BACKGROUND:During bone tissue healing,promoting the vascularization of new bone is a common strategy to accelerate the repair of bone tissue.However,the rapid fibrosis process during bone defect repair is often ignored.OBJECTIVE:To design and prepare a core-shell structure bionic scaffold to regulate the process of fibrosis and vascularization in new callus,characterize physical characteristics of the scaffold,and verify the anti-fibrosis and osteogenic properties in vitro and in vivo.METHODS:A core-shell structure bionic scaffold to regulate the process of fibrosis and vascularization in new callus was designed and prepared.The outer shell structure of the scaffold was composed of polycaprolactone electrospun nanofibers loaded with fibroblast activating protein inhibitor;and the inner core structure was composed of gelatin methacrylate hydrogel loaded with deferoxamine.The physical characteristics of electrospun and hydrogel were characterized,and the biocompatibility of the material was verified by live-dead staining and CCK-8 assay.The antifibrotic effect of core-shell structure was analyzed by fibroblast in vitro assay.The osteogenic effect of fibroblast activating protein inhibitor in core-shell structure was analyzed by MC3T3-E1 cells in vitro assay.The vasogenic effect of deferoxamine in core-shell structure was analyzed by human umbilical vein endothelial cells.The effect of bionic core-shell scaffold on bone repair was evaluated by critical bone defect test in rats.RESULTS AND CONCLUSION:(1)The core-shell structure bionic scaffold had good biocompatibility.Hydrophobic polycaprolactone electrospun fibers prepared by electrospinning technology could effectively block the ingrowth of exogenous fibrous tissue on the physical level.The electrospun fiber membrane could effectively release the anti-fibrosis drug fibroblast activating protein inhibitor within 2 weeks,and the released anti-fibrosis drug could inhibit the growth and adhesion of fibroblasts around bone defects,effectively reduced the expression of fibroblast-related proteins,promoted the expression of osteoblast protein in MC3T3-E1 cells,and accelerated its mineralization rate.The deferoxamine in the core-shell structure could promote the migration and vascular formation ability of human umbilical vein endothelial cells,and promoted their strong expression of"H"vascular characteristic protein.(2)In critical bone defect model of SD rats established in the femur,compared with polycaprolactone membrane,the core-shell structure bionic scaffold could effectively repair bone defects.(3)These findings indicate that the core-shell structure bionic scaffold can prevent excessive fibrosis of callus and promote the formation of"H"vessels in the new callus,which can effectively avoid the occurrence of nonunion and accelerate the repair process of critical bone defect.

BACKGROUND:Cell senescence is one of the major risk factors for osteoarthritis,but there is no widely accepted anti-osteoarthritis therapy targeting senescent cells.OBJECTIVE:To develop a feasible treatment strategy targeting senescent cells in osteoarthritis.METHODS:The cationic liposome containing rapamycin,RAPA@Lipo,was prepared by thin film dispersion method.Methylallylated hyaluronic acid hydrogel was synthesized,and RAPA@Lipo was added to the methylallylated hyaluronic acid hydrogel aqueous phase solution.The hydrogel microspheres were prepared by microfluidic equipment.Solid hydrogel microspheres(RAPA@Lipo@MS)were crosslinked under violet light.Primary human chondrocytes were co-cultured with RAPA@Lipo and RAPA@Lipo@MS,respectively.The biocompatibility of the materials was evaluated by CCK-8 assay and live/dead staining.Primary rat chondrocytes were cultured in four groups.Normal control group was cultured for 48 hours.The model group was stimulated with H2O2 for 24 hours to establish senescent cell model.RAPA@Lipo group and RAPA@Lipo@MS group were cultured for 24 hours after establishing senescent cell model with RAPA@Lipo and RAPA@Lipo@MS,respectively.After culture,immunofluorescence was used to observe the expression of p62 and type Ⅱ collagen.RT-PCR was used to detect the mRNA expression of interleukin 6,matrix metalloproteinase 13,type Ⅱ collagen,aggrecan,and ADAMTS-5.RESULTS AND CONCLUSION:(1)The results of CCK-8 assay and live/dead staining showed that RAPA@Lipo and RAPA@Lipo@MS had good biocompatibility.(2)Compared with the normal control group,the protein expression of p62 was increased(P<0.05);the expression of type Ⅱ collagen was decreased(P<0.05),and the mRNA expression levels of interleukin 6,matrix metalloproteinase 13,and ADAMTS-5 were increased(P<0.05);mRNA expression levels of type Ⅱ collagen and aggrecan were decreased(P<0.05)in the model group.Compared with the model group,the expression of p62 protein was decreased(P<0.05);the expression of type Ⅱ collagen was increased(P<0.05),and the mRNA expression levels of interleukin 6,matrix metalloproteinase 13,and ADAMTS-5 were decreased(P<0.05);mRNA expression of type Ⅱ collagen and aggrecan increased(P<0.05)in the RAPA@Lipo@MS group.(3)These findings indicate that RAPA@Lipo@MS can control the quality of cells in vivo by enhancing autophagy,reduce senescent cells in vivo,and locally eliminate senescent cells and senescence-associated secretory phenotype factors in osteoarthritis,thereby slowing the progression of osteoarthritis and creating a cartilage microenvironment that promotes regeneration.

