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

Objective:To analyze the immune microenvironment characteristics of human dental follicle tissues from the third molars and to explore the mutual communication and the effects of innate immune cells and adaptive immune cells within the dental follicle.Methods:Sequencing data(GSA-Human:HRA008022)in the GSA database were analyzed.Bioinformatics tools were employed for gene identification and GO enrichment analysis was performed to define the biological function of innate and adaptive immune cells.CellChat analysis was used for explaining intercellular communication among immune cell populations.Results:Using t-SNE dimen-sionality reduction analysis for immune cell populations,innate immune cell populations were obtained,including innate lymphoid cells,dendritic cells,mast cells and macrophages,and adaptive immune cell populations including T cells and B cells.Pearson corre-lation analysis showed that innate immune cells,specifically innate lymphoid cells and macrophages,had a strong correlation with adap-tive immune cell populations.GO enrichment analysis revealed mutual coordination among innate immune cell populations and regulato-ry effects on adaptive immune cell populations.Further CellChat analysis indicated biological signal transmission between innate and a-daptive immune cell populations,with CLEC,MIF,ADGRE5,COLLAGEN and MIF signaling pathways is the most significant.Con-clusion:Dental follicle tissues are rich in immune cells and innate immune cell populations interact with adaptive immune cells to regulate immune responses and participate in maintaining the homeostasis of dental follicle.

Objective To explore the clinical values of voxel-based morphometry(VBM)analysis in magnetic resonance imaging(MRI)for detecting secondary damage to the distant thalamus and substantia nigra in patients with cerebral infarction.Methods A total of nineteen patients with first-time unilateral middle cerebral artery(MCA)ischemic stroke were prospectively recruited.Three-dimensional whole-brain MRI scans were performed at 1 week,1 month,and 3 months after onset.VBM analysis was used to analyze changes in the thalamus and substantia nigra volumes.Results VBM analysis revealed that compared to ipsilateral thalamic volume at 1 week after onset,ipsilateral thalamic volume was significantly reduced at 1 month or 3 months after onset(reduced by 637 mm3 and 1488 mm3,respectively;P<0.01),with the atrophy primarily located in the dorsomedial nucleus of the thalamus.Similarly,compared to ipsilateral substantia nigra volume at 1 week after onset,the ipsilateral substantia nigra volume was significantly reduced at 1 month or 3 months after onset(reduced by 64 mm3 and 76 mm3,respectively;P<0.05).Conclusions VBM technology can be used to evaluate the ipsilateral thalamic and substantia nigra volume reduction in patients with cerebral infarction in the MCA supply area at 1-3 months after stroke,and to detect secondary damage.

Objective:To investigate the predictive values of baseline hematoma mean CT value and shape regularity (SR) for hematoma enlargement (HE) in patients with spontaneous intracerebral hemorrhage (ICH).Methods:Patients with ICH admitted to Yulin First Hospital from June 2018 to December 2021 were retrospectively included. The first head CT scan was performed within 24 h of onset, and the second head CT scan was performed within 72 h of the first scan. HE was defined as an increase in hematoma volume of at least 6 ml or 33% from the first CT. 3D Slicer software was used to reconstruct 3D images and SR was calculated. Multivariate logistic regression analysis was used to determine the independent factor for HE. Receiver operator characteristic (ROC) curve was used to evaluate the predictive value of baseline hematoma mean CT value for HE. Results:A total of 249 patients with ICH were enrolled, including 134 males (53.8%), and aged 62.2±12.1 years. The median baseline Glasgow Coma Scale score was 12, and the median time from onset to first CT scan was 3.1 h. The median baseline hematoma volume was 10.9 ml, and 58 patients (23.3%) showed HE. The baseline hematoma mean CT value in the HE group (58.5±3.2 HU vs. 60.3±3.3 HU; P<0.01) and baseline SR (0.615±0.146 vs. 0.688±0.100; P<0.001) were significantly lower in the non-HE group. Multivariate logistic regression analysis showed that the time from onset to first CT scan (odds ratio [ OR] 0.867, 95% confidence interval [ CI] 0.786-0.957; P=0.004), the baseline hematoma volume ( OR 1.050, 95% CI 1.028-1.073; P<0.001), and the baseline hematoma mean CT value ( OR 0.809, 95% CI 0.725-0.902; P<0.001) were the independent predictors of HE, while the baseline SR had no significant independent correlation with HE. ROC curve analysis showed that the area under the curve of baseline hematoma mean CT value for predicting HE was 0.652 (95% CI 0.573-0.731; P<0.001), with an optimal cutoff value of 57.97 HU. The sensitivity and specificity for predicting HE were 50% and 75.9%, respectively. Conclusion:The baseline hematoma mean CT value is an independent factor for HE in patients with ICH and has certain predictive value for HE.

