Virus-related lymphoma exhibits a dual nature as both a hematologic malignancy and a viral infectious disease， making it more resistant to treatment and associated with poorer prognosis. This paper analyzes the understanding and therapeutic advantages of traditional Chinese medicine （TCM） in virus-related lymphoma. It proposes a TCM-based approach centered around syndrome differentiation， using standardized measurements of the overall TCM condition， multi-omics research of hematologic tumors， and artificial intelligence technologies to identify the "pre-condition" of virus-related lymphoma. A risk warning model will be established to early identify high-risk populations with viral infections that may develop into malignant lymphoma， thereby establishing a risk warning system for virus-related lymphoma. At the same time， a TCM health management approach will be applied to manage and regulate virus-related lymphoma， interrupting its progression and forming a human-centered， comprehensive， continuous health service model. Based on this， a standardized， integrated clinical prevention and treatment decision-making model for virus-related lymphoma， recognized by both Chinese and western medicine， will be established to provide TCM solutions for primary prevention of major malignant tumors.

Objective: To investigate the distribution of traditional Chinese medicine (TCM) syndromes and syndrome elements in lymphoma, as well as the correlation between TCM syndromes and Western clinical indicators, in order to analyze associations between TCM syndromes and these indicators. Methods: From January 2023 to May 2024, 216 patients with lymphoma who met the inclusion criteria in the Department of Hematology, Third People′s Hospital Affiliated to Fujian University of Traditional Chinese Medicine were enrolled. Four diagnostic methods were applied to perform TCM syndrome differentiation and extract syndrome elements. The correlations between various syndromes and blood test indicators of lactate dehydrogenase (LDH), β2-microglobulin (β2-MG), immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin A (IgA), white blood cell (WBC), hemoglobin (Hb), platelet count (PLT), neutrophil (NEUT), immunohistochemical markers of B-cell lymphoma-6 (BCL6), B-cell lymphoma-2 (BCL2), proto-oncogene MYC, and Ki67 protein expression, Ann Arbor staging, international prognostic index (IPI) score, bone marrow infiltration, concurrent infections during chemotherapy, and post-chemotherapy bone marrow suppression rate were analyzed. Results: Five TCM syndromes, ranked by frequency, were syndromes of yin deficiency with phlegm accumulation(41.67%), qi depression with phlegm obstruction(30.56%), cold-phlegm congelation and stagnation(12.96%), phlegm-blood stasis toxin(12.04%), and lingering pathogen due to deficient vital qi(2.77%). Yin deficiency(50.93%) and phlegm(45.37%) were the more prevalent syndrome elements. The TCM syndromes were correlated with β2-MG, PLT, MYC, BCL2/MYC, Ki67 protein expression, and bone marrow infiltration (P<0.05). No statistically significant differences were observed in Ann Arbor staging or IPI score across the syndromes. Compared to the syndrome of cold-phlegm congelation and stagnation, the syndrome of qi depression with phlegm obstruction exhibited higher levels of NEUT, MYC, BCL2/MYC, and Ki67 protein expression, as well as a higher rate of post-chemotherapy bone marrow suppression (P<0.05); the syndrome of phlegm-blood stasis toxin showed higher MYC and BCL2/MYC protein expression and a higher rate of post-chemotherapy bone marrow suppression rate (P<0.05); the syndrome of yin deficiency with phlegm accumulation demonstrated higher MYC and BCL2/MYC protein expression and bone marrow infiltration rates, whereas PLT level was lower (P<0.05); the syndrome of lingering pathogen due to deficient vital qi had higher MYC, BCL2/MYC, and Ki67 protein expression levels, as well as a higher rate of post-chemotherapy bone marrow suppression rate (P<0.05). Compared to the syndrome of qi depression with phlegm obstruction, the syndrome of phlegm-blood stasis toxin exhibited lower Ki67 protein expression (P<0.05); the syndrome of yin deficiency with phlegm accumulation had higher β2-MG level, bone marrow infiltration rate, and rate of concurrent infections during chemotherapy, whereas PLT and NEUT levels and the rate of post-chemotherapy bone marrow suppression rate were lower (P<0.05). Compared to the syndrome of phlegm-blood stasis toxin, the syndrome of yin deficiency with phlegm accumulation had higher β2-MG level, whereas NEUT and the rate of post-chemotherapy bone marrow suppression were lower(P<0.05); the syndrome of lingering pathogen due to deficient vital qi exhibited a higher Ki67 protein expression (P<0.05). Compared to the syndrome of yin deficiency with phlegm accumulation, the syndrome of lingering pathogen due to deficient vital qi also showed a higher Ki67 protein expression(P<0.05). Conclusion The syndrome of yin deficiency with phlegm accumulation is relatively common in lymphoma. There is a correlation between TCM syndromes and Western medicine clinical indicators. The presence of heat signs in the syndromes may indicate active disease and poor prognosis, while the presence of strong pathogenic factors and weak vital qi in the syndromes may indicate a severer chemotherapy-related bone marrow suppression.