Objective:To retrospectively analyze the efficacy and feasibility of surgical management in patients with cervical dysphagia secondary to Diffuse idiopathic skeletal hyperostosis(DISH)of the cervical spine.Methods:A retrospective analysis was conducted on 6 patients who presented with dysphagia as the primary symptom, were diagnosed with cervical DISH, and underwent surgical treatment in the Department of Otorhinolaryngology Head and Neck Surgery of The Second Xiangya Hospital of Central South University from January 2018 to February 2024. There were 5 males and 1 female, aged from 65 to 78 years (70.2±4.7 years). The duration of dysphagia prior to admission was 13 to 18 months (14.7±2.2 months). All patients had the symptom of dysphagia, and at least one other clinical manifestation of cervical DISH (dyspnea, restricted neck mobility, sleep apnea, odynophagia). One patient had undergone tracheotomy due to laryngeal obstruction before surgery. Surgical intervention was performed after failure of conservative management in all patients. All patients underwent anterior cervical osteophyte resection via the Smith-Robinson approach without concomitant spinal fusion. In the patient with prior tracheotomy for airway obstruction, epiglottoplasty and right arytenoidectomy were performed simultaneously. The swallowing function was evaluated by water swallow test, FEES, M. D. Anderson Dysphagia Inventory. Clinical and imaging evaluations were conducted for follow-uppostoperatively. Preoperative and 30-day post operative data were statistically analyzed using paired samples t-test.Results:Cervical computed tomography revealed osteophyte involvement from C2 to T1 with a median of 4 vertebral segments affected. The most frequently involved vertebral segments were C4-C6 (all 6 patients were involved). The anteroposterior diameter of the most prominent osteophyte was 12.0 to 20.0 mm (16±3.1 mm). The time to resumption of a regular diet was 6 to 20 days(12.7±5.3 days), and the time to remove the nasogastric tube was 8 to 25 days(15.2±6.2 days). In the patient with prior tracheotomy, the tracheostomy tube was successfully decannulated 30 days after initial tube capping following conversion to a metal tube. All cervical DISH-related symptoms except for limited neck mobility improved postoperatively. Both water swallow test and the Rosenbek Penetration-Aspiration Scale showed significant improvement postoperatively. At 30 days postoperatively, MDADI scores significantly improved in all domains: l global (73.33±10.33), emotional (85.56±8.35), functional (83.33±5.89), and physical (82.08±6.60). No major perioperative complications occurred. and the length of hospital stay was 7 to 10 days (7.8±1.2 days). The follow-up time was 12 to 84 months (43.7±27.2 months). All patients maintained sustained symptom relief, with no evidence of osteophyte recurrence during follow-up.Conclusion:Cervical DISH is an under-recognized causes of dysphagia in elderly patients and warrants attention from otolaryngologists. For patients erefractory to conservative treatment, anterior resection of cervical osteophytes via the Smith-Robinson approach is a safe, minimally invasive procedure with favorable short-and long-term outcomes in improving swallowing function.

