Objective:To investigate the clinicopathological features, immunophenotype, molecular characteristics, and differential diagnosis of MED15-TFE3 gene fusion renal cell carcinoma (MED15-TFE3 RCC).Methods:A total of 12 MED15-TFE3 RCCs, diagnosed from 2016 to 2023, were collected from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China for clinicopathologic, immunohistochemical, fluorescence in situ hybridization (FISH) and RNA sequencing (RNA-seq) analyses and follow-up. In addition, its diagnosis and differential diagnosis were also explored.Results:There were five males and seven females. The patients′ ages ranged from 16 to 60 years, with an average age of 40.4 years. The follow-up time ranged from 15 to 92 months, and no recurrence or metastasis was observed. Histologically, 6 cases exhibited extensive cystic structures with almost no solid sheet components, while the remaining 6 cases displayed a cysto-solid growth pattern. The cytoplasm of the tumor cells appeared flocculent, with a clear or faintly eosinophilic appearance, and nucleoli were inconspicuous. Psammoma bodies were observed in 12 cases. There was deposition of basement membrane-like material in 5 cases. All cases showed strong expression of TFE3, GPNMB, Cathepsin K, Melan A, and PAX8, while no expression of CAⅨ or CK7. FISH analyses showed that all 12 cases were positive for the MED15-TFE3 fusion, while the MED15-TFE3 fusion gene and specific fusion sites were detected in 2 cases using RNA-seq.Conclusions:MED15-TFE3 RCC is a type of TFE3-rearranged renal cell carcinoma that exhibits both identifiable diagnostic characteristics and highly deceptive morphology. Its distinct extensive cystic structure can be easily confused with multilocular cystic renal neoplasm of low malignant potential, necessitating careful differentiation in routine practice.

Objective:To explore the efficacy and safety of negative-pressure wound therapy (NPWT) in treating infected wounds in orthopedic trauma patients.Methods:China National Knowledge Infrastructure, China Biomedical Literature Database, Wanfang Data Knowledge Service Platform, PubMed, Web of Science, Cochrane Library, and CINAHL were searched for randomized controlled trials (RCT) and cohort studies examining the impact of NPWT on wound healing in orthopedic trauma infections. The retrieval time was from the establishment of the databases to October 2024. RevMan 5.4 software was used for Meta-analysis. The patients were divided into two groups according to different treatment methods: the intervention group, treated with NPWT, and the control group, treated with conventional treatment. The observed indicators included clinical efficacy, wound healing quality, length of hospital stay, wound healing time, incidence of complications, secondary surgery rate, and duration of antibiotic use. Publication bias analysis was performed on the observed indicators through Begg and Egger tests.Results:A total of 13 studies were included, comprising 11 RCT and 2 cohort studies, involving a total of 3 538 patients, with 1 762 in the intervention group and 1 776 in the control group. The meta-analysis results indicated that the intervention group had better clinical efficacy ( OR=7.08, 95% CI 5.31, 9.45, P<0.01), higher wound healing quality ( MD=4.15, 95% CI 3.99, 4.32, P<0.01), shorter length of hospital stay ( MD=-13.38, 95% CI -14.39, -12.38, P<0.01), shorter wound healing time ( MD=-8.11, 95% CI -10.22, -6.00, P<0.01), lower incidence of complications, lower secondary surgery rate ( OR=0.22, 95% CI 0.09, 0.57, P<0.01), and shorter duration of antibiotic use ( MD=-7.61, 95% CI -8.06, -7.16, P<0.01) when compared with the control group. No significant publication bias was observed in the aforementioned indicators ( P>0.05). Conclusion:Compared with the conventional treatment, NPWT can enhance the clinical efficacy and wound healing quality of infected wounds in orthopedic trauma patients, shorten length of hospital stay and wound healing time, reduce the incidence of complications and secondary surgery rates, and shorten the duration of antibiotic use.