Periodontal bone defects, primarily caused by periodontitis, are highly prevalent in clinical settings and manifest as bone fenestration, dehiscence, or attachment loss, presenting a significant challenge to oral health. In regenerative medicine, harnessing developmental principles for tissue repair offers promising therapeutic potential. Of particular interest is the condensation of progenitor cells, an essential event in organogenesis that has inspired clinically effective cell aggregation approaches in dental regeneration. However, the precise cellular coordination mechanisms during condensation and regeneration remain elusive. Here, taking the tooth as a model organ, we employed single-cell RNA sequencing to dissect the cellular composition and heterogeneity of human dental follicle and dental papilla, revealing a distinct Platelet-derived growth factor receptor alpha (PDGFRA) mesenchymal stem/stromal cell (MSC) population with remarkable odontogenic potential. Interestingly, a reciprocal paracrine interaction between PDGFRA⁺ dental follicle stem cells (DFSCs) and CD31⁺ Endomucin⁺ endothelial cells (ECs) was mediated by Vascular endothelial growth factor A (VEGFA) and Platelet-derived growth factor subunit BB (PDGFBB). This crosstalk not only maintains the functionality of PDGFRA⁺ DFSCs but also drives specialized angiogenesis. In vivo periodontal bone regeneration experiments further reveal that communication between PDGFRA⁺ DFSC aggregates and recipient ECs is essential for effective angiogenic-osteogenic coupling and rapid tissue repair. Collectively, our results unravel the importance of MSC-EC crosstalk mediated by the VEGFA and PDGFBB-PDGFRA reciprocal signaling in orchestrating angiogenesis and osteogenesis. These findings not only establish a framework for deciphering and promoting periodontal bone regeneration in potential clinical applications but also offer insights for future therapeutic strategies in dental or broader regenerative medicine.
Receptor, Platelet-Derived Growth Factor alpha/metabolism* ; Humans ; Neovascularization, Physiologic/physiology* ; Dental Sac/cytology* ; Single-Cell Analysis ; Transcriptome ; Mesenchymal Stem Cells/metabolism* ; Bone Regeneration ; Animals ; Dental Papilla/cytology* ; Periodontium/physiology* ; Stem Cells/metabolism* ; Regeneration ; Angiogenesis

(±)-Talapyrones A-F (1-6), six pairs of dimeric polyketide enantiomers featuring unusual 6/6/6 and 6/6/6/5 ring systems, were isolated from the fungus Talaromyces adpressus. Their structures were determined by spectroscopic analysis and HR-ESI-MS data, and their absolute configurations were elucidated using a modified Mosher's method and electronic circular dichroism (ECD) calculations. (±)-Talapyrones A-F (1-6) possess a 6/6/6 tricyclic skeleton, presumably formed through a Michael addition reaction between one molecule of α-pyrone derivative and one molecule of C₈ poly-β-keto chain. In addition, compounds 2/3 and 4/5 are two pairs of C-18 epimers, respectively. Putative biosynthetic pathways of 1-6 were discussed.
Polyketides/isolation & purification* ; Talaromyces/chemistry* ; Stereoisomerism ; Molecular Structure ; Circular Dichroism ; Pyrones/chemistry*

Objective:To study the whole bone marrow cellular composition of jaw and long bones, and further analyze the heterogeneity of mesenchymal stem cells (MSCs) derived from these two tissue, aiming at exploring the differences in functional characteristics of bone MSCs from different lineage sources.Methods:The Seurat package of R language was used to analyze the mandibular and femur whole bone marrow single-cell RNA-sequencing (scRNA-seq) datasets in the literature, and the subpopulations were annotated by reference to the marker genes reported by previous studies. The differentially expressed genes between mandible-derived MSCs (M-MSCs) and femur-derived MSCs (F-MSCs) were calculated, and cell-cell communication analysis between M-MSCs or F-MSCs with other cell populations was performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on up-regulated and down-regulated differentially expressed genes of M-MSCs, and Gene Set Enrichment Analysis (GSEA) was performed on M-MSCs or F-MSCs.Results:cRNA-seq analysis showed that the mandible and femur had the same bone marrow cell composition, but there were differences in the proportion of specific cell populations. Also, there were significantly differentially expressed genes between M-MSCs and F-MSCs. In addition, cell-cell communication analysis revealed differences in numbers of ligand-receptor pairs between M-MSCs or F-MSCs with other cell populations. Furthermore, GO, KEGG and GSEA analysis showed that M-MSCs had higher extracellular matrix production potential than F-MSCs, but had lower ability to regulate other cells in the bone marrow, especially immune cells.Conclusions:M-MSCs and F-MSCs showed distinct differences in the gene expression pattern and up-regulated signaling pathways, which may be closely related to the developmental sources and functional characteristics of jaw and long bones.

