Background At present, the treatment of silicosis is still limited, and no method is available to cure the disease. miRNAs are involved in the process of fibrosis at the transcriptional level by directly degrading target gene mRNA or inhibiting its translation. However, how miR-130a-3p regulates silicosis fibrosis has not been fully elucidated yet. Objective To investigate whether miR-130a-3p promotes epithelial-mesenchymal transition (EMT) by inhibiting peroxisome proliferators-activated receptors gamma (PPAR-γ), thereby pro-moting the process of silicotic fibrosis. To identify effective new targets for the treatment of silicotic fibrosis. Methods (1) Animal experiments: C57BL/6J mice were intratracheally injected with a one-time dose of 10 mg silica suspension (dissolved in 100 μL saline) as positive lung exposure. A silicosis model group was established 28 d after the exposure. A control group was injected with the same amount of normal saline into the trachea. Hematoxylin-eosin staining and Sirius red staining were used to observe the pathological changes and collagen deposition in lung tissues respectively. Realtime fluorescence-based quantitative polymerase chain reaction (RT-qPCR) was used to assay the expression of miR-130a-3p and PPAR-γ mRNA in lung tissues. Western blotting was used to detect the protein expression of PPAR-γ, transforming growth factor (TGF)-β1, E-cadherin, α-smooth muscle actin (α-SMA), and Collagen Ⅰ in lung tissues. (2) Cells experiments: Mouse lung epithelial cells (MLE-12) were induced with 5 µg·L⁻¹ TGF-β1 for different time (0, 12, 24, 48 h). RT-qPCR was used to detect the expression of miR-130a-3p and PPAR-γ mRNA in cells. The binding relationship between miR-130a-3p and PPAR-γ mRNA was verified by dual luciferase reporter gene assay. MLE-12 cells were stimulated by 5 µg·L⁻¹ TGF-β1 after transfection of miR-130a-3p inhibitor, and Western blotting was used to measure the protein expression of PPAR-γ, E-cadherin, and α-SMA in the TGF-β1-induced cells. Results In the silicosis model group, the alveolar septum was widened and the pulmonary nodules were formed. The Sirius red staining collagen deposition in pulmonary nodules indicated that a silicosis fibrosis model was successfully established. The expressions of TGF-β1, α-SMA, and Collagen Ⅰ proteins were increased, and the expressions of E-cadherin and PPAR-γ proteins were decreased in lung tissues of the silicosis group, compared with the control group (P<0.05 or P<0.01). The expression of miR-130a-3p was increased and the expression of PPAR-γ mRNA was decreased in lung tissues of the silicosis model (P<0.01). The expression of miR-130a-3p was significantly increased, while the expression of PPAR-γ mRNA was decreased in the TGF-β1 induced MLE-12 cells (P<0.05 or P<0.01). The dual luciferase reporter assay showed a direct relationship between miR-130a-3p and PPAR-γ mRNA in MLE-12 cells. The transfection of miR-130a-3p inhibitor in the TGF-β1 induced MLE-12 cells inhibited the decrease of PPAR-γ and E-cadherin proteins, and the increase of α-SMA protein in the MLE-12 cells induced by TGF-β1 (P<0.05 or P<0.01). Conclusion miR-130a-3p promotes the development of silicosis fibrosis by targeting PPAR-γ to increase pulmonary EMT.

