[Efficacy and safety of tranexamic acid in total hip arthroplasty via direct anterior approach].

OBJECTIVE: To evaluate the efficacy and safety of local application of tranexamic acid (TXA) in reducing perioperative blood loss in total hip arthroplasty via direct anterior approach (DAA). METHODS: From July 2013 to September 2018, 46 patients with avascular necrosis of the femoral head were divided into tranexamic acid group (n=23) and saline group (n=23). In the tranexamic acid group, there were 14 males and 9 females, aged 52 to 72(63.70±5.34) years old. They were diluted with 3 g tranexamic acid in 50 ml normal saline and immersed in the joint cavity for 3 min after prosthesis replacement;in the normal saline group, there were 13 males and 10 females, aged 55 to 73 (61.26±5.78) years, who were treated with the sameamount of normal saline. The blood loss, hemoglobin value, number of blood transfusion cases, the time of first landing after operation, the incidence of thrombosis and incision adverse events were compared between the two groups. Harris score was used to evaluate hip joint function at 1 and 3 months after operation. RESULTS: The incision healed well and no obvious complications occurred in the two groups. All patients were followed up for 12 to 59 months(averaged 31.11 months). No hip pain was found in the follow-up patients. Hip joint function was improved effectively and no prosthesis loosening occurred. The total perioperative blood loss in tranexamic acid group and normal saline group was(740.09±77.14) ml and (1 069.07±113.53) ml respectively, 24 hours after operation, the drainage volume was (87.61±9.28) ml, (233.83±25.62) ml, the hidden blood loss was (409.65±38.01) ml and (588.33±57.16) ml. the difference of hemoglobin before and after operation was (24.78±2.19) g / L and (33.57±2.95) g / L, the difference was statistically significant (P<0.05). There was no significant difference in blood loss, incidence of deep vein thrombosis and pulmonary embolism, and Harris score of hip joint between the two groups (P>0.05). CONCLUSION: local application of tranexamic acid in total hip arthroplasty through direct anterior approach can safely and effectively reduce perioperative blood loss, and does not increase the risk of thrombosis, and does not affect the normal recovery of joint function.

WRN functions in a RAD18-dependent damage avoidance pathway.

Werner syndrome (WS), caused by mutations in a gene (WRN) that encodes a RecQ DNA helicase, is characterized by premature aging and cancer predisposition. Cells derived from WS patients show sensitivity to several DNA damaging agents. Previous studies revealed that the WRN protein plays roles in DNA repair or damage tolerance, although it was not yet assigned to a specific pathway. Here we examined the relationship between WRN and the post-replication repair protein RAD18 by generating deletion derivatives in chicken DT40 cells. The frequency of spontaneous sister chromatid exchange in WRN(-/-)/RAD18(-/-) double mutant cells was slightly increased compared to that of either single mutant. However, the sensitivity of WRN(-/-)/RAD18(-/-) cells to 4-nitroquinoline 1-oxide and methyl methanesulfonate was almost the same as that of RAD18(-/-) cells. Moreover, the cisplatin sensitivity of RAD18(-/-) cells was slightly suppressed by disruption of WRN. These data suggest that WRN functions in a pathway involving RAD18 under damage-inducing conditions.

Possible involvement of RecQL4 in the repair of double-strand DNA breaks in Xenopus egg extracts.

Mutations in RecQL4 are a causative factor in Rothmund-Thomson syndrome, a human autosomal recessive disorder characterized by premature aging. To study the role of RecQL4, we employed a cell-free experimental system consisting of Xenopus egg extracts. RecQL4 loading onto chromatin was observed regardless of the presence or absence of EcoRI. However, in the absence of EcoRI, RecQL4 loading was suppressed by geminin, an inhibitor of pre-replicative complex formation, while in the presence of EcoRI, it was not affected. These results suggest that under the former condition, RecQL4-loading depended on DNA replication, while under the latter, the interaction occurred in response to double-stranded DNA breaks (DSBs) induced by EcoRI. DSB-induced RecQL4 loading depended on the function of the ataxia-telangiectasia mutated protein, DNA-dependent protein kinase (DNA-PK), and replication protein A, while there were only minor changes in DNA replication-associated RecQL4 loading upon suppression of these proteins. Furthermore, analyses using a chromatin-immunoprecipitation assay and quantification of gammaH2AX after induction of DSBs suggested that RecQL4 is loaded adjacent to Ku heterodimer-binding sites on damaged chromatin, and functions in the repair of DSBs.

WRN counteracts the NHEJ pathway upon camptothecin exposure.

We investigated the function of the interaction between WRN (Werner syndrome gene product) and Ku70 and between WRN and DNA-PKcs, which are components of the DNA-PKcs/Ku70/Ku80 complex, by generating KU70(-/-)/WRN(-/-) and DNA-PKcs(-/-/-)/WRN(-/-) double-gene knockout chicken DT40 cells. When treated with camptothecin (CPT), an inhibitor of DNA topoisomerase I, WRN(-/-) cells showed higher sensitivity than wild-type cells, whereas KU70(-/-) and DNA-PKcs(-/-/-) cells showed hyper-resistance. Disruption of KU70 or DNA-PKcs suppressed the sensitivity of WRN(-/-) cells to CPT, rendering them as resistant to CPT treatment as KU70(-/-) and DNA-PKcs(-/-/-) cells. On the other hand, CPT sensitivity of BLM(-/-) cells, which are defective in a RecQ helicase similar to WRN, was enhanced by deletion of KU70. The implications for the function of WRN in the non-homologous end-joining pathway of DNA repair involving Ku70 and DNA-PKcs, which may be the cause of lethality in the presence of CPT, will be discussed.