Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a severe critical condition marked by rapid progression and high fatality. It results from direct/indirect lung-related or systemic triggers, leading to widespread injury of lung epithelial and endothelial cells. Its pathogenesis involves uncontrolled inflammation and breakdown of the lung's blood-air barrier due to leaky blood vessels and epithelial damage. Current management of ALI/ARDS remains primarily supportive, offering symptomatic relief but limited improvement in prognosis, necessitating deeper exploration of upstream pathogenic mechanisms to identify safer and more effective therapies. Exosomal microRNAs (miRNA), small extracellular vesicles (40-150 nm) containing non-coding single-stranded RNAs, regulate post-transcriptional cellular processes and participate in ALI/ARDS pathophysiology. Studies reveal that exosomes transport proteins, nucleic acids, and miRNAs to recipient cells, mediating intercellular communication. In ALI/ARDS models, exosomal miRNAs delivered to alveolar epithelial cells, endothelial cells, macrophages, and neutrophils critically modulate autophagy, pyroptosis, apoptosis, proliferation, inflammatory signaling, macrophage polarization, and neutrophil activation, either exacerbating or alleviating disease progression. Recent advances in engineering techniques have enhanced the therapeutic potential of exosomal miRNAs by overcoming limitations of natural exosomes. This review focuses on exosomal miRNA-mediated regulation of ALI/ARDS pathogenesis across key cell types, providing insights for novel therapeutic strategies.
Exosomes ; Humans ; MicroRNAs ; Acute Lung Injury ; Respiratory Distress Syndrome ; Animals

Objective To investigate the damage of pepsin to the mucosal epithelium of the pharynx under a-cidic and non-acidic conditions,and to provide new ideas for the treatment of refractory laryngopharyngeal reflux diseases.Methods A total of 30 healthy guinea pigs were selected and randomly divided into 3 groups(with 10 in each group).The animals in group A were perfused with 0.3％pepsin+hydrochloric acid solution(pH=2),the animals in group B were perfused with 0.3％pepsin+sterilized distilled water(pH=7),and the animals in group C were perfused with sterilized distilled water(pH=7).After 14 days of perfusion,the mucosal tissues of the post-cyclic area were examined by HE staining,immunohistochemistry,and transmission electron microscopy to detect the degree of inflammatory cell infiltration,the expression of occludin and claudin-3 proteins,the degree of epithelial cell gap widening,and also to analyze the changes of cell submicroscopic structure under electron microscopy.Re-sults ① The submucosal leukocyte count was 28.61±7.10 in group A,29.89±7.04 in group B,and 7.81±1.40 in group C.Compared with group C,the leukocyte count was higher in group A and group B(P＜0.05).② Com-pared with group C,both occludin and claudin-3 protein expression were downregulated in group A(P＜0.05),compared with group C,the difference between occludin and claudin-3 protein expression in group B was not statisti-cally significant(P＞0.05).③ Under electron microscopy,the mucosal epithelial cell gap was widened,the mito-chondria was swollen and the cristae was degraded in group A.In group B,there was no widening of the mucosal epithelial cell gap,but the mitochondria in the cytoplasm was swollen and the cristae was degraded,and there was no widening of mucosal epithelial cell gap and the morphological markers of mitochondria were clear in group C.Conclusion Under non-acidic conditions,pepsin still can cause inflammatory changes and mitochondrial damage in the mucosal epithelium of the pharynx.

BACKGROUND:At present,the surgical treatment of atlantoaxial dislocation mainly adopts the posterior atlantoaxial screw-rod internal fixation system for lifting and reduction.During the operation,the curvature of the connecting rod is often increased to increase the drop between the atlantoaxial vertebrae to improve the reduction effect,but it increases the difficulty and risk of surgery.The axis pivot screw directly increases the reduction drop between the atlantoaxial vertebrae,but the extent to which it increases the reduction capacity is unclear.OBJECTIVE:To test the reduction ability of axis pivot screw and compare it with ordinary screw.METHODS:Six fresh human craniocervical specimens were used in study.The joint capsules of two lateral mass joints and atlanto-odontoid joint and transverse ligament were removed to make an atlantoaxial instability model.Three kinds of internal fixation were performed successively on both sides of the axis of each specimen:uniaxial axis pivot screws(group A),multi-axial axis pivot screws(group B)and ordinary screws(group C).Flexible ultra-thin film pressure sensors were placed in the anterior atlanto-odontoid space.Two connecting rods with the same curvature were placed to simulate the lifting and reduction,and the pressure of the anterior atlanto-odontoid space was obtained.Comparative analysis was conducted among the three groups.RESULTS AND CONCLUSION:(1)The anterior atlanto-odontoid space pressure of groups A-C was(97.59±8.58),(60.43±5.09),and(22.74±0.81)N,respectively.There were significant differences among the three groups(F=251.603,P=0.000).The pairwise comparison among the three groups showed significant differences(P=0.000).(2)The axis pivot screw applied to the posterior atlantoaxial screw-rod internal fixation system can improve the reduction capacity compared with the common cervical posterior screw,and the uniaxial axis pivot screw has more reduction capacity than the multi-axis uniaxial axis pivot screw to improve the posterior atlantoaxial screw-rod internal fixation system.

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.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

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.

BACKGROUND:At present,the surgical treatment of atlantoaxial dislocation mainly adopts the posterior atlantoaxial screw-rod internal fixation system for lifting and reduction.During the operation,the curvature of the connecting rod is often increased to increase the drop between the atlantoaxial vertebrae to improve the reduction effect,but it increases the difficulty and risk of surgery.The axis pivot screw directly increases the reduction drop between the atlantoaxial vertebrae,but the extent to which it increases the reduction capacity is unclear.OBJECTIVE:To test the reduction ability of axis pivot screw and compare it with ordinary screw.METHODS:Six fresh human craniocervical specimens were used in study.The joint capsules of two lateral mass joints and atlanto-odontoid joint and transverse ligament were removed to make an atlantoaxial instability model.Three kinds of internal fixation were performed successively on both sides of the axis of each specimen:uniaxial axis pivot screws(group A),multi-axial axis pivot screws(group B)and ordinary screws(group C).Flexible ultra-thin film pressure sensors were placed in the anterior atlanto-odontoid space.Two connecting rods with the same curvature were placed to simulate the lifting and reduction,and the pressure of the anterior atlanto-odontoid space was obtained.Comparative analysis was conducted among the three groups.RESULTS AND CONCLUSION:(1)The anterior atlanto-odontoid space pressure of groups A-C was(97.59±8.58),(60.43±5.09),and(22.74±0.81)N,respectively.There were significant differences among the three groups(F=251.603,P=0.000).The pairwise comparison among the three groups showed significant differences(P=0.000).(2)The axis pivot screw applied to the posterior atlantoaxial screw-rod internal fixation system can improve the reduction capacity compared with the common cervical posterior screw,and the uniaxial axis pivot screw has more reduction capacity than the multi-axis uniaxial axis pivot screw to improve the posterior atlantoaxial screw-rod internal fixation system.

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 investigate the damage of pepsin to the mucosal epithelium of the pharynx under a-cidic and non-acidic conditions,and to provide new ideas for the treatment of refractory laryngopharyngeal reflux diseases.Methods A total of 30 healthy guinea pigs were selected and randomly divided into 3 groups(with 10 in each group).The animals in group A were perfused with 0.3％pepsin+hydrochloric acid solution(pH=2),the animals in group B were perfused with 0.3％pepsin+sterilized distilled water(pH=7),and the animals in group C were perfused with sterilized distilled water(pH=7).After 14 days of perfusion,the mucosal tissues of the post-cyclic area were examined by HE staining,immunohistochemistry,and transmission electron microscopy to detect the degree of inflammatory cell infiltration,the expression of occludin and claudin-3 proteins,the degree of epithelial cell gap widening,and also to analyze the changes of cell submicroscopic structure under electron microscopy.Re-sults ① The submucosal leukocyte count was 28.61±7.10 in group A,29.89±7.04 in group B,and 7.81±1.40 in group C.Compared with group C,the leukocyte count was higher in group A and group B(P＜0.05).② Com-pared with group C,both occludin and claudin-3 protein expression were downregulated in group A(P＜0.05),compared with group C,the difference between occludin and claudin-3 protein expression in group B was not statisti-cally significant(P＞0.05).③ Under electron microscopy,the mucosal epithelial cell gap was widened,the mito-chondria was swollen and the cristae was degraded in group A.In group B,there was no widening of the mucosal epithelial cell gap,but the mitochondria in the cytoplasm was swollen and the cristae was degraded,and there was no widening of mucosal epithelial cell gap and the morphological markers of mitochondria were clear in group C.Conclusion Under non-acidic conditions,pepsin still can cause inflammatory changes and mitochondrial damage in the mucosal epithelium of the pharynx.

Background Suicidal ideation serves as a sensitive predictive indicator for non-suicidal self-injury(NSSI)behavior,and NSSI behavior brings profound effects to both mental and physical health of senior high school students.Existing studies have made exploration on the relationship among insomnia,anxiety and NSSI behavior in the general population,but the internal mechanism of NSSI behavior in senior high school students with suicidal ideation requires further study.Objective To explore the pathway of anxiety between insomnia and NSSI behavior in senior high school students,so as to provide references for the intervention on NSSI behavior in such demographic.Methods From December 10 to 15,2021,cluster sampling was adopted to select 2 572 senior high school students across three senior high schools in Hubei Province as the research objects.Assessment was conducted by using Insomnia Severity Index(ISI),Generalized Anxiety Disorder Scale-7 item(GAD-7)and Adolescents Self-Harm Scale.Spearman correlation analysis was conducted to examine the correlation among scores of scales finished by senior high school students with suicidal ideation.Model 4 from the SPSS 20.0 Process 4.2 was employed to test the mediating path of anxiety between insomnia and NSSI behavior.Results A total of 2 421 valid questionnaires(94.13%)were recovered,which revealed 554 cases(22.88%)with suicidal ideation and 408 cases(16.85%)with NSSI behavior.The scores of ISI,GAD-7 and Adolescents Self-Harm Scale of senior high school students with suicidal ideation were higher than those of students without suicidal ideation(Z=17.124,20.611,21.314,P<0.01).As correlation analysis showed,the ISI score of senior high school students with suicidal ideation was positively correlated with scores of GAD-7 and Adolescents Self-Harm Scale(r=0.646,0.354,P<0.01),and GAD-7 score was positively correlated with the score of Adolescents Self-Harm Scale(r=0.375,P<0.01).Among senior high school students with suicide ideation,anxiety acted in a mediating role between insomnia and NSSI behavior,with effect value of 0.111(95%CI:0.053～0.185),accounting for 53.88%of the total effect.Conclusion Insomnia of senior high school students with suicidal ideation can not only directly affect NSSI behavior,but also indirectly affect NSSI behavior through anxiety.