Human brucellosis and fever of unknown origin.

BACKGROUND: Human brucellosis has become one of the major public health problems in China, and increases atypical manifestations, such as fever of unknown origin (FUO), and misdiagnosis rates has complicated the diagnosis of brucellosis. To date, no relevant study on the relationship between brucellosis and FUO has been conducted. METHODS: We retrospectively reviewed the medical charts of 35 patients with confirmed human brucellosis and prospectively recorded their outcomes by telephone interview. The patients were admitted to the Second Affiliated Hospital of Nanchang University between January 01, 2013 and October 31, 2019. Patient data were collected from hospital medical records. RESULTS: The percentage of males was significantly higher than that of female in FUO (78.95% vs. 21.05%, P < 0.05), and 80% of the patients had a clear history of exposure to cattle and sheep. Moreover, 19 (54%) cases were hospitalized with FUO, among which the patients with epidemiological histories were significantly more than those without (P < 0.05). The incidence of toxic hepatitis in FUO patients was higher than that in non-FUO patients (89% vs. 50%, P < 0.05). Meanwhile, the misdiagnosis rate was considerably higher in the FUO group than in the non-FUO group (100% vs. 63%; P < 0.05). CONCLUSION: Brucellosis is predominantly FUO admission in a non-endemic area of China, accompanied by irregular fever and toxic hepatitis. Careful examination of the epidemiological history and timely improvement of blood and bone marrow cultures can facilitate early diagnosis and prevent misdiagnosis.

Host proteins interact with viral elements and affect the life cycle of highly pathogenic avian influenza A virus H7N9.

Host-virus interactions can significantly impact the viral life cycle and pathogenesis; however, our understanding of the specific host factors involved in highly pathogenic avian influenza A virus H7N9 (HPAI H7N9) infection is currently restricted. Herein, we designed and synthesized 65 small interfering RNAs targeting host genes potentially associated with various aspects of RNA virus life cycles. Afterward, HPAI H7N9 viruses were isolated and RNA interference was used to screen for host factors likely to be involved in the life cycle of HPAI H7N9. Moreover, the research entailed assessing the associations between host proteins and HPAI H7N9 proteins. Twelve key host proteins were identified: Annexin A (ANXA)2, ANXA5, adaptor related protein complex 2 subunit sigma 1 (AP2S1), adaptor related protein complex 3 subunit sigma 1 (AP3S1), ATP synthase F1 subunit alpha (ATP5A1), COPI coat complex subunit alpha (COP)A, COPG1, heat shock protein family A (Hsp70) member 1A (HSPA)1A, HSPA8, heat shock protein 90 alpha family class A member 1 (HSP90AA1), RAB11B, and RAB18. Co-immunoprecipitation revealed intricate interactions between viral proteins (hemagglutinin, matrix 1 protein, neuraminidase, nucleoprotein, polymerase basic 1, and polymerase basic 2) and these host proteins, presumably playing a crucial role in modulating the life cycle of HPAI H7N9. Notably, ANXA5, AP2S1, AP3S1, ATP5A1, HSP90A1, and RAB18, were identified as novel interactors with HPAI H7N9 proteins rather than other influenza A viruses (IAVs). These findings underscore the significance of host-viral protein interactions in shaping the dynamics of HPAI H7N9 infection, while highlighting subtle variations compared with other IAVs. Deeper understanding of these interactions holds promise to advance disease treatment and prevention strategies.

[Inhibitive mechanisms of Pim-3 affecting fulminant hepatic apoptosis].