BACKGROUND:Cervical disc herniation can cause pain in the neck and shoulder area,as well as radiating pain in the upper limbs.The incidence rate is increasing year by year and tends to affect younger individuals.Fully understanding the biomechanical characteristics of the cervical spine in adolescents is of great significance for preventing and delaying the onset of cervical disc herniation in this age group. OBJECTIVE:To reconstruct cervical spine models for both healthy adolescents and adolescent patients with cervical disc herniation utilizing finite element analysis techniques,to analyze the motion range of the C1-T1 cervical vertebrae as well as the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and the cartilage of the small joints. METHODS:A normal adolescent's cervical spine and an adolescent patient with cervical disc herniation were selected in this study.The continuous scan cervical spine CT raw image data were imported into Mimics 21.0 in DICOM format.The C1-T1 vertebrae were reconstructed separately.Subsequently,the established models were imported into the 3-Matic software for disc reconstruction.The perfected models were then imported into Hypermesh software for meshing of the vertebrae,nucleus pulposus,annulus fibrosus,and ligaments,creating valid geometric models.After assigning material properties,the final models were imported into ABAQUS software to observe the joint motion range of the C1-C7 cervical vertebrae segments under different conditions,and to analyze the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and small joint cartilage of each cervical spine segment. RESULTS AND CONCLUSION:(1)In six different conditions,the joint motion range of the C1 vertebra in the cervical spine models of both normal adolescent and adolescent patient with cervical disc herniation was higher than that of the other vertebrae.Additionally,the joint motion range of each cervical spine segment in normal adolescent was greater than that in adolescent patient with cervical disc herniation.(2)In the cervical spine model of normal adolescent,the maximum stress values in the annulus fibrosus and nucleus pulposus were found on the left side during C2-3 flexion conditions(0.43 MPa and 0.17 MPa,respectively).In the cervical spine model of adolescent patient with cervical disc herniation,the maximum stress values were found on the left side during C7-T1 flexion conditions(0.54 MPa and 0.18 MPa,respectively).(3)In the cervical spine model of normal adolescent,the maximum stress value on the endplate was found on the left side of the upper endplate of C3 during flexion conditions(1.46 MPa).In the model of adolescent patient with cervical disc herniation,the maximum stress value on the endplate was found on the left side of the lower endplate of C7 during flexion conditions(1.32 MPa).(4)In the cervical spine model of normal adolescent,the maximum stress value in the small joint cartilage was found in the C2-3 left rotation conditions(0.98 MPa).In adolescent patient with cervical disc herniation,the stress in the small joint cartilage significantly increased under different conditions,especially in C1-2,with the maximum stress found during left flexion(3.50 MPa).(5)It is concluded that compared to normal adolescent,adolescent patient with cervical disc herniation exhibits altered cervical curvature and a decrease in overall joint motion range in the cervical spine.In adolescent with cervical disc herniation,there is a significant increase in stress on the annulus fibrosus,nucleus pulposus,and endplates in the C7-T1 segment.The stress on the left articular cartilage of the C1-2 is notable.Abnormal cervical curvature may be the primary factor causing these stress changes.

Objective: To understand the moderating effect of cohabitation with parents on the association between peer dating behavior and sexual behaviors among secondary vocational school students, so as to provide a scientific basis for preventing sexual behaviors among secondary vocational school students. Methods: From March to April 2021, an electronic questionnaire survey was conducted among 3 180 students from 6 vocational schools in Shanghai (urban, suburban, exurban) and Shaanxi (Shangluo, Ankang, Baoji) using cluster sampling. Spearman correlation analysis was used to investigate the relationship of cohabitation with parents, peer dating behavior and sexual behaviors among secondary vocational school students. Binary Logistic regression analysis was performed to investigate the role of cohabitation with parents on peer dating behavior and sexual behaviors among secondary vocational students. Results: There was a significant negative between cohabitation with parents and sexual ( r =-0.04); and there was a positive correlation between peer dating behavior and sexual behaviors ( r =0.24), as well as cohabitation with parents and peer dating behavior ( r =0.04)( P <0.05). Multivariable Logistic regression analysis showed an association between peer dating behavior and the occurrence of sexual behaviors ( OR=2.79-12.95, P <0.05). Cohabitation with parents played a moderating role in the association between peer dating behavior and sexual behaviors, and a signification interaction was found between cohabitation with parents and reporting that a small part or about half of their peers had dating behavior ( OR =0.48, P <0.05). Conclusions The more peers dating behavior are associated with a higher risk of sexual behaviors among secondary vocational school students, and cohabitation with parents can partly reduce this risk. School and family sexuality education for secondary vocational students should be strengthened to improve their interpersonal skills and decision-making, and ability to resist peer pressure, so as to reduce their risk of sexual behaviors.

