First case report of complete paternal isodisomy of chromosome 10 harbouring a novel variant in COL17A1 that causes junctional epidermolysis bullosa intermediate.

BACKGROUND: Uniparental disomy (UPD) is a condition in which both chromosomes are inherited from the same parent, except for imprinting disorders. Uniparental isodisomy (UPiD) may result in a homozygous variant contributing to an autosomal recessive disorder in the offspring of a heterozygous carrier. Junctional epidermolysis bullosa intermediate (JEB intermediate) is an autosomal recessive inherited disease that is associated with a series of gene variants, including those of COL17A1. CASE PRESENTATION: We report the first case of complete paternal UPiD of chromosome 10 harbouring a novel homozygous variant in COL17A1: c.1880(exon23)delG (p.G627Afs*56). This variant led to the clinical phenotype of junctional epidermolysis bullosa intermediate in a 5-year-old child. Trio-whole exome sequencing (Trio-WES) and in silico data analysis were used for variant identification, Sanger sequencing was performed for variant validation, and pathological examination was performed as the gold standard for phenotype confirmation. CONCLUSIONS: We recommend the use of WES as a first-tier test for the diagnosis of epidermolysis bullosa, especially for paediatric patients. Moreover, UPD events should be detected and analysed routinely through WES data in the future.

Assessment of four screening tools and retrieval of key questions to detect undiagnosed psoriatic arthritis in Chinese patients with psoriasis: A multicenter study.

Several screening tools have been developed to facilitate early diagnosis of psoriatic arthritis (PsA); however, their performance varied greatly across different studies. In this study, we validated and compared the performance of four screening tools in detecting undiagnosed PsA Chinese patients with psoriasis, and determined the key questions and their weights. The four screening tools were the Early Arthritis for Psoriatic Patients (EARP) questionnaire, Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire, Psoriasis and Arthritis Screening Questionnaire (PASQ), and Psoriasis Epidemiology Screening Tool (PEST). The receiver-operator curve (ROC) with area under curve (AUC) was used to determine sensitivity, specificity, and accuracy. Least absolute shrinkage and selection operator and logistic regression were utilized to retrieve key questions, and a nomogram was utilized to visualize their weights. Of 482 psoriasis patients from dermatology clinics, 77 were newly diagnosed with PsA. Another 68 patients with newly diagnosed PsA from rheumatology clinics were incorporated in the analysis. ROC analysis indicated that the optimal cut-off values for EARP, PASE, PASQ, and PEST were 3, 40, 7, and 3, with corresponding sensitivities of 91.4%, 88.6%, 86.2%, and 88.5%, and specificities of 88.6%, 75.2%, 80.2%, and 83.6%, respectively. The AUC of EARP (0.925) was higher than those of PASE (0.885), PASQ (0.905), and PEST (0.827). However, none of them were sufficiently sensitive to identify pure axial PsA (sensitivities of EARP, PASQ, and PASE were 25.0%, 36.8%, and 42.1%, respectively). Twelve key questions were retrieved from these four tools to establish a nomogram with a high discrimination (C-index = 0.993) and a good calibration (mean absolute error = 0.014). In conclusion, to screen undiagnosed PsA, EARP has slightly better balanced sensitivity and specificity, and higher accuracy. The retrieval of key questions and nomogram signify the necessity of attributing different scores to differently weighted questions when developing a new screening tool to make it function more efficiently.

Peripheral T-cell lymphoma at the injection site of influenza vaccination.

Pseudolymphomas or B-cell lymphoma at the vaccination site have been reported by several authors. However, onset of cutaneous T-cell lymphoma with cytotoxic features is a rare complication of vaccination. We report a 27-year-old man who developed a nodule and ulcer that arose at the site of injection of influenza vaccine. The neoplastic cells reacted positively for CD56, CD3, CD2, perforin, and granzyme B, but negatively for CD4, CD8, CD10, CD19, CD30, CD34, CD79, and betaF1. Molecular studies showed T-cell receptor γ (TCR-γ) chain monoclonal rearrangement. A diagnosis of peripheral T-cell lymphoma, not otherwise specified (NOS) was established. The patient had high fever, progressive liver dysfunction and a rapid fatal evolution.

Transposition of the Zorro2 retrotransposon is activated by miconazole in Candida albicans.

Zorro2 is a member of a non-long terminal repeat (LTR) retrotransposon family in Candida albicans, but as yet no clear evidence has been provided to establish either transcription or transposition activity for Zorro2. In this study, the relative expression changes of two open reading frames in Zorro2, ORF19.7274 and ORF19.7275, were examined in response to miconazole (MCZ), and were found to be increased by this treatment. As well, the copy number and the transcripts of Zorro2 in MCZ-induced resistant daughter strains were increased compared to the parental strain, indicating that transposition of Zorro2 occurred during long-term MCZ treatment. Intriguingly, the transcription activity of Zorro2 retrotransposons was significantly inhibited when the cells were treated with MCZ together with antioxidant N-acetyl-L-cysteine (NAC). As both the level of intracellular reactive oxygen species (ROS) and the expression of genes involving DNA repair activated by MCZ were reduced when combined with the treatment of NAC, we propose that the damage caused by accumulation of ROS under MCZ stress is a major reason for the transcription and transposition activation of the Zorro2 retrotransposon.

Comparison of clinical features in patients with persistent and nonpersistent cryptococcal meningitis: twelve years of clinical experience in four centers in China.

BACKGROUND AND AIMS: Cryptococcal meningitis (CM) has gradually increased in the recent 20 years in the whole world. Although the mortality decreased significantly in recent years, it was still high, especially in patients with persistent infection. Therefore, we compare differences of clinical features between persistent and nonpersistent CM patients. METHODS: We conducted a retrospective review of medical records of patients diagnosed with CM from January 2000 to December 2011 in four centers in China, including demographic features, underlying diseases, clinical presentations, laboratory data