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Objective This study aims to explore the etiology, clinical manifestations, diagnosis and treatment, and prognosis of acquired hemophilia A (AHA), and to improve the clinical understanding, diagnosis, and treatment of AHA. Methods A retrospective analysis was conducted on 7 cases of AHA diagnosed at our hospital from January 2013 to December 2023. Relevant literature was searched in PubMed, CNKI, and Wanfang databases using the terms “Acquired hemophilia A”. A comparative analysis was performed on general data, etiology, diagnosis time, clinical manifestations, treatment, and prognosis. Results All 7 AHA patients were female, with a median age of 44.1 years (range 26-68 years). One case was secondary to hepatitis B virus infection; one was secondary to pregnancy; one developed after gastrointestinal surgery; and one was secondary to Sjögren’s syndrome. Skin ecchymosis was the most common clinical manifestation of AHA（7/7）, with increased activated partial thromboplastin time (APTT), decreased coagulation factor Ⅷ(FⅧ) activity (FⅧ:C), and increased FⅧ antibody (FⅧ: Ab). Six patients received hemostatic therapy, and all patients received antibody clearance therapy. The median follow-up time was 391 days (28-777 days), with one patient lost to follow-up. Four patients achieved complete response (CR), with a median time to CR of 40 days (27-48 days). One patient achieved partial response (PR), and no recurrence occurred. One patient had no response (NR) and no new clinical bleeding during the follow-up period. The literature review found that AHA can occur in both men and women, with a predominance of women of childbearing age. 56.8% of the patients had idiopathic AHA, while 11.4%, 11.1%, and 6.7% patients of AHA associated with tumors, autoimmune diseases, and pregnancy, respectively. The male to female ratio is 1.18:1, with median ages of 65.6 years and 55.8 years, respectively. Bypass pathway drugs were the first choice for hemostatic treatment, and antibody clearance therapy was mostly based on glucocorticoids, cyclophosphamide, and rituximab. Conclusions AHA can be secondary to tumors, autoimmune diseases, infections, pregnancy, etc. Patients may have skin bruising; The use of bypass routes for hemostasis and immunosuppressive therapy to clear antibodies results in a good prognosis for most patients.

A growing body of evidence suggests interplay between the gut microbiota and the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the role of the gut microbiome in early detection of NAFLD is unclear. Prospective studies are necessary for identifying reliable, microbiome markers for early NAFLD. We evaluated 2487 individuals in a community-based cohort who were followed up 4.6 years after initial clinical examination and biospecimen sampling. Metagenomic and metabolomic characterizations using stool and serum samples taken at baseline were performed for 90 participants who progressed to NAFLD and 90 controls who remained NAFLD free at the follow-up visit. Cases and controls were matched for gender, age, body mass index (BMI) at baseline and follow-up, and 4-year BMI change. Machine learning models integrating baseline microbial signatures (14 features) correctly classified participants (auROCs of 0.72 to 0.80) based on their NAFLD status and liver fat accumulation at the 4-year follow up, outperforming other prognostic clinical models (auROCs of 0.58 to 0.60). We confirmed the biological relevance of the microbiome features by testing their diagnostic ability in four external NAFLD case-control cohorts examined by biopsy or magnetic resonance spectroscopy, from Asia, Europe, and the United States. Our findings raise the possibility of using gut microbiota for early clinical warning of NAFLD development.

Background: Myocardial inflammation and apoptosis induced by cirrhosis are among the primary mechanisms of cirrhotic cardiomyopathy. CD73, a common extracellular nucleotidase also known as 5'-nucleotidase, is associated with the progression of inflammation and immunity in multiple organs. However, the mechanism by which CD73 contributes to myocardial inflammation and apoptosis in cirrhosis remains unclear., Methods: In this study, a cirrhotic cardiomyopathy model in mice was established by bile duct ligation. Myocardial-specific overexpression of CD73 was achieved by tail vein injection of AAV9 (adeno-associated virus)-cTNT-NT5E-mCherry, and cardiac function in mice was assessed using echocardiography. Myocardial inflammation infiltration and apoptosis were evaluated through pathological observation and ELISA assays. The expression of CD73, A2AR, apoptotic markers, and proteins related to the NF-κB pathway in myocardial tissue were measured., Results: In the myocardial tissue of the cirrhotic cardiomyopathy mouse model, the expression of CD73 and A2AR increased. Overexpression of CD73 in the myocardium via AAV9 injection and stimulation of A2AR with CGS 21680 inhibited myocardial inflammation and cardiomyocyte apoptosis induced by cirrhosis. Additionally, overexpression of CD73 suppressed the activation of the NF-κB pathway by upregulating the expression of the adenosine receptor A2A., Conclusion: Our study reveals that the CD73/A2AR signaling axis mitigates myocardial inflammation and apoptosis induced by cirrhosis through negative feedback regulation of the NF-κB pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Shao, Xia, Liu, Zhang, Zhao, Dang, Qian, Xu, Yu and Wang.)

