Mandibular condylar fractures are common injuries in oral and maxillofacial surgery. The unique anatomical structure and mechanical environment of the condyle render its fracture healing process distinct from that of long bones. Parathyroid hormone (PTH) and its active fragment PTH(1-34) (such as the drug teriparatide) are among the few clinically available agents with bone-anabolic properties, and have shown promise in fracture repair. However, the anatomical and mechanical discrepancies between the condyle and long bones raise doubts as to whether the efficacy of PTH observed in long bones can be directly extrapolated to condylar fractures. Elucidating how mechanical loading modulates the bone remodeling effects of PTH within the specific mechanical environment of the mandibular condyle thus constitutes a critical entry point for addressing this question. This review summarizes recent advances regarding how mechanical loading influences PTH-promoted healing of mandibular condylar fractures from three perspectives: the mechanical sensitivity of condylar fracture healing, the molecular mechanisms by which PTH regulates bone remodeling, and the synergy between mechanical and pharmacological interventions, with the aim of clarifying the existing molecular evidence for mechanical-PTH synergy derived from long-bone and in vitro models, and critically evaluating the feasibility and limitations of extrapolating these findings to condylar fractures. Evidence from long-bone fracture models and in vitro mechanical loading systems indicates that mechanical loading modulates the direction of PTH-mediated bone remodeling through the receptor activator of the nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) axis and the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK3β)/nuclear factor of the activated T-cells c1 (NFATc1) pathway, an effect that exhibits marked intensity- and time-dependent characteristics. Nevertheless, critical challenges remain in this field, including the standardization of quantitative mechanical loading parameters, the accumulation of direct evidence from condyle-specific fracture models, and the in-depth elucidation of the regulatory mechanisms governing mechanical-drug synergy. Future research should integrate finite element analysis, standardized mechanical loading techniques, and single-cell omics to establish a quantitative relationship between mechanical parameters, cellular responses, and PTH effects, thereby providing a theoretical basis for optimizing postoperative masticatory load management and PTH administration strategies in condylar fractures.

Solitay iliac aneurysms are a rare clinical condition characterized by insidious onset.Once they rupture,treatment becomes difficult,and the mortality rate is extremely high.Therefore,it is extremely important to detect the disease,classify it appropriately and select appropriate treatment options.In recent years,endovascular treatment has gradually replaced traditional laparotomy as the first-line therapeutic approach.Some scholars have proposed clinical classification of isolated iliac aneurysms based on anatomical morphology and imaging studies to better select appropriate endovascular treatment strategies.This review aims to summarize the treatment advancements for solitary iliac aneurysms and the classifications based on the published literature.

OBJECTIVES: To investigate the effect of in vitro cultured calculus bovis (ICCB) on cerebral ischemia/reperfusion injury (CIRI) and its mechanism. METHODS: A CIRI rat model and a cell model were induced by middle cerebral artery occlusion (MCAO) in Sprague Dawley rats and oxygen glucose deprivation/reperfusion (OGD/R) in BV2 cells, respectively. The CIRI rat model was evaluated using the modified neurological severity score (mNSS), brain water content, and cerebral infarction volume after 1.5 h of ischemia followed by 72 h of reperfusion. Histopathological changes in the cortex and hippocampal CA1 region were observed with hematoxylin and eosin staining. Microglial polarization and NOD-like receptor thermal protein domain associated protein (NLRP) 3 inflammasome expression in the cortex were examined by immunofluorescence. BV2 cell viability was measured via MTT assay after treatment with ICCB and Nigericin. The expressions of NLRP3, ASC, caspase-1 proteins and inflammatory cytokines were detected with Western blotting in OGD/R treated BV2 cells (0.5 h OGD+24 h reperfusion) and in cells pretreated with Nigericin for 24 h. RESULTS: ICCB treatment significantly improved neurological function, reduced cerebral infarct volume and brain water content, and mitigated pathological damage in the cortical and hippocampal CA1 regions of rats subjected to CIRI (all P<0.05). ICCB promoted the transition of cortical microglia from M1 to M2 phenotypes and suppressed NLRP3 activation in microglial cells (all P<0.01). ICCB significantly down-regulated the expression of NLRP3, ASC, and caspase-1 proteins, and reduced the secretion of IL-18 and IL-1β in BV2 cells of OGD/R model (all P<0.01). In addition, Nigericin significantly reversed the salvage effect of ICCB on model cells (both P<0.01) and the modulation of inflammatory cytokines (P<0.05). CONCLUSIONS ICCB exerts a protective effect against CIRI by mitigating neuroinflammation, through the reduction of M1 microglial polarization, promotion of M2 conversion, and suppression of the NLRP3/ASC/caspase-1 signaling pathway.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/prevention & control* ; Microglia/metabolism* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein ; Brain Ischemia/metabolism* ; Male

