Enrichment of Wee1/CDC2 and NF-κB Signaling Pathway Constituents Mutually Contributes to CDDP Resistance in Human Osteosarcoma / Journal of the Korean Cancer Association, 대한암학회지

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.

Comparison of temporary occlusion of abdominal aorta, temporary occlusion of common iliac artery and internal iliac artery ligation in the treatment of complex acetabular fracture / 中华创伤骨科杂志

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.

Development of a New Molecular Marker for the Resistance to Tomato Yellow Leaf Curl Virus.

Tomato yellow leaf curl virus (TYLCV) responsible for tomato yellow leaf curl disease (TYLCD) causes a substantial decrease in tomato (Solanum lycopersicum L.) yield worldwide. The use of resistant variety as a sustainable management strategy has been advocated. Tremendous progress has been made in genetically characterizing the resistance genes (R gene) in tomato. Breeding tomato for TYLCV resistance has been based mostly on Ty-3 as a race-specific resistance gene by introgression originating from wild tomato species relatives. Improvement or development of a cultivar is achievable through the use of marker-assisted selection (MAS). Therefore, precise and easy use of gene-targeted markers would be of significant importance for selection in breeding programs. The present study was undertaken to develop a new marker based on Ty-3 gene sequence that can be used for MAS in TYLCV resistant tomato breeding program. The new developed marker was named ACY. The reliability and accuracy of ACY were evaluated against those of Ty-3 linked marker P6-25 through screening of commercial resistant and susceptible tomato hybrids, and genetic segregation using F2 population derived from a commercial resistant hybrid AG208. With the use of bioinformatics and DNA sequencing analysis tools, deletion of 10 nucleotides was observed in Ty-3 gene sequence for susceptible tomato variety. ACY is a co-dominant indel-based marker that produced clear and strong polymorphic band patterns for resistant plant distinguishing it from its susceptible counterpart. The obtained result correlates with 3:1 segregation ratio of single resistant dominant gene inheritance, which depicted ACY as gene-tag functional marker. This marker is currently in use for screening 968 hybrids varieties and one thousand breeding lines of tomato varieties stocked in Jiangsu Green Port Modern Agriculture Development Company (Green Port). So far, ACY has been used to identify 56 hybrids and 51 breeding lines. These newly detected breeding lines were regarded as potential source of resistance for tomato breeding. This work exploited the sequence of Ty-3 and subsequently contributed to the development of molecular marker ACY to aid phenotypic selection. We thus recommend this marker to breeders, which is suitable for marker-assisted selection in tomato.

Comparison of abdominal aorta disruption and internal iliac artery ligation for management of complex acetabular fractures / 中华创伤杂志

Objective To compare the value of abdominal aorta occlusion and internal iliac artery ligation in preventing massive bleeding during surgical treatment of complex acetabular fractures.Methods The study enrolled 67 cases of complicated acetabular fractures,of which 35 had control of hemorrhage via abdominal aorta blockage and 32 via internal iliac artery ligation.Intraoperative bleeding and postoperative drainage volumes were compared of the two operations.Results Of the two operations to control hemorrhage,abdominal aorta occlusion was significantly different from internal iliac artery ligation with regard to amount of blood loss [(648.00 ± 170.20) ml vs (231.18 ± 21.90) ml,t =1.693,P ＜ 0.05],but there was no significant difference between abdominal aorta occlusion and internal iliac artery ligation in postoperative drainage volume [(1 631.50 ± 675.50) ml vs (236.00 ±23.80) ml].Conclusion During surgical treatment of complex acetabular fractures,abdominal aorta occlusion is superior to internal iliac artery ligation in preventing bleeding and can be safe and effective for the fact that the bilateral common iliac arteries are occluded completely for a clear operation field.

Clinical study of applying low molecular weight heparin calcium in different periods of reteplase for acute myocardial infarction / 中国医师进修杂志

Objective To compare the effect of applying low molecular weight heparin calcium in different periods of reteplase for acute myocardial infarction(AMI).Methods Ninety-one cases of AMI were divided into group A(30 cases),group B(30 cases)and group C(31 cases)by random digits table.The patients in three groups were given reteplase intravenous thrombolysis,and 5000 U low molecular weight heparin calcium was abdominal wall subcutaneous injections once 12 h at intravenous thrombolysis immediately(group A),after intravenous thrombolysis 6 h(group B)and 12 h(group C).They all were treated for 7-10 d.The rate of coronary artery recanalization,acute phase complication and adverse reaction were compared among three groups.Results The rate of coronary artery recanalization in group A,B and C was 76.7％(23/30),96.7％(29/30),74.2％(23/31)respectively.The rate of coronary artery recanalization in group B was significantly higher than that in group A and C(P ＜ 0.05).The rate of acute phase complication and adverse reaction in group B[33.3％(10/30)]was significantly lower than that in group A and C[70.0％ (21/30)and 61.3％(19/31)](P ＜ 0.05).Conclusions After reteplase intravenous thrombolysis in 6 h,applying low molecular weight heparin calcium can significantly improve the rate of coronary artery recanalization and reduce the rate of acute phase complication and adverse reaction.

Management of acetabular comminuted fractures combined with compressive defects / 中华创伤骨科杂志

Objective To discuss the therapy for acetabular comminuted fractur e combined with compressive defects. Methods From July 1997 to February 2005, 43 cases of comminuted acetabular fracture combined with compressive defect were t reated. 25 cases were obsolete, 16 fresh, and 2 malformed (90 days after injury) . 34 cases were complicated fractures with defects, and 9 simple fractures with defects. The defect volumes ranged from 3 to 9 cm3, averaging 4.5 cm3. They were treated with ATMFS (acetabular tridimensional memory fixation system) to fixate the comminuted bone fragments tridimensionally. The modified acetabular approac h, reduction of acetabular comminuted articular face, anatomical reconstruction of posterior wall of acetabulum with autogenous ilium, autogenous and artificial bone implantation and bone wax isolation were used. The follow-ups lasted from 5 to 86 months, averaging 15.7 months. Results 31 cases achieved anatomical red uction by filling up the compressive defects. 12 cases were treated by anatomica l reconstruction of posterior wall. On average, 5.3 months after operation, the injured hip joint was as good as the healthy one in 40 cases. Ischemia necrosis of femoral head occurred in 1 case, and 2 cases experienced heterotopic ossifica tion with ischemia necrosis of femoral head which led to osseous fusion of hip j oint. Conclusion The new methods for treatment of acetabular fractures with comp ressive defects elevate the reduction rate of acetabulum and femoral head, and a re effective for the functional recovery of hip joint.