Emerging evidences have indicated the role of ferroptosis in the progression of metabolic-associated fatty liver disease (MAFLD); thus, inhibiting ferroptosis is a promising strategy for the development of MAFLD therapeutics. Recent studies have demonstrated the antioxidative effect of the gut commensal bacterium Akkermansia muciniphila (A. muc); however, whether it can alleviate ferroptosis remains unclear. The current study indicates A. muc intervention efficiently reversed high-fat high-fructose diet (HFHFD)-induced lipid peroxidation and ferroptosis in the liver. These beneficial effects were mediated by activation of the hepatic AMPK/SIRT1/PGC-1α axis, as evidenced by the finding that AMPK deficiency abrogated the amelioration of lipid peroxidation in vitro and in vivo. Furthermore, the short-chain fatty acids (SCFAs) were enriched upon A. muc treatment, and acetate was identified as a key activator of hepatic AMPK signalling. Mechanistically, microbiota-derived acetate was transported to the liver and metabolized to adenosine monophosphate (AMP), which triggered AMPK activation. Furthermore, a colonization assay in germ-free mice confirmed that A. muc mediated antiferroptotic effects in the absence of other microbes. These data indicated that A. muc exerts antiferroptotic effects against MAFLD, at least partially by producing acetate, which activates the hepatic AMPK/SIRT1/PGC-1α axis to alleviate ferroptosis via the inhibition of polyunsaturated fatty acid (PUFA) synthesis.

Objective:To investigate efficacy and advantages of combined local flaps in repairing large defects in patients with nasal and perinasal non-melanoma skin cancers after Mohs micrographic surgery.Methods:From March 2018 to November 2020, 11 patients with nasal and perinasal non-melanoma skin cancers, who underwent Mohs micrographic surgery followed by repair with combined local flaps, were collected from Department of Dermatology, the Second Hospital of Hebei Medical University. According to the location and size of postoperative defects, flaps were designed based on the nasal aesthetic subunit principle. For large defects that could not be directly sutured or covered by a single local flap, 2 or 3 kinds of flaps were applied in combination, such as kite flap, modified diamond flap, nasolabial skin flap, bilobed skin flap, etc.Results:Among the 11 patients, 10 were diagnosed with basal cell carcinoma and 1 with squamous cell carcinoma, and the area of defects ranged from 2.0 cm × 2.3 cm to 2.7 cm × 3.6 cm. After Mohs micrographic surgery combined with local skin flap repair, all skin flaps survived well without blood supply obstruction, the texture, color and contour of the skin flaps were similar to those of the surrounding normal skin, and no obvious scars were formed. During the postoperative follow-up of 4 to 32 months, no recurrence of the tumors occurred, and the patients was satisfied with the appearance.Conclusion:To repair large defects using combined skin flaps of 2 or 3 kinds after Mohs micrographic surgery in patients with nasal and perinasal non-melanoma skin cancers can maintain the normal nasal or perinasal morphological structure and aesthetic appearance, and yield a satisfactory cosmetic effect.

Objective:To evaluate the safety and efficacy of eltrombopag combined with immunosuppressive therapy in patients with aplastic anemia (AA) in China.Methods:We investigated and analyzed the clinical data of AA patients from 14 hematological treatment centers who were treated with oral eltrombopag for at least 3 mon.Results:We enrolled 56 AA patients, including 19 treatment-na?ve patients and 37 IST-refractory patients. The median administration period for eltrombopag was 7 (3-31) months, and the median maximum stable dosage was 75 mg/d (50-150 mg/d) . The 3-month hematological response (HR) rate was 60%, and the complete response (CR) rate was 30% in 10 SAA patients who were treated with first-line eltrombopag and standard IST (ATG+CsA) . Eight of 9 eltrombopag and CsA ± androgen first-line treated SAA patients responded (8/9, 89%) and 4 (44%) gave CR. The overall HR and CR rates were 79% and 52.6%, respectively, among these 19 patients by the end of the follow-up period. Of the 19 AA patients who were refractory to CsA ± androgen, 11 achieved HR (57.9%) at 3 mon, and the best HR rate was 44% in standard IST (ATG+CsA) refractory 18 patients after eltrombopag treatment. Fifty-one percent of the patients experienced mild or moderate adverse events, and gastrointestinal discomfort was the most common adverse effect reported by the study subjects.Conclusion:Adding Eltrombopag in first-line IST can accelerate the acquisition and improve the quality of hematological responses in AA patients. AA with relatively more residual hematopoietic cells may be well treated with eltrombopag and non-ATG IST. Eltrombopag can be used as salvage therapy for CsA±androgen refractory patients. Eltrombopag was generally safe and well tolerated by AA patients in China.