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 the characteristics of HIV-1 molecular transmission network among HIV/AIDS patients in Zhoushan City, Zhejing Province. Methods: The newly reported HIV/AIDS cases in Zhoushan City from 2020 to 2022 were selected. Basic information was collected and whole blood samples were obtained at the initial follow-up. The pol gene sequences of HIV-1 were amplified by RT-PCR and nested-PCR. HIV-1 subtypes were identified by Neighbor-Joining phylogenetic trees. The HIV-1 molecular transmission network was built and analyzed using Cytoscape 3.6.1 software. Results: A total of 222 HIV/AIDS cases were reported in Zhoushan City from 2020 to 2022, 200 whole blood samples were collected, and 152 sequences were obtained successfully, including 122 males (80.26%), 75 cases aged 50 years and above (49.34%), 109 cases with a junior high school education or below (71.71%), and 63 cases with commercial heterosexual contact (41.45%). The main subtypes were CRF07_BC and CRF01_AE, accounting for 45.39% and 21.05%, respectively. When the threshold of genetic distance was set to 1%, 20 molecular clusters were formed in 69 cases, with a clustering rate of 45.39%. Using the molecular network constituted by reported HIV/AIDS cases in 2020 as the baseline network, there were 2 active molecular clusters with ≥5 new cases in 2022, each with 9 cases, characterized mainly by individuals aged 50 or above, with a junior high school education or below, and transmission through commercial heterosexual sex. Conclusions The predominant HIV-1 subtypes among HIV/AIDS cases in Zhoushan City are CRF07_BC and CRF01_AE. Transmission through commercial heterosexual contact among middle-aged and elderly people is a main mode of HIV transmission.

Objective To observe the pathological changes of cerebellar injury in rats with alcoholism.Methods An animal model of chronic alcoholism was established in Wistar male rats by gavage of 50%edible alcohol at increasing doses for 4 weeks.The pathological changes of cerebellar injury in rats after alcoholism were observed using an optical mi-croscope and a transmission electron microscope.Results Optical microscopy in rats with alcoholism showed signifi-cantly reduced number of granule cells and Purkinje cells in the cerebellum,and significant cell degeneration,especially in Purkinje cells.Electron microscopy showed significantly reduced organelles,irregularly shaped nucleus,and unobvi-ous and irregularly shaped nucleolus in cerebellar capillary endothelial cells.Conclusion Alcoholism induces damages to the cerebellar cells and their ultrastructure,providing a basic theoretical basis for the resulting motor and cognitive dys-function.

Objective:To screen host cell proteins interacting with rotavirus nonstructural protein 2(NSP2) and provide a theoretical basis for the discovery of antiviral targets.Methods:E. coli BL21(DE3) was transformed with a recombinant plasmid NSP2-pGEX-6P-1 and induced by IPTG to express NSP2-GST. GST affinity chromatography was used to purify NSP2-GST and Western blot was performed for verification. NSP2-GST and GST proteins were used as targets to capture interacting proteins in MA104 cells via GST pull-down. After silver staining, differential proteins were screened by in-gel enzymatic hydrolysis and mass spectrometry. Protein pilot platform was used to filter peptides, and the names and the biological functions of the proteins were obtained by Paragon algorithm. The potential connection between the interacting proteins was demonstrated by protein interaction network diagrams and GO functional annotation analysis. Moreover, the molecular docking of the top three proteins with NPS2 was predicted using HDOCK server and verified by docking and confidence scores, so as to investigate the visual docking model between interacting proteins. Results:SDS-PAGE and Western blot showed the successful purification of the recombinant protein NSP2. Ten host proteins including PKM2, which might interact with NSP2, were identified by GST pull-down and protein profiling. GO analysis and interaction diagrams revealed that RPS4X, EZR, SUPT16H and EIF2S3 mediated molecular expression; PKM2, LDHA and ATP5A1 participated in energy metabolism; HSP90, ACTB and ANXA2 were involved in biological movement. Besides, there were functional connections and interaction networks among them. Molecular docking further verified PKM2, HSP90 and RPS4X did interact with NSP2, and the interaction force were strong enough to form a stable structure.Conclusions:This study successfully discovered several host proteins including PKM2, HSP90 and RPS4X that could interact with NSP2, providing reference for investigating the process of rotavirus infection and making related prevention and control strategies.