Periodontal disease is a risk factor for many systemic diseases such as Alzheimer's disease and adverse pregnancy outcomes. Cleft palate (CP), the most common congenital craniofacial defect, has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection. A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring. However, the precise relationship remains unclear. In this study, the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P. gingivalis injected intravenously and orally into pregnant mice. We investigated an obvious increasing CP (12.5%) in sonicated P. gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium. Then glycolysis and H4K12 lactylation (H4K12la) were detected to elevate in both mouse embryonic palatal mesenchyme (MEPM) cells and macrophages under P. gingivalis exposure which further promoted the transcription of metallopeptidase domain17 (ADAM17), subsequently mediated the shedding of transforming growth factor-beta receptor 1 (TGFBR1) in MEPM cells and mer tyrosine kinase (MerTK) in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate, eventually caused abnormalities in palate fusion and ossification. The abnormal efferocytosis also led to a predominance of M1 macrophages, which indirectly inhibited palatal osteogenesis via extracellular vesicles. Furthermore, pharmacological ADAM17 inhibition could ameliorate the abnormality of P. gingivalis-induced abnormal palate development. Therefore, our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.
Animals ; Female ; Porphyromonas gingivalis ; Pregnancy ; Mice ; Cleft Palate/etiology* ; Glycolysis

Myocardial infarction (MI) is the leading cause of cardiovascular disease-related death worldwide. Nonetheless, existing therapeutic approaches for MI are hampered by issues such as reliance on pharmacological agents and suboptimal patient adherence. Caffeic acid (CA) is a bioactive polyphenolic compound with important anti-inflammatory, anti-bacterial and anti-oxidant functions. Still, its specific role and mechanism in treating cardiovascular disease remain to be further studied. In recent years, a large number of studies have shown that the kelch-like ECH-associated protein 1/nuclear factor erythroid 2 related factor 2 (Keap1/Nrf2) pathway is a key factor in the occurrence and development of cardiovascular diseases. In this study, H₂O₂-induced oxidative stress model of H9c2 cells and left anterior descending branch (LAD) conjunctival induced acute myocardial infarction reperfusion (AMI/R) model were used to evaluate the protective effect of CA on the heart. The interaction between CA and Keap1 was analyzed by CA-labeled fluorescence probe, target fishing, isothermal titration calorimetry (ITC), protein crystallography and surface plasmon resonance (SPR). Our results suggested that CA binds Keap1 and degrades Keap1 in a p62-dependent manner, further promoting nuclear transcription of Nrf2 and thus effectively reducing oxidative stress. In addition, based on the three-dimensional eutectic structure, it was confirmed that CA directly targets Keap1 protein by interacting with residues M550 and N532, inducing conformation changes in Keap1 protein. We also found that the CA analog chlorogenic acid (GCA) can bind Keap1. In conclusion, this study elucidates a novel molecular mechanism and structural basis for the protective effects of CA against oxidative damage via the Keap1-Nrf2 pathway.

Objective To optimize the platelet enrichment method,and to analyze the concentration changes of key molecules in platelet-rich plasma(PRP)before and after activation,as well as the impact of its activated products on the proliferation of rat endothelial progenitor cells.Methods The tube double-centrifu-gation method was employed to optimize platelet enrichment,and the platelet count in the enriched PRP was measured.ELISA was used to detect the concentration changes of vascular endothelial growth factor(VEGF),endostatin(ES),and P-selectin(CD62P)in PRP before and after activation.The PRP was activated by using liquid nitrogen freeze-thaw method,and the effect of its activated products on the proliferation of rat endothelial progenitor cells was evaluated by using the methyl thiazolyl tetrazolium(MTT)assay.Results The optimal enrichment coefficient of platelets achieved by the double-centrifugation method was 4.63.After low-speed,long-duration double centrifugation,the platelet count was highest in the upper layer of the buffy coat.For PRP with a platelet count of 500× 109/L obtained by machine collection,the VEGF con-centrations before and after activation were(3 418.12±488.80)pg/mL and(4 530.04±308.30)pg/mL,re-spectively,the ES concentrations were(6 168.98±253.22)pg/mL and(6 594.65±82.47)pg/mL,respec-tively,the CD62P concentrations were(6 678.23±324.15)pg/mL and(17 630.53±746.24)pg/mL,respec-tively,statistically significant differences were observed in the above indicators before and after activation(P＜0.01).The activated PRP was diluted in a gradient manner by using a specialized culture medium for en-dothelial progenitor cells.MTT assay results indicated that,in the basal medium,the optimal volume fraction for promoting endothelial progenitor cell proliferation was 0.25％after 48 hours of culture;in the complete medium,the optimal volume fractions for promoting endothelial progenitor cell proliferation were 0.062 5％after 24 hours and 0.125％after 48 hours.Conclusion The concentrations of VEGF,ES,and CD62P in the optimized,enriched PRP exhibited significant changes before and after activation.The optimal volume fraction for promoting endothelial progenitor cell proliferation in the basal medium was 0.25％.

