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 compare the biomechanical stability of a novel interlocking intramedullary nail (nIMN) with that of a traditional interlocking intramedullary nail (tIMN) in the treatment of type AO 32-A3 femoral shaft fractures using a finite element analysis.Methods:A healthy adult male volunteer, aged 30 years old and weighing 70 kg, was selected for collection of his CT scan data of the femur. A three-dimensional finite element model of the femur was established using software Mimics 17.0 and Geomagic Studio. After femoral shaft fractures of AO/OTA types 32-A3a, 32-A3b, and 32-A3c were simulated, nIMN and tIMN were assembled respectively. After boundary conditions and material properties of the models were set based on reference literature, 4 load states were simulated: vertical standing, slow walking, fast walking, and descending stairs. The displacements and stress distribution at the femoral fracture ends under the same conditions were compared between nIMN and tIMN schemes of fixation. The stabilities of each fracture model at different fixation schemes and load states were analyzed.Results:In the 4 load states simulated, the displacements of the fracture ends averaged 0.129 mm, and the maximum stresses 111.00 MPa. The smallest displacement and maximum stress (0.014 mm and 29.48 MPa) were found in the vertical standing in the femoral shaft fracture of type 32-A3c fixed with nIMN. The largest displacement and maximum stress (0.325 mm and 242.98 MPa) were found in descending stairs in the femoral shaft fracture of type 32-A3a fixed with tIMN. In femoral shaft fractures of types 32-A3a, 32-A3b, and 32-A3c, regardless of tIMN or nIMN fixation, the displacement and maximum stress increased with the load, with the femoral shaft fracture of type 32-A3a being particularly evident. nIMN fixation resulted in lower displacements and maximum stresses in AO/OTA types 32-A3a, 32-A3b, and 32-A3c than tIMN fixation. Taking descending stairs as an example, the overall maximum stress occurred on the proximal part of the femur and the surrounding area of Adams'arc, with the maximum stress fluctuating between 86.62 and 242.98 MPa. The maximum stress at the fracture end fluctuated between 0.44 and 56.49 MPa. The stress mainly concentrated on the medial part, and decreased from type 32-A3a to type 32-A3b to type 32-A3c.Conclusion:In type AO 32-A3 femoral shaft fractures, nIMN leads to a smaller fracture end displacement and a lower maximum stress than tIMN, indicating better rotational stability.

Objective:To investigate the impact of sliding distance of the fmoral neck system (FNS) on the curative efficacy of displaced femoral neck fractures.Methods:A retrospective study was conducted to analyze the clinical data of the 179 patients with displaced femoral neck fracture who had been treated by FNS fixation at Department of Orthopaedics, The Second General Hospital of Fuzhou between September 2019 and September 2023. Based on the FNS sliding distance measured on X-ray films on the day after surgery or one day after surgery, the patients were assigned into 2 groups: a short sliding distance group [sliding distance ≤5 mm, n=55; 35 males, 20 females; median age: 50.0 (34.0, 59.0) years; body mass index (BMI): (24.0±2.4) kg/m 2] and a long sliding distance group [5 mm 0.05). At postoperative 3, 6, and 12 months, the distances of femoral neck shortening in the short sliding distance group [2.5 (0.7, 3.5) mm, 2.6 (0.7, 3.5) mm, and 2.7 (0.7, 3.5) mm] were significantly shorter than those in the long sliding distance group [3.2 (1.3, 5.7) mm, 3.2 (1.3, 7.1) mm, and 3.2 (1.4, 7.1) mm] ( P<0.05). The incidence of moderate-to-severe shortening at one year after surgery in the long sliding distance group [26.6% (33/124)] was significantly higher than that in the short sliding distance group [3.6%(2/55)] ( P<0.05). No significant differences were found between the 2 groups in tip-apex distance, operation time, intraoperative blood loss, fracture reduction quality, fracture healing time, or incidence of complications ( P>0.05). At the last follow-up, the Harris Hip Score in the short sliding distance group [93.5 (88.7, 96.2) points] was significantly higher than that in the long sliding distance group [90.1 (82.9, 94.9) points] ( P<0.05). Conclusion:In the treatment of displaced femoral neck fractures with FSN fixation, compared with those with a long sliding distance, the patients with a short sliding distance demonstrate superior outcomes in postoperative femoral neck shortening and functional recovery of the hip, but no significant difference in the incidence of complications.