Objective:To evaluate the effect of sleep fragmentation on postoperative cognitive dysfunction (POCD) and hippocampal glutaminergic metabolism in aged mice anesthetized with isoflurane.Methods:Forty healthy SPF-grade male C57BL/6J mice, aged 18 months, weighing 20-30 g, were divided into 4 groups ( n= 10 each) by the random number table method: normal control group (group C), sleep fragmentation group (group SF), isoflurane anesthesia/surgery group (group I/S), and sleep fragmentation plus isoflurane anesthesia/surgery group (group SF+ I/S). Group C did not received any treatment. Group SF received sleep fragmentation for 24 h. The right carotid artery exposure was performed under isoflurane anesthesia in group I/S. Group SF+ I/S received isoflurane anesthesia/right carotid artery exposure at 24 h after sleep fragmentation. The metabolic levels of glutamate (Glu), glutamine (Gln), Glu/Gln complex (Glx), and N-acetylaspartate (NAA) and their ratio to creatine (Cr) were measured by in vivo 9.4T hydrogen proton magnetic resonance spectroscopy at 2 h after anaesthesia. Y maze and Morris water maze tests were used to evaluate the cognitive function at 1-7 days after surgery. The mice were sacrificed after the behavioral testing, brain tissues were immediately obtained, and the number of Nissl bodies and density of dendritic spines in the hippocampal CA1 region were measured by Nissl staining and Golgi staining, respectively. Results:Compared with group C, the percentage of exploration time and shuttle times at the novel arm were significantly decreased, the number of crossing the original platform was decreased, the time of stay at the target quadrant was shortened, the ratios of Glu/Cr, Gln/Cr and Glx/Cr in the hippocampal CA1 region were increased, and the ratio of NAA/Cr was decreased, and the number of Nissl bodies and density of dendritic spines were decreased in SF, I/S and SF+ I/S groups ( P<0.05). Compared with group SF and group I/S, the percentage of exploration time and shuttle times at the novel arm were significantly decreased, the number of crossing the original platform was decreased, the time of stay at the target quadrant was shortened, the ratios of Glu/Cr and Glx/Cr in hippocampal CA1 region was increased, the ratio of NAA/Cr was decreased, and the number of Nissl bodies and density of dendritic spines were decreased in group SF+ I/S ( P<0.05). Conclusions:Sleep fragmentation exacerbates POCD in aged mice anesthetized with isoflurane, and the mechanism is related to nerve injury induced by abnormality in hippocampal glutaminergic metabolism excitability.

Objective:To investigate the causes and prognosis of salvage cholecystectomy for relapsing cholecystolithiasis after gallbladder-preserving gall stones removal surgery.Methods:From Jul 2015 to Dec 2019, 24 referral patients with gallstone recurrence after gallbladder-preserving cholelithotomy surgery received salvage cholecystectomy. The clinical data was analyzed to explore the causes for re-operation and the prognosis.Results:Twenty-two cases had definite gallstone recurrence, among them 19 cases were symptomatic, 2 cases were operated on suspected gallbladder tumor and common bile duct stones induced acute cholangitis. Laparoscopic cholecystectomy was successfully performed in 23 cases and 1 case was converted to open surgery. No severe complication were observed in all the patients.Conclusions:Symptomatic gallstone recurrence is the most common causes of salvage cholecystectomy after gallbladder-preserving cholelithotomy. Laparoscopic surgery procedure is still highly successful.

Objective:To analyze clinical and pathological features of follicular porokeratosis.Methods:Clinical and histopathological data were collected from 8 patients who were diagnosed with follicular porokeratosis in Department of Dermatology, Xijing Hospital, the Fourth Military Medical University from January 2015 to February 2022, and analyzed retrospectively.Results:Among the 8 patients, 6 were males and 2 were females. Their average age at onset was 36 years (range, 6 - 67 years) , and the average duration from onset to diagnosis was 6 years (range, 0.5 - 20 years) . No obvious precipitating factors were found. The patients presented with multiple or solitary, small (diameter < 1 cm) , round, long-standing stable reddish-brown maculopapules or plaques with few or no scales on their surface. Most patients had no subjective symptoms, but for some occasional mild itching sensation. Dermoscopic examination of 4 patients showed that keratotic plugs were all present at the opening of hair follicles. Histopathological manifestations of the 8 skin lesions were similar: roughly normal epidermal thickness or mildly irregular acanthosis, parakeratotic columns only at the infundibulum of hair follicles, and thinner or disappeared granular layer containing some dyskeratotic cells. Of the 8 patients, 6 were treated with surgical excision, topical drugs, or laser cautery, etc. The follow-up results showed that surgical excision could cure the primary skin lesions, but could not prevent new skin lesions, and other treatments were basically ineffective.Conclusions:Follicular porokeratosis, a special type of porokeratosis, mostly occurs on the facial area of middle-aged males. This disease usually progresses slowly, and is histopathologically characterized by unique parakeratotic columns only present at the opening of hair follicles. The diagnosis of follicular porokeratosis should rely on both clinical manifestations and histopathological findings.