Objective:To explore the biological process of liver tissue-derived extracellular vesicle (LT-EV) in promoting osteogenic differentiation of mesenchymal stem cells and healing of jaw defects to provide a feasible treatment method for the clinical treatment of jaw bone defects.Methods:Enzymatic hydrolysis and differential centrifugation were used to extract LT-EV, scanning electron microscopy, Western blotting, and nanoparticle tracking analyzers were used to identify and characterize LT-EV, and further to explore the biological functions of LT-EV through proteomics and Kyoto Encyclopedia of Genes and Genomes. Flow cytometry was used to detect LT-EV plasma concentration and to calculate the plasma half-life of LT-EV. Small animal in vivo imaging system was used to detect the biological distribution of LT-EV 24 hours after injection. Six C57BL/6 mice were divided into control group and LT-EV group (3 mice in each group) by simple random sampling method. All mice underwent jaw bone defect surgery and tail vein injection every 7 days (the control group was injected with phosphoric buffer saline, LT-EV group was injected with LT-EV), micro-CT was used to evaluate the degree of mouse jaw bone healing 28 days after surgery, HE staining was used to analyze the multi-organ biosafety of LT-EV, and immunofluorescence staining was used to detect the jaw bone expression of osteogenic marker proteins in the defect area. Human jaw bone mesenchymal stem cells (hJBMSC) induced by osteogenic differentiation were treated with LT-EV (obtained from orthognathic surgery patients provided by the Department of Traumatology and Orthognathic Surgery of School of Stomatology of The Fourth Military Medical University resected normal jaw bone fragments), and the difference in osteogenic differentiation ability between the hJBMSC group and the control group (phosphate buffer saline treatment) was compared, and the in vitro bone differentiation promoting effect of LT-EV was verified through alkaline phosphatase (ALP) staining and real-time fluorescence quantitative PCR. Results:The yield of LT-EV was high, and proteomics and Kyoto Encyclopedia of Genes and Genomes showed that LT-EV contained a series of proteins that regulated cell biological functions. LT-EV injected into the tail vein could reach the mouse jaw bone defect area and promote the regeneration and repair of the jaw bone defect [the bone volume fractions of the LT-EV group and the control group were (36.06±4.20)% and (18.58±5.61)%, respectively; t=4.32, P=0.013], and had good biosafety. LT-EV could promote osteogenic differentiation of hJBMSC in vitro. Compared to the control group, ALP staining and osteogenic gene expression levels were significantly enhanced after osteogenic differentiation of hJBMSC ( P<0.05). Conclusions:LT-EV exhibits a high yield, ease of acquisition, high biological safety, and excellent bone-promoting effects. It holds promise as a novel cell-free therapy strategy for regenerating craniofacial bone defects.

Objective To analyze the clinical efficacy of Yunnan Baiyao in middle aged and elderly lung cancer patients undergoing the uniportal video-assisted thoracoscopic.Methods A total of 90 patients with non-small cell lung cancer meeting the criterias were screened and divided into two groups according to random number table method,which respectively received conventional treatment(control group)and Yunnan Baiyao treatment(experimental group).The perioperative period related indexes,coagulation function related indexes,and the occurrence rate of complications were observed and compared between the two groups.Results The intraoperative bleeding volume and thoracic drainage volume for the first day of experimental group were significantly lower than control group(P＜0.05).However,there were no significant difference in the coagulation function related indexes between two groups before and after surgery(P＞0.05).Additionally,there were also no significant difference in the occurrence rate of complication between two groups(P＞0.05).Conclusion Yunnan Baiyao can reduce intraoperative bleeding volume and chest tube drainage volume for the first day,promots the recovery of patients,and has a good clinical application value.