Objective:To explore the causal relationships between human inflammatory proteins and keloids.Methods:This study was based on Mendelian randomization (MR) analysis. Human inflammatory proteins were considered as the exposure factors, and keloid was considered as the outcome. Data on 91 inflammatory proteins (14 824 samples) and keloids (668 samples) were obtained from the genome-wide association study database. A significance threshold was established to discern single nucleotide polymorphisms (SNPs) significantly associated with inflammatory proteins as instrumental variables with the influence of weak instrumental variables being excluded. For the analysis of a single instrumental variable, the Wald ratio method was used; for the analysis of multiple instrumental variables, the inverse variance weighted (IVW) method was used as the primary method, with the weighted median method, simple mode method, weighted mode method, and MR-Egger method as supplementary methods to employ two-sample MR analysis to analyze the causal relationships between inflammatory proteins and keloids. Using the IVW method, weighted median method, and MR-Egger method to employ multi-sample MR (MVMR) analysis to evaluate the statistically significant inflammatory proteins in the above-mentioned two-sample MR analysis, thus validating their independent causal relationships with keloids. For SNPs of inflammatory proteins conformed to the hypothesis, the Cochran Q test was used to assess heterogeneity, the MR-Egger regression test and MR-PRESSO outlier test were used to evaluate horizontal pleiotropy, and the leave-one-out analysis was performed to assess reliability.Results:Seventy-five inflammatory proteins met the exposure factor criteria, with the number of SNPs reaching a significance threshold ranging from 1 to 7 082 (with F values all >10), indicating minimal potential for weak instrumental variable bias in this study. The IVW method analysis revealed significant causal relationships between eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), CD5, and osteoprotegerin and keloids (with odds ratios of 0.50, 0.61, and 0.71, respectively, 95% confidence intervals of 0.32-0.77, 0.41-0.89, and 0.52-0.97, respectively, P<0.05); the weighted median method confirmed a significant causal relationship between CD5 and keloids (with odds ratio of 0.61, 95% confidence interval of 0.38-0.97, P<0.05); the simple mode method, weighted mode method, and MR-Egger method confirmed no significant causal relationships between CD5 and osteoprotegerin and keloids ( P>0.05). The Wald ratio method analysis revealed a significant causal relationship between programmed death-ligand 1 (PD-L1) and keloids (with odds ratio of 1.83, 95% confidence interval of 1.06-3.15, P<0.05). Thus IVW method results were considered as the standard. The IVW method analysis confirmed that 4E-BP1, CD5, osteoprotegerin, and PD-L1 maintained significant causal relationships with keloids (with odds ratios of 0.43, 0.58, 0.70, and 1.95, respectively, 95% confidence intervals of 0.28-0.67, 0.39-0.86, 0.51-0.95, and 1.16-3.27, respectively, P<0.05). The MR-Egger method confirmed significant causal relationships between 4E-BP1 and CD5 and keloids (with odds ratios of 0.41 and 0.58, respectively, 95% confidence intervals of 0.22-0.77 and 0.39-0.88, respectively, P<0.05). The weighted median method confirmed significant causal relationships between 4E-BP1 and PD-L1 and keloids (with odds ratios of 0.46 and 2.06, respectively, 95% confidence intervals of 0.26-0.82 and 1.11-3.81, respectively, P<0.05). The Cochran Q test assessment indicated no significant heterogeneity in the SNPs of CD5 and osteoprotegerin that had significant causal relationships with keloids ( P>0.05). The MR-Egger regression test and MR-PRESSO outlier test showed no significant horizontal pleiotropy in the SNPs of CD5 and osteoprotegerin that had significant causal relationships with keloids ( P>0.05). The leave-one-out analysis confirmed that the significant causal relationships between CD5 and osteoprotegerin and keloids remained stable after sequentially removing individual SNP. Conclusions:Two-sample MR analysis and MVMR analysis confirmed significant causal relationships between 4E-BP1, CD5, and osteoprotegerin and keloids, all of which are protective factors for keloids.