BACKGROUND:During bone tissue healing,promoting the vascularization of new bone is a common strategy to accelerate the repair of bone tissue.However,the rapid fibrosis process during bone defect repair is often ignored.OBJECTIVE:To design and prepare a core-shell structure bionic scaffold to regulate the process of fibrosis and vascularization in new callus,characterize physical characteristics of the scaffold,and verify the anti-fibrosis and osteogenic properties in vitro and in vivo.METHODS:A core-shell structure bionic scaffold to regulate the process of fibrosis and vascularization in new callus was designed and prepared.The outer shell structure of the scaffold was composed of polycaprolactone electrospun nanofibers loaded with fibroblast activating protein inhibitor;and the inner core structure was composed of gelatin methacrylate hydrogel loaded with deferoxamine.The physical characteristics of electrospun and hydrogel were characterized,and the biocompatibility of the material was verified by live-dead staining and CCK-8 assay.The antifibrotic effect of core-shell structure was analyzed by fibroblast in vitro assay.The osteogenic effect of fibroblast activating protein inhibitor in core-shell structure was analyzed by MC3T3-E1 cells in vitro assay.The vasogenic effect of deferoxamine in core-shell structure was analyzed by human umbilical vein endothelial cells.The effect of bionic core-shell scaffold on bone repair was evaluated by critical bone defect test in rats.RESULTS AND CONCLUSION:(1)The core-shell structure bionic scaffold had good biocompatibility.Hydrophobic polycaprolactone electrospun fibers prepared by electrospinning technology could effectively block the ingrowth of exogenous fibrous tissue on the physical level.The electrospun fiber membrane could effectively release the anti-fibrosis drug fibroblast activating protein inhibitor within 2 weeks,and the released anti-fibrosis drug could inhibit the growth and adhesion of fibroblasts around bone defects,effectively reduced the expression of fibroblast-related proteins,promoted the expression of osteoblast protein in MC3T3-E1 cells,and accelerated its mineralization rate.The deferoxamine in the core-shell structure could promote the migration and vascular formation ability of human umbilical vein endothelial cells,and promoted their strong expression of"H"vascular characteristic protein.(2)In critical bone defect model of SD rats established in the femur,compared with polycaprolactone membrane,the core-shell structure bionic scaffold could effectively repair bone defects.(3)These findings indicate that the core-shell structure bionic scaffold can prevent excessive fibrosis of callus and promote the formation of"H"vessels in the new callus,which can effectively avoid the occurrence of nonunion and accelerate the repair process of critical bone defect.

Objective:To retrospectively analyze the efficacy and feasibility of surgical management in patients with cervical dysphagia secondary to Diffuse idiopathic skeletal hyperostosis(DISH)of the cervical spine.Methods:A retrospective analysis was conducted on 6 patients who presented with dysphagia as the primary symptom, were diagnosed with cervical DISH, and underwent surgical treatment in the Department of Otorhinolaryngology Head and Neck Surgery of The Second Xiangya Hospital of Central South University from January 2018 to February 2024. There were 5 males and 1 female, aged from 65 to 78 years (70.2±4.7 years). The duration of dysphagia prior to admission was 13 to 18 months (14.7±2.2 months). All patients had the symptom of dysphagia, and at least one other clinical manifestation of cervical DISH (dyspnea, restricted neck mobility, sleep apnea, odynophagia). One patient had undergone tracheotomy due to laryngeal obstruction before surgery. Surgical intervention was performed after failure of conservative management in all patients. All patients underwent anterior cervical osteophyte resection via the Smith-Robinson approach without concomitant spinal fusion. In the patient with prior tracheotomy for airway obstruction, epiglottoplasty and right arytenoidectomy were performed simultaneously. The swallowing function was evaluated by water swallow test, FEES, M. D. Anderson Dysphagia Inventory. Clinical and imaging evaluations were conducted for follow-uppostoperatively. Preoperative and 30-day post operative data were statistically analyzed using paired samples t-test.Results:Cervical computed tomography revealed osteophyte involvement from C2 to T1 with a median of 4 vertebral segments affected. The most frequently involved vertebral segments were C4-C6 (all 6 patients were involved). The anteroposterior diameter of the most prominent osteophyte was 12.0 to 20.0 mm (16±3.1 mm). The time to resumption of a regular diet was 6 to 20 days(12.7±5.3 days), and the time to remove the nasogastric tube was 8 to 25 days(15.2±6.2 days). In the patient with prior tracheotomy, the tracheostomy tube was successfully decannulated 30 days after initial tube capping following conversion to a metal tube. All cervical DISH-related symptoms except for limited neck mobility improved postoperatively. Both water swallow test and the Rosenbek Penetration-Aspiration Scale showed significant improvement postoperatively. At 30 days postoperatively, MDADI scores significantly improved in all domains: l global (73.33±10.33), emotional (85.56±8.35), functional (83.33±5.89), and physical (82.08±6.60). No major perioperative complications occurred. and the length of hospital stay was 7 to 10 days (7.8±1.2 days). The follow-up time was 12 to 84 months (43.7±27.2 months). All patients maintained sustained symptom relief, with no evidence of osteophyte recurrence during follow-up.Conclusion:Cervical DISH is an under-recognized causes of dysphagia in elderly patients and warrants attention from otolaryngologists. For patients erefractory to conservative treatment, anterior resection of cervical osteophytes via the Smith-Robinson approach is a safe, minimally invasive procedure with favorable short-and long-term outcomes in improving swallowing function.