Objective·To study the alterations in vestibular hair cell morphology and function of ATPase plasma membrane Ca2+transporting 2 oblivion(Atp2b2 Oblivion)heterozygous mice at different ages.Methods·Atp2b2 Oblivion heterozygous male mice aged 2 months and 8 months were selected with ten in each kind and C57BL/6J wild-type mice with the same gender,age and number were selected as the control group.Expression patterns of ATP2B2 in vestibular hair cells and numbers of hair cells in the striola zone and the extra striola zone in the two groups of mice at different ages were observed and calculated respectively through immunofluorescence assay.Hair bundle structures were detected by scanning electron microscopy(SEM),and mitochondria and ribbon synapse structures were observed by transmission electron microscopy(TEM).Vestibular evoked potential(VsEP),vestibular evoked myogenic potential(VEMP),rotarod rod test,and balance beam test were adopted for the evaluation of vestibular functions.Results·ATP2B2 was mainly expressed in the hair bundle of vestibular hair cells in the two groups of mice.Hair cell numbers in the striola zone and the extra-striola zone did not exhibit any differences between Atp2b2 Oblivion heterozygous mutant mice and wild-type mice of 2-month-old and 8-month-old.No visible structural abnormality in the hair bundle could be seen through SEM.TEM results implied no morphological abnormality in mitochondria or ribbon synapses in the 2-month-old heterozygous mutant mice,while vacuolar degeneration was discovered in the mitochondria under the cuticular plate in the 8-month-old heterozygous mutant mice with the normal ribbon synapses and the normal mitochondria near the innervation site.VsEP and VEMP thresholds of 2-month-old and 8-month-old Atp2b2 Oblivion heterozygous mutant mice were significantly elevated compared with the wild-type mice.Analysis of VsEP waveform manifested prolonged P1 latency and declined P1N1 amplitude in heterozygous mutant mice(P＜0.05).Results of rotarod rod test and balance beam test acquired from 2-month-old Atp2b2 Oblivion heterozygous mutant mice were not significantly different from the wild-type mice,while the ability of the mutant mice to accomplish the tests descended significantly at 8 months of age compared with the wild-type mice(P＜0.05).Conclusion·Atp2b2 Oblivion heterozygous mutant mice showed defective vestibular electrophysiological function at 2 months old,and abnormalities in vestibule-related behaviors can be detected at 8 months old.The vestibular function ofAtp2b2 Oblivion heterozygous mutant mice deteriorate progressively.

Severe muscle injury is hard to heal and always results in a poor prognosis. Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine, however, whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown. Herein, we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells (MSCs-ApoEVs) to treat cardiotoxin induced tibialis anterior (TA) injury and found that MSCs-ApoEVs promoted muscles regeneration and increased the proportion of multinucleated cells. Besides that, we also found that apoptosis was synchronized during myoblasts fusion and MSCs-ApoEVs promoted the apoptosis ratio as well as the fusion index of myoblasts. Furthermore, we revealed that MSCs-ApoEVs increased the relative level of creatine during myoblasts fusion, which was released via activated Pannexin 1 channel. Moreover, we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived ApoEVs (Myo-ApoEVs) instead of apoptotic myoblasts, and creatine was the pivotal metabolite involved in myoblasts fusion. Collectively, our findings firstly revealed that MSCs-ApoEVs can promote muscle regeneration and elucidated that the new function of ApoEVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel, which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles.
Creatine/metabolism* ; Extracellular Vesicles ; Muscle, Skeletal/metabolism* ; Myoblasts/metabolism* ; Regeneration ; Connexins/metabolism*

Mononuclear macrophages are versatile cells that can have different responses to various microenvironmental signals. Under different stimuli of circumstances, macrophages can be fully polarized into classically activated macrophages (M1) and alternatively activated macrophages (M2), which are the extremes of a continuum of functional states. Nuclear factor-κB, cyclooxygenase 2, anoxia status, proto-oncogene MYC, Toll-like receptor signaling pathway, Notch signaling pathway and cytokines are all closely involved in the transition of tumor-associated macrophages from M1 to M2 phenotype. Macrophages that infiltrate tumor tissues are driven by tumor-derived cytokines to acquire a polarized M2 phenotype. These functionally polarized cells play a key role in the subversion of adaptive immunity and in inflammatory circuits that promote tumor development and progression. Exosomes derived from tumors have the characteristics of tumor cells and could participate in multiple processes of tumorigenesis and development. This review focused on exosomes derived from various cancer cells and discussed the role of the payloads of tumor-derived exosomes in modulating macrophage polarization in the tumor immune microenvironment and the intracellular signal mechanisms involved.