Objective:To compare the biomechanical stability of a novel interlocking intramedullary nail (nIMN) with that of a traditional interlocking intramedullary nail (tIMN) in the treatment of type AO 32-A3 femoral shaft fractures using a finite element analysis.Methods:A healthy adult male volunteer, aged 30 years old and weighing 70 kg, was selected for collection of his CT scan data of the femur. A three-dimensional finite element model of the femur was established using software Mimics 17.0 and Geomagic Studio. After femoral shaft fractures of AO/OTA types 32-A3a, 32-A3b, and 32-A3c were simulated, nIMN and tIMN were assembled respectively. After boundary conditions and material properties of the models were set based on reference literature, 4 load states were simulated: vertical standing, slow walking, fast walking, and descending stairs. The displacements and stress distribution at the femoral fracture ends under the same conditions were compared between nIMN and tIMN schemes of fixation. The stabilities of each fracture model at different fixation schemes and load states were analyzed.Results:In the 4 load states simulated, the displacements of the fracture ends averaged 0.129 mm, and the maximum stresses 111.00 MPa. The smallest displacement and maximum stress (0.014 mm and 29.48 MPa) were found in the vertical standing in the femoral shaft fracture of type 32-A3c fixed with nIMN. The largest displacement and maximum stress (0.325 mm and 242.98 MPa) were found in descending stairs in the femoral shaft fracture of type 32-A3a fixed with tIMN. In femoral shaft fractures of types 32-A3a, 32-A3b, and 32-A3c, regardless of tIMN or nIMN fixation, the displacement and maximum stress increased with the load, with the femoral shaft fracture of type 32-A3a being particularly evident. nIMN fixation resulted in lower displacements and maximum stresses in AO/OTA types 32-A3a, 32-A3b, and 32-A3c than tIMN fixation. Taking descending stairs as an example, the overall maximum stress occurred on the proximal part of the femur and the surrounding area of Adams'arc, with the maximum stress fluctuating between 86.62 and 242.98 MPa. The maximum stress at the fracture end fluctuated between 0.44 and 56.49 MPa. The stress mainly concentrated on the medial part, and decreased from type 32-A3a to type 32-A3b to type 32-A3c.Conclusion:In type AO 32-A3 femoral shaft fractures, nIMN leads to a smaller fracture end displacement and a lower maximum stress than tIMN, indicating better rotational stability.

Objective:To investigate the impact of sliding distance of the fmoral neck system (FNS) on the curative efficacy of displaced femoral neck fractures.Methods:A retrospective study was conducted to analyze the clinical data of the 179 patients with displaced femoral neck fracture who had been treated by FNS fixation at Department of Orthopaedics, The Second General Hospital of Fuzhou between September 2019 and September 2023. Based on the FNS sliding distance measured on X-ray films on the day after surgery or one day after surgery, the patients were assigned into 2 groups: a short sliding distance group [sliding distance ≤5 mm, n=55; 35 males, 20 females; median age: 50.0 (34.0, 59.0) years; body mass index (BMI): (24.0±2.4) kg/m 2] and a long sliding distance group [5 mm 0.05). At postoperative 3, 6, and 12 months, the distances of femoral neck shortening in the short sliding distance group [2.5 (0.7, 3.5) mm, 2.6 (0.7, 3.5) mm, and 2.7 (0.7, 3.5) mm] were significantly shorter than those in the long sliding distance group [3.2 (1.3, 5.7) mm, 3.2 (1.3, 7.1) mm, and 3.2 (1.4, 7.1) mm] ( P<0.05). The incidence of moderate-to-severe shortening at one year after surgery in the long sliding distance group [26.6% (33/124)] was significantly higher than that in the short sliding distance group [3.6%(2/55)] ( P<0.05). No significant differences were found between the 2 groups in tip-apex distance, operation time, intraoperative blood loss, fracture reduction quality, fracture healing time, or incidence of complications ( P>0.05). At the last follow-up, the Harris Hip Score in the short sliding distance group [93.5 (88.7, 96.2) points] was significantly higher than that in the long sliding distance group [90.1 (82.9, 94.9) points] ( P<0.05). Conclusion:In the treatment of displaced femoral neck fractures with FSN fixation, compared with those with a long sliding distance, the patients with a short sliding distance demonstrate superior outcomes in postoperative femoral neck shortening and functional recovery of the hip, but no significant difference in the incidence of complications.

