Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca²⁺, K⁺, and Na⁺, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca²⁺ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca²⁺ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca²⁺ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

BACKGROUND:The highest incidence of spinal fracture is in the thoracolumbar segment,and its symptoms are back pain,posterior convexity deformity,activity limitation,or with spinal cord nerve injury causing lower limb pain,numbness,and even paraplegia and other complications.The finite element method is a digital computer modeling technique,which can simulate the physical model and carry out force analysis realistically.OBJECTIVE:To review the application of finite element method in thoracolumbar spine fractures.METHODS:We searched the Chinese and English literature databases PubMed,Web of Science,and CNKI for relevant literature on the application of the finite element analysis method in spinal thoracolumbar fracture published before March 2024.The search terms in Chinese and English were:finite element analysis methods,biomechanical phenomena,stress analysis,thoracolumbar fractures,spinal fractures.Finally,55 papers were included.RESULTS AND CONCLUSION:(1)The exploration of thoracolumbar fractures caused by different etiologies(osteoporotic,traumatic,and pathological)through the finite element method is conducive to a deeper understanding of the biomechanics of various types of thoracolumbar fractures,and to improve the individualized and fine-tuned treatment of thoracolumbar fractures.(2)The finite element analysis of a single sample or a small number of samples has the chance,and a larger number of samples are required for the future finite element analysis to reduce the chance caused by the sample.(3)The rigid structure of bones alone cannot meet the biomechanical working conditions of the integrity of the physical object,and future finite element models need to incorporate all the structures of the physical object(e.g.,soft tissues,such as muscles and ligaments)as far as possible.(4)The finite element method has been used in more studies on osteoporotic and traumatic thoracolumbar spine fractures,which will need to be more in-depth in the future,and less in the field of pathologic thoracolumbar fractures,which has a wider scope for future research.

Objective:To evaluate the causal relationship between IL-7 and IL-7Rα and ankylosing spondylitis(AS)using the Mendelian randomization(MR)method.Methods:This study was based on gene-wide association study(GWAS)summary data,con-structing instrumental variables(IV)using single nucleotide polymorphisms(SNPs).We respectively adopt Inverse variance weighted(IVW),MR-Egger mode and Weighted median(WM)mode to assess the causal relation between IL-7/IL-7Rα and AS.In addition,we also conducted sensitivity tests,including the heterogeneity test,the pleiotropy test,the leave-one-out approach and the MR-PRESSO test.Results:IL-7 and IL-7Rα were respectively included in 9 and 5 IVs that could be used for MR analysis.Results of IVW analysis revealed a reliable causal relationship between IL-7 and IL-7Rα and AS[IL-7:P=0.025 2,OR(95%CI)=0.999 4(0.989 1～0.999 9);IL-7Rα:P=0.008 3,OR(95%CI)=1.000 6(1.000 2～1.001 0)].Cochranes Q test(IL-7:P=0.999 7;IL-7Rα:P=0.946 9)showed that all studies had good homogeneity.The results of a leave-one-out sensitivity analysis suggested that causal associations were not strongly influenced by any selected IVs.The intercept of the MR-Egger regression further showed that pleiotropy did not bias the causal effect in this study.Conclusion:Both IL-7 and IL-7Rα have a strong causal relationship with AS,among which IL-7 is a protec-tive factor for AS,and IL-7Rα is a risk factor for AS.

Objective:To evaluate the causal relationship between IL-7 and IL-7Rα and ankylosing spondylitis(AS)using the Mendelian randomization(MR)method.Methods:This study was based on gene-wide association study(GWAS)summary data,con-structing instrumental variables(IV)using single nucleotide polymorphisms(SNPs).We respectively adopt Inverse variance weighted(IVW),MR-Egger mode and Weighted median(WM)mode to assess the causal relation between IL-7/IL-7Rα and AS.In addition,we also conducted sensitivity tests,including the heterogeneity test,the pleiotropy test,the leave-one-out approach and the MR-PRESSO test.Results:IL-7 and IL-7Rα were respectively included in 9 and 5 IVs that could be used for MR analysis.Results of IVW analysis revealed a reliable causal relationship between IL-7 and IL-7Rα and AS[IL-7:P=0.025 2,OR(95%CI)=0.999 4(0.989 1～0.999 9);IL-7Rα:P=0.008 3,OR(95%CI)=1.000 6(1.000 2～1.001 0)].Cochranes Q test(IL-7:P=0.999 7;IL-7Rα:P=0.946 9)showed that all studies had good homogeneity.The results of a leave-one-out sensitivity analysis suggested that causal associations were not strongly influenced by any selected IVs.The intercept of the MR-Egger regression further showed that pleiotropy did not bias the causal effect in this study.Conclusion:Both IL-7 and IL-7Rα have a strong causal relationship with AS,among which IL-7 is a protec-tive factor for AS,and IL-7Rα is a risk factor for AS.

