ObjectiveTo explore the ethical issues and coping strategies in the diagnosis and treatment of 46, XY disorders of sex development （46, XY DSD） under a multidisciplinary team （MDT） model， and to deepen the understanding of relevant ethical issues while accumulating experience. MethodsA retrospective collection was conducted on the data of children with 46, XY disorders of sex development under a single-center MDT model from January 2017 to December 2024， and the ethical issues involved in the diagnosis and treatment process were analyzed. ResultsA total of 24 MDT discussion documents involving 20 children were collected， including 17 with female social gender and 3 with male social gender. The age ranged from 0.5 to 15.8 years， with children under 8 years accounting for 75%. The ethical issues primarily involved how to ensure adequate informed consent， whether surgery was necessary and its timing， and whether gender selection is reasonable and its timing. Among the 10 children raised as females who completed the gender role psychological scale assessment， 5 demonstrated masculine tendencies， all of whom had pathogenic genetic variants. Furthermore， only 1 patient changed the social gender to male. ConclusionThe diagnosis and treatment of 46, XY DSD is relatively complex， requiring multidisciplinary collaboration. This process involves numerous ethical issues and necessitates adhering to medical ethical principles. Ensuring adequate informed consent is crucial， especially for younger children. The surgery and its timing selection must adhere to the principles of beneficence， non-maleficence， and leaving room for the future. Gender selection constitutes a focus and challenge in diagnosis and treatment. Psychological scales and genetic etiologies are conducive to judgments regarding gender selection， yet multiple factors in the real world may interfere with the gender selection.

Objective To explore the effects and mechanisms of bone marrow mesenchymal stem cell(BMMSC)-derived exosomes(BMMSC-Exo)on hypoxia/reoxygenation(H/R)-induced injury in rat cardiomyocyte cell line(H9c2).Methods BMMSC-Exosomes were isolated by ultracentrifugation.The cells were divided into three groups:control,H/R,and H/R+BMMSC-Exo(H/R+Exo).A hypoxia/reoxygenation(H/R)injury model was es-tablished by exposing cells to 12 hours of hypoxia followed by 6 hours of reoxygenation.Flow cytometry was used to detect cell apoptosis,DHE staining was used to assess cellular ROS levels,JC-1 immunofluorescence staining was used to evaluate mitochondrial membrane potential,and Western blot was used to detect mitochondrial autophagy-re-lated proteins.Results BMMSC-Exo treatment significantly alleviated oxidative stress,restored mitochondrial mem-brane potential,reduced mitochondrial autophagy levels,and effectively decreased cardiomyocyte apoptosis.Conclu-sions Bone marrow mesenchymal stem cell-derived exosomes alleviate H/R-induced cardiomyocyte injury.

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.

Oral cancer, as one kind of mucosal epithelial tumor, constitutes approximately 2% of all cancers, while the most common type, oral squamous cell carcinoma (OSCC) represents around 90% histopathology of oral cancers. Although the treatment of OSCC has been improved in recent 20 years, its 5-year survival rate has not raised significantly. The crux to improve the survival rate and prognosis of OSCC patients lies in the early diagnosis and intervention of this disease. Hence, exploring new diagnostic and therapeutic strategies for OSCC is therefore an urgent priority. Exosomes, the small membrane vesicles originated from endosomes, have been detected in a wide array of bodily fluids. Exosomes have biological properties of derived cells based on containing a diversity of proteins, lipids, DNA fragments, mRNAs, and non-coding RNAs, including microRNAs, long non-coding RNAs, piRNAs, circular RNAs, tsRNAs, and ribosomal RNAs, which are delivered to neighboring cells or even transported to distant sites. They participate in cellular communication as well as play an important role in many diseases and immune response. Exosomes have been associated with the tumorigenesis of OSCC, promoting the proliferation, colonization, and metastasis of OSCC by transferring their cargos to the target cells. Furthermore, exosomes participate in the regulation of the tumor microenvironment to affect cancer progression in vivo. In this review, we summarize the crucial role of exosomes in the tumorigenesis and progression of OSCC and discuss the potential clinical application of exosomes in OSCC treatment.

