulate autophagy by applying traditional Chinese medicine in order to treat intestinal acute graft-versus-host disease is a worthwhile research issue nowadays. OBJECTIVE:To investigate the mechanism of Huangqintang modulating intestinal flora for the treatment of intestinal acute graft-versus-host disease. METHODS:CB6F1 mice were irradiated with 60Co X radiation at a total dose of 8 Gy,and then single nucleated cell suspensions(bone marrow cells+splenocytes)from Balb/c H-2d mice were injected into the tail vein in order to prepare a model of intestinal acute graft-versus-host disease.These samples were randomly divided into the model group and the high-,moderate-,and low-dose Huangqintang groups.After modeling,the model,high-,moderate-,and low-dose groups received different doses of Huangqintang or an equal volume of saline by continuous gavage for 14 days.Clinical acute graft-versus-host disease grading,and survival time was recorded.Small intestinal tissues from each group were stained with hematoxylin and eosin for small intestinal mucosal pathology scoring.The intestinal flora of mice in each group was detected using 16S rDNA sequencing.Autophagy-related markers were detected using immunofluorescence,immunohistochemistry,and PCR. RESULTS AND CONCLUSION:(1)Compared with the model group,the survival time of mice was significantly prolonged(P<0.01);the clinical acute graft-versus-host disease scores were significantly reduced(P<0.01);the pathological grading scores of the small intestinal mucosa were significantly diminished(P<0.01);the levels of the small intestinal tissue inflammatory factors tumor necrosis factor-α,interleukin-1β,and interleukin-6,were significantly decreased(P<0.01);the structural integrity of the small intestinal mucosal epithelium was partially restored in mice after the intervention of moderate and high-dose Huangqintang.(2)The study of intestinal flora found that compared with the model group,the pro-inflammatory strain Enterococcus was significantly reduced(P<0.05),while beneficial bacteria such as Clostridium_innocuum and Rhodococcus,a pro-autophagy bacterium,were significantly elevated(P<0.05)in the moderate-dose Huangqintang group.(3)Compared with the model group,the autophagy markers were significantly elevated in the moderate-dose Huangqintang group(P<0.05);under transmission electron microscopy,the number of autophagic vacuoles of moderate-dose Huangqintang group increased significantly.(4)The results showed that Huangqintang significantly reduced the abundance of conditionally pathogenic bacteria and the level of inflammatory factors in small intestinal tissues,and increased the relative abundance of beneficial bacteria and promoted the expression of autophagy in the small intestinal mucosa,which resulted in a significant improvement of intestinal symptoms in mice with acute graft-versus-host disease.

This study aims to explore the protective effect of Chaihu Jia Longgu Muli Decoction on rats with heart failure after myocardial infarction, and to clarify its possible mechanisms, providing a new basis for basic research on the mechanism of classic Chinese medicinal formula-mediated inflammatory response in preventing and treating heart failure induced by apoptosis after myocardial infarction. A heart failure model after myocardial infarction was established in rats by coronary artery ligation. The rats were divided into sham group, model group, and low, medium, and high-dose groups of Chaihu Jia Longgu Muli Decoction, with 10 rats in each group. The low-dose, medium-dose, and high-dose groups of Chaihu Jia Longgu Muli Decoction were given 6.3, 12.6, and 25.2 g·kg~(-1) doses by gavage, respectively. The sham group and model group were given an equal volume of distilled water by gavage once daily for four consecutive weeks. Cardiac function was assessed using color Doppler echocardiography. Myocardial pathology was detected by hematoxylin-eosin(HE) staining, apoptosis was measured by TUNEL assay, and mitophagy was observed by transmission electron microscopy. The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and N-terminal pro-B-type natriuretic peptide(NT-proBNP) in serum were detected by enzyme-linked immunosorbent assay(ELISA). The expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), and cleaved caspase-3 was detected by Western blot. Additionally, the expression of phosphorylated nuclear transcription factor-κB(NF-κB) p65(p-NF-κB p65)(upstream) and nuclear factor kappa B inhibitor alpha(IκBα)(downstream) in the NF-κB signaling pathway was assessed by Western blot. The results showed that compared with the sham group, left ventricular ejection fraction(LVEF) and left ventricular short axis shortening(LVFS) in the model group were significantly reduced, while left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD) increased significantly. Myocardial tissue damage was severe, with widened intercellular spaces and disorganized cell arrangement. The apoptosis rate was increased, and mitochondria were enlarged with increased vacuoles. Levels of TNF-α, IL-1β, and NT-proBNP were elevated, indicating an obvious inflammatory response. The expression of pro-apoptotic factors Bax and cleaved caspase-3 increased, while the anti-apoptotic factor Bcl-2 decreased. The expression of p-NF-κB p65 was upregulated, and the expression of IκBα was downregulated. In contrast, the Chaihu Jia Longgu Muli Decoction groups showed significantly improved of LVEF, LVFS and decreased LVEDD, LVESD compared to the model group. Myocardial tissue damage was alleviated, and intercellular spaces were reduced. The apoptosis rate decreased, mitochondrial volume decreased, and the levels of TNF-α, IL-1β, and NT-proBNP were lower. The expression of pro-apoptotic factors Bax and cleaved caspase-3 decreased, while the expression of the anti-apoptotic factor Bcl-2 increased. Additionally, the expression of p-NF-κB p65 decreased, while IκBα expression increased. In summary, this experimental study shows that Chaihu Jia Longgu Muli Decoction can reduce the inflammatory response and apoptosis rate in rats with heart failure after myocardial infarction, which may be related to the regulation of the IκBα/NF-κB signaling pathway.
Animals ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Myocardial Infarction/physiopathology* ; Male ; NF-kappa B/genetics* ; Heart Failure/etiology* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; NF-KappaB Inhibitor alpha/genetics* ; Humans ; Tumor Necrosis Factor-alpha/genetics*

