A false positive serology test of SARS­CoV­2 in a patient with Waldenström's macroglobulinemia: A case report.

The serology test of SARS-CoV-2 is one of the critical assays to make a diagnosis of SARS-CoV-2 infection. The gold immunochromatography assay (GICA) is a common measure to test SARS-CoV-2 specific IgG and IgM. The sensitivity and specificity of the assay are ~>80%. It has been reported that the result of GICA could be compromised in various situations, such as auto-immune diseases, Kawasaki disease, pregnancy or other conditions. However, following the European Hematology Association's consensus statement on the management of Waldenström's Macroglobulinemia (WM) patients, serological tests for SARS-CoV-2 specific IgM should not be affected by the total IgM or paraprotein levels. The present study reports a patient with duplicate positive serology tests of SARS-CoV-2 which is hypothesized to be due to monoclonal IgM caused by WM.

Interferon characterization associates with asthma and is a potential biomarker of predictive diagnosis.

Interferon (IFN) plays a role in immune and inflammation responses. However, the effect of IFN in asthma is still not fully clear. The present study was conducted to better understand the role of IFN signatures in asthma. Blood samples from case-control studies (study 1: 348 asthmas and 39 normal controls and validation study 2: 411 asthmas and 87 normal controls) were enrolled. The single-sample gene set enrichment analysis (ssGSEA) method was used to quantify the levels of 74 IFN signatures. Gene Ontology analysis and pathway function analysis were performed for functional analysis and a protein-protein interaction (PPI) network was constructed. The area under the curve (AUC) value was used to evaluate the diagnostic ability. In our work, IFN-γ response-DN, negative regulation of IFN-γ secretion, IFNG pathway, negative regulation of response to IFN-γ, and type 1 IFN biosynthetic process showed higher levels in asthma. Functional analysis demonstrated that pathway and biological process involved in IFN signaling pathway, regulation of type 1 IFN production and response to IFN-γ. Hub IFN-related genes were identified, and their combination as biomarker exhibited a good diagnostic capacity for asthma (AUC = 0.832). These findings offered more insight into the underlying mechanism of how IFN signatures affected asthma. The use of the easy-to-apply IFN-related genes might serve as a promising blood-based biomarker for early diagnosis of asthma.

circRNA circ_102049 Implicates in Pancreatic Ductal Adenocarcinoma Progression through Activating CD80 by Targeting miR-455-3p.

Emerging evidence has shown that circular RNAs (circRNAs) and DNA methylation play important roles in the causation and progression of cancers. However, the roles of circRNAs and abnormal methylation genes in the tumorigenesis of pancreatic ductal adenocarcinoma (PDAC) are still largely unknown. Expression profiles of circRNA, gene methylation, and mRNA were downloaded from the GEO database, and differentially expressed genes were obtained via GEO2R, and a ceRNA network was constructed based on circRNA-miRNA pairs and miRNA-mRNA pairs. Inflammation-associated genes were collected from the GeneCards database. Then, functional enrichment analysis and protein-protein interaction (PPI) networks of inflammation-associated methylated expressed genes were investigated using Metascape and STRING databases, respectively, and visualized in Cytoscape. Hub genes of PPI networks were identified using the NetworkAnalyzer plugin. Also, we analyzed the methylation, protein expression levels, and prognostic value of hub genes in PDAC patients through the UALCAN, Human Protein Atlas (HPA), and Kaplan-Meier plotter databases, respectively. The circRNA_102049/miR-455-3p/CD80 axis was identified by the ceRNA network and hub genes. In vitro and in vivo experiments were performed to evaluate the functions of circRNA_102049. The regulatory mechanisms of circRNA_102049 and miR-455-3p were explored by RT-PCR, western blot, and dual-luciferase assays. In the present study, twelve hub genes (STAT1, CCND1, KRAS, CD80, ICAM1, ESR1, RAF1, RPS6KA2, KDM6B, TNRC6A, FOSB, and DNM1) were determined from the PPI networks. Additionally, the circRNA_102049 was upregulated in PDAC cell lines. Functionally, the knockdown of circRNA_102049 by siRNAs inhibited cell growth, inflammatory factors, and migratory and invasive potential and promoted cell apoptosis. Mechanistically, circRNA_102049 functioned as a sponge of miR-455-3p and partially reversed the effect of miR-455-3p and consequently upregulated CD80 expression. Our findings showed that circRNA_102049 and methylated hub genes play an important role in the proliferation, apoptosis, migration, invasion, and inflammatory response of PDAC, which might be selected as a promising prognostic marker and therapeutic target for PDAC.