Objective:To investigate the surgical regimen of butterfly-shape ear combine with cup ear and restore the appearance of auricle.Methods:From January 2012 to December 2019, 13 patients with butterfly-shape ear combined with cup ear deformity were treated in the Department of Plastic Surgery, Union Hospital, Huazhong University of Science and Technology. There were 6 males and 7 females, with an average age of 9.2 years (ranged from 6 to 15 years old). All patients were treated by folding cartilaginous flap to correct cup ear deformity, pushing forward the lobe flap and auricle composite tissue flap to repair the cleft on the ear. A piece of conchal cartilage was harvested and sutured to the outer edge of the cleft as the internal support for the cleft. The physiognomic ear length and breadth of two ears in the patients were measured immediately post operation. The results were evaluated after 6 months follow-up.Results:The appearance of all of the ears was significantly improved, no upper auricle hanging . A slight hypertrophic scar was found on the surface of one ear. The scar resolved after 6 months of ointment application and prosthesis. In all patients with unilateral ear deformity, the reconstructed ear length on the affected side was smaller than that on the contralateral side. In one patient, the difference between two sides ranged from 0.5 cm to 0.7 cm. For other patients, the difference between two sides was less than 0.5 cm. The difference between the reconstructed ear breadth of the affected ear and that of the reverse ear was less than 0.3 cm.Conclusions:This method can be applied to correct both the butterfly-shape ear deformity and cup ear malformation. The result was satisfactory.

Objective:To investigate the surgical regimen of butterfly-shape ear combine with cup ear and restore the appearance of auricle.Methods:From January 2012 to December 2019, 13 patients with butterfly-shape ear combined with cup ear deformity were treated in the Department of Plastic Surgery, Union Hospital, Huazhong University of Science and Technology. There were 6 males and 7 females, with an average age of 9.2 years (ranged from 6 to 15 years old). All patients were treated by folding cartilaginous flap to correct cup ear deformity, pushing forward the lobe flap and auricle composite tissue flap to repair the cleft on the ear. A piece of conchal cartilage was harvested and sutured to the outer edge of the cleft as the internal support for the cleft. The physiognomic ear length and breadth of two ears in the patients were measured immediately post operation. The results were evaluated after 6 months follow-up.Results:The appearance of all of the ears was significantly improved, no upper auricle hanging . A slight hypertrophic scar was found on the surface of one ear. The scar resolved after 6 months of ointment application and prosthesis. In all patients with unilateral ear deformity, the reconstructed ear length on the affected side was smaller than that on the contralateral side. In one patient, the difference between two sides ranged from 0.5 cm to 0.7 cm. For other patients, the difference between two sides was less than 0.5 cm. The difference between the reconstructed ear breadth of the affected ear and that of the reverse ear was less than 0.3 cm.Conclusions:This method can be applied to correct both the butterfly-shape ear deformity and cup ear malformation. The result was satisfactory.

The chemotherapy combined with photothermal therapy has been a favorable approach for the treatment of breast cancer. In present study, nanoparticles with the characteristics of photothermal/matrix metalloproteinase-2 (MMP-2) dual-responsive, tumor targeting, and size-variability were designed for enhancing the antitumor efficacy and achieving "on-demand" drug release markedly. Based on the thermal sensitivity of gelatin, we designed a size-variable gelatin nanoparticle (GNP) to encapsulate indocyanine green (ICG) and doxorubicin (DOX). Under an 808 nm laser irradiation, GNP-DOX/ICG responded photothermally and swelled in size from 71.58 ± 4.28 to 160.80 ± 9.51 nm, which was beneficial for particle retention in the tumor sites and release of the loaded therapeutics. Additionally, GNP-DOX/ICG showed a size reduction of the particles to 33.24 ± 4.11 nm and further improved drug release with the degradation of overexpressed MMP-2 in tumor. In the subsequently performed