Sympathetic cues via the adrenergic signaling critically regulate bone homeostasis and contribute to neurostress-induced bone loss, but the mechanisms and therapeutics remain incompletely elucidated. Here, we reveal an osteoclastogenesis-centered functionally important osteopenic pathogenesis under sympatho-adrenergic activation with characterized microRNA response and efficient therapeutics. We discovered that osteoclastic miR-21 was tightly regulated by sympatho-adrenergic cues downstream the β2-adrenergic receptor (β₂AR) signaling, critically modulated osteoclastogenesis in vivo by inhibiting programmed cell death 4 (Pdcd4), and mediated detrimental effects of both isoproterenol (ISO) and chronic variable stress (CVS) on bone. Intriguingly, without affecting osteoblastic bone formation, bone protection against ISO and CVS was sufficiently achieved by a (D-Asp₈)-lipid nanoparticle-mediated targeted inhibition of osteoclastic miR-21 or by clinically relevant drugs to suppress osteoclastogenesis. Collectively, these results unravel a previously underdetermined molecular and functional paradigm that osteoclastogenesis crucially contributes to sympatho-adrenergic regulation of bone and establish multiple targeted therapeutic strategies to counteract osteopenias under stresses.
Adrenergic Agents/pharmacology* ; Apoptosis Regulatory Proteins/pharmacology* ; Bone Diseases, Metabolic/metabolism* ; Humans ; Liposomes ; MicroRNAs/genetics* ; Nanoparticles ; Osteoclasts ; Osteogenesis/physiology* ; RNA-Binding Proteins/pharmacology*

Objective:To investigate the predominant serotypes and diversification of Echovirus (ECHOV) from viral encephalitis children in Quzhou area of Zhejiang province and the molecular characteristics of the ECHOV VP1 genes.Methods:Cerebrospinal fluid samples from 53 children with viral encephalitis were collected for viral isolation/culture. Fluorescent RT-PCR or PCR was used to detect human enteroviruses (HEV) including ECHOV, coxsackievirus(CoV) and new enterovirus (EV), and japanese encephalitis virus(JEV), mumps virus(MuV), west Nile virus(WNV) and chikungunya virus(CHLKV) or herpes simplex virus(HSV) and cytomegalovirus(CMV) in the cerebrospinal fluid samples. The complete VP1 gene sequence of HEV-B group in the HEV-positive cerebrospinal fluid samples was amplified by RT-PCR and sequenced, and then the typing of Echovirus isolates was performed. The VP1 genotypes of Echovirus isolates, gene recombination, inheritance and evolution characteristics were analyzed using multiple bioinformatic software.Results:Six viral strains were isolated by cell culture using rhabdomyosarcoma (RD) cells but not human epithelial-2 (Hep-2) cells. Eleven cerebrospinal fluid samples were positive for HEV by RT-PCR but the detection result of all the other viruses were negative. In the 11 HEV-positive samples, 6 samples were positive for ECHOV (4 for ECHO6, 1 for ECHO7 and 1 for ECHO30 serotype), which was coincident with the isolation result , but CoV and EV were undetectable. The 4 ECHO6 isolates belonged to ECHO6-C2 subgenotype but can be divided into two epidemic clones (ECHO6-41/46 and ECHO6-45/48). The ECHO7 and ECHO30 isolates belonged to ECHO7-C and ECHO30-C genotypes. The VP1 gene recombination between the ECHO6 and ECHO30 isolates were found during their evolutionary process.Conclusions:ECHOV is the major pathogen of viral encephalitis children in the area, and there is a possibility of local outbreak or epidemic. Because of the possibility of recombination of the VP1 gene of ECHO6 and ECHO30 virus, ECHO6 may become the dominant ECHOV serotype.