Objective:To explore the causal relationships between human inflammatory proteins and keloids.Methods:This study was based on Mendelian randomization (MR) analysis. Human inflammatory proteins were considered as the exposure factors, and keloid was considered as the outcome. Data on 91 inflammatory proteins (14 824 samples) and keloids (668 samples) were obtained from the genome-wide association study database. A significance threshold was established to discern single nucleotide polymorphisms (SNPs) significantly associated with inflammatory proteins as instrumental variables with the influence of weak instrumental variables being excluded. For the analysis of a single instrumental variable, the Wald ratio method was used; for the analysis of multiple instrumental variables, the inverse variance weighted (IVW) method was used as the primary method, with the weighted median method, simple mode method, weighted mode method, and MR-Egger method as supplementary methods to employ two-sample MR analysis to analyze the causal relationships between inflammatory proteins and keloids. Using the IVW method, weighted median method, and MR-Egger method to employ multi-sample MR (MVMR) analysis to evaluate the statistically significant inflammatory proteins in the above-mentioned two-sample MR analysis, thus validating their independent causal relationships with keloids. For SNPs of inflammatory proteins conformed to the hypothesis, the Cochran Q test was used to assess heterogeneity, the MR-Egger regression test and MR-PRESSO outlier test were used to evaluate horizontal pleiotropy, and the leave-one-out analysis was performed to assess reliability.Results:Seventy-five inflammatory proteins met the exposure factor criteria, with the number of SNPs reaching a significance threshold ranging from 1 to 7 082 (with F values all >10), indicating minimal potential for weak instrumental variable bias in this study. The IVW method analysis revealed significant causal relationships between eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), CD5, and osteoprotegerin and keloids (with odds ratios of 0.50, 0.61, and 0.71, respectively, 95% confidence intervals of 0.32-0.77, 0.41-0.89, and 0.52-0.97, respectively, P<0.05); the weighted median method confirmed a significant causal relationship between CD5 and keloids (with odds ratio of 0.61, 95% confidence interval of 0.38-0.97, P<0.05); the simple mode method, weighted mode method, and MR-Egger method confirmed no significant causal relationships between CD5 and osteoprotegerin and keloids ( P>0.05). The Wald ratio method analysis revealed a significant causal relationship between programmed death-ligand 1 (PD-L1) and keloids (with odds ratio of 1.83, 95% confidence interval of 1.06-3.15, P<0.05). Thus IVW method results were considered as the standard. The IVW method analysis confirmed that 4E-BP1, CD5, osteoprotegerin, and PD-L1 maintained significant causal relationships with keloids (with odds ratios of 0.43, 0.58, 0.70, and 1.95, respectively, 95% confidence intervals of 0.28-0.67, 0.39-0.86, 0.51-0.95, and 1.16-3.27, respectively, P<0.05). The MR-Egger method confirmed significant causal relationships between 4E-BP1 and CD5 and keloids (with odds ratios of 0.41 and 0.58, respectively, 95% confidence intervals of 0.22-0.77 and 0.39-0.88, respectively, P<0.05). The weighted median method confirmed significant causal relationships between 4E-BP1 and PD-L1 and keloids (with odds ratios of 0.46 and 2.06, respectively, 95% confidence intervals of 0.26-0.82 and 1.11-3.81, respectively, P<0.05). The Cochran Q test assessment indicated no significant heterogeneity in the SNPs of CD5 and osteoprotegerin that had significant causal relationships with keloids ( P>0.05). The MR-Egger regression test and MR-PRESSO outlier test showed no significant horizontal pleiotropy in the SNPs of CD5 and osteoprotegerin that had significant causal relationships with keloids ( P>0.05). The leave-one-out analysis confirmed that the significant causal relationships between CD5 and osteoprotegerin and keloids remained stable after sequentially removing individual SNP. Conclusions:Two-sample MR analysis and MVMR analysis confirmed significant causal relationships between 4E-BP1, CD5, and osteoprotegerin and keloids, all of which are protective factors for keloids.