Objective To explore the expression levels of NOD-like receptor thermal protein domain-asso-ciated protein 3(NLRP3)and interleukin-6(IL-6)in children with bronchial asthma combined with pulmona-ry infection and its relationship with prognosis.Methods A sample of 150 children with bronchial asthma combined with pulmonary infection hospitalized in Nanjing University Medical College Teaching Hospital,North Jiangsu People's Hospital from January 2021 to December 2022 were prospectively enrolled as observa-tion group,All children were followed up for one year.Another 164 healthy children underwent health check-ups were concurrently selected as control group.According to the prognosis,the children in the observation group were divided into good prognosis groups(n=92)and poor prognosis groups(n=58).Serum IL-6 and NLRP3 expression levels were detected in all participants,and receiver operating characteristic(ROC)curve was plotted to evaluate the value of IL-6 and NLRP3 in predicting the poor prognosis in children with bronchi-al asthma combined with pulmonary infection.Results Serum IL-6 and NLRP3 expression levels in the obser-vation group were significantly higher than those in the control group(P＜0.05).Serum IL-6 and NLRP3 ex-pression levels in the poor prognosis group were higher than those in the good prognosis group(P＜0.05).The results of ROC curve analysis showed that the area under the curve of IL-6 alone for predicting the poor prognosis of children with asthma combined with pulmonary infection was 0.772,with a sensitivity of 79.3％and a specificity of 73.9％.The area under the curve(AUC)of NLRP3 alone for predicting the poor prognosis of children with asthma combined with pulmonary infection was 0.735,with a sensitivity of 55.2％and a spe-cificity of 88.0％.The AUC of the combination of IL-6 and NLRP3 for predicting poor prognosis in children with asthma combined with pulmonary infection was 0.851,which was higher than those of IL-6 and NLRP 3 alone for predicting poor prognosis in children(Z=1.563,2.003,P=0.059,0.045),and the sensitivity was 82.8％and specificity was 75.0％,with high predictive value.Conclusion The expression levels of serum IL-6 and NLRP3 is abnormally up-regulated in children with bronchial asthma combined with pulmonary infec-tion,and the two could serve as predictive indicators for poor prognosis.

Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

Objective In response to the clinical needs for personalized wrist orthoses,a topological optimization design method was proposed to achieve an integrated macro-and micro-structural optimization of a personalized,lightweight,and comfortable wrist orthosis.Methods A composite biomechanical finite element model of the wrist orthosis and upper limb was established to quantify the effects of the orthosis geometry on its fixation performance and comfort.A multi-condition topological optimization and microstructure design approach was employed to optimize the non-load-bearing areas of the orthosis.The orthosis was manufactured using three-dimensional(3D)-printed polyether ether ketone(PEEK),and the feasibility of the design was validated.Results While maintaining mechanical strength,the weight of the 3D-printed PEEK orthosis was reduced by 28％compared to the traditional orthoses.Both the pressure at the skin contact interface and the results of a subjective questionnaire indicated that test subjects experienced a high level of comfort wearing the orthosis.Conclusions The orthosis design achieved personalization,lightweight structure,and high comfort while ensuring mechanical strength and fixation performance.