To investigate the mechanisms of serine/threonine kinase Pim-3 inhibition of fulminant hepatic apoptosis. Thirty-two rats were randomly divided into four groups (n = 8 each): normal controls (A); pretreatment with Ringer's solution (B), vector plasmid (C), or Pim-3 recombinant plasmid (D) by hydrodynamics-based procedure followed by intraperitoneal injections of lipopolysaccharide (LPS) and D-galactosamine (D-GalN) after one day. At 8 h after the LPS/D-GalN injections, liver tissues were collected from all groups of mice and analyzed for cell apoptosis by detecting caspase-3 activity (measured in relative fluorescence units, RFU). Changes in expression of relevant genes were determined by RT-PCR and Western blotting. Caspase-3 activity was induced in response to LPS/D-GalN injection. Pim-3-pretreated rats showed a lower level of caspase-3 activity than the Ringer's-pretreated or vector plasmid-pretreated rats [(141.7+/-13.7)RFU vs. (508.1+/-32.0) or (493.5+/-33.1) RFU; all P less than 0.01]. High expressions of the liver injury marker gene, iNOS, and the apoptosis-induced genes, p53 and Bax, were found after LPS/D-GalN challenge, and were suppressed by exogenous Pim-3 gene injection. In addition, exogenous Pim-3 gene injection induced high expression of the liver anti-apoptosis protein, Bcl-2, but had no effect on Bax protein expression. The Pim-3 gene can block fulminant hepatic apoptosis by affecting the expression of the iNOS liver injury gene and the p53, Bax and Bcl-2 apoptosis-related genes.

[Role of hepatocellular apoptosis and mechanisms of liver injury in lipopolysaccharide-induced acute liver failure in D-galactosamine-sensitized rats].

OBJECTIVE: To investigate the situation of hepatocellular apoptosis in D-galactosamine (D-GalN)-sensitized rats with lipopolysaccharide (LPS)-induced acute liver failure and the mechanisms of liver injury therein. METHODS: Forty eight Wistar rats were randomly divided into 6 equal groups to be injected peritoneally with LPS (50 microg/kg) and D-GalN (300 mg/kg) (treatment groups) or normal saline of the same volume (control groups), and then were killed 6, 24, or 48 hours later. Blood samples were collected from the portal vein or vena cava inferior to detect the contents of serum alanine aminotransferase (ALT), livers were take out to detect the hepatocellular apoptosis by TUNEL assay or ultrastructural observations, and the expressions of iNOS, p53, and p21waf1/cip1 gene were detected by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The ALT levels of the treatment groups were all significantly higher than those of the corresponding control groups, with the peaks 24 hours after treatment. Transmission electron microscopy showed that apoptotic cells were rare in the control subgroups, but were abundant in the liver tissues of the treatment subgroups. The apoptotic indices of liver cells of the 6, 24, and 48 hours treatment subgroups were 7.3% +/- 1.5%, 71.8% +/- 10.3%, and 68.2% +/- 11.9% respectively, all significantly higher than those of the control groups (2.6% +/- 1.1%, all P < 0.05). The apoptotic index increased gradually along with the time, however, the apoptotic indices of the 24 and 48 hours treatment subgroups were not significantly different (P > 0.05). The mRNA expression levels of iNOS gene of the control subgroups, 6 hours treatment subgroup, 24 hours treatment subgroups, and 48 hours treatment subgroup were 0, 0.53 +/- 0.11, 0.36 +/- 0.08, and 0.15 +/- 0.04 respectively with a significant difference among different subgroups, and with a peak 6 hours after treatment. The p53 expressions of the control subgroups, 6 hours treatment subgroup, 24 hours treatment subgroups, and 48h treatment subgroup were 0.031 +/- 0.006, 0.022 +/- 0.008, 0.49 +/- 0.11, and 0.39 +/- 0.17 respectively, being low in both control subgroups and 6h treatment subgroup and significantly upregulated in the 24 and 48 hours treatment groups. Expression of p21waf1/cip1 was not detected in the control subgroups and 48 hours treatment subgroup, but was found in the 6 hours and 24 hours treatment subgroups, with a peak in the 24 hours treatment subgroup. CONCLUSION: Acute liver failure can be induced by low dose LPS in D-GalN-sensitized rats, which may be associated with the early high expression of iNOS gene; Apoptosis is the important morphological feature in this process.