1.Total Hip Arthroplasty on Treatment of Traumatic Arthritis Caused by Internal Fixation Failures of Intertrochanteric Fractures
Ning LIU ; Songwei HUAN ; Huige HOU ; Huantian ZHANG ; Guorong SHE ; Simin LUO ; Hong ZHANG ; Zhengang ZHA
Journal of Sun Yat-sen University(Medical Sciences) 2017;38(2):273-277
[Objective]To investigate the efficacy of total hip arthroplasty(THA)on the treatment of traumatic arthritis that caused by internal fixation failures of intertrochanteric fractures.[Methods]During January 2009 and March 2016,35 cases of trau?matic arthritis(male:18 cases;female17 cases;49 ~ 86 years old,with an average age of 68.5 years)caused by internal fixation failures or malunion of intertrochanteric fractures,were undergo THA. Among 35 cases,13 cases were performed with the proximal femoral fixation stems,10 cases were with distal fixation stems,and 12 cases were with extended stems.[Results]With 3~65 months follow-up,the hip joint HSS score was elevated from 44.1(31 ~ 65)preoperative to 82.5(58 ~ 94)postoperative without obvious loosening. No postoperative deep infectionwas found. The femoral stems in 2 cases were found to sink 5 mm and 10 mm,respectively. No obvious prosthesis loosening was found. Taken together ,the satisfaction rate of THA on the joint function of traumatic arthritis was 91.4%.[Conclusion]Total hip arthroplasty is recommended as an effective approach for treating traumatic arthritis caused by internal fixation failures of intertrochanteric fractures. Distal fixed prosthesis was recommended due to bone sclerosis or defects of proximal femur. Coupled with emphasis on reconstruction of the greater trochanter ,good therapeutic effects could be achieved.
2.knocking out mediated by CRISPR-Cas9 genome editing for PD-L1 attenuation and enhanced antitumor immunity.
Huan DENG ; Songwei TAN ; Xueqin GAO ; Chenming ZOU ; Chenfeng XU ; Kun TU ; Qingle SONG ; Fengjuan FAN ; Wei HUANG ; Zhiping ZHANG
Acta Pharmaceutica Sinica B 2020;10(2):358-373
Blocking the programmed death-ligand 1 (PD-L1) on tumor cells with monoclonal antibody therapy has emerged as powerful weapon in cancer immunotherapy. However, only a minority of patients presented immune responses in clinical trials. To develop an alternative treatment method based on immune checkpoint blockade, we designed a novel and efficient CRISPR-Cas9 genome editing system delivered by cationic copolymer aPBAE to downregulate PD-L1 expression on tumor cells specifically knocking out Cyclin-dependent kinase 5 () gene . The expression of PD-L1 on tumor cells was significantly attenuated by knocking out , leading to effective tumor growth inhibition in murine melanoma and lung metastasis suppression in triple-negative breast cancer. Importantly, we demonstrated that aPBAE/Cas9-Cdk5 treatment elicited strong T cell-mediated immune responses in tumor microenvironment that the population of CD8 T cells was significantly increased while regulatory T cells (Tregs) was decreased. It may be the first case to exhibit direct PD-L1 downregulation CRISPR-Cas9 genome editing technology for cancer therapy. It will provide promising strategy for preclinical antitumor treatment through the combination of nanotechnology and genome engineering.