The BRD4-SRPK2-SRSF2 signal modulates the splicing efficiency of ACSL3 pre-mRNA and influences erastin-induced ferroptosis in osteosarcoma cells.

Lipid metabolism is the key to ferroptosis susceptibility. However, little is known about the underlying mechanisms in osteosarcoma cells. Functional restriction of bromodomain-containing protein 4 (BRD4) reduced the susceptibility to erastin-induced ferroptosis of osteosarcoma cells both in vitro and in vivo. Mechanically, BRD4 controls the splicing efficiency of the RNA precursor (pre-mACSL3) of ACSL3 (ACSL3) by recruiting serinerich/threonine protein kinase 2 (SRPK2) to assemble the splicing catalytic platform. Moreover, the AMP-binding domain of ACSL3 significantly influences arachidonic acid synthesis and thus determines the susceptibility to erastin-induced ferroptosis. Overall, we found a BRD4-mediated pre-mACSL3 splicing influences erastin-induced ferroptosis by affecting arachidonic acid synthesis in osteosarcoma cells. Data in this study fills some of the gap in understanding the post-transcriptional regulatory mechanisms of ACSL3 and provides new insights into the mechanisms of lipid metabolism regulation and its effect on susceptibility to ferroptosis in osteosarcoma cells.

Effect of Intra-wound Vancomycin for Spinal Surgery: A Systematic Review and Meta-analysis.

Intra-site prophylactic vancomycin in spine surgery is an effective method of decreasing the incidence of postsurgical wound infection. However, there are differences in the prophylactic programs used for various spinal surgeries. Thus, this systematic review and meta-analysis aimed to evaluate the effectiveness of using intra-wound vancomycin during spinal surgery and to explore the effects of dose-dependence and the method of administration in a subgroup analysis. A total of 628 citations or studies were searched in PubMed, Ovid, Web of Science, and Google Scholar that were published before August 2016 with the terms "local vancomycin", "intra-wound vancomycin", "intraoperative vancomycin", "intra-site vancomycin", "topical vancomycin", "spine surgery", and "spinal surgery". Finally, 19 retrospective cohort studies and one prospective case study were eligible for inclusion in the systematic review and meta-analysis. The odds of developing postsurgical wound infection without prophylactic local vancomycin use were 2.83-fold higher than the odds of experiencing wound infection with the use of intra-wound vancomycin (95% confidence interval, 2.03-3.95; P = 0.083; I2 = 32.2%). The subgroup analysis including the dosage and the method of administration, revealed different results compared to previous research. The value of I2 in the 1-g group was 27.2%, which was much lower than in the 2-g group (I2 = 57.6%). At the same time, the value of I2 was 0.0% (P = 0.792, OR = 2.70) when vancomycin powder was directly sprinkled into all layers of the wound. However, there is high heterogenicity (I2 = 60.0%, P = 0.007, OR = 2.83) when vancomycin powder is not exposed to the bone graft and instrumentation. There are differences found with the method of local application of vancomycin for reducing postoperative wounds and further studies are necessary, including investigations focusing on the dose-dependent effects during spinal or the topical pharmacokinetic and other orthopaedic surgeries.

Influence of flap factors on partial necrosis of reverse sural artery flap: a study of 179 consecutive flaps.

BACKGROUND: Partial necrosis is a main complication of reverse sural artery flap. The purpose of this article is to evaluate effect of flap factors on partial necrosis in the flap. PATIENTS AND METHODS: We retrospectively reviewed data of 175 patients with 179 flaps used to reconstruct soft tissue defects in the distal lower leg, heel, and foot between April 2001 and April 2010. Posterior aspect of the lower leg was equally divided into nine zones. The flap factors were compared between the survival flaps and the partial-necrosis flaps. RESULTS: There were 141 flaps surviving completely; distal de-epithelialization and wound dehiscence developed in 12 flaps and 6 flaps, respectively; partial necrosis occurred in 20 (11.2%) flaps. Partial-necrosis rate was significantly higher in the flaps with top-edge locating in the upper 1/9 of the calf (32.3%, 10 of 31), in the flaps with length-width ratio (LWR) ≥5:1 (17.8%, 13 of 73), or in the flaps with width of skin island (width) ≥8 cm (15.2%, 16 of 105); it was significantly lower in the flaps with top-edge locating in the lower 7/9 of the calf (3.8%, 3 of 80). Seventeen (80.9%) of 21 flaps with LWR ≥6:1 survived, and the maximal LWR of completely survival flap was 7.00:1. CONCLUSION: Probability of partial necrosis occurring in reverse sural artery flap significantly increase when top-edge of the flap locates in the upper 1/9 of the calf, when LWR of the flap is 5:1 or more, or when width is 8 cm or more. The flap with top-edge locating lower 7/9 of the calf is safe and reliable.

[Relationship between proximal-tip location and partial necrosis in distally based sural neuro fasciocutaneous flap: an analysis of 157 flaps].

OBJECTIVE: To explore the influence of proximal-tip location on partial necrosis in distally based sural neuro fasciocutaneous flap. METHODS: From April 2001 to May 2009,157 distally based sural neuro fasciocutaneous flaps were conducted to repair the soft tissue defect in distal region of lower leg, ankle and feet in 153 patients. Date of the flaps and the patients were retrospectively analyzed. From the tip of lateral malleolus to the popliteal crease, posterior aspect of the lower leg was equally divided into 9 regions that were 1st to 9th region from inferiorly to superiorly, respectively. The flaps were divided into 2 groups: survival group (including uneventfully survived flaps, flaps with distally epidermal necrosis and with wound dehiscence) and partial necrosis group. Based on the location of the proximal tip of flaps, the flaps were stratified into 4 groups: flaps with the proximal tip locating in the 6th or lower region (group A), the 7th region (group B), the 8th region (group C) and the 9th region (group D). Harvesting the flaps started from exploring the perforator of peroneal vessel in the adipofascial pedicle, then the flaps were elevated retrogradely. RESULTS: Of the 157 flaps, 125 survived uneventfully,8 showed distal epidermal necrosis,wound dehiscence occurred in 6 flaps, 18 flaps (11.5%) showed distal partial necrosis. Partial necrosis occurred in zero of 19 flaps in group A (0), 1 of 44 flaps in group B (2.3% ), 7 of 62 flaps in group C (11.3% ) and 10 of 32 flaps in group D (31.3% ). The differences in partial necrosis rate between group A and group B , group B and group C, were not statistically significant (P > 0.05). Partial necrosis rate was higher in group D than in group C (P = 0.012), it was lower in group A + group B (1.6%) than in group C + group D (18. 1% ) (P = 0. 001). CONCLUSIONS: Distally based sural neuro fasciocutaneous flap can survive reliably when the proximal tip of flap is not beyond the junction between lower 7/9 and upper 2/9 of the lower leg, whereas probability of partial necrosis occurring in the flap increase significantly when the proximal tip of flap locates in upper 1/9 of the lower leg.