Treatment analysis of complex Schatzker type Ⅳ tibial plateau fractures / 中国骨伤

OBJECTIVE@#To explore treatment strategy for complex Schatzker Ⅳ tibial plateau fracture.@*METHODS@#Forty-one patients with complex Schatzker type Ⅳ tibial plateau fractures were treated from January 2016 to January 2021, including 28 males and 13 females, aged from 19 to 65 years old with an average of (35.3±19.8) years old. Individualized treatment plan was developed according to preoperative imaging characteristics, medial surgical approach was mainly combined with other auxiliary incisions. Posteromedial inverted L approach was used in 18 patients, posteromedial approach and anterolateral extended approach in 19 patients, and posteromedial approach with anterolateral and lateral condylar osteotomy in 4 patients. Articular surface and facture healing were observed, range of knee joint motion was measured at 12 months after opertaion, and function of knee joint was evaluated by Lysholm scoring system.@*RESULTS@#Forty-one patients were followed up for 12 to 26 months with an average of (13.3±6.8) months. Twenty-nine patients and 10 patients were obtained complete fracture healing at 6 and 12 months after operation respectively, and fracture healing time was 4 to 13 months with an average of (5.0±3.7) months. Two patients occurred posterior medial internal fixation failure and varus deformity of knee joint, and the fracture healed and varus deformity was corrected after the second operation. Range of knee joint motion was (118±29) °, and Lysholm score was(83.0±16.0) points.@*CONCLUSION@#Individualized treatment should be reasonably selected for complex Schatzker Ⅳ tibial plateau fractures, the characteristics of lateral plateau fractures are an important reference for selecting surgical approaches, the effective fixation of posteromedial bone blocks should be pay full attention, and the overall treatment results are satisfied.

Saponins from Paris forrestii(Takht.)H.Li displays potent activity against acute myeloid leukemia by suppressing RNF6/AKT/mTOR signaling pathway / 中国药理学与毒理学杂志

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the accu-mulation of immature myeloid progenitor cells in the bone marrow,compromising of normal hematopoi-esis and ultimately resulting in bone marrow failure. Chemotherapy is the mainstay treatment for all AML patients,however,drug resistance and clinical relapse limits its efficacy.The 5-year survival rate of AML patients is only 26.6%.Survival rates are even lower among patients ages 65 to 74 years (5.3%)and 75 years or older(1.6%).Therefore,exploring novel therapeutic agents is urgent for improving the outcome of patients with AML. Saponins are amphipathic glycosides found in traditional Chinese medicines. In the present study, we isolated a panel of saponins from Paris forrestii (Takht.) H. Li, a unique plant found in Tibet and Yunnan provinces, China. By examining their activities in suppressing acute myeloid leukemia cell proliferation, total saponins from Paris forrestii (TSPf) displayed more potent activity than individual ones.TSPf induced more than 40% AML cell apoptosis within 24 h and decreased the viability of all leukemia cell lines. TSPf-induced apoptosis was confirmed by both Annexin V staining and caspase-3 activation.TSPf downregulated pro-survival proteins Mcl-1,Bcl-xL and Bcl-2,but upreg-ulated the expression of tumor suppressor proteins p53,p27,Bax and Beclin 1.The AKT/mTOR signaling pathway is frequently over activated in various AML cells,and TSPf was found to suppress the activa-tion of both AKT and mTOR,but had no effects on their total protein expression.This was further con-firmed by the inactivation of 4EBP-1 and p70S6K,two typical downstream signal molecules in the AKT/mTOR pathway. More specifically, TSPf-inactivated AKT/mTOR signaling was found to be associated with downregulated RNF6, a recently identified oncogene in AML. RNF6 activated AKT/mTOR, and consistently, knockdown of RNF6 led to inactivation of the AKT/mTOR pathway. Furthermore, TSPf suppressed the growth of AML xenografts in nude mice models. Oral administration of 100 mg·kg-1 body weight almost fully suppressed tumor growth within 14 d, without gross toxicity. This study thus demonstrated that TSPf displays potent anti-AML activity by suppressing the RNF6/AKT/mTOR pathway. Given its low toxicity,TSPf could be developed for the treatment of AML.