TFE3/TFEB translocation renal cell carcinoma(TFE3/TFEB tRCC)occupies a prominent position in the molecular pathological classification of renal cancers due to its distinctive genetic abnormalities and its clinical pre-dilection for younger patients.Over nearly two decades of research,the spectrum of TFE3/TFEB fusion partner genes has expanded,highlighting the increasing morphological heterogeneity of TFE3/TFEB tRCC.This article reviews the clinicopathological and molecular features of TFE3/TFEB tRCC,emphasizing the associations between the major fusion subtypes and their morphological manifestations as well as immunophenotypes.Additionally,the practical value of an-cillary diagnostic techniques,such as molecular testing,is summarized,aiming to provide a reference for the routine and differential diagnosis of TFE3/TFEB tRCC.

TFE3/TFEB translocation renal cell carcinoma(TFE3/TFEB tRCC)occupies a prominent position in the molecular pathological classification of renal cancers due to its distinctive genetic abnormalities and its clinical pre-dilection for younger patients.Over nearly two decades of research,the spectrum of TFE3/TFEB fusion partner genes has expanded,highlighting the increasing morphological heterogeneity of TFE3/TFEB tRCC.This article reviews the clinicopathological and molecular features of TFE3/TFEB tRCC,emphasizing the associations between the major fusion subtypes and their morphological manifestations as well as immunophenotypes.Additionally,the practical value of an-cillary diagnostic techniques,such as molecular testing,is summarized,aiming to provide a reference for the routine and differential diagnosis of TFE3/TFEB tRCC.

Objective:To explore the efficacy and safety of negative-pressure wound therapy (NPWT) in treating infected wounds in orthopedic trauma patients.Methods:China National Knowledge Infrastructure, China Biomedical Literature Database, Wanfang Data Knowledge Service Platform, PubMed, Web of Science, Cochrane Library, and CINAHL were searched for randomized controlled trials (RCT) and cohort studies examining the impact of NPWT on wound healing in orthopedic trauma infections. The retrieval time was from the establishment of the databases to October 2024. RevMan 5.4 software was used for Meta-analysis. The patients were divided into two groups according to different treatment methods: the intervention group, treated with NPWT, and the control group, treated with conventional treatment. The observed indicators included clinical efficacy, wound healing quality, length of hospital stay, wound healing time, incidence of complications, secondary surgery rate, and duration of antibiotic use. Publication bias analysis was performed on the observed indicators through Begg and Egger tests.Results:A total of 13 studies were included, comprising 11 RCT and 2 cohort studies, involving a total of 3 538 patients, with 1 762 in the intervention group and 1 776 in the control group. The meta-analysis results indicated that the intervention group had better clinical efficacy ( OR=7.08, 95% CI 5.31, 9.45, P<0.01), higher wound healing quality ( MD=4.15, 95% CI 3.99, 4.32, P<0.01), shorter length of hospital stay ( MD=-13.38, 95% CI -14.39, -12.38, P<0.01), shorter wound healing time ( MD=-8.11, 95% CI -10.22, -6.00, P<0.01), lower incidence of complications, lower secondary surgery rate ( OR=0.22, 95% CI 0.09, 0.57, P<0.01), and shorter duration of antibiotic use ( MD=-7.61, 95% CI -8.06, -7.16, P<0.01) when compared with the control group. No significant publication bias was observed in the aforementioned indicators ( P>0.05). Conclusion:Compared with the conventional treatment, NPWT can enhance the clinical efficacy and wound healing quality of infected wounds in orthopedic trauma patients, shorten length of hospital stay and wound healing time, reduce the incidence of complications and secondary surgery rates, and shorten the duration of antibiotic use.

