Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.

Objective To evaluate the in vitro synergistic antifungal activity of HDAC inhibitors in combination with azole drugs against azoles-resistant Candida strains. Methods The checkerboard microdilution method was used to evaluate the antifungal activity of the HDAC inhibitors in combination with azole drugs against clinically drug-resistant strains. The fungistatic activity and toxicity of Rocilinostat was determined through time-growth curve assay and cytotoxicity assay. Results The compound Rocilinostat combined with azole drugs showed excellent synergistic antifungal activity against a variety of azoles-resistant Candida albicans and Candida glabrata. The combination of high concentration Rocilinostat with FLC exhibited fungistatic effects. Very low toxicity was detected with Rocilinostat towards normal cells. Rocilinostat showed better HDAC inhibitory activity than SAHA. Conclusion As a fungi HDAC inhibitor, Rocilinostat has excellent in vitro synergistic antifungal activity and no severe toxicity to normal human cells.

Objective:To investigate the clinical efficacy of the vascularised semi-split fibular flap with lateral approach in ankle fusion.Methods:A total of 54 patients who underwent ankle fusion through the lateral menstrual approach by the Department of Trauma and Micro Orthopaedics, Zhongnan Hospital of Wuhan University from June 2015 to December 2020 was retrospectively analysed. Of the 54 patients, 27 patients who underwent ankle fusion with a semi-split fibular flap carrying blood supply were assigned to the fibular flap group, while other 27 patients who had ankle fusion with lateral plate were assigned to the plate group. The ankle fusions for both groups were performed by the same surgical team. The clinical efficacy of the 2 groups was evaluated by the success rate of bone fusion, the American Orthopedic Foot and Ankle Surgery(AOFAS) Ankle-Hindfoot Score System, and the Visual analog score(VAS). All the patients entered the postoperative follow-up at outpatient clinic.Results:The follow-up lasted for 12-24 months, with an average of 15 months. At 6 months after surgery, 24 patients in the fibular flap group achieved osseous union with 88.9% in the success rate of bone fusion. While 17 patients in the plate group achieved osseous union, with the success rate of bone fusion at 63.0%. There was a statistically significant difference between the groups( P<0.05). At 1 year after surgery, all 27 patients in the fibular flap group achieved bony union, with a 100% of the success rate of bone fusion, while 23 patients in the plate group achieved bony union at a 85.2% success rate of bone fusion, with 4 patients failed to heal. The difference was statistically significant( P<0.05). The AOFAS scores of the fibular flap group were 41.3±12.0, 65.6±5.6, and 79.1±7.0 before operation, at 6 months after operation and 1 year after operation, respectively, while the scores for the plate group at the same time were 40.8±11.3, 64.5±4.1 and 69.3±7.2. There was no significant difference in the scores between the groups before surgery and at 6 months after the operation ( P>0.05). The scores at 1 year after surgery in the fibular flap group was significantly higher than the plate group, and there was a statistically significant difference( P<0.05). The preoperative VAS score in the fibular flap group was 7.6±1.3, while it was 7.5±1.1 in the plate group. There was no significant difference between the groups in VAS score( P>0.05). However, the VAS score at 1 year after surgery was found at 1.8±0.9 in the plate group, and 1.9±0.8 in the fibular flap group and the difference between groups was statistically significant( P<0.05). Conclusion:The surgical procedure of semi-split fibular flap through the lateral approach has lower complications and higher success rate in ankle fusion in comparison with those of the fusion with lateral plate. Thus, further clinical investigations can be considered.

Objective To discuss indications,operation method and clinical outcome of posterior short-segment pedicle fixation at the injured level for treatment of thoracolumbar spine fractures.Methods A total of 38 patients with thoracolumbar spine fractures were equally randomized to Group A(treated with classic short-segment pedicle screw fixation)and Group B(treated with short-segment pedicle screw fixation at the injured level)based on fixation methods(19 patients per group).Preoperative and postoperative JOA score,segmental lordosis(Cobb' s angle),R value(anterior fractured vertebral body height/mean normal vertebral body height×100%),VSA score and internal fixation condition were assessed and compared clinically.Results All patients were followed up for 6-37 months(mean 20.5 months),which showed no statistical difference upon Frankel scores of two operation modes,while the segmental lordosis,VAS score and R value in Group B were than those in Group A.There occurred nuts loosening in one patient and screw bending in one in Group A.There was no implant breakage,loosening or emersion in Group B.Conclusion Posterior short-segmental fixation at the injured level is an adequate and effective procedure for compression fractures and mild to moderate burst fractures of the thoracolumbar spine.

Objective To investigate the safety and efficacy of ultrasound ablation in treatment of uterine fibroids. Methods Ninety-nine patients with 117 leiomyomas in total treated by Haifu JC focused ultrasound tumor therapeutic system were enrolled in prospective and non-randomized clinical trial in First Affiliated Hospital of Chongqing Medical University and Academy of Military Medical Sciences. Ultrasound ablation was performed guided by real-time ultrasonography under conscious sedation for single session. All patients were followed up at 6 months after treatment. On the day of treatment and after 1 month, patients were given by magnetic resonance imaging(MRI) exam to evaluate the effect of fibroids ablation. At 3 and 6months after treatment, the ratio of ablated area and volume reduction of fibroids more than 50% were evaluated by MRI exam again. The symptoms improvements were evaluated by uterine fibroid symptom (UFS) and complications were analyzed by guideline of society of international radiation (SIR). Results The average ablated area ratio of the target fibroid was (76 ± 24)%. The average reduction in fibroid volume determined by MRI at 3 and 6 months after treatment was (45 ± 21)% and (59 ± 26)%. Which were significantly decreased than those before treatment (P < 0. 05). At 6 months after treatment, 84. 6% (99/117) of patients showed more than 50% volume reduction, the rate of improved symptom score was 92%(66/72). All patients could resume normal daily activities at 2 hours after treatment. The adverse reactions of SIR C - D included delayed hospitalization, repeat treatment and increased level of nursing. E - F included permanent sequelae and death. In this study, no adverse reactions of C - F were recorded. Common complications (SIR A- B, only observation or simple management without sequelae) were 35% (35/99).Four cases with adverse reactions B of SIR were found, including 2 cases with skin burning of degree Ⅱ and 2 cases with febrile, they were administered by symptomatic therapy and changing dressing The other adverse reaction A of SIR included sorness of buttock, vaginal discharge, dysuria and painful urination, they were only suggested by follow-up. Conclusion It was efficacy and safe that ultrasound ablation as a single strategy were used in treatment of uterine fibroids.