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 application of outcome indicators and measurement tools in randomized controlled trials(RCTs)of TCM treatment for coronary heart disease(CHD)complicated with anxiety and depression in recent years;To facilitate the construction of core outcome set in this field.Methods The RCTs of TCM treatment for CHD complicated with anxiety and depression were retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed,Web of Science,Embase,Cochrane Library,and the included RCTs were evaluated for bias risk,data extracted and analyzed.Results A total of 163 articles were included,with 157 outcome indicators categorized into 6 indicator domains according to their functional attributes.The application rates in descending order were symptoms and signs(98.16%),physiological and chemical tests(58.90%),TCM syndromes(48.47%),safety events(44.17%),quality of life(39.88%),and long-term prognosis(9.20%).By analyzing the frequency and distribution of outcome indicators,indicator combinations,measurement time points and tools found that the experimental design and the registration of study protocols were ignored,and the diagnosis and evaluation criteria of anxiety and depression and TCM diagnosis/syndrome differentiation were not standardized.The selection of outcome indicators was characterized by lack of comorbidity between CHD and anxiety and depression,no separation of primary and secondary,excessive number of indicators,irregular composite indicators,inconsistent application of TCM-specific indicators,lack of long-term prognosis,safety indicators and health economics evaluation.Conclusion There are some limitations in the RCT design and outcome indicators in the TCM treatment of CHD complicated with anxiety and depression.It is imperative to establish a core outcome set and standardize trial designs to enhance research quality.

Objective To analyze the application of outcome indicators and measurement tools in randomized controlled trials(RCTs)of TCM treatment for coronary heart disease(CHD)complicated with anxiety and depression in recent years;To facilitate the construction of core outcome set in this field.Methods The RCTs of TCM treatment for CHD complicated with anxiety and depression were retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed,Web of Science,Embase,Cochrane Library,and the included RCTs were evaluated for bias risk,data extracted and analyzed.Results A total of 163 articles were included,with 157 outcome indicators categorized into 6 indicator domains according to their functional attributes.The application rates in descending order were symptoms and signs(98.16%),physiological and chemical tests(58.90%),TCM syndromes(48.47%),safety events(44.17%),quality of life(39.88%),and long-term prognosis(9.20%).By analyzing the frequency and distribution of outcome indicators,indicator combinations,measurement time points and tools found that the experimental design and the registration of study protocols were ignored,and the diagnosis and evaluation criteria of anxiety and depression and TCM diagnosis/syndrome differentiation were not standardized.The selection of outcome indicators was characterized by lack of comorbidity between CHD and anxiety and depression,no separation of primary and secondary,excessive number of indicators,irregular composite indicators,inconsistent application of TCM-specific indicators,lack of long-term prognosis,safety indicators and health economics evaluation.Conclusion There are some limitations in the RCT design and outcome indicators in the TCM treatment of CHD complicated with anxiety and depression.It is imperative to establish a core outcome set and standardize trial designs to enhance research quality.

Mitochondrial myopathy is a group of multi-system diseases in which mitochondrial DNA(mtDNA)or nuclear DNA(nDNA)defects lead to structural and functional dysfunction of mitochondria.The clinical manifestations of mitochondrial myopathy are complex and varied,and the testing for mtDNA and nDNA is not widely available,so misdiagnosis or missed diagnosis is common.Chronic progressive external ophthalmoplegia(CPEO)is a common type of mitochondrial myopathy,which is characterized by blepharoptosis.Here we report a 38-year-old female with mitochondrial myopathy presented with chronic numbness and weakness of the limbs,accompanied by blepharoptosis that was recently noticed.Laboratory and head magnetic resonance imaging(MRI)examinations showed no obvious abnormalities.Muscle and nerve biopsies showed characteristic ragged red fibers(RRFs)and large aggregates of denatured mitochondria.Testing for mtDNA and nDNA showed a known mutation c.2857C＞T(p.R953C)and a novel variant c.2391G＞C(p.M797I)in the polymerase gamma(POLG)gene,so the patient was diagnosed as mitochondrial myopathy.Clinicians should pay more attention to long-term unexplained skeletal muscle diseases with recent onset blepharoptosis.Histopathologic examination and genetic testing are of great value in the early diagnosis and therapeutic intervention.