Objective:To investigate the clinicopathological features, immunophenotype, molecular characteristics, and differential diagnosis of MED15-TFE3 gene fusion renal cell carcinoma (MED15-TFE3 RCC).Methods:A total of 12 MED15-TFE3 RCCs, diagnosed from 2016 to 2023, were collected from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China for clinicopathologic, immunohistochemical, fluorescence in situ hybridization (FISH) and RNA sequencing (RNA-seq) analyses and follow-up. In addition, its diagnosis and differential diagnosis were also explored.Results:There were five males and seven females. The patients′ ages ranged from 16 to 60 years, with an average age of 40.4 years. The follow-up time ranged from 15 to 92 months, and no recurrence or metastasis was observed. Histologically, 6 cases exhibited extensive cystic structures with almost no solid sheet components, while the remaining 6 cases displayed a cysto-solid growth pattern. The cytoplasm of the tumor cells appeared flocculent, with a clear or faintly eosinophilic appearance, and nucleoli were inconspicuous. Psammoma bodies were observed in 12 cases. There was deposition of basement membrane-like material in 5 cases. All cases showed strong expression of TFE3, GPNMB, Cathepsin K, Melan A, and PAX8, while no expression of CAⅨ or CK7. FISH analyses showed that all 12 cases were positive for the MED15-TFE3 fusion, while the MED15-TFE3 fusion gene and specific fusion sites were detected in 2 cases using RNA-seq.Conclusions:MED15-TFE3 RCC is a type of TFE3-rearranged renal cell carcinoma that exhibits both identifiable diagnostic characteristics and highly deceptive morphology. Its distinct extensive cystic structure can be easily confused with multilocular cystic renal neoplasm of low malignant potential, necessitating careful differentiation in routine practice.

Objective To investigate the risk factors of postoperative complications in patients with spinal tuberculosis and analyze the value of prognostic nutritional index(PNI)in predicting these complications.Methods The clinical data of 156 patients with spinal tuberculosis who underwent surgery in the Affiliated Hospital of Zunyi Medical University from January 2018 to July 2022 were retrospectively analyzed.The patients were divided into a complication group and a non-complication group based on the presence or absence of postoperative complications.Baseline data,laboratory indicators,and surgery-related indicators were compared between the two groups.The risk factors for postoperative complications in spinal tuberculosis were analyzed,and receiver operating characteristic(ROC)curves were plotted to evaluate the predictive value of PNI for postoperative complications in the patients.Results Among all of 156 patients,68 contracted a total of 82 instances of postoperative complications,with an incidence of 43.59%.Coinfection with pulmonary tuberculosis,preoperative anti-tuberculosis treatment duration more than 4 weeks,surgical operation duration,and drainage days were identified as independent risk factors for postoperative complications in spinal tuberculosis(P<0.05).On the other hand,a higher PNI was found to be a protective factor against postoperative complications of the spinal tuberculosis(P<0.05).The area under the ROC curve for PNI predicting postoperative complications ofthe spinal tuberculosis was 0.805.Conclusion The risk of postoperative complications in patients with spinal tuberculosis is subject to such factors ascoexistence of pulmo-nary tuberculosis,preoperative anti-tuberculosis treatment duration,surgery duration,drainage duration,and preoperative PNI.Preoperative PNI has a certain value for predicting the postoperative complications in the patients.