Objective: To investigate the expression and functional role of FK506 binding protein 10 (FKBP10) in oral squamous cell carcinoma (OSCC), and to provide a research basis for the estimated prognosis and targeted therapy of OSCC. Methods: A total of 284 OSCC samples and 19 normal samples were selected from the Cancer Genome Atlas (TCGA) database, and diagnostic analysis was performed to determine mRNA expression. Survival analysis for FKBP10 and OSCC was conducted on a gene expression profile interaction analysis website. Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and protein expression of FKBP10 in four OSCC cell lines and SAS and SCC9 cells transfected with siRNA. The cell proliferation ability of FKBP10-silenced cells was detected using the CCK8 method, and the cell cycle distribution and apoptosis were detected by flow cytometry. Cell migration and invasion ability were detected through wound healing and invasion experiments. The expression changes of total protein and phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT) after FKBP10 silencing were analyzed by proteomics and Western Blot. Results: According to the analysis of gene expression levels, the mRNA expression level of FKBP10 in OSCC was significantly higher than that in normal tissues (P < 0.001). In terms of diagnosis, the expression level of FKBP10 has unique diagnostic value for OSCC (P < 0.05). The survival analysis of FKBP10 and OSCC showed that a high expression of FKBP10 led to a decrease in patient survival and poor prognosis (P < 0.05). The expression of FKBP10 mRNA and protein in OSCC cell lines was higher than that in normal oral keratinocytes (P < 0.001). Silencing FKBP10 can reduce the proliferation, invasion, and migration ability of SAS and SCC9 (P < 0.001), and also block their cell cycle in the G0/G1 phase (P < 0.001), with a significant increase in apoptosis (P < 0.05). Protein mass spectrometry and Western blot analysis revealed that FKBP10 silencing significantly downregulated the expression of multiple proteins in the RAP1 signaling pathway, mainly RAP guanine nucleotide exchange factor 1 (RAPGEF1) (P < 0.05) and the phosphorylation of PI3K-AKT proteins (P < 0.05). Conclusion FKBP10 is highly expressed in OSCC, leading to poor prognosis for patients. Downregulated FKBP10 expression can inhibit the proliferation, migration, and invasion ability of OSCC cells, hinder cell cycle progression, and promote apoptosis via the RAP1-PI3K-AKT axis. FKBP10 is a potential therapeutic target and prognostic biomarker for OSCC.

ObjectiveThe nucleolar protein PES1 (Pescadillo homolog 1) plays critical roles in ribosome biogenesis and cell cycle regulation, yet its involvement in cellular senescence remains poorly understood. This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role. MethodsInitially, we assessed PES1 expression patterns in two distinct senescence models: replicative senescent mouse embryonic fibroblasts (MEFs) and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells. Subsequently, PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types. Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays, respectively. The expression of senescence-associated proteins (p53, p21, and Rb) and SASP factors (IL-6, IL-1β, and IL-8) were analyzed by Western blot or qPCR. Furthermore, Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology. ResultsPES1 expression was significantly downregulated in senescent MEFs and HepG2 cells. PES1 knockdown resulted in decreased EdU-positive cells and increased SA‑β‑gal-positive cells, indicating proliferation inhibition and senescence induction. Mechanistically, PES1 suppression activated the p53-p21 pathway without affecting Rb expression, while upregulating IL-6, IL-1β, and IL-8 production. Notably, PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress, as evidenced by aberrant nucleolar morphology. ConclusionOur findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent (but Rb-independent) cellular senescence, highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.

[摘 要] 目的：探讨贝母素乙对结肠癌HCT116细胞增殖的抑制作用及其分子机制。方法：利用不同浓度的贝母素乙处理人结肠癌细胞HCT116和正常结肠上皮细胞CCD841 CON，通过CCK-8法和结晶紫染色法检测贝母素乙对HCT116和CCD841 CON细胞增殖活力的影响，流式细胞术和WB法检测贝母素乙对HCT116细胞周期及其细胞周期相关蛋白表达的影响。构建HCT116移植瘤裸鼠模型和AOM/DSS结肠癌小鼠模型，观察贝母素乙对小鼠模型肿瘤生长和OS的影响，免疫组化法和WB法检测对移植瘤或肿瘤组织中细胞周期相关蛋白CDK4、CDK6和cyclin D1表达的影响。结果：贝母素乙可显著抑制结肠癌HCT116细胞的增殖能力（P<0.01），诱导HCT116细胞周期G0/G1期阻滞（P<0.01），降低CDK4、CDK6和cyclin D1的蛋白表达水平（均P<0.01）。荷瘤小鼠实验结果显示，贝母素乙（0.75 mg/kg）显著抑制HCT116细胞移植瘤的生长并延长荷瘤裸鼠的OS（P<0.05或P<0.01），降低AOM/DSS模型小鼠的体质量、延长OS、减少癌变肠组织的肿瘤个数和肿瘤体积，下调肿瘤组织中CDK4、CDK6和cyclin D1的蛋白表达（P<0.01或P<0.05）。结论：贝母素乙通过下调CDK4、CDK6和cyclin D1的表达水平，引起细胞周期G0/G1期阻滞，从而抑制结肠癌HCT116细胞的增殖。

