Radiotherapy is a crucial treatment modality for head and neck tumors. However, while effectively killing tumor cells, it significantly disrupts the homeostasis of the oral microecology, which is closely associated with various complications such as radiation-induced oral mucositis. Literature review indicates that as radiotherapy doses accumulate and treatment durations extend, the richness and diversity of the oral microbiota show a declining trend, with the genus Streptococcus decreasing most markedly. In contrast, radiotherapy selectively promotes the proliferation of bacterial phyla such as Proteobacteria and Bacteroidetes, which are rich in opportunistic pathogens. Mechanistically, radiotherapy activates the nuclear factor-kappa B pathway, triggering chronic inflammation and oxidative stress, damaging the epithelial barrier, suppressing local immunity, and causing damage to organs such as the salivary glands. It can also induce systemic diseases via the oral-gut axis, forming a multi-level, interconnected pathogenic network. In terms of interventions, treatment strategies including probiotics and prebiotics have shown promising efficacy against side effects such as radiation-induced oral mucositis. Saliva-based oral microbiota transplantation is an emerging strategy that is expected to become widely utilized for restoring oral microecological balance. Existing interventions provide preliminary pathways for clinical practice, but this field still faces several key scientific questions. The association between oral microecology and systemic diseases remains largely correlative, lacking causal evidence. Furthermore, critical parameters for oral microbiota transplantation, such as donor screening criteria, transplantation protocols, and long-term safety, are not yet well-defined. Therefore, future research should focus on conducting large-scale clinical trials to establish standardized protocols and safety evaluation systems for oral microecological interventions, and explore combined treatment therapies such as probiotics, prebiotics, and microbiota transplantation to advance the development of personalized precision modulation. These will enable more effective management of radiotherapy-induced oral microecological dysbiosis and improve treatment outcomes and quality of life for patients with head and neck tumors.

Objective: To evaluate the diagnostic potential of fluid suppression (FS) techniques combined with amide proton transferweighted imaging (APTw) for assessment of isocitrate dehydrogenase (IDH) mutation status, glioma subtypes, and tumor proliferation. Materials and Methods: This retrospective study included 117 patients with adult-type diffuse gliomas. Conventional APTw, FSAPTw, and spillover-corrected FS-APTw (SCFS-APTw) metrics were calculated from 3T MRI data in tumor parenchyma, necrotic or cystic regions, and contralateral normal-appearing white matter. APTw signals were compared across the three techniques within each region, between IDH-mutant and IDH-wildtype gliomas, and among astrocytoma, oligodendroglioma, and glioblastoma subtypes. Diagnostic performance for distinguishing IDH mutation status and glioma subtypes was assessed using receiver operating characteristic (ROC) analysis. Correlations between APTw metrics and Ki-67 expression were also analyzed. Results: Both FS-APTw and SCFS-APTw significantly reduced signal intensity in tumor parenchyma and necrotic or cystic regions, with SCFS-APTw demonstrating a stronger suppression effect. IDH-wildtype gliomas showed significantly higher APTw metrics than IDH-mutant gliomas (all P < 0.001). Glioblastomas exhibited significantly higher metrics than oligodendrogliomas (all corrected P ≤ 0.015) and astrocytomas (all corrected P < 0.001). SCFS-APTw achieved the highest area under the ROC curve (AUC) of 0.846 for identification of IDH mutation status. For differentiation between astrocytomas and glioblastomas, the 90th percentile of APTw yielded the highest AUC (0.860), followed by SCFS-APTw (0.849). For discrimination between oligodendrogliomas and glioblastomas, the highest AUC (0.832) was obtained using the 90th percentile of SCFS-APTw. None of these metrics successfully differentiated oligodendrogliomas from astrocytomas. SCFS-APTw demonstrated the strongest correlation with Ki-67 expression (r = 0.451). Conclusion FS techniques effectively reduce elevated APTw signals originating from fluid compartments. Their combination with APTw imaging enables evaluation of IDH mutation status, glioma subtypes, and tumor proliferative activity in adulttype diffuse gliomas.

OBJECTIVE A clinical comprehensive evaluation of five biologic targeted drugs for the treatment of severe eosinophilic asthma （SEA） was conducted to provide objective evidence for the rational selection of these medications in medical institutions. METHODS Using the evaluation methods from the Chinese Medical Institution Drug Evaluation and Selection Rapid Guide （ Third Edition ）， the effectiveness， safety， pharmaceutical characteristics， cost-effectiveness， and other attributes of five biologics targeting SEA （omalizumab， mepolizumab， benralizumab， dupilumab， and tezepelumab） already marketed in China were quantitatively scored across five dimensions， and their recommendation levels were categorized based on the scores. RESULTS The comprehensive scoring results showed that mepolizumab scored 81.29， making it a highly recommended variety； benralizumab scored 78.05， dupilumab scored 77.84 and omalizumab scored 70.14，all of which are recommended varieties； tezepelumab scored 67.77， considered weakly recommended variety. CONCLUSIONS Mepolizumab shows excellent performance in eosinophil clearance， good accessibility， and is more cost-effective than the others， making it more selective in SEA treatment； omalizumab has more advantages in the treatment of SEA patients with elevated immunoglobulin E levels； dupilumab can be used as the preferred treatment for SEA patients with chronic obstructive pulmonary disease.