Background: Nonresolving inflammation is a major driver of disease and needs to be taken seriously. Hypoxia-inducible factor (HIF) is closely associated with inflammation. Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs), as stabilizers of HIF, have recently been reported to have the ability to block inflammation. We used MK8617, a novel HIF-PHI, to study its effect on macrophage inflammation and to explore its possible mechanisms., Methods: Cell viability after MK8617 and lipopolysaccharide (LPS) addition was assessed by Cell Counting Kit-8 (CCK8) to find the appropriate drug concentration. MK8617 pretreated or unpretreated cells were then stimulated with LPS to induce macrophage polarization and inflammation. Inflammatory indicators in cells were assessed by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR), western blot (WB) and immunofluorescence (IF). The level of uridine diphosphate glucose (UDPG) in the cell supernatant was measured by ELISA. Purinergic G protein-coupled receptor P2Y 14 , as well as hypoxia-inducible factor-1α (HIF-1α) and glycogen synthase 1 (GYS1) were detected by qRT-PCR and WB. After UDPG inhibition with glycogen phosphorylase inhibitor (GPI) or knockdown of HIF-1α and GYS1 with lentivirus, P2Y 14 and inflammatory indexes of macrophages were detected by qRT-PCR and WB., Results: MK8617 reduced LPS-induced release of pro-inflammatory factors as well as UDPG secretion and P2Y 14 expression. UDPG upregulated P2Y 14 and inflammatory indicators, while inhibition of UDPG suppressed LPS-induced inflammation. In addition, HIF-1α directly regulated GYS1, which encoded glycogen synthase, an enzyme that mediated the synthesis of glycogen by UDPG, thereby affecting UDPG secretion. Knockdown of HIF-1α and GYS1 disrupted the anti-inflammatory effect of MK8617., Conclusions: Our study demonstrated the role of MK8617 in macrophage inflammation and revealed that its mechanism of action may be related to the HIF-1α/GYS1/UDPG/P2Y 14 pathway, providing new therapeutic ideas for the study of inflammation., Competing Interests: The authors declare that they have no competing interests., (© 2023 Qian et al.)

Objective: The purpose of this study was to analyze the quality of MDCT images obtained using iopromide with two different concentrations of iodine (300 and 370 mg I/mL) in daily clinical settings., Subjects and Methods: Patients from 38 hospitals in China undergoing abdominal or pelvic CT with iopromide were prospectively recruited. MDCT was performed using iopromide with an iodine concentration of 300 or 370 mg I/mL. CT quality image was graded as excellent, good, adequate, and poor. Objective indicators were the contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR). Outcomes were compared according to organ studied, tumor type (benign vs malignant), saline usage, and type of MDCT (16-MDCT vs 64-MDCT)., Results: A total of 4506 patients (63.7% men) with a mean (± SD) age of 56.3 ± 14.1 years and mean body mass index (weight in kilograms divided by the square of height in meters) of 23.2 ± 3.3 were included. Iopromide with 300 mg I/mL was used for 3042 patients (67.5%), and 370 mg I/mL was used for 1464 patients (32.2%). A total of 1847 scans (41.0%) had excellent image quality, 2454 (54.5%) had good quality, 176 (3.9%) had adequate quality, and 29 (0.6%) had poor quality. No differences were noted between CT scans that did or did not use saline, 16-MDCT versus 64-MDCT scans, and 300 versus 370 mg I/mL iopromide. Variations in the CNR and SNR were noted between the two iodine concentrations with respect to other parameters examined., Conclusion: Iopromide with both concentrations of iodine provided acceptable image quality, though according to CNR and SNR, one or the other may provide better quality in different situations.