Objective:To investigate the clinical features and prognosis associated risk factors of non-eosinophilic esophagitis eosinophilic gastrointestinal diseases (non-EoE EGID) in children.Methods:A retrospective cohort study was conducted. Clinical data, including symptoms, laboratory test results, endoscopic findings, treatment and prognosis of 48 children diagnosed with non-EoE EGID at Children′s Hospital, Zhejiang University School of Medicine from May 2015 to March 2023 were collected. Patients were grouped according to the eosinophils (EOS) diagnostic threshold of new guideline for non-EoE EGID. Independent sample t tests, Wilcoxon rank-sum test, chi-squared test or Fisher exact test were used for intergroup comparisons. Kaplan-Meier method was used to plot the survival curve of disease recurrence in children with non-EoE EGID. Log-Rank test and the proportional hazards model were respectively used for univariate analysis and multivariate analysis. Results:Of the 48 children with non-EoE EGID, there were 38 males and 10 females. Twenty-six patients (54%) with onset age >6-10 years accounted for the highest proportion. The most common symptom was abdominal pain, occurring in 34 patients (71%). Laboratory test results showed that 32 patients (67%) had increased EOS count in peripheral blood. A total of 35 imaging examination showed thickened intestinal wall in 17 patients (49%) and bowel dilatation in 3 patients (9%). Twenty-five patients (52%) received glucocorticoid treatment. The serum albumin level in the high diagnostic threshold group was lower than that in the low diagnostic threshold group ( Z=2.17, P=0.030), no statistically significant difference was found in other clinical characteristics (all P>0.05). The 1-year, 2-year, and 3-year recurrence-free survival rates for non-EoE EGID children were (81±6)%, (81±6)%, and (44±13)% respectively. Multivariate analysis showed that bowel dilatation ( HR=5.87, 95% CI 1.06-32.48) was an independent predictor of disease recurrence. Conclusions:A higher proportion of non-EoE EGID patients are male. The most common symptom is abdominal pain, and the peripheral blood EOS counts are often elevated. Among children with non-EoE EGID, those with higher pathological EOS counts have lower serum albumin levels. Bowel dilatation is a risk factor for disease recurrence in non-EoE EGID children.

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*

Oral cancer, as one kind of mucosal epithelial tumor, constitutes approximately 2% of all cancers, while the most common type, oral squamous cell carcinoma (OSCC) represents around 90% histopathology of oral cancers. Although the treatment of OSCC has been improved in recent 20 years, its 5-year survival rate has not raised significantly. The crux to improve the survival rate and prognosis of OSCC patients lies in the early diagnosis and intervention of this disease. Hence, exploring new diagnostic and therapeutic strategies for OSCC is therefore an urgent priority. Exosomes, the small membrane vesicles originated from endosomes, have been detected in a wide array of bodily fluids. Exosomes have biological properties of derived cells based on containing a diversity of proteins, lipids, DNA fragments, mRNAs, and non-coding RNAs, including microRNAs, long non-coding RNAs, piRNAs, circular RNAs, tsRNAs, and ribosomal RNAs, which are delivered to neighboring cells or even transported to distant sites. They participate in cellular communication as well as play an important role in many diseases and immune response. Exosomes have been associated with the tumorigenesis of OSCC, promoting the proliferation, colonization, and metastasis of OSCC by transferring their cargos to the target cells. Furthermore, exosomes participate in the regulation of the tumor microenvironment to affect cancer progression in vivo. In this review, we summarize the crucial role of exosomes in the tumorigenesis and progression of OSCC and discuss the potential clinical application of exosomes in OSCC treatment.

Objective:To investigate the clinical features and prognosis associated risk factors of non-eosinophilic esophagitis eosinophilic gastrointestinal diseases (non-EoE EGID) in children.Methods:A retrospective cohort study was conducted. Clinical data, including symptoms, laboratory test results, endoscopic findings, treatment and prognosis of 48 children diagnosed with non-EoE EGID at Children′s Hospital, Zhejiang University School of Medicine from May 2015 to March 2023 were collected. Patients were grouped according to the eosinophils (EOS) diagnostic threshold of new guideline for non-EoE EGID. Independent sample t tests, Wilcoxon rank-sum test, chi-squared test or Fisher exact test were used for intergroup comparisons. Kaplan-Meier method was used to plot the survival curve of disease recurrence in children with non-EoE EGID. Log-Rank test and the proportional hazards model were respectively used for univariate analysis and multivariate analysis. Results:Of the 48 children with non-EoE EGID, there were 38 males and 10 females. Twenty-six patients (54%) with onset age >6-10 years accounted for the highest proportion. The most common symptom was abdominal pain, occurring in 34 patients (71%). Laboratory test results showed that 32 patients (67%) had increased EOS count in peripheral blood. A total of 35 imaging examination showed thickened intestinal wall in 17 patients (49%) and bowel dilatation in 3 patients (9%). Twenty-five patients (52%) received glucocorticoid treatment. The serum albumin level in the high diagnostic threshold group was lower than that in the low diagnostic threshold group ( Z=2.17, P=0.030), no statistically significant difference was found in other clinical characteristics (all P>0.05). The 1-year, 2-year, and 3-year recurrence-free survival rates for non-EoE EGID children were (81±6)%, (81±6)%, and (44±13)% respectively. Multivariate analysis showed that bowel dilatation ( HR=5.87, 95% CI 1.06-32.48) was an independent predictor of disease recurrence. Conclusions:A higher proportion of non-EoE EGID patients are male. The most common symptom is abdominal pain, and the peripheral blood EOS counts are often elevated. Among children with non-EoE EGID, those with higher pathological EOS counts have lower serum albumin levels. Bowel dilatation is a risk factor for disease recurrence in non-EoE EGID children.