OBJECTIVE A clinical comprehensive evaluation of five biologic targeted drugs for the treatment of severe eosinophilic asthma （SEA） was conducted to provide objective evidence for the rational selection of these medications in medical institutions. METHODS Using the evaluation methods from the Chinese Medical Institution Drug Evaluation and Selection Rapid Guide （ Third Edition ）， the effectiveness， safety， pharmaceutical characteristics， cost-effectiveness， and other attributes of five biologics targeting SEA （omalizumab， mepolizumab， benralizumab， dupilumab， and tezepelumab） already marketed in China were quantitatively scored across five dimensions， and their recommendation levels were categorized based on the scores. RESULTS The comprehensive scoring results showed that mepolizumab scored 81.29， making it a highly recommended variety； benralizumab scored 78.05， dupilumab scored 77.84 and omalizumab scored 70.14，all of which are recommended varieties； tezepelumab scored 67.77， considered weakly recommended variety. CONCLUSIONS Mepolizumab shows excellent performance in eosinophil clearance， good accessibility， and is more cost-effective than the others， making it more selective in SEA treatment； omalizumab has more advantages in the treatment of SEA patients with elevated immunoglobulin E levels； dupilumab can be used as the preferred treatment for SEA patients with chronic obstructive pulmonary disease.

BACKGROUND:During tissue repair and regeneration,macrophages exhibit multiple activities such as promoting inflammation,anti-inflammation,fibrosis,and wound healing at various stages of tissue damage.The heterogeneity and balanced polarization of macrophages are decisive in organ repair. OBJECTIVE:To explore the research hotspots and development trends in the field of macrophage polarization in tissue repair through visualization analysis methods,as well as the research level of global scientific and clinical workers in this field. METHODS:Using bibliometric analysis methods,this study employed Citespace literature visualization analysis software and VOSviewer tools,retrieving related literature from 2013 to 2023 in the Web of Science Core Collection's Science Citation Index Expanded(SCI-Expanded)and Social Sciences Citation Index Expanded(SSCI-Expanded)databases.The analysis results were presented in a dynamic map format,revealing the main trends and focuses of the research. RESULTS AND CONCLUSION:The number of publications in this field had dramatically increased from 2013 to 2023,with a significant rise starting in 2017.Chinese researchers had the highest number of publications,with 642 papers,while American researchers began focusing on this field early on.Professor Elisseeff Hennifer H had made a substantial contribution to the research in this area.Shanghai Jiao Tong University had produced the most publications.In recent years,keywords such as"hyaluronic acid"and"regulation"had been prevalent.Macrophage polarization research in tissue repair primarily concentrates on its multifunctional regulatory mechanisms,interactions with other cell types,and its behavior under specific pathological conditions.The main research areas include the role of macrophages in wound healing,cardiovascular diseases,chronic inflammation,tumor microenvironments,and regenerative medicine.A deeper understanding of the multifunctionality and polarization mechanisms of macrophages can lead to the development of new therapeutic strategies to enhance tissue repair and regeneration,thereby improving patient treatment outcomes.

The Solomon four-group design， a critical method for improving internal validity in clinical research， can reduce bias and control the interference of Hawthorne effects and pretest sensitization on research results， which offers unique advantages in evaluating complex intervention outcomes. This paper systematically outlined the core framework and key points of statistical analysis of the Solomon four-group design， summarized its applications in clinical research at home and abroad， explored its advantages and limitations， and discussed the potential value in traditional Chinese medicine （TCM） clinical trials. It is believed that the Solomon four-group design can help distinguish between testing effects and intervention effects in TCM clinical studies， and reduce the bias in the evaluation of subjective indicators. Meanwhile， given the complexity of the Solomon four-group design and the particularity of TCM clinical research， it is proposed that future TCM clinical studies should focus on using psychological scales， know-ledge， attitude， and behavior measurements， and other similat evaluations as endpoints. It also advocates strengthening interdisciplinary collaboration to provide new methodological paths for TCM clinical research.