Objective:To compare the biomechanical properties of posterolateral distal humeral plate, inverted anterior proximal humerus internal locking system (PHILOS), and anterior reconstruction plate in the treatment of distal humeral shaft fractures by a finite element analysis.Methods:One healthy adult male volunteer, aged 27 years, with a height of 171 cm and a weight of 70 kg, was recruited for this study. The finite element method was used to establish a simulation model of distal humeral shaft fracture. The maximum displacement and maximum stress were compared between fixation with posterolateral distal humeral plate (group A), fixation with inverted anterior PHILOS (group B), and fixation with anterior reconstruction plate (group C).Results:In groups A, B, and C, respectively, the overall stress peak values were 409.07 MPa, 217.04 MPa, and 370.64 MPa; the peak stresses under torsional load were 234.55 MPa, 348.80 MPa and 458.17 MPa; the overall stress peaks under bending load were 250.22 MPa, 466.76 MPa, and 582.32 MPa. The smaller the stress, the smaller the risk of fatigue fracture. In groups A, B, and C, respectively, the overall displacement peak values were 5.18 mm, 3.04 mm and 3.75 mm; the peak displacements under torsional load were 1.20 mm, 1.02 mm and 2.05 mm; the peak displacements under bending load were 3.85 mm, 5.28 mm and 9.04 mm. The smaller the displacement, the better the fixation stability.Conclusions:In the treatment of distal humeral shaft fractures, fixation with inverted anterior PHILOS leads to the best mechanical stability under axial compression and torsional stress, while fixation with the posterolateral distal humeral plate leads to the best mechanical stability under bending stress.

At present, implant surgery robots have basically achieved "surgical intelligence", but "brain-inspired intelligence" of robots is still in the stage of theory and exploration. The formulation of a clinical implantation plan depends on the timing of implantation, implantation area, bone condition, surgical procedure, patient factors, etc., which need to evaluate the corresponding clinical decision indicators and clinical pathways. Inspired by evidence-based medicine and the potential of big data and deep learning, combined with the data characteristics of clinical decision indicators and clinical pathways that can be quantitatively or qualitatively analyzed, this review simulates the cognitive behavior and neural mechanisms of the human brain and proposes a feasible brain-inspired intelligence scheme by predicting the decision indices and executing clinical pathways intelligently, that is, "select clinical indicators and clarify clinical pathways -- construct database -- use deep learning to intelligently predict decision indicators -- intelligent execution of clinical pathways -- brain-inspired intelligence of implant decision-making". Combined with the previous research results of our team, this review also describes the process of realization of brain-inspired intelligence for immediate implant timing decisions, providing an example of the comprehensive realization of brain-inspired intelligence of implant surgery robots in the future. In the future, how to excavate and summarize other clinical decision factors and select the best way to realize the automatic prediction of evidence-based clinical indicators and pathways and finally realize the complete intellectualization of clinical diagnosis and treatment processes will be one of the directions that dental clinicians need to strive for.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.