OBJECTIVES: To fabricate an injectable composite microsphere hydrogel reinforced with silk fibroin/hyaluronic acid microspheres, achieving synergistic enhance-ment of mechanical robustness and biofunctionality. METHODS: Methacrylated hyaluronic acid (HAMA) and thiolated silk fibroin (TSF) were synthesized. Monodisperse microspheres generated via microfluidics were UV-cured (420 nm) through thiol-ene click reaction. These microspheres were embedded in a TSF/HAMA matrix to form photo-cured composites. The grafting rate of TSF and HAMA was characterized by H1-NMR; particle size distribution of microsphere hydrogels in soybean oil was observed by optical microscopy; gel point of composite microsphere hydrogels was determined by advanced extensional rheometer; microscopic morphology of microsphere hydrogels was observed by scanning electron microscopy; elemental distribution of microsphere hydrogels was detected by X-ray energy dispersive spectroscopy; tunability of composite microsphere hydrogels was observed by inverted confocal microscopy; mechanical properties of composite microsphere hydrogels were tested by compression testing; swelling ratio, degradation rate and water retention rate of composite microsphere hydrogels were measured by gravimetric method. Cytotoxicity of the composite microsphere hydrogels was determined by Calcein-AM/propidium iodide dual staining and CCK-8 assay; cell migration capability was observed by scratch assay. RESULTS: The grafting rates of HAMA and TSF was 48.03% and 17.99%, respectively. Microsphere hydrogels with particle sizes of (43.3±1.2), (78.1±3.0), and (130.8±1.9) μm were prepared. The gel time of the composite microsphere hydrogels was 48-115s. The laser confocal imaging confirmed dynamic regulation characteristics of the composite microsphere hydrogels. The compressive strength of the composite microsphere hydrogels reached 22.7 kPa and maintained structural integrity at 40% strain after 20 compression cycles. The composite microsphere hydrogels exhibited differential deswelling behaviors in simulated physiological environments, and reducing microsphere particle size could significantly enhance its stability under moist conditions. The degradation rate of the composite microsphere hydrogels was (49.1±0.9)% after 200 h, and water retention rate was maintained at 40%-60% after 96 h. Biocompatibility assays confirmed >95% cell viability and unimpaired cell migration abilities. CONCLUSIONS The TSF/HAMA composite microsphere hydrogel developed in this study has characteristics of rapid fabrication, adjustable mechanical properties, enhanced environmental stability and excellent biocom-patibility, thus providing a new material solution for tissue repair and regenerative medicine.
Fibroins/chemistry* ; Hydrogels/chemistry* ; Microspheres ; Hyaluronic Acid/chemistry* ; Humans

Exosomes, as crucial mediators of intercellular communication, exhibit a wide range of biological functions in the onset and treatment of atherosclerosis (AS). Recent studies have indicated that exosomes can carry various active substances, including miRNA, lncRNA, proteins, and lipids. By regulating inflammatory responses, lipid metabolism, vascular endothelial function, and the immune microenvironment, they mediate the formation, progression, and reversal of AS at multiple levels. Specifically, miRNAs within exosomes can target and regulate the expression of inflammatory factors, inhibiting macrophage activation and foam cell formation. Meanwhile, exosomes derived from endothelial cells (EC) or stem cells can enhance vascular endothelial integrity and suppress endothelial dysfunction (ED). Furthermore, exosomes have been extensively explored as natural carriers for delivering drugs and nucleic acid molecules. Their membrane structure possesses excellent biocompatibility and targeting capabilities, showcasing significant potential as a novel therapeutic tool. Starting from basic mechanistic studies, this article summarizes the molecular pathways and key biological effects of exosomes in AS intervention, and further explores their current clinical application and multiple challenges they face, aiming to provide theoretical support and research directions for novel cardiovascular disease intervention strategies.

Objective:To investigate the role of microchromosome maintenance protein 5 (MCM5) in promoting malignant progression and its mechanism in glioblastoma.Methods:(1) Three freshly excised brain tissues from non-tumor patients and 3 grading IV glioblastoma tissues were collected in our hospital from September 2020 to September 2021; mass spectrometry and quantitative proteomic analysis were performed to screen differentially expressed proteins for functional enrichment analysis. (2) The target protein MCM5, which was highly expressed in glioblastoma, was screened on the basis of proteomics, and its expression in glioblastoma was verified using The Cancer Genome Atlas (TCGA) database and further validated at the mRNA level in the collected clinical specimens. (3) U251 cells were divided into negative control group, knockdown group-1 (si-1 group) and knockdown group-2 (si-2 group) by siNRA transfection. The regulation role of MCM5 in malignant phenotype of glioblastoma was detected by CCK-8 assay, clone formation assay, 5-ethynyl-2'-deoxyuridine (EdU)staining, Transwell invasion assay and flow cytometry. (4) The transcriptome data of glioma patients from TCGA database were used to explore the possible molecular mechanisms of MCM5 regulation in the malignant process of glioblastoma by gene set enrichment analysis (GSEA) algorithm.Results:(1) In clinical samples of glioblastoma, 322 up-regulated proteins and 94 down-regulated proteins were screened out; MCM5 was highly expressed in these 3 glioblastoma samples. (2) Based on TCGA database, results of 163 patients with glioblastoma and 207 patients with non-tumor brain tissues showed that MCM5 expression was statistically up-regulated in glioblastoma ( t=3.340, P<0.001). Real-time quantitative PCR results of 3 glioblastoma tissues and 3 non-tumor brain tissues clinically collected in our hospital also indicated that significantly increased MCM5 expression in glioblastoma was noted as compared with that in the non-tumor brain tissues ( t=3.876, P<0.001). (3) As compared with the negative control group, the si-1 and si-2 groups had significantly decreased MCM5 mRNA and protein expressions, significantly lower proliferation rate 5 d after inoculation, statistically decreased number of cell clones, significantly decreased proportion of EdU positive cells, and significantly increased proportion of cells at G1 phase, and significantly impaired migration ability ( P<0.05). (4) GSEA analysis showed that mRNA in MCM5 high expression group was enriched in DNA damage repair gene, E2F target gene, MYC target gene, epithelial-mesenchymal transformation (EMT), nterleukin 6-Janus kinase-signal transduction and transcription activation factor 3 (IL6-JAK-STAT3), interferon, KRAS, NOTCH, transforming growth factor-β (TGF-β), Wnt/β-Catenin and other characteristic genes. Conclusion:MCM5 is highly expressed in glioblastoma, and MCM5 regulates the malignant progression of glioblastoma through multiple mechanisms including E2F, MYC, EMT, and Wnt/β-Catenin.

