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.The mechanism of Bufei Tongbi Decoction in treatment of systemic lupus erythematosus interstitial lung disease based on network pharmacology and verification of key regulation pathway
Shangwen WU ; Huan LI ; Xiaohong GONG ; Chaoqun LU ; Yiming CHEN ; Ximeng LI ; Yan LI ; Songwei LI
Journal of Beijing University of Traditional Chinese Medicine 2024;47(9):1256-1271
Objective To explore the effect and possible pharmacological mechanism of Bufei Tongbi Decoction in the treatment of systemic lupus erythematosus interstitial lung disease (SLE-ILD).Methods The effective components and related targets of Bufei Tongbi Decoction were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Uniprot database. Key genes for SLE-ILD were screened based on DrugBank,DisGeNET,GeneCards,PharmGKB,OMIM,and GEO databases. Using Cytoscape software,a drug active ingredient-target-disease relationship network diagram was constructed to obtain the effective active ingredients and possible mechanisms of action of Bufei Tongbi Decoction in the treatment of SLE-ILD. Gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to reveal related target genes and pathway functions. Taking C57BL/6 mice as normal group,MRL/lpr mice were injected with bleomycin 5mg/kg in the nasal cavity. According to the random number table method,the mice were divided into model group,Bufei Tongbi Decoction low-dose group (10.4 g/(kg·d)),Bufei Tongbi Decoction medium-dose group (20.8 g/(kg·d)),Bufei Tongbi Decoction high-dose group (41.6 g/(kg·d)) and prednisone group (3 mg/(kg·d)). The intervention lasted for 28 days. Hematein eosin and Masson staining were used to observe the pathological changes of mouse lung tissue,the expressions of transforming growth factor-β1 (TGF-β1) and collagen type Ⅲ (Col-Ⅲ) in lung tissue were detected by immunohistochemistry,and the expressions of interleukin-1β(IL-1β),interleukin-10 (IL-10) and interleukin-17 (IL-17) in serum were detected by ELISA. The mRNA expressions of matrix metallopeptidase 1(MMP-1),hypoxia inducible factor-1α(HIF-1α),retinoid-related orphan receptor γt (RORγt ) and forkhead box P3 (FOXP3) in lung tissue were analyzed by RT-PCR,the protein expressions of HIF-1α and MMP-1 in lung tissue were detected by Western blotting,and the expressions of T helper 17 cells (Th17) and regulatory T cells (Treg cells) in blood were detected by cytometry.Results A total of 163 effective ingredients,259 targets,1729 SLE-ILD disease targets,958 SLE-ILD differential genes and 40 drug-disease interaction targets were obtained by screening. GO functional enrichment and KEGG pathway enrichment showed that IL-17 signaling pathway activated by IL-1β and MMP-1,and Th17 cell differentiation activated by IL-1β and HIF-1α were the main pathways. Animal experiments showed that Bufei Tongbi Decoction could effectively improve the degree of lung interstitial lesion and reduce the expressions of TGF-β1 and Col-Ⅲ in SLE-ILD mice (P<0.01). The expressions of IL-1β,HIF-1α and IL-17 were decreased (P<0.01). Medium and high doses of Bufei Tongbi Decoction decreased the expressions of MMP-1 and RORγt mRNA (P<0.01),and increased the expressions of IL-10 and FOXP3 mRNA (P<0.01). Bufei Tongbi Decoction could reduce the proportion of Th17 cells,increase the proportion of Treg cells,downregulate the balance of Th17/Treg (P<0.05),and improve the immune disorder. Conclusion Bufei Tongbi Decoction has the characteristics of multi-target and multi-pathway in treating SLE-ILD,and its mechanism may be related to the regulation of Th17/Treg cell balance.
3.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.