Background: Extensive hepatocyte mortality and the absence of specific medical therapy significantly contribute to the unfavorable prognosis of acute liver failure (ALF). Ferroptosis is a crucial form of cell death involved in ALF. In this study, we aimed to determine the impact of Mediator complex subunit 1 (Med1) on ferroptosis and its potential hepatoprotective effects in ALF. Results: Med1 expression is diminished in the liver of lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced ALF mice, as well as in hepatocytes damaged by H₂O₂ or TNF-α/D-GalN in vitro. Med1 overexpression mitigates liver injury and decreases the mortality rate of ALF mice by ferroptosis inhibition. The mechanism by which Med1 inhibits erastin-induced ferroptosis in hepatocytes involves the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant genes heme oxygenase-1 (HO-1), glutamate cysteine ligase catalytic (GCLC), and NAD(P)H quinone oxidoreductase 1 (NQO1). Furthermore, Med1 overexpression suppresses the transcription of proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the liver of mice with LPS/D-GalN-induced ALF. Conclusion: Overall, our research findings indicate that Med1 suppresses ferroptosis and alleviates liver injury in LPS/D-GalN-induced ALF through the activation of Nrf2. These findings substantiate the therapeutic viability of targeting the Med1-Nrf2 axis as a means of treating individuals afflicted with ALF. Graphical

Disseminated Cryptococcosis infection typically occurs in immunocompromised patients, often manifested as pneumonia or meningoencephalitis. Cases with involvement of either prostate or adrenal glands are less frequent. We describe a case of an immunocompromised 62-year-old man with new-found Idiopathic CD4 + T lymphocytopenia who presented with urinary irritation symptoms followed by headache. The patient was finally diagnosed as disseminated cryptococcosis of prostate, adrenal gland involvement with the help of combining histopathology of formalin-fixed, paraffin-embedded tissue with metagenomic next-generation sequencing technique to identify C neoformans sensu stricto in prostate, adrenal gland tissues. Clinicians should be aware of atypical presentations of cryptococcal disease. In this case of cryptococcosis in immunocompromised patients, we find that cryptococcosis can affect varied organs simultaneously and should be considered in the differential of infectious diseases. And mNGS technology helps to confirm the diagnosis.

Background: Streptococcus suis is an emerging zoonotic pathogen that mainly causes meningitis, sepsis, arthritis, endocarditis, and endophthalmitis in human. To the best of our knowledge, Spinal canal infection caused by Streptococcus suis has rarely been reported. Case presentation: Here we report a case of spinal canal infection caused by Streptococcus suis in a 50-year-old male patient. The patient had a history of close contact with sick pigs days before disease onset. Initially he presented with headache and fever. After admission, the patient began to experience lower back pain, which led physicians to perform a lumber puncture. Meta-genomic next generation sequencing helped identify Streptococcus suis in the cerebrospinal fluid. MRI imaging indicated a spinal canal infection caused by Streptococcus suis. Conclusions: Spinal canal infection is an uncommon disease of Streptococcus suis infection. This case report indicates that people presented with fever, headache and lower back pain should also be suspected as Streptococcus suis infection, especially for those who have had a history of sick pig contact.

Vertebral osteomyelitis (VO) is an infection of the spine with increasing prevalence due to improved diagnostics and aging populations. Multiple pathogens, including Mycobacterium tuberculosis, Brucella spp., and pyogenic bacteria, can cause VO, making differential diagnosis complex, especially in regions with endemic brucellosis and tuberculosis. Early and accurate diagnosis is essential for appropriate treatment. This was a single-center, retrospective, observational study performed between 2019 and 2022 in Kashi, Xinjiang. In this study, a total of 319 patients were enrolled, comprising 45.5% with tuberculous vertebral osteomyelitis (TVO; 52.4% females), 37.9% with brucellar vertebral osteomyelitis (BVO; 19.8% females), and 16.6% with pyogenic vertebral osteomyelitis (PVO; 52.8% females). Demographically, TVO had a longer mean time to diagnosis compared to BVO and PVO. BVO was more prevalent in male, and PVO patients had higher rates of spinal surgery history (45.3%) and diabetes (13.2%). Clinically, TVO patients presented with fever (72.4%), sweating (83.4%), weight loss (71.7%), and appetite loss (84.8%) more frequently, while BVO patients reported more lower back pain (86.0%). Laboratory investigations revealed significantly higher leucocyte and neutrophil levels in PVO, whereas TVO patients had elevated monocyte-to-lymphocyte and platelet-to-lymphocyte ratios. Radiologically, TVO patients exhibited a higher incidence of thoracic involvement (56.6%) and skip lesions (20%). Microbiologically, BVO and PVO had high positive culture rates (84.3 and 84.9%, respectively), with M. tuberculosis isolated from only 4.1% of TVO patients. These findings underscore the distinct clinical, laboratory, and radiological characteristics of TVO, BVO, and PVO.

Background: Acute-on-chronic liver failure (ACLF) is a common clinical type of liver failure, and patients with acute-on-chronic liver failure are prone to fungal infections, especially the increasing incidence of invasive pulmonary aspergillosis (IPA). Voriconazole is recommended as the first-line antifungal agent in the treatment of invasive aspergillosis; however, no recommendation has been given for patients with severe liver cirrhosis (Child–Pugh C) and liver failure. This trial aims to examine the therapeutic effects and safety of voriconazole in the treatment of IPA in patients with liver failure. Methods: This study is a non-double-blind randomized controlled trial. The 96 eligible acute-on-chronic liver failure patients complicated with invasive pulmonary aspergillosis will be randomly assigned to receive either the optimized voriconazole regimen or the recommended voriconazole regimen for patients with mild to moderate liver cirrhosis (Child–Pugh A and B), at a 1:1 ratio, with an 8-week follow-up period. The antifungal efficacy of voriconazole will be the primary outcome measure. Plasma voriconazole trough concentration, the laboratory examination (CRP, PCT, ESR, etc.), chest CT, adverse events, and mortality at week 4 and 8 will be the secondary outcome measures. Discussion: This trial aims to demonstrate the efficacy and safety of voriconazole in the treatment of IPA in patients with liver failure, which is expected to provide a reference for scientific optimization of voriconazole regimens and a realistic basis for the standardized treatment of acute-on-chronic liver failure patients complicated with invasive pulmonary aspergillosis. Trial registration: The trial was registered with the Chinese Clinical Trial Registry, ChiCTR2100048259. Registered on 5 July 2021.

Carbapenem-resistant Enterobacteriaceae (CRE) are the highest priority pathogens of the World Health Organization, and their prevalence in end-stage liver disease (ESLD) patients is increasing. CRE colonization is an independent risk factor for CRE infections. We aimed to assess risk factors and explore the relationship between CRE colonization, infection, and prognosis in patients with ESLD. A total of 311 patients with ESLD were screened for CRE colonization by fecal swabs from October 2020 to January 2022. Antimicrobial susceptibility was tested using the broth microdilution method. Carbapenem resistance genes, multilocus sequence type, and capsular serotype were analyzed by polymerase chain reaction (PCR). Seventeen CRE strains were detected, among which the most common was Klebsiella pneumoniae. The CRE colonization rate was 5.5%. Artificial liver support was an independent risk factor for CRE colonization. Compared to the non-CRE colonization group, the colonization group had a higher incidence of CRE infection and a worse prognosis. Furthermore, these strains were not closely related, and all were sensitive to polymyxin and tigecycline. There was a high colonization rate in ESLD patients, and colonization strains were highly diverse. CRE colonization deserves attention in these patients, especially when treated with artificial liver support.