OBJECTIVE To investigate the improvement effects and mechanism of Zhichi suanzaoren decoction （ZSD） on hippocampal oxidative stress injury in hippocampal neurons of mice with perimenopausal insomnia. METHODS The potential targets of active ingredients in ZSD were predicted using TCMSP and TCMIP databases； the targets related to insomnia were searched through GeneCards， OMIM and DisGeNET databases； protein-protein interaction network of intersecting targets of ZSD ingredients and insomnia was constructed； Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted on key targets. Sixty mice were divided into sham operation group， model group， ZSD low-， medium-， and high-dose groups （11， 22， and 33 g/kg）， and eszopiclone group （positive control， 1 mg/kg）. Except for sham operation group， the perimenopausal insomnia model was constructed by ovariectomy （OVX） in the other groups. After successful modeling， mice in each group were gavaged with normal saline or the corresponding drug solution， once a day， for three consecutive weeks. The sleep status of mice was evaluated through the pentobarbital sodium sleep synergy experiment， and the pathological changes of hippocampal neurons and the expressions of related genes and proteins in mice were observed by HE staining， immunohistochemistry staining， immunofluorescence staining， transcriptome sequencing technology and Western blot. RESULTS The results of network pharmacology showed that there were 296 intersection targets between ZSD and perimenopausal insomnia. Protein kinase B1 （Akt1） was a key target for treating insomnia with ZSD. After administration of ZSD， the sleep latency of mice was shortened， the sleep duration was prolonged significantly， and the mean optical density value of neuron-specific nuclear protein in the hippocampal CA1 region was significantly increased （P＜0.01）. Additionally， hippocampal neuron damage in OVX mice was significantly alleviated. The results of transcriptome sequencing showed that ZSD significantly upregulated the transcriptional levels of Nfe2l2 gene in hippocampal tissue of OVX mice （P＜0.05）. After administration of ZSD， protein expressions of nuclear factor E2 related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） in hippocampal tissue of OVX mice， as well as the phosphorylated Akt level， were increased significantly （P＜0.01）. CONCLUSIONS ZSD can ameliorate hippocampal oxidative stress injury of hippocampal neurons in perimenopausal insomnia mice by activating the Akt/Nrf2/HO-1 signaling pathway.

OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

The enterotoxigenic Escherichia coli (ETEC) infection is a major factor restricting the development of animal husbandry. However, the abuse of antibiotics will lead to the antibiotic residues and emergence of antibiotic-resistant bacteria. The existing vaccines face challenges in stimulating intestinal immunity, demonstrating limited prevention effects. Therefore, it is indispensable to develop a new vaccine that is safe and suitable as a feed additive to activate intestinal immunity. This study constructed yeast-cell microcapsules (YCM) carrying the DNA vaccine against ETEC by genetic engineering. Furthermore, animal experiments were carried out to explore the regulatory effects of feeding YCM on the intestinal immune system and intestinal microbiota. Saccharomyces cerevisiae was selected as the oral delivery vehicle (microcapsules) of the DNA vaccine. The codon-optimized nucleic acid sequence of K88, the main antigen of mammal-derived ETEC, was synthesized, and the yeast shuttle vector containing the corresponding DNA vaccine expression cassette was constructed by DNA recombination. The recombinant strain of YCM was prepared by transforming JMY1. Additionally, the characteristics of the YCM strain and its feasibility as an oral vaccine were comprehensively evaluated by the fluorescence reporter assay, gastrointestinal fluid tolerance assay, intestinal epithelial cell adhesion assay, intestinal retention assessment, antiserum detection, and intestinal microbiota detection. The experimental results showed that the DNA vaccine expression cassette was expressed in mammals, and the recombinant strain of YCM could tolerate up to 8 hours of gastrointestinal fluid digestion and had good adhesion to intestinal epithelial cells. The results of mouse feeding experiments indicated that the recombinant strain of YCM could stay in the intestinal tract for at least two weeks, and the DNA vaccine expression cassette carried by YCM entered the intestinal immune system and triggered an immune response to induce the production of specific antibodies. Moreover, feeding YCM recombinant bacteria also improved the abundance of gut microbiota in mice, demonstrating a positive effect in regulating intestinal flora. In summary, we prepared the recombinant strain of YCM carrying the DNA vaccine against ETEC and comprehensively evaluated its characteristics and feasibility as an oral vaccine. Feeding the recombinant YCM could induce specific immune responses and regulate intestinal microbiota. The findings provide a reference for the immunoprevention of ETEC-related animal diseases.
Animals ; Enterotoxigenic Escherichia coli/genetics* ; Saccharomyces cerevisiae/metabolism* ; Vaccines, DNA/genetics* ; Mice ; Escherichia coli Infections/immunology* ; Escherichia coli Vaccines/genetics* ; Capsules ; Mice, Inbred BALB C ; Female