The incidence of stroke increases year by year.It seriously affects the quality of life in patients.The pathogenesis of stroke is related to a variety of factors,involving genetic polymorphisms,biochemical mechanisms,and inflammatory effect.Among them,vascular endothelial growth factor (VEGF) has become one of the hotspots of research on the pathogenesis of stroke in recent years.This article reviews the correlation between VEGF gene polymorphism and stroke.

Objective To explore the risk factors for postoperative hypoxemia in patients undergoing Stanford type A aortic dissection surgery.Methods The clinical data of 77 patients with Stanford type A aortic dissection surgery were analyzed retrospectively.Among the patients, 40 patients occurred hypoxemia(hypoxemia group),and 37 patients did not occur hypoxemia(non-hypoxemia group).The preoperative,intraoperative and postoperative clinical data were compared between 2 groups,and the independent risk factors for postoperative hypoxemia were analyzed by multiple Logistic regression analysis.Results The incidence of postoperative hypoxemia in patients with Stanford type A aortic dissection was 51.9% (40/77).The multiple Logistic regression analysis result showed that age (OR =1.088,95% CI 1.018-1.164,P=0.013),body mass index≥25 kg/m2(OR=6.495,95% CI 1.327-31.789,P=0.021),pericardial effusion(OR=6.384,95% CI 1.426-28.576,P=0.015),white blood cell count(OR=1.289,95% CI 1.033-1.609,P=0.024)and using recombinant human coagulationⅦa (OR = 23.757, 95% CI 2.849 - 198.085, P = 0.003) were the independent predictive factors for postoperative hypoxemia in patients with Stanford type A aortic dissection.Conclusions The postoperative hypoxemia in patients with Stanford type A aortic dissection is related with perioperative systemic inflammation, especially in obese patients who should be given anti-inflammatory treatment during perioperative period.Control of bleeding and reducing the recombinant human coagulationⅦa as far as possible can reduce the incidence of postoperative hypoxemia.

After ischemic stroke, secondary damages such as neuron loss, gliosis, and axonal degeneration occur in the nonischemic remote brain regions that have synaptic connections with the primary infarction site.These secondary damages in the remote brain regions may affect the recovery of neurological function.Several advanced neuroimaging techniques have been used to detect these secondary damages.This article reviews the research progress in this field.

Objective:To study the clinical effect of early postoperative enteral nutrition and parenteral nutrition after radical ex-cision of gastric cancer to provide a better way of treating gastric cancers. Methods:Retrospective analysis of 140 gastric cancer pa-tients who were admitted to the PLA General Hospital between February 2009 and February 2011 was conducted. These patients were randomized into two groups based on the clinical trial, i.e., 70 in the control group received an intravenous parenteral nutrition for the treatment, and for the other 70 in the observation group, jejunostomy was done 1 to 5 days after the radical surgery by using Supportan as the enteral nutritional agent with a dose of at TPF-T 500 mL/d to 1 000 mL/d. The postoperative long-term survival rate of the pa-tients, the serum albumin, hemoglobin, alanine aminotransferase, aspartate aminotransferase levels before and after the treatment, as well as the situation of IgA, IgG, IgM and CD4+cells, NK cells, and B lymphocytes in the blood at the first and the seventh day after surgery were observed in the patients. Results:After the implementation of early enteral nutrition in the observation group, the 1-and 3-year survival rates were 84.29% (59/70) and 61.43% (43/70) respectively, whereas in the control group, the survival rates were 64.29% (45/70) and 47.143% (33/70) respectively, with statistically significant differences between the two groups (P<0.05). At the first and seventh day after surgery, the serum albumin, hemoglobin, alanine aminotransferase, and aspartate aminotransferase levels were significantly better in the observation group than in the control group, with statistically significant differences between the two (P<0.05). Compared with the parameters in the observation group at the first day after surgery and those in the control groups at the eighth day after surgery, the levels of IgA , IgG, IgM and CD42+cells, NK cells, and B lymphocytes were significantly increased in the obser-vation group at the seventh day after surgery. The differences among them were statistically significant (P<0.05). Conclusion: Early postoperative enteral nutrition for the gastric cancer patients undergoing radical surgery can be effective in improving the nutrition level of the patients and in enhancing their long-term survival rate, Thus, the treatment has value in clinical application.