Objectives To investigate the etiology, renal pathology, treatment, and prognosis of children's urinary system injury after hematopoietic stem cell transplantation (HSCT). Methods Clinical data of 81 children with urinary dysfunction after HSCT admitted to the Hematology Department in Children's Hospital of Soochow University were analyzed, and relevant literatures were reviewed. Results In 81 cases (50 males and 31 females), the age ranges from 8 months to 17 years old. Thirty cases (37%) with prerenal injury were recovered after active rehydration and other symptom specific treatment. There were 9 (11.1%) children with renal injury, four cases were given up therapy or transferred to other hospitals, thus lead to an unknown prognosis. Kidney biopsy was performed in the remaining five cases for pathological investigation. After active symptom-speific and etiology-based treatment, serum creatinine and glomerular filtration rate of four cases return to normal. But in the long-term follow-up,one case died of recurrence of primary disease, reinfusion of hematopoietic stem cell combined with renal failure. The remaining 3 patients were with chronic kidney disease (CKD). One case with renal thrombotic microangiopathy was in the chronic dialysis. Postrenal renal injuries were mainly hemorrhagic cystitis (28.4%) and urinary tract infection (16%). After a large dose of rehydration, urine alkalization and anti-infection therapy, they were recovered in the short term with a good prognosis. Conclusions Urinary injury after HSCT is mainly divided into three categories: prerenal, renal and postrenal, in which renal injury is prone to frequent recurrence.

Objective To investigate the clinical effect of old thoracolumbar vertebral fracturekyphosis with spinal stenosis by pedicle of vertebral archosteotomy and internal fixation.Methods Twenty patients with old thoracolumbar fracture with kyphosis,and associated with spinal stenosis,were treated by using transpedicular osteotomy and internal fixation treatment in the First People's Hospital of Shangqiu from June 2012 to May 2014.Radiographical assessments including localized kyphosis,thoracic kyphosis,lumber lordosis,sacral tilt angle,sagittal vertical axis,bony fusion and the relative height of the ifiterbody fusion vertebra.Visual analogue scale(VAS),and ASIA were evaluated before and after surgery,and the operative duration,blood loss were recorded.Results The operation carried out in 120-200 min,800-1600 ml of bleeding statistics through operation process.Localized kyphosis was reduced from an average of (42.6±4.2) ° to (8.2± 1.6) °,the difference was statistically significant (P =0.012).All patients were followed up for 10.0 -26.0 months,average (18.0±6.2) months.The average VAS score was 6.88±0.82 before operation and 2.10 ±0.84 at final follow-up,the difference was statistically significant(P=0.023).The bone healed well,no false joints.Neurological function improved from C to D in 2 patients,from C to E in 4 patients,and from D to E in 14 patients.Conclusion Old thoracolumbar vertebral fracture kyphosis with spinal stenosis by transpedicularosteotomy and internal fixation in the treatment of simple operation,definite effect,less complications and can effectively improve the prognosis.

Objective To investigate the clinical effect of high developmental dislocation of the hip in patients with total hip replacement operation to take biology.Methods Thirty-six cases of high developmental dislocation of the hip by patients as the object of study from January 2011 to February 2014 in the First People' s Hospital of Shangqiu, all patients underwent cementless total hip joint replacement operation, 6 months to 2 years after surgery, observed the clinical effect of all patients before and after treatemnt.Results The operation time was 1.20-3.0 h,the average operation time was (2.13±1.01) h,amount of bleeding during the operation of 300.00-700.00 ml,the average amount of bleeding was (342.43±34.23) ml;follow up of 6 months to 2 years, all patients had no prosthesis loosening and dislocation of the hip;all patients after treatment, Harris score (81.56± 14.34) points, better than that before treatment, the difference was statistically significant ((54.34 ± ±9.78) points,P=0.009);The excellent and good rate of all the patients after the treatment (97.22％) .Conclusion The clinical effect of high developmental dislocation of the hip by total hip replacement operation in patients taking biological type significantly, has the advantages of simple operation, effectively relieve pain, improve the life quality of patients and other advantages, the ideal treatment method can be used as high developmental dislocation of hip.