The utilization of optimal orthodontic force is crucial to prevent undesirable side effects and ensure efficient tooth movement during orthodontic treatment.However,the sensitivity of existing detection techniques is not sufficient,and the criteria for evaluating optimal force have not been yet established.Here,by employing 3D finite element analysis methodology,we found that the apical distal region(A-D region)of mesial roots is particularly sensitive to orthodontic force in rats.Tartrate-resistant acidic phosphatase(TRAP)-positive osteoclasts began accumulating in the A-D region under the force of 40 grams(g),leading to alveolar bone resorption and tooth movement.When the force reached 80 g,TRAP-positive osteoclasts started appearing on the root surface in the A-D region.Additionally,micro-computed tomography revealed a significant root resorption at 80 g.Notably,the A-D region was identified as a major contributor to whole root resorption.It was determined that 40 g is the minimum effective force for tooth movement with minimal side effects according to the analysis of tooth movement,inclination,and hyalinization.These findings suggest that the A-D region with its changes on the root surface is an important consideration and sensitive indicator when evaluating orthodontic forces for a rat model.Collectively,our investigations into this region would aid in offering valuable implications for preventing and minimizing root resorption during patients'orthodontic treatment.

Objective:To study the different factors affecting platelet production post transplantation of hematopoietic stem cells (HSCs) isolated from different sources in order to explore novel options for treating platelet depletion following HSCs transplantation.Methods:HSCs and their downstream derivatives including myeloid and lymphoid cells (i.e., collective of mononuclear cells (MNCs)), were isolated from E14.5 fetal liver (FL) and bone marrow (BM) of 8-week-old mice by Ficoll separation technique. These cells were subsequently transplanted into the tibia bone marrow cavity of recipient mice post lethal myeloablative treatment in order to construct the FL-MNCs and BM-MNCs transplantation mouse model. Routine blood indices were examined in these recipient mice. The chimeric rate of donor cells in recipient peripheral blood cells were determined by flow cytometry. Different groups of cells involved in platelet reconstruction were analyzed. CD41 +megakaryocytes were sorted from fetal liver or bone marrow using magnetic beads, which were then induced to differentiate into platelets in an in vitro assay . Quantitative RT-PCR was used to detect the expression of platelet-related genes in CD41 +megakaryocytes from the two sources. Results:Both the FL-MNCs and the BM-MNCs transplantation groups resumed normal hematopoiesis at the 4th week after transplantation, and the blood cells of the recipient mice were largely replaced by the donor cells. Compared with the mice transplanted with BM-MNCs, the platelet level of mice transplanted with FL-MNCs recovered faster and were maintained at a higher level. At week 4, the PLT level of the FL-MNCs group was (1.45±0.37)×10 12/L, and of the BM-MNCs group was (1.22±0.24)×10 12/L, P<0.05. The FL-MNCs contain a higher proportion of hematopoietic stem cells (Lin -Sca-1 +c-Kit +)(7.60%±1.40%) compared to the BM-MNCs (1.10%±0.46%), P<0.01; the proportion of the megakaryocyte progenitor cells (Lin -Sca-1 -c-Kit +CD41 +CD150 +) and mature megakaryocyte cells (CD41 +CD42b +), also differ significantly between the FL-MNCs (3.05%±0.22%, 1.60%±0.06%, respectively) and the BM-MNCs (0.15%±0.02%, 0.87%±0.11%, respectively) groups, both P<0.01. In vitro functional studies showed that FL-MNCs-CD41 +megakaryocytes could produce proplatelet-like cells more quickly after induction, with proplatelet-like cells formation on day 3 and significant platelet-like particle formation on day 5, in contrast to bone marrow-derived BM-MNCs-CD41 +megakaryocytes that failed to form proplatelet-like cell on day 5. In addition, FL-MNCs-CD41 +cells expressed higher levels of platelet-related genes, Mpl (3.25-fold), Fog1 (3-fold), and Gata1 (1.5-fold) ( P<0.05). Conclusion:Compared with the BM-MNCs group, the FL-MNCs transplantation group appears to have a more efficient platelet implantation effect in the HSCs transplantation recipient in vivo , as well as a higher platelet differentiation rate in vitro. This might be related to a higher proportion of megakaryocytes and higher expression levels of genes such as Mpl, Fog1, and Gata1 that could be important for platelet formation in FL-MNCs-CD41 +cells. Further exploration of the specific functions of these genes and the characteristics of the different proportions of the donor cells will provide valuable clues for the future treatment of platelets reconstitution after HSCs transplantation clinically.

Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.

Objective To apply cone beam CT measurements(CBCT)to analyze the effect of skeletal Class Ⅲ high angle with devia-tion on upper airway morphology and hyoid position.Methods A total of 120 patients with skeletal Class Ⅲ high angle malocclusion who visited our hospital from September 2019 to December 2022 were selected.CBCT was taken in all subjects.According to the degree of mandibular deviation(MD)of the point under the chin from the median sagittal plane,the 120 patients were divided into three groups:non-migratory,mildly migratory,and severely migratory groups,and the volume of the upper airway as well as the position of the hyoid bone of three groups were measured and analyzed respectively.Results There was no significant difference in the volume and minimum cross-sectional area of the nasopharyngeal segment,palatopharyngeal segment,and minimum cross-sectional area of the laryngopharyngeal segment.No siginificant difference was found between the position of the hyoid bone(HB)on the Y-axis(Y-HB)and the position of the hyoid bone on the Z-axis(Z-HB)among the three groups(P＞0.05).Compared with the other two groups,the vol-ume and total volume of the nasopharyngeal segment,the laryngopharyngeal segment,and minimum cross-sectional area of the laryngo-pharyngeal segment in the group of severe deviation were significantly reduced(P＜0.05)and X-HB was significantly larger(P＜0.05).Conclusion In patients with skeletal ClassⅢhyperkeratosis with severe deviation,the total volume of the glossopharyngeal segment,laryngopharyngeal segment,and upper airway,as well as the minimum cross-sectional area of the glossopharyngeal segment were smal-ler than those of the othertwo groups.In patients with severe deviation,the position of the hyoid bone(HB)in the X-axis(X-HB)was larger than that of the non-migratory group,indicating that migratory jaws mainly affect the morphology of the lingual-pharyngeal seg-ment as well as the laryngopharyngeal segment of the upper airway;the effect of migratory jaws on the hyoid bone is reflected in the X-HB,indicating that migratory jaws can lead to the deviation of the hyoid bone from the median sagittal plane.

Cardiovascular disease is still the leading cause of mortality worldwide. Vascular endothelial dysfunction is viewed as the initial step of most cardiovascular diseases. Many studies have indicated that periodontal pathogens, especially Porphyromonas gingivalis, are closely correlated with vascular endothelial homeostasis, but the function of P. gingivalis and the underlying mechanisms are still elusive. To illuminate the effects and elucidate the mechanisms of P. gingivalis on endothelial structural integrity, we developed P. gingivalis infection models in vivo and in vitro. Endothelial cell proliferation, differentiation and apoptosis were detected. Here, we showed that P. gingivalis can impair endothelial integrity by inhibiting cell proliferation and inducing endothelial mesenchymal transformation and apoptosis of endothelial cells, which reduce the cell levels and cause the endothelium to lose its ability to repair itself. A mechanistic analysis showed that TLR antagonist or NF-κB signalling inhibitor can largely rescue the damaged integrity of the endothelium caused by P. gingivalis, suggesting that TLR-NF-κB signalling plays a vital role in vascular endothelial homeostasis destroyed by P. gingivalis. These results suggest a potential intervention method for the prevention and treatment of cardiovascular disease.

Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Mice ; Animals ; Gliosis/pathology* ; Cicatrix/pathology* ; Spinal Cord Injuries ; Astrocytes/metabolism* ; Spinal Cord/pathology* ; Fibrosis ; Mammals ; Receptors, G-Protein-Coupled