Donor graft METTL3 gene transfer ameliorates rat liver transplantation ischemia-reperfusion injury by enhancing HO-1 expression in an m6A-dependent manner.

Ischemia-reperfusion injury (IRI) is one of the most common complications in liver transplantation. METTL3 regulates inflammation and cellular stress response by modulating RNA m6A modification level. Here, the study aimed to investigate the role and mechanism of METTL3 in IRI after rat orthotopic liver transplantation. The total RNA m6A modification and METTL3 expression level was consistently down-regulated after 6 h or 24 h reperfusion in OLT, which is negatively associated with the hepatic cell apoptosis. Functionally, METTL3 pretreatment in donor significantly inhibited liver grafts apoptosis, improved liver function and depressed the proinflammatory cytokine/chemokine expression. Mechanistically, METTL3 inhibited apoptosis of grafts via upregulating HO-1. Moreover, m6A dot blot and MeRIP-qPCR assay revealed that METTL3 promoted HO-1 expression in an m6A-dependent manner. In vitro, METTL3 alleviated hepatocytes apoptosis by upregulating HO-1 under hypoxia/reoxygenation condition. Taken together, these findings demonstrate that METTL3 ameliorates rat OLT-stressed IRI by inducing HO-1 in an m6A-dependent manner, highlighting a potential target for IRI in liver transplantation.

The safety and ablation efficacy of ultrasound-guided high-intensity focused ultrasound ablation for desmoid tumors.

OBJECTIVE: To evaluate the safety and efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation for desmoid tumors (DTs). METHOD: A total of 111 patients with histologically proven DTs were included and treated by USgHIFU ablation. Adverse events were continuously evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 until 3 months after treatment. The incidence of non-perfused areas within the treated tumors, non-perfused volume rate (NPVR) and tumor volume reduction were evaluated using contrast-enhanced MRI before and one week and 3 months after the procedure. RESULTS: The enrolled patients (32 male, 79 female, mean age 29.5 ± 1.0 years) with 145 DTs (118 extra-abdominal, 16 abdominal wall, 11 intra-abdominal; median maximum diameter: 9.6 cm, range: 3-34.5 cm) underwent 188 sessions of HIFU ablation, and the mean number of ablations was 1.7 (range, 1-7) per patient. In majority of cases (143/145 cases, 98.6%), no serious adverse events were observed. There was no significant difference in the incidence of adverse events between patients who received a single treatment and those who received multiple treatments. Non-perfused area was observed within every treated tumor, and the median NPVR was 84.9% (range, 1.9-100%). The tumor volume reduction rate was 36.1 ± 4.2% at 3 months after treatment. CONCLUSION: USgHIFU ablation, as a noninvasive and easily repeatable local treatment, is a promising treatment for DTs.

High-Intensity Focused Ultrasound Ablation for Postoperative Recurrent Desmoid Tumors: Preliminary Results.

This study was aimed at evaluating the feasibility, safety and therapeutic effects of high-intensity focused ultrasound ablation (HIFUA) in the treatment of post-operative recurrent desmoid tumors. From September 2017 to May 2020, 42 consecutive patients with pathologically proven desmoid tumors treated with HIFUA for the first time were enrolled. These were divided into two groups: post-operative recurrent group (30 cases) and non-surgery group (12 cases). The basic characteristics, treatment parameters, ablation efficacy, tolerance and adverse events were recorded and compared between groups. The minimum distance between the tumor and skin surface in the post-operative recurrent group was significantly smaller than that in the non-surgery group (6.9 mm vs. 10.8 mm, p = 0.011), but there was no significant difference in the other basic characteristics (p > 0.05). The average acoustic power and intensity of treatment in the post-operative recurrent group were significantly lower than those in the non-surgery group (p = 0.006 and 0.036, respectively), but there was no significant difference in the remaining parameters or in ablation efficacy between groups (p > 0.05). HIFUA was successfully performed, and a large volume of coagulation necrosis was obtained from all patients without serious or life-threatening adverse events. Furthermore, there was no significant difference in the incidence of moderate adverse events and average length of stay between groups (p > 0.05). The average power and intensity of HIFUA treatment were adversely affected by surgical scar and tumor infiltration along the surgical path. However, HIFUA can still be used as an effective minimally invasive therapy for the local control of post-operative recurrent desmoid tumors.

Rothia nasimurium as a Cause of Disease: First Isolation from Farmed Chickens.

Rothia nasimurium is a facultative anaerobic Gram-positive coccus belonging to the Rothia genus of the Micrococcaceae family. While Rothia nasimurium is considered an opportunistic pathogen, to date few studies have investigated its pathogenicity and drug resistance. In January 2022, chickens at a poultry farm in China's Xinjiang Uygur Autonomous Region became ill and died. Treatment with commonly used Chinese medicines and antibiotics was ineffective, causing economic losses to the poultry farm. In order to determine the cause of the disease in these poultry farm chickens, the isolation and identification of the pathogens in the livers and other internal organs of the sick and dead chickens were performed. Further, animal pathogenicity tests, antibiotic susceptibility tests, and the detection of antibiotic resistance genes were carried out to analyze the pathogenicity and drug resistance of the identified pathogens. A Gram-positive coccus was isolated from the livers of the diseased chickens. The isolate was resistant to 17 antibiotics, including ciprofloxacin, chloramphenicol, and florfenicol, and was only sensitive to penicillin, amikacin, and tigecycline, to varying degrees. The results of the drug resistance gene testing indicated that the isolated bacterium carried 13 kinds of resistance genes. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, morphological observations, biochemical tests, and 16S rRNA gene sequence analysis were performed on the isolated bacterium, and it was determined that the isolated bacterial strain was Rothia nasimurium. The animal pathogenicity tests showed that the isolate caused feather loss and death in chicks; the clinical symptoms and necropsy lesions of the test chicks were consistent with those observed in the farmed chickens. A review of the literature revealed that, to date, there are no reports of infection with Rothia nasimurium in chickens. Thus, in this study, Rothia nasimurium was isolated from chickens for the first time and an investigation of the biological characteristics of the bacterium was carried out in order to provide a reference for the clinical treatment, prevention, and control of Rothia nasimurium infection.