PPAR agonists are often used in HBV infected patients with metabolic disorders. However, as liver-enriched transcriptional factors, PPARs would activate HBV replication. Risks exsit in such patients. This study aimed to assess the influence of commonly used synthetic PPAR agonists on hepatitis B virus (HBV) transcription, replication and expression through HBV replicative mouse models, providing information for physicians to make necessary monitoring and therapeutic adjustment when HBV infected patients receive PPAR agonists treatment. The HBV replicative mouse model was established by hydrodynamic injection of HBV replicative plasmid and the mice were divided into four groups and treated daily for 3 days with saline, PPAR pan-agonist (bezafibrate), PPARα agonist (fenofibrate) and PPARγ agonist (rosiglitazone) respectively. Their serum samples were collected for ECLIA analysis of HBsAg and HBeAg and real-time PCR analysis of Serum HBV DNA. The liver samples were collected for DNA (Southern) filter hybridization of HBV replication intermediates, real-time PCR analysis of HBV mRNA and immunohistochemistry (IHC) analysis of hepatic HBcAg. The alternation of viral transcription, replication and expression were compared in these groups. Serum HBsAg, HBeAg and HBV DNA were significantly elevated after PPAR agonist treatment. So did the viral replication intermediates in mouse livers. HBV mRNA was also significantly increased by these PPAR agonists, implying that PPAR agonists activate HBV replication at transcription level. Moreover, hepatic HBcAg expression in mouse livers with PPAR agonist treatment was elevated as well. Our in vivo study proved that synthetic PPAR agonists bezafibrate, fenofibrate and rosiglitazone would increase HBV replication. It suggested that when HBV infected patients were treated with PPARs agonists because of metabolic diseases, HBV viral load should be monitored and regimens may need to be adjusted, an antiviral therapy may be added.

Leishmaniasis is a zoonotic disease caused by Leishmania spp. and spreads through sandfly bites. Owing to the wide range of nonspecific clinical symptoms, patients with leishmaniasis are frequently misdiagnosed or underdiagnosed. The study participants were 7 metagenomic next-generation sequencing (mNGS)–diagnosed patients with leishmaniasis who could not be diagnosed using conventional methods. Clinical data were retrospectively collected and analyzed. When searching PubMed for mNGS and leishmaniasis, 8 peer-reviewed case reports in English were retrieved. A total of 7 patients with recurrent fever, pancytopenia, and significant splenomegaly were included in this study. Only 3 individuals tested positive for rK39. Two individuals, 1 of whom was HIV-positive, had Leishmania amastigotes identified in their bone marrow. However, all patients’ blood mNGS findings pointed to Leishmania infection, and they were finally diagnosed with leishmaniasis. Sodium stibogluconate therapy with a short course of amphotericin B was administered to all patients. The prognosis for the remaining patients was good, except for 1 who died of multiple organ failure. mNGS could be used to identify leishmaniasis, particularly in patients who are difficult to diagnose using conventional approaches.

Case Report Hereditary spherocytosis complicated by intrahepatic cholestasis: two case reports Ning Han, Wei Huang, Juan Wang, Lang Bai, Libo Yan, Hong Tang

Background: Abdominal aorta-duodenal fistulas are rare abnormal communications between the abdominal aorta and duodenum. Secondary abdominal aorta-duodenal fistulas often result from endovascular surgery for aneurysms and can present as severe late complications. Case presentation: A 50-year-old male patient underwent endovascular reconstruction for an infrarenal abdominal aortic pseudoaneurysm. Prior to the operation, he was diagnosed with Acquired Immune Deficiency Syndrome and Syphilis. Two years later, he was readmitted with lower extremity pain and fever. Blood cultures grew Enterococcus faecium, Salmonella, and Streptococcus anginosus. Sepsis was successfully treated with comprehensive anti-infective therapy. He was readmitted 6 months later, with blood cultures growing Enterococcus faecium and Escherichia coli. Although computed tomography did not show contrast agent leakage, we suspected an abdominal aorta-duodenal fistula. Esophagogastroduodenoscopy confirmed this suspicion. The patient underwent in situ abdominal aortic repair and received long-term antibiotic therapy. He remained symptom-free during a year and a half of follow-up. Conclusions: This case suggests that recurrent infections with non-typhoidal Salmonella and gut bacteria may be an initial clue to secondary abdominal aorta-duodenal fistula.

Hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC), one of the most prevalent malignant tumors worldwide that poses a significant threat to human health. The multifunctional regulator known as Hepatitis B virus X-protein (HBx) interacts with host factors, modulating gene transcription and signaling pathways and contributing to hepatocellular carcinogenesis. The p90 ribosomal S6 kinase 2 (RSK2) is a member of the 90 kDa ribosomal S6 kinase family involved in various intracellular processes and cancer pathogenesis. At present, the role and mechanism of RSK2 in the development of HBx-induced HCC are not yet clear. In this study, we found that HBx upregulates the expression of RSK2 in HBV-HCC tissues, HepG2, and SMMC-7721 cells. We further observed that reducing the expression of RSK2 inhibited HCC cell proliferation. In HCC cell lines with stable HBx expression, RSK2 knockdown impaired the ability of HBx to promote cell proliferation. The extracellularly regulated protein kinases (ERK) 1/2 signaling pathway, rather than the p38 signaling pathway, mediated HBx-induced upregulation of RSK2 expression. Additionally, RSK2 and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) were highly expressed and positively correlated in HBV-HCC tissues and associated with tumor size. This study showed that HBx upregulates the expression of RSK2 and CREB by activating the ERK1/2 signaling pathway, promoting the proliferation of HCC cells. Furthermore, we identified RSK2 and CREB as potential prognostic markers for HCC patients.