Post-traumatic stress disorder (PTSD) is a relatively common but complex mental illness with a range of diverse risk factors. Typical symptoms include the re-experience or avoidance of traumatic events, cognitive impairment, and hypervigilance. While the exact pathogenesis of PTSD is unclear, many studies indicate that epigenetic regulation plays a key role in its development. Specifically, numerous studies have indicated that the levels of histone acetylation and methylation, DNA methylation, and noncoding RNA are altered in PTSD patients. Further to this, natural products have been found to achieve epigenetic regulation of PTSD by regulating the expression of epigenetic enzymes, long noncoding RNA (lncRNA), and miRNA, thereby playing a role in improving PTSD symptoms. To date, however, no epigenetic regulation related drugs have been used in the treatment of PTSD. Furthermore, while natural products that can epigenetically regulate PTSD have received increasing levels of attention, there have not yet been any systematic reports on the topic. Here, we summarized the roles and mechanisms of natural products in the epigenetic regulation of PTSD, providing a novel and unique perspective that will help to guide the development and application of new PTSD treatments.

The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence ; Humans ; Delivery of Health Care ; Generative Artificial Intelligence

Ambient air pollution is increasingly being recognized as a risk factor for heart failure; however, its effects on cardiac biomarkers remain unclear. This scoping review assessed the existing evidence on the association between air pollution and cardiac biomarkers in heart failure, described the key concepts, synthesized data, and identified research gaps. Following the PRISMA-ScR guidelines, PubMed, Embase, Web of Science, and CNKI databases were searched for studies on air pollution, heart failure, and biomarkers. A total of 765 records were screened, and 81 full texts were assessed for eligibility, resulting in 15 studies. The results showed that the exposure to particulate matter was associated with elevated N-terminal pro-B-type natriuretic peptide and troponin levels. Several studies have linked particulate matter exposure to a higher cardiovascular risk and heart failure biomarkers. Inflammatory and oxidative stress markers were consistently elevated across studies, supporting the biological relevance of these associations. However, few studies have focused specifically on populations with heart failure or clinically relevant biomarkers, and the evidence for gaseous pollutants remains inconclusive. These findings highlight the need to integrate environmental risk assessment into heart failure care and inform policy efforts to reduce the pollution-related cardiovascular burden. Further research should address these gaps through improved exposure assessments and the integration of mechanistic evidence.
Heart Failure/epidemiology* ; Biomarkers/metabolism* ; Humans ; Air Pollution/adverse effects* ; Air Pollutants/adverse effects* ; Particulate Matter/adverse effects* ; Environmental Exposure ; Natriuretic Peptide, Brain/blood* ; Oxidative Stress ; Troponin/blood*