Overexpression of hypoxia-inducible factor 1α is associated with neutrophilic inflammation in chronic rhinosinusitis with nasal polyps.

OBJECTIVE: This study aimed to assess the possible role of hypoxia-inducible factor 1α (HIF-1α) in promoting neutrophilic inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) patients. METHODS: We examined HIF-1α expression in sinonasal tissues from CRSwNP patients and healthy controls by using immunohistochemistry, qRT-PCR, and western blot. Next, the stimulatory effects of several cytokines (IFN-γ, IL-17A, IL-6, etc.) and reagents (dexamethasone (DEX), clarithromycin (CAM) and curcumin (CUM)) on HIF-1α expression in cultured normal nasal epithelial cells (NECs) were also evaluated. Moreover, the effects of CAM and glucocorticoid on nasal symptoms and signs of uncontrolled neutrophilic CRSwNP patients were evaluated. RESULTS: The mRNA and protein expression of HIF-1α were significantly increased in polyp tissues compared with healthy controls (P < 0.05), and the HIF-1α level in polyp tissues was positively associated with IL-17A production and tissue neutrophilia (P < 0.05). Moreover, in cultured NECs, HIF-1α expression was upregulated in the presence of IL-17A and IL-6 (P < 0.05). Both CAM and CUM showed an additive effect with DEX in inhibiting HIF-1α expression (P < 0.05). Moreover, combined glucocorticoid and CAM significantly improved nasal symptoms and signs compared with glucocorticoid alone in uncontrolled neutrophilic CRSwNP patients (P < 0.05). CONCLUSION: Our findings indicate that HIF-1α is associated with neutrophilic inflammation and glucocorticoid resistance in CRSwNP patients.

Inhibition of TLR4 inhibits allergic responses in murine allergic rhinitis by regulating the NF-κB pathway.

The present study investigated the underlying mechanisms and effects of toll-like receptor 4 (TLR4) on a mouse model of allergic rhinitis (AR). An ovalbumin (OVA)-induced mouse model of AR was treated with TLR4-short hairpin RNA (shRNA). Allergic symptoms were then subsequently assessed. Protein levels of OVA-specific immunoglobulin E (IgE), eosinophil cation protein (ECP), leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) in mice serum and nasal lavage fluid, as well as various inflammatory cytokine mediators in mice serum, were determined by ELISA. Protein level detection was performed using reverse transcription-quantitative PCR and western blot analysis. The results revealed that TLR4 was highly expressed in the nasal mucosa of AR mice. TLR4 inhibition significantly relieved OVA-induced AR symptoms. Relief of symptoms was evidenced by a decreased frequency of sneezing and nose friction, reduced levels of OVA-specific IgE, ECP, LTC4, PGD2, less inflammatory cells and decreased levels of T-helper 2 type cytokines. In addition, the data indicated that OVA-induced activation of the NF-κB pathway was repressed by TLR4-shRNA. The results of the current study indicate that TLR4 may be a promising therapeutic target of AR.

Targeted exome sequencing reveals novel USH2A mutations in Chinese patients with simplex Usher syndrome.

