A case of chronic wounds caused by Sporothrix schenckii infection was rapidly detected by metagenomic next generation sequencing.

The dimorphic fungus Sporothrix schenckii is widely distributed in soil, vegetation, and decaying organic matter, and can cause sporotrichosis when the patient's skin trauma was exposed to contaminated material with Sporothrix spp. The cases of Sporothrix schenckii infection in chronic wounds are rarely reported. Here we reported a 53-year-old male construction worker who was admitted to our hospital on July 9, 2022, without underlying disease presented with a painless subcutaneous hard nodule on his right calf, which later ulcerated and oozed, with an enlarged wound and no fever during the course of the disease. His procalcitonin, C-reactive protein, erythrocyte sedimentation rate increased, and necrotic histopathology suggested chronic granulomatous inflammation. Then his necrotic tissue and pus were sent for metagenomic next generation sequencing(mNGS), the result reported Sporothrix schenckii after 43 hours, which was consistent with the result of culture after 18 days. mNGS might be more useful and valuable in diseases such as sporotrichosis where it is difficult to see the yeast cells in the tissues.

Spirometra mansoni sparganosis identified by metagenomic next-generation sequencing: a case report.

A 30-year-old male patient had a cyst on the left hip and progressive enlargement for more than 2 months. Combined blood tests, magnetic resonance imaging, and pathology findings, cysticercosis infection was suspected. However, the treatment for cysticercosis was ineffective. We conducted a metagenomic next-generation sequencing (mNGS) analysis on the formalin-fixed, paraffin-embedded specimen of the patient's surgically excised tissue, and the results suggested Spirometra mansoni, mNGS was further confirmed by polymerase chain reaction and phylogenetic analysis of cytochrome c oxidase subunit 1 (cox1) gene. Based on these results, we found that mNGS provided a better method of diagnosing parasitic infections.

Pyroptosis associated with immune reconstruction failure in HIV-1- infected patients receiving antiretroviral therapy: a cross-sectional study.

BACKGROUND: Highly active anti-retroviral therapy (HAART) can successfully suppress human immunodeficiency virus (HIV) viral replication and reconstruct immune function reconstruction in HIV-1-infected patients. However, about 15-30% of HIV-1-infected patients still fail to recover their CD4+ T cell counts after HAART treatment, which means immune reconstruction failure. Pyroptosis plays an important role in the death of CD4+ T cells in HIV-1- infected patients. The study aims to explore the association between the expression of pyroptosis in peripheral blood and immune function reconstruction in HIV-1- infected patients. METHODS: One hundred thirty-five HIV-1-infected patients including immunological non-responders (INR) group, immunological responders (IR) group and normal immune function control (NC) group were analyzed. The expression of GSDMD and Caspase-1 in peripheral blood of HIV-1-infected patients were measured by qPCR. The concentrations of GSDMD, Caspase-1, IL-1ß and IL-18 in the peripheral serum were quantified by ELISA. The associations between the expression of pyroptosis in peripheral blood and immune function reconstruction were analyzed using multivariate logistic models. RESULTS: The relative expression of GSDMD mRNA and caspase-1 mRNA in peripheral blood, as well as the expression of IL-18 cytokine in the INR, were significantly higher than those in the IR and NC (P < 0.05). There was no significant difference in the expression of IL-1ß cytokine (P > 0.05). Multivariate logistic analysis showed that the patients with baseline CD4+ T cell counts less than 100 cells/µL (aOR 7.051, 95% CI 1.115-44.592, P = 0.038), high level of expression of Caspase-1mRNA (aOR 2.803, 95% CI 1.065-7.377, P = 0.037) and IL-18 cytokine (aOR 10.131, 95% CI 1.616-63.505, P = 0.013) had significant poor CD4+ T cell recovery. CONCLUSIONS: The baseline CD4+ T cell counts less than 100 cells/µL, high relative expression of Caspase-1 mRNA, and high expression of IL-18 cytokine are associated factors that affect the reconstruction of immune function.

Serum Exosomal microRNA Profiling in AIDS Complicated with Talaromyces marneffei Infection.

INTRODUCTION: In order to find the early diagnostic markers of AIDS combined with TM infection, we detected and analyzed the serum exosomal miRNAs of AIDS patients with or without TM infection. MATERIALS AND METHODS: We profiled the expression levels of miRNAs via RNA sequencing in serum exosomes from the pooled samples of 17 AIDS patients combined without TM infection and 15 AIDS combined with TM infection patients. For external validation, we validated these results using real-time quantification polymerase chain reaction (qRT-PCR) in an independent cohort of 35 AIDS patients combined without TM infection and 33 AIDS combined with TM infection patients. Finally, bioinformatics was used to predict the target genes and pathways of meaningful miRNAs. RESULTS: A total of 131 serum exosomal miRNAs including 73 up-regulated and 59 down-regulated miRNAs were found to be differentially expressed (log2FC≥1 and FDR <0.01) in the two groups. A validation analysis revealed that three miRNAs (miR-192-5p, miR-194-5p and miR-1246) were upregulated in exosomes from AIDS combined with TM infection patients. ROC analyses showed that the AUC in combined diagnosis of the three miRNAs was 0.742, and the diagnostic sensitivity and specificity were 0.568 and 0.861, respectively. In the biological process analysis, all the 3 miRNAs were involved in transcription, DNA-templated and positive regulation of transcription from RNA polymerase II promoter. At the same time, the related pathways were involved in TGF-ß signaling pathway, AMPK signaling pathway, Wnt signaling pathway, MAPK signaling pathway, cGMP-PKG and cAMP signaling pathway, etc. CONCLUSION: miR-192-5p, miR-194-5p and miR-1246 in serum exosomes might be a potential biomarker for AIDS combined with TM infection patients, which may be involved in TGF-ß signaling pathway, AMPK signaling pathway, Wnt signaling pathway, MAPK signaling pathway, cGMP-PKG and cAMP signaling pathway, etc. Further research is needed on the biological functions and mechanisms of these miRNAs.

Chronic Mycobacterium avium skin and soft tissue infection complicated with scalp osteomyelitis possibly secondary to anti-interferon-γ autoantibody formation.

BACKGROUND: Nontuberculous mycobacterial (NTM) disease is commonly an opportunistic infection frequently found in immunocompromised individuals, but sometimes can also be found in the immunocompetent hosts, especially in East Asians. The NTM separation rate in China is increasing, which reminds us to focus on NTM infections in immunocompromised populations. CASE PRESENTATION: A 43-year-old woman with a recurrent fever for more than 8-month and a right forehead surgical wounds unhealed for more than 6-month was admitted to our hospital on February 22, 2018. On arrival, several elliptic ulcers were obvious on the right forehead with pus and fibrin exudation, and the skin around the lesions was tender, reddish, no sense of fluctuation. The result of HIV serology test was negative. CD4+ T cell count was normal and tuberculosis antibody was negative. CT of the chest and head showed bone destruction. Skin biopsy on the right forehead was performed on March 13, 2018, and pathological examination of the excisional biopsy specimen found inflammatory granuloma and suppurative inflammatory changes. Broad-spectrum antibiotics were treated but the effect seemed discontent. Then debridement and skin grafting were performed on the right frontal ulcer under general anesthesia on April 3, 2018. The skin tissue culture that resected on March 13, 2018 found Nontuberculous mycobacteria grown after 78 days, so clarithromycin, ethambutol, protionamide, and amoxicillin clavulanate potassium were prescribed for anti-nontuberculous mycobacteria treatment beginning on May 31, 2018. In reviewing the case, Mycobacterium avium (M. avium) was identified in the skin tissue resected on April 3, 2018 by polymerase chain reaction (PCR) and the serum test of anti-interferon-γ autoantibodies was positive. CONCLUSIONS: This is a case report of "Mycobacterium avium SSTI (skin and soft tissue infection) and OM (osteomyelitis) with possible secondary immunodeficiency syndrome induced by anti-interferon-γ autoantibody".

Comparative proteomic profiles indicating genetic factors may involve in hepatocellular carcinoma familial aggregation.

Familial aggregation of hepatocellular carcinoma (HCC), the third leading cause of cancer death worldwide, has shown to be a common phenomenon. We investigated the association between the genetic background and HCC familial aggregation. Serum samples were collected from HCC family members and normal control family members for screening the differentially expressed protein peaks with the approach of surface-enhanced laser desorption ionization time-of-flight mass spectrometry. Potential genetically associated protein peaks were selected and further identified by matrix assisted laser desorption ionization-time of flight mass spectrometry. A panel of six protein peaks (m/z 6432.94, 8478.35, 9381.91, 17284.67, 17418.34, and 18111.04) were speculated to reflect the genetic susceptibility of HCC familial aggregation. Three of them (m/z 6432.94, 8478.35, and 9381.91) were selected to identify as the candidate proteins. Nine identified proteins, including mostly apolipoprotein family (ApoA1, ApoA2, ApoC3, ApoE) and serum amyloid A protein (SAA), were found overexpressed in the multiple HCC cases family members. The comparative proteomic profiles have suggested that genetic factors ought to be taken into account for familial aggregation of HCC.

[Correlation between serum anti-P53 and familial clustering of hepatocellular carcinoma in Guangxi].

OBJECTIVE: To assess the correlation between familial clustering of hepatocellular carcinoma (HCC) and the level of anti-P53 in human serum in Guangxi. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-P53 in 164 members from 20 HCC families and 164 members from non-cancer control families. Univariate analysis was performed to assess the correlation between seral level of P53 antibody and familial clustering of HCC. RESULTS: The level of P53 antibody was significantly higher in the members of HCC families than controls (Z=-3.04, P=0.002). After eliminating the interference of hepatitis B virus infection, this tendency still remains (P=0.011). And there was a significant difference between relatives of different degrees from HCC families (chi-square=11.593, P=0.021), with the expression of anti-P53 declining along with decrease in relationship coefficient. Furthermore, the number of individuals with high anti-P53 expression was also significantly greater in HCC families (95/164) than controls (71/164) (P=0.006). And the expression was rising along with the increasing HCC numbers (chi-square=16.068, P=0.000). Anti-P53 level was also greater in HCC families featuring sibling affection than parental affection (chi-square=12.679, P=0.002). Univariate analysis indicated that high expression of anti-P53 is a risk factor for development of HCC (OR=2.087, 95%CI: 1.270-3.431). CONCLUSION: High level of anti-P53 expression may be a factor for the clustering of HCC families in Guangxi, China.