BACKGROUND:Cell senescence is one of the major risk factors for osteoarthritis,but there is no widely accepted anti-osteoarthritis therapy targeting senescent cells.OBJECTIVE:To develop a feasible treatment strategy targeting senescent cells in osteoarthritis.METHODS:The cationic liposome containing rapamycin,RAPA@Lipo,was prepared by thin film dispersion method.Methylallylated hyaluronic acid hydrogel was synthesized,and RAPA@Lipo was added to the methylallylated hyaluronic acid hydrogel aqueous phase solution.The hydrogel microspheres were prepared by microfluidic equipment.Solid hydrogel microspheres(RAPA@Lipo@MS)were crosslinked under violet light.Primary human chondrocytes were co-cultured with RAPA@Lipo and RAPA@Lipo@MS,respectively.The biocompatibility of the materials was evaluated by CCK-8 assay and live/dead staining.Primary rat chondrocytes were cultured in four groups.Normal control group was cultured for 48 hours.The model group was stimulated with H2O2 for 24 hours to establish senescent cell model.RAPA@Lipo group and RAPA@Lipo@MS group were cultured for 24 hours after establishing senescent cell model with RAPA@Lipo and RAPA@Lipo@MS,respectively.After culture,immunofluorescence was used to observe the expression of p62 and type Ⅱ collagen.RT-PCR was used to detect the mRNA expression of interleukin 6,matrix metalloproteinase 13,type Ⅱ collagen,aggrecan,and ADAMTS-5.RESULTS AND CONCLUSION:(1)The results of CCK-8 assay and live/dead staining showed that RAPA@Lipo and RAPA@Lipo@MS had good biocompatibility.(2)Compared with the normal control group,the protein expression of p62 was increased(P<0.05);the expression of type Ⅱ collagen was decreased(P<0.05),and the mRNA expression levels of interleukin 6,matrix metalloproteinase 13,and ADAMTS-5 were increased(P<0.05);mRNA expression levels of type Ⅱ collagen and aggrecan were decreased(P<0.05)in the model group.Compared with the model group,the expression of p62 protein was decreased(P<0.05);the expression of type Ⅱ collagen was increased(P<0.05),and the mRNA expression levels of interleukin 6,matrix metalloproteinase 13,and ADAMTS-5 were decreased(P<0.05);mRNA expression of type Ⅱ collagen and aggrecan increased(P<0.05)in the RAPA@Lipo@MS group.(3)These findings indicate that RAPA@Lipo@MS can control the quality of cells in vivo by enhancing autophagy,reduce senescent cells in vivo,and locally eliminate senescent cells and senescence-associated secretory phenotype factors in osteoarthritis,thereby slowing the progression of osteoarthritis and creating a cartilage microenvironment that promotes regeneration.

Objective:To investigate the influence of low-dose ionizing radiation on the expression level of serum insulin-like growth factor binding protein-3 (IGFBP-3) in radiation workers in hospitals.Methods:183 radiation workers were randomly selected and grouped by work type including interventional radiology ( n=37), nuclear medicine ( n=43), radiotherapy ( n=48), and diagnostic radiology ( n=55). The content of IGFBP-3 in the serum of radiation workers was detected by ELISA assay. Results:It was observed that the expression level of serum IGFBP-3 in the four groups had significant differences ( F=6.056, P<0.05), and the content of serum IGFBP-3 in the interventional radiology group was significantly higher than that of nuclear medicine, radiotherapy, and diagnostic radiology groups ( t= 2.815, 3.611, 3.936, P<0.05). The concentration of IGFBP-3 in the serum of radiation workers among different annual effective dose groups was statistically different ( F=8.380, P<0.05), which gradually increased with the increase of annual effective dose and length of service ( rs=0.202, 0.151, P<0.05). Conclusions:The expression level of serum IGFBP-3 has the potential to be used as a biomarker to reflect the cumulative exposure of long-term chronic low-dose ionizing radiation.