BACKGROUND: Usher syndrome (USH) is an autosomal recessive disorder characterized by hearing impairment and vision dysfunction due to retinitis pigmentosa. Phenotypic and genetic heterogeneities of this disease make it impractical to obtain a genetic diagnosis by conventional Sanger sequencing. METHODS: In this study, we applied a next-generation sequencing approach to detect genetic abnormalities in patients with USH. Two unrelated Chinese families were recruited, consisting of two USH afflicted patients and four unaffected relatives. We selected 199 genes related to inherited retinal diseases as targets for deep exome sequencing. Through systematic data analysis using an established bioinformatics pipeline, all variants that passed filter criteria were validated by Sanger sequencing and co-segregation analysis. RESULTS: A homozygous frameshift mutation (c.4382delA, p.T1462Lfs*2) was revealed in exon20 of gene USH2A in the F1 family. Two compound heterozygous mutations, IVS47 + 1G > A and c.13156A > T (p.I4386F), located in intron 48 and exon 63 respectively, of USH2A, were identified as causative mutations for the F2 family. Of note, the missense mutation c.13156A > T has not been reported so far. CONCLUSION: In conclusion, targeted exome sequencing precisely and rapidly identified the genetic defects in two Chinese USH families and this technique can be applied as a routine examination for these disorders with significant clinical and genetic heterogeneity.

[Mammary serine proteinase inhibitor subcellular expression in oral squamous cell carcinoma and its clinical significance].

OBJECTIVE: To investigate the subcellular expression of mammary serine proteinase inhibitor (Maspin) in oral squamous cell carcinoma and its relationship to the clinicopathological features. METHODS: The Maspin protein subcellular expression was detected in 45 patients with oral squamous cell carcinoma by immunohistochemical staining. The relationship between the Maspin protein subcellular expression and the clinicopathological parameters was analyzed. RESULTS: The negative rate of nuclear maspin expression was 64% (29/45), and the weakly positive rate was 11% (5/45), and the strong positive rate was 24% (11/45). Nuclear maspin expression was negatively correlated with T stage (P = 0.019), lymph node metastasis (P = 0.038) and postoperative metastasis (P = 0.004), but positively correlated with the patients' survival rate (P = 0.014). The negative rate of cytoplasmatic maspin expression was 38% (17/45), and the weakly positive rate was 31% (14/45), and the strong positive rate was 31% (14/45). Cytoplasmatic maspin expression was negatively correlated with lymph node metastasis (P = 0.038) and postoperative metastasis (P = 0.004), but positively correlated with the patients' survival rate (P = 0.014). CONCLUSIONS: Maspin expression may be a significant marker in predicting prognosis of oral squamous cell carcinoma.

Novel RPGR-ORF15 mutations in X-linked retinitis pigmentosa patients.

X-linked retinitis pigmentosa (XLRP) is the most severe type of retinitis pigmentosa (RP), with patients consistently showing early onset and rapid deterioration. Obtaining a genetic diagnosis for a family with XLRP is important for counseling purposes. In this study, we aimed to identify disease-causing mutations in two unrelated XLRP families. Genetic analysis was performed on two unrelated XLRP families. Genomic DNA was extracted from peripheral blood or amniotic fluid samples. The coding regions and intron/exon boundaries of the Retinitis Pigmentosa GTPase Regulator (RPGR) and RP2 genes were amplified by PCR and then sequenced directly. A clinically unaffected pregnant female and the four month old fetus were found to have a hemizygous 2 base pair deletion (g.ORF15+484_485delAA) in the exon ORF15 of RPGR gene. In another XLRP family, a nonsense mutation (g.ORF15+810G>T) was identified. Neither mutation has been reported previously. Both are predicted to cause premature termination of the protein. In conclusion, we identified a micro-deletion through prenatal genetic diagnosis and another novel nonsense mutation in RPGR-ORF15. Identifying a disease-causing mutation facilitated early diagnosis and genetic counseling for the patients. Discovery of novel mutations also broadens knowledge of XLRP and the spectrum of its pathogenic genotypes.

[The determination of endothelin in patients with bell palsy and its significances bell palsy and its significances].

OBJECTIVE: To detect the role of the plasma endothelin in the process of Bell palsy and its relationship to prognosis. METHOD: The plasma endothelin were respectively determined with radioimmunoassay in 21 patients with Bell palsy and 20 normal control subjects. RESULT: The patients who were suffering from Bell palsy exhibited a statistically significant (P < 0.01) increase in the endothelin level compared with that in the 20 normal control subjects. A significantly higher level of the plasma endothelin was found in unsatisfactory recovery group compared with that in satisfactory recovery group. CONCLUSION: Endothelin may play an important role in the process of Bell palsy, and may be a useful marker for the assessment of prognosis to the patients.