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Purpose@#Osteosarcoma (OS) universally exhibits heterogeneity and cisplatin (CDDP) resistance. Although the Wee1/CDC2 and nuclear factor кB (NF-κB) pathways were reported to show abnormal activation in some tumor cells with CDDP resistance, whether there is any concrete connection is currently unclear. We explored it in human OS cells. @*Materials and Methods@#Multiple OS cell lines were exposed to a Wee1 inhibitor (AZD1775) and CDDP to assess the half-maximal inhibitory concentration values. Western blot, coimmunoprecipitation, confocal immunofluorescence, cell cycle, and Cell Counting Kit-8assays were performed to explore the connection between the Wee1/CDC2 and NF-κB pathways and their subsequent physiological contribution to CDDP resistance. Finally, CDDP-resistant PDX-OS xenograft models were established to confirm that AZD1775 restores the antitumor effects of CDDP. @*Results@#A sensitivity hierarchy of OS cells to CDDP and AZD1775 exists. In the highly CDDP-tolerant cell lines, Wee1 and RelA were physically crosslinked, which resulted in increased abundance of phosphorylated CDC2 (Y15) and RelA (S536) and consequent modulation of cell cycle progression, survival, and proliferation. Wee1 inhibition restored the effects of CDDP on these processes in CDDP-resistant OS cells. In addition, animal experiments with CDDP-resistant PDX-OS cells showed that AZD1775 combined with CDDP not only restored CDDP efficacy but also amplified AZD1775 in inhibiting tumor growth and prolonged the median survival of the mice. @*Conclusion@#Simultaneous enrichment of molecules in the Wee1/CDC2 and NF-κB pathways and their consequent coactivation is a new molecular mechanism of CDDP resistance in OS cells. OS with this molecular signature may respond well to Wee1 inhibition as an alternative treatment strategy.
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Objective To compare the effectiveness of controlling blood loss in the treatment of complex acetabular fracture between temporary occlusion of abdominal aorta by interventional balloon (TOAAIB),temporary occlusion of common iliac artery by interventional balloon (TOCAIIB) and internal iliac artery ligation (IIAL).Methods Included for this study were 113 complex acetabular fractures which had been treated at Department of Orthopaedic Trauma,Shaoguang Hospital Affiliated to Southern Medical University from January 2000 through January 2017.There were 68 males and 45 females,aged from 23 to 61 years (average,42.3 years).According to the Letournel classification,all of them belonged to complex fractures,including 10 T-type,24 double-column,16 posterior column & posterior wall,46 transverse & posterior wall and 15 anterior & posterior half-transverse ones.They were all treated by open reduction and internal fixation but differed in surgical hemostasis techniques:TOAAIB was used in 37cases,TOCAIIB in 31 and IIAL in 45.Fracture reduction was evaluated by Matta criteria.Intraoperative bleeding and postoperative wound drainage,fracture union and complications related to interventions were recorded.Hip function was evaluated by Modified d'Aubigne & Postal clinical grading system after fracture healing.Results The 3 groups (TOAAIB,TOCAIIB and IIAL) were comparable because there were no significant differences in gender,age,time from injury to surgery,Letournel classification or surgical approaches between the patients in the 3 groups (P ＞ 0.05).Anatomical reduction was achieved in 91.15％ of the patients (103/113) and satisfactory reduction in 8.85％ (10/113).Intraoperative hemorrhage was 1,631.5 ±675.5 mL in the HAL group,892.6 ±217.7 mL in the TOCAIIB group and 648.0 ± 170.2 mL in the TOAAIB group,showing significant differences between the 3 groups (P ＜ 0.05).One case of femoral artery thrombosis occurred in the TOAAIB group at the end of operation but was cured by symptomatic treatment of anticoagulation.There were no interventional complications in the other 2 groups.There were no significant differences between the 3 groups in postoperative wound drainage,fracture union time,hip function score or complications (P ＞ 0.05).Conclusions In controlling intraoperative bleeding in the surgery for complex acetabular fracture,TOAAIB may be the best,followed by TOCAIIB,and IIAL may be the worst.However,choice of a proper surgical hemostasis technique should also depend on the specific intraoperative condition of a specific patient.
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OBJECTIVE:To systematically review the efficacy and safety of Shenxian shengmai oral liquid in the treatment of slow arrhythmia,and provide evidence-based reference for clinical treatment. METHODS:Cochrane library,EMbase,PubMed, CJFD,CBM and VIP database were retrieved to collect the randomized controlled trails(RCT)of Shenxian shengmai oral liquid(tri-al group)vs.other Chinese medicines(control group)in the treatment of slow arrhythmia. After quality evaluation,the Meta-analysis was performed using Rev Man 5.14 software. RESULTS:A total of 13 RCTs were included,involving 1 023 patients. The results of Meta-analysis showed that the effective rate [RR=1.26,95%CI(1.18,1.35),P<0.001] and average heart rate [MD=5.80,95%CI (4.01,7.58),P<0.001] in test group were significantly higher than control group;there were no significant difference in the inci-dence of adverse reactions between test group and control group[OR=0.46,95%CI(0.17,1.22),P=0.12]. CONCLUSIONS:Shenx-ian shengmai oral liquid is effective with good safety in the treatment of slow arrhythmia. However,due to low quality of included studies,it remains to be further verified by high-quality and large-sample long-term RCT.