BACKGROUND:Degenerative scoliosis is defined as a condition that occurs in adulthood with a coronal cobb angle of the spine>10° accompanied by sagittal deformity and rotational subluxation,which often produces symptoms of spinal cord and nerve compression,such as lumbar pain,lower limb pain,numbness,weakness,and neurogenic claudication.The finite element method is a mechanical analysis technique for computer modelling,which can be used for spinal mechanics research by building digital models that can realistically restore the human spine model and design modifications. OBJECTIVE:To review the application of finite element method in the etiology and treatment of degenerative scoliosis. METHODS:The literature databases CNKI,PubMed,and Web of Science were searched for articles on the application of finite element method in degenerative scoliosis published before October 2023.Search terms were"finite element analysis,biomechanics,stress analysis,degenerative scoliosis,adult spinal deformity"in Chinese and English.Fifty-four papers were finally included. RESULTS AND CONCLUSION:(1)The biomechanical findings from the degenerative scoliosis model constructed using the finite element method were identical to those from the in vivo experimental studies,which proves that the finite element method has a high practical value in degenerative scoliosis.(2)The study of the etiology and treatment of degenerative scoliosis by the finite element method is conducive to the prevention of the occurrence of the scoliosis,slowing down the progress of the scoliosis,the development of a more appropriate treatment plan,the reduction of complications,and the promotion of the patients'surgical operation.(3)The finite element method has gradually evolved from a single bony structure to the inclusion of soft tissues such as muscle ligaments,and the small sample content is increasingly unable to meet the research needs.(4)The finite element method has much room for exploration in degenerative scoliosis.

OBJECTIVE To explore the mechanism of Qingwen Baidu Drink in treating sepsis-induced lung injury.METHODS One hundred C57BL/6 mice were randomly divided into blank group,model group,Qingwen Baidu Drink low-dose group,Qingwen Baidu Drink medium-dose group,and Qingwen Baidu Drink high-dose group,with 20 mice in each group.HE staining was used to examine the pathological changes of lung tissues.ELISA was used to detect the expression levels of serum interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),chemokine ligand 10(CXCL10)and plasma coagulation factor Ⅲ(F3).qPCR was used to detect the mRNA expression levels of monocyte chemoattractant protein-1(MCP-1),cyclooxygenase-2(COX-2)and interferon-γ(IFN-γ)in lung tissues.The number of platelets(PLT)in plasma was analyzed by routine blood analysis instrument.Immunofluorescence a-nalysis was used to detect vascular endothelial cadherin(VE-cadherin),endothelial adhesion junction marker occludin 5(CLDN5)and pericyte marker neuronal collagen antigen 2(NG2)in alveolar capillary endothelial cells.Western blot was used to detect the pro-tein expression levels of cysteine-containing aspartate proteinase 11(Caspase11),GSDMD and GSDMD-N in mouse lung tissues.RESULTS Compared with the blank group,the lung tissue of the mice in the model group showed obvious pathological dam-age.The levels of serum IL-1β,TNF-α,and CXCL10 and the mRNA expression levels of MCP-1,COX-2,and IFN-γ in lung tis-sue were significantly increased(P<0.01),and the number of PLT and the content of F3 in plasma were significantly decreased(P<0.01).The fluorescence expression of VE-cadherin,CLDN5,and NG2 proteins in lung tissue was significantly enhanced(P<0.01),while the expression of Caspase11 and GSDMD-N proteins was increased(P<0.01).Compared with the model group,the pathological damage of the lung tissue of the mice in all doses of Qingwen Baidu Drink groups was alleviated,the levels of serum IL-1β,TNF-α,and CXCL10 and the mRNA expression levels of MCP-1,COX-2,and IFN-γ in lung tissue were significantly decreased(P<0.05,P<0.01),and the number of PLT and the content of F3 in plasma were increased(P<0.05,P<0.01);the fluorescence expression of VE-cadherin,CLDN5,and NG2 proteins in lung tissues was weakened(P<0.05,P<0.01),and the expression of Caspase11 and GSDMD-N/GSDMD proteins was reduced(P<0.05,P<0.01).CONCLUSION Qingwen Baidu Drink can inhibit the activation of GSDMD-N and Caspase11,reduce the release of inflammatory factors,decrease blood loss and damage to vascular barrier function,and thus improve the lung injury caused by sepsis.

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry

BACKGROUND:The highest incidence of spinal fracture is in the thoracolumbar segment,and its symptoms are back pain,posterior convexity deformity,activity limitation,or with spinal cord nerve injury causing lower limb pain,numbness,and even paraplegia and other complications.The finite element method is a digital computer modeling technique,which can simulate the physical model and carry out force analysis realistically.OBJECTIVE:To review the application of finite element method in thoracolumbar spine fractures.METHODS:We searched the Chinese and English literature databases PubMed,Web of Science,and CNKI for relevant literature on the application of the finite element analysis method in spinal thoracolumbar fracture published before March 2024.The search terms in Chinese and English were:finite element analysis methods,biomechanical phenomena,stress analysis,thoracolumbar fractures,spinal fractures.Finally,55 papers were included.RESULTS AND CONCLUSION:(1)The exploration of thoracolumbar fractures caused by different etiologies(osteoporotic,traumatic,and pathological)through the finite element method is conducive to a deeper understanding of the biomechanics of various types of thoracolumbar fractures,and to improve the individualized and fine-tuned treatment of thoracolumbar fractures.(2)The finite element analysis of a single sample or a small number of samples has the chance,and a larger number of samples are required for the future finite element analysis to reduce the chance caused by the sample.(3)The rigid structure of bones alone cannot meet the biomechanical working conditions of the integrity of the physical object,and future finite element models need to incorporate all the structures of the physical object(e.g.,soft tissues,such as muscles and ligaments)as far as possible.(4)The finite element method has been used in more studies on osteoporotic and traumatic thoracolumbar spine fractures,which will need to be more in-depth in the future,and less in the field of pathologic thoracolumbar fractures,which has a wider scope for future research.

OBJECTIVE To explore the mechanism of Qingwen Baidu Drink in treating sepsis-induced lung injury.METHODS One hundred C57BL/6 mice were randomly divided into blank group,model group,Qingwen Baidu Drink low-dose group,Qingwen Baidu Drink medium-dose group,and Qingwen Baidu Drink high-dose group,with 20 mice in each group.HE staining was used to examine the pathological changes of lung tissues.ELISA was used to detect the expression levels of serum interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),chemokine ligand 10(CXCL10)and plasma coagulation factor Ⅲ(F3).qPCR was used to detect the mRNA expression levels of monocyte chemoattractant protein-1(MCP-1),cyclooxygenase-2(COX-2)and interferon-γ(IFN-γ)in lung tissues.The number of platelets(PLT)in plasma was analyzed by routine blood analysis instrument.Immunofluorescence a-nalysis was used to detect vascular endothelial cadherin(VE-cadherin),endothelial adhesion junction marker occludin 5(CLDN5)and pericyte marker neuronal collagen antigen 2(NG2)in alveolar capillary endothelial cells.Western blot was used to detect the pro-tein expression levels of cysteine-containing aspartate proteinase 11(Caspase11),GSDMD and GSDMD-N in mouse lung tissues.RESULTS Compared with the blank group,the lung tissue of the mice in the model group showed obvious pathological dam-age.The levels of serum IL-1β,TNF-α,and CXCL10 and the mRNA expression levels of MCP-1,COX-2,and IFN-γ in lung tis-sue were significantly increased(P<0.01),and the number of PLT and the content of F3 in plasma were significantly decreased(P<0.01).The fluorescence expression of VE-cadherin,CLDN5,and NG2 proteins in lung tissue was significantly enhanced(P<0.01),while the expression of Caspase11 and GSDMD-N proteins was increased(P<0.01).Compared with the model group,the pathological damage of the lung tissue of the mice in all doses of Qingwen Baidu Drink groups was alleviated,the levels of serum IL-1β,TNF-α,and CXCL10 and the mRNA expression levels of MCP-1,COX-2,and IFN-γ in lung tissue were significantly decreased(P<0.05,P<0.01),and the number of PLT and the content of F3 in plasma were increased(P<0.05,P<0.01);the fluorescence expression of VE-cadherin,CLDN5,and NG2 proteins in lung tissues was weakened(P<0.05,P<0.01),and the expression of Caspase11 and GSDMD-N/GSDMD proteins was reduced(P<0.05,P<0.01).CONCLUSION Qingwen Baidu Drink can inhibit the activation of GSDMD-N and Caspase11,reduce the release of inflammatory factors,decrease blood loss and damage to vascular barrier function,and thus improve the lung injury caused by sepsis.