Fluorescence anisotropy(FA)analysis has many advantages such as no requirement of separation,high throughput and real-time detection,and thus has been widely used in many fields,including biochemical analysis,food safety detection,environmental monitoring,etc.However,due to the small volume or mass of the target,its combination with the fluorescence probe cannot produce significant signal change.To solve this issue,researchers often use nanomaterials to enhance the mass or volume of fluorophore to improve the sensitivity.Nevertheless,this FA amplification strategy also has some disadvantages.Firstly,nanomaterials are easy to quench fluorescence.As a result,the FA value is easily influenced by light scattering,which reduces the detection accuracy.Secondly,fluorescent probes in most methods require complex modification steps.Therefore,it is necessary to develop new FA probes that do not require the amplification of volume and mass or modification.As a new kind of nanomaterials,luminescent metal-organic framework(MOF)has a large volume(or mass)and strong fluorescence emission.It does not require additional signal amplification materials.As a consequence,it can be used as a potential FA probe.This study successfully synthesized a lanthanide metal organic framework(Ce-TCPP MOF)using cerium ion(Ce3+)as the central ion and 5,10,15,20-tetra(4-carboxylphenyl)porphyrin(H2TCPP)as the ligand through microwave assisted method,and used it as a novel unmodified FA probe to detect phosphate ions(Pi).In the absence of Pi,Ce-TCPP MOF had a significant FA value(r).After addition of Pi,Pi reacted with Ce3+in MOF and destroyed the structure of MOF into the small pieces,resulting in a decrease in r.The experimental results indicated that with the increase of Pi concentration,the change of the r of Ce-TCPP MOF(Δr)gradually increased.The Δr and Pi concentration showed a good linear relationship within the range of 0.5-3.5 μmol/L(0.016-0.108 mg/L).The limit of detection(LOD,3σ/k)was 0.41 μmol/L.The concentration of Pi in the Jialing River water detected by this method was about 0.078 mg/L,and the Pi value detected by ammonium molybdate spectrophotometry was about 0.080 mg/L.The two detection results were consistent with each other,and the detection results also meet the ClassⅡwater quality standard,proving that this method could be used for the detection of Pi in complex water bodies.

Objective:To summarize the clinical characteristics of eosinophilic esophagitis (EoE) in children.Methods:Clinical data of children with EoE who were hospitalized in the Department of Gastroenterology, Beijing Children′s Hospital, Capital Medical University from January 1, 2017, to December 31, 2022, were retrospectively analyzed.Results:A total of 18 children with EoE were included in the study, including 13 males and 5 females, with the age of 11.96 (4.96, 12.81) years.Vomiting was more common in preschool children (4/5), while abdominal pain was the main symptom in school-age and adolescent children (11/13). There were 22.22% (4/18) of the children with EoE had an increased white blood cell count, and 33.33%(6/18) had an increased eosinophil count.Allergic history in the first-degree relatives was detected in 55.56%(10/18) of the children with EoE.Total immunoglobulin E (IgE) level was elevated in 68.75% (11/16) of the children.Food-specific IgE was positive in 66.67% (12/18) of the children with EoE.Milk, eggs, and wheat were the most common allergens.Esophageal mucosal hyperemia and erythema, rough, erosion, linear ulcers, annular changes, furrow or wrinkled paper changes, granular changes, polypoid or relaxation of the cardia were seen under endoscopy, whereas 27.78% (5/18) of the children showed normal esophageal mucosa.The histopathology showed chronic inflammation of the esophagus and increased eosinophil count.Three patients were lost of follow-up, and the remaining 15 were followed up for 6-24 months.All children with EoE were treated with the elimination diet.Nine children treated with glucocorticoids experienced clinical remission in a short period of time, involving 1 case with recurrence after withdrawal and being effectively treated by hormone therapy, and 2 cases of repeated digestive system symptoms or increased eosinophil count after withdrawal and being effectively relieved by the elimination diet.Conclusions:EoE is more common in elderly children and boys.Vomiting is the main symptom in pre-school aged children, whereas abdominal pain is the main symptom in school-aged children and adolescents.Increased peripheral white blood cell count and eosinophil count can be detected in some cases, and most of them are positive for food allergen tests.Gastrointestinal endoscopy and histopathology are important in the diagnosis of EoE.Elimination diet may be effective in some patients.Glucocorticoids are of great significance in the treatment of EoE, but a few children are steroid-dependent.

An adult female presented with severe closed overbite,class Ⅱ skeletal and dental malocclusion,low angle and straight face.Helped with the clear aligners,the class Ⅱ dental malocclusion was corrected by maxillary molars distalization,the occlusion of anterior teeth were opened by posterior teeth extention and anterior teeth intrusion,and finally a balanced occlusion and an ideal smile line were obtained.

BACKGROUND:Ankylosing spondylitis is a chronic inflammatory disease with chronic rheumatic immunity.Soft tissue ossification and fusion and spinal stiffness can cause biomechanical changes. OBJECTIVE:To reconstruct the lumbar-sacral intervertebral disc in ankylosing spondylitis patients with lumbar kyphosis by finite element analysis,and to study the range of motion of each segment of T11-S1 and the biomechanical characteristics of annulus fibrosus and nucleus pulposus. METHODS:The imaging data were obtained from an ankylosing spondylitis patient with lumbar kyphosis.The original CT image data of continuously scanned spine were imported into Mimics 21.0 in DICOM format,and T11-S1 was reconstructed respectively.The established model was imported into 3-Matic software in the format of"Stl"to reconstruct the intervertebral disc,and the fibrous intervertebral disc model was obtained.The improved model was further imported into Hypermesh software,and the vertebra,nucleus pulposus,annulus fibrosus and ligament were mesh-divided.After the material properties were given,the model was imported into ABAQUS software to observe the range of motion of each vertebral body in seven different working conditions of T11-S1,and analyze the biomechanical characteristics of each segment of annulus fibrosus and nucleus pulposus. RESULTS AND CONCLUSION:(1)The range of motion of L1 vertebrae was higher than that of other vertebrae under six different working conditions:extension,forward flexion,rotation(left and right),and lateral flexion(left and right).The maximum range of motion was 2.18° during L1 vertebral flexion,and the minimum range of motion was 0.12° during L5 vertebral extension.(2)The annular fiber flexion at L2-L3 segments was greater than the extension(P<0.05),and the annular fiber flexion at L3-L4 and L4-L5 segments was less than the extension(P<0.05).The left rotation of L1-L2 annular fibers was greater than the right rotation(P<0.05).The left flexion of the annulus was greater than the right flexion in L1-L2,L2-L3,L3-L4,L4-L5 and L5-S1 segments(P<0.05).(3)The nucleus pulposus stresses of T11-L12,L1-L2,L2-L3,L3-L4 and L4-L5 segments in forward flexion were greater than in extension(P<0.05).The left rotation of T12-L1 and L3-L4 segments was smaller than the right rotation(P<0.05),and that of T11-T12,L1-L2,and L2-L3 segments was larger than the right rotation(P<0.05).The left flexion was larger than the right flexion in the T11-S1 segment.(4)It is concluded that in ankylosing spondylitis patients with lumbar kyphosis,the minimum range of motion of the vertebral body is located at the L5 vertebral body in extension.To prevent fractures,it is recommended to avoid exercise in the extension position.During the onset of lumbar kyphosis in patients with ankylosing spondylitis,the maximum stress of the annulus fibrosus and nucleus pulposus is located in the L1-L2 segment,which is fixed and will not alter with the change of body position.The late surgical treatment and correction of deformity should focus on releasing the pressure of the annulus fibrosus and nucleus pulposus in this segment to avoid the rupture of the annulus fibrosus and the injury of the nucleus pulposus.