Objective: To explore new therapeutic strategies for periodontitis, this study prepared extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) loaded with saikosaponin D (SSD) and evaluated their efficacy in a mouse model of periodontitis. Methods: This study was approved by the Medical Ethics Committee and the Laboratory Animal Ethics Committee of the unit. hUC-MSCs at logarithmic growth phase were seeded into 96 well plates and then treated with various concentrations of SSD for 24 hours. The CCK-8 assay was used to determine the SSD concentration that preserves hUC-MSC viability. Flow cytometry (FCM) assessed SSD-induced apoptosis in hUC-MSCs and determined drug loading and loading efficiency. Nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) characterized the morphology and size of hUC-MSCs-EVs and hUC-MSCs-SSD-EVs. C57BL/6J mice were divided into five groups with six mice per group: control group, periodontitis model group (PD), PD+SSD group (2 mg/kg), PD+hUC-MSCs-EVs group (10 μg/μL) and PD+hUC-MSCs-SSD-EVs group (10 μg/μL). Administration was performed 3 times a week for 4 consecutive weeks. Micro-CT and hematoxylin-eosin (HE) staining evaluated alveolar bone resorption in periodontal tissues of a mouse model of periodontitis. RT-qPCR measured inflammatory cytokine expression in periodontal tissues of a mouse model of periodontitis. Immunofluorescence analyzed macrophage M1/M2 polarization and runt-related transcription factor 2 (RUNX2) protein expression in periodontal tissues of a mouse model of periodontitis. Results: The CCK-8 assay showed that 10 μmol/L SSD had little effect on hUC-MSCs viability (P>0.05). FCM confirmed the successful loading of SSD into EVs with a loading efficiency of 11.40%. TEM and NTA revealed that hUC-MSCs-SSD-EVs presented round or oval membranous structures with diameters ranging from 200 to 300 nm. Micro CT and HE staining showed that, compared with the PD group, the distance from cementoenamel junction to alveolar bone crest (CEJ-ABC) was markedly shortened (P<0.01）.The alveolar bone of periodontitis‑model bone volume fraction (BV/TV) and trabecular number (Tb.N) were significantly elevated in the PD+hUC-MSCs-SSD-EVs group (P<0.01). RT-qPCR and IF results showed that hUC-MSCs-SSD-EVs in periodontal tissues markedly downregulated the expression of pro-inflammatory cytokines including interleukin-1β, interleukin-6, tumor necrosis factor-α, interleukin-12 and interleukin-22 (P<0.01), upregulated the expression of the anti-inflammatory factor interleukin-10 (P<0.01), promoted the polarization of macrophages from the M1 phenotype to the M2 phenotype, and elevated the protein expression level of RUNX2 (P<0.01). Conclusion hUC-MSC-SSD-EVs effectively alleviated inflammatory responses in a mouse model of maxillary periodontitis and reduced alveolar bone loss, providing a new idea for the treatment of periodontitis.

BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

OBJECTIVE To detect the effects of miR-107 on the proliferation, apoptosis and inflammatory factors of human nasal mucosal epithelial cells(HNMECs) induced by Lipopolysaccharides(LPS), and to elucidate the potential molecular mechanism. METHODS The expression changes of miR-107 and HMGBl(High mobility group box 1) in 1 mg/L LPS induced HNMECs before and after LPS induction were detected by using quantitative realtime PCR. LPS induced-HNMECs were transfected with miR-107 agomir and agomir control, and 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide(MTT) assay, flow cytometry and enzyme-linked immunosorbent assay(ELISA) were performed to detect cell proliferation, apoptosis and inflammatory factors. Dual luciferase reporter assay and Western blots were applied to verify whether HMGB1 was a target gene of miR-107. RESULTS The expression of miR-107 in HNMECs after LPS induction was significantly lower than that before induction(t =9.35, P ＜0.05), while the expression of HMGB1 in HNMECs after LPS induction was significantly higher than that before induction(t =13.07, P＜0.05). Compared with transfected agomir control, transfection of miR-107 agomir in HNMECs significantly inhibited cell proliferation (F =17.12, P ＜0.05) and decreased inflammatory factor TNF-α(t =6.11, P ＜0.05). IL-1β(t =6.90, P ＜0.05) and IL-6(t =8.18, P ＜0.05) expression levels, and increased apoptosis rate(t =7.49, P ＜0.05). HMGB1 was a target gene of miR-107, and transfection of miR-107 agomir in HNMECs after LPS induction could significantly reduce the expression of HMGB1 protein (t =28.56, P ＜0.05). CONCLUSION miR-107 is upregulated in HNMECs after LPS induction, while HMGB1 is down-regulated. Overexpression of miR-107 significantly inhibits the proliferation of HNMECs and the expression of inflammatory factors after LPS induction, and promotes apoptosis. HMGB1 is a target gene of miR-107, suggesting that miR-107 may play a regulatory role by regulating HMGB1.

Purpose To perform MRI examination after the death of SD rat model due to cerebral infarction and to investigate the changing characteristics of cerebral infarction during postmortem examination. Materials and Methods Middle cerebral artery occlusion (MCAO) model was established on 21 SD rats by applying modified suture method. 13 to 56 h after modeling, 12 dead SD rats were collected for the experiment. The bodies were stored at an environment with a temperature of 10-15°C and relative humidity of 45%-55%. Head MRI was performed 12 h after modeling and at 8, 24, 48, 72 and 96 h after death respectively, and apparent diffusion coefficient (ADC) values of infarction and contralateral brain tissue were calculated. At each post-mortem time point, ADC values of bilateral cerebral hemispheres, ADC values of infarction and living infarction, and ADC values of non-infarcted brain and living non-infarcted zone were compared. Brain tissue was taken after scan for pathological diagnosis and compared with diagnostic results of postmortem MRI (pmMRI). Results The right cerebral signal of rats was abnormal 12 h after cerebral infarction and after death. Eight rats were found to have shifted cerebral middle-line structure to the left. ADC values of infarction at each time point after death were lower than that of non-infarction, the difference of which was statistically significant (P<0.05); ADC values of infarction were lower than that of living infarction, the difference of which was statistically significant (P<0.05); ADC value of non-infarcted area at each time point was lower than that of living non-infarcted area, the difference of which was statistically significant (P<0.05). Necrosis and disintegration of neurons, disintegration and liquefaction of glial fibers, infiltration of inflammatory cells and leakage of red blood cells were spotted in necrotic areas after receiving cerebral HE staining in rat. HE staining was consistent with the infarction zone indicated by pmMRI. Conclusion pmMRI can be used for the diagnosis of cerebral infarction via virtual necropsy.

OBJECTIVE To study the antiinflammatory function of human beta defensin 2(hβD-2) on acute rhinosinusitis in rats,in order to provide a new therapy for acute rhinosinusitis.METHODS Acute rhinosinusitis model were established on SD rats before and after the transfection of plasmid,the rats in experimental group were dropped with recombinant hβD-2 plasmid mixture in nose,while with empty plasmid mixture in control group.Immunohistochemistry method was used to prove the transfection results,nasal mucosa were hematoxylineosin stained to compare the pathological difference of nasal mucosa,nasal lavage fliud was collected and cultured to compare the colony number of the bacteria.RESULTS The expression of hβD-2 was confirmed by immunohistochemistry method,which mainly distributed in mucosal epithelium and gland,pathological results showed that the inflammation of nasal mucosa in experimental group was significantly relieved than that in control group.The number of Staphylococcus auresus colony number was significantly decreased in experimental group,while there was no significantly change in the control group.CONCLUSION Recombinant hβD-2 plasmid can be successfully transfected into the nasal mucosa of rats and expressed effectively.The anti-inflammatory ability of nasal mucosa was increased after the transfection,which is expected to provide a new treatment approach for acute rhinosinusitis.

The patient presented with dry cough, lending, fever and progressive dyspnea for two weeks. The patient had a prior respiratory infection history and the symptoms were not obvious, Early X-ray showed lung infection. Under the fibrolaryngoscope, the lingual surfaces of the epiglottis, epiglottic vallecula, and bilateral vocal cords were covered by yellow pseudomembrane. The motion of vocal cords was normal with poor glottic closure, and no ulcer was noted. Endotracheal mucosa was swelling and congested with an uneven surface, and purulent discharge and pseudomembrane was formed. Pathological examination revealed Aspergillus. The disease was diagnosed as Aspergillus laryngotracheobronchitis.
Adult ; Aspergillosis ; diagnosis ; physiopathology ; Aspergillus ; Bronchitis ; diagnosis ; microbiology ; physiopathology ; Humans ; Male

objective:To study the etiopathogenisis、clinical features、diagnosis and treatments of monostotic fibrous dysplasia of the sphenoid sinus. Method:Two cases of monostotic fibrous dysplasia of the sphenoid sinus without any symptoms was reported with relevant literature review.Result: No aggravation was found after 6 months-follow-up.Conclusion:The cranial fibrous displasia has low incidence rate with non-specific symptoms and high rate of misdiagnosis. The monostotic fibrous dysplasia of the sphenoid sinus without any symptom is rarely seen clinically. Imageological examination,for example,CT and MRI,is valuable for the diagnosis of this disease. The histopathological evidence is absolutely necessary to make definite diagnosis. The conservative treatment may be chosen for the asymptomatic cases. Nasal Endoscopic surgery can not only remove the diseased region but also make diagnosis.The long-term follow-up should be carried out in all of these patients.

OBJECTIVE: To study the etiopathogenesis, clinical features, diagnosis and treatments of monostotic fibrous dysplasia of the sphenoid sinus. METHOD: Two cases of monostotic fibrous dysplasia of the sphenoid sinus without any symptoms was reported with relevant literature review. RESULT: No aggravation was found after 6 months-follow-up. CONCLUSION The cranial fibrous dysplasia has low incidence rate with non-specific symptoms and high rate of misdiagnosis. The monostotic fibrous dysplasia of the sphenoid sinus without any symptom is rarely seen clinically. Imagiological examination, for example, CT and MRI, is valuable for the diagnosis of this disease. The histopathological evidence is absolutely necessary to make definite diagnosis. The conservative treatment may be chosen for the asymptomatic cases. Nasal Endoscopic surgery can not only remove the diseased region but also make diagnosis. The long-term follow-up should be carried out in all of these patients.
Adult ; Female ; Fibrous Dysplasia, Monostotic ; Humans ; Male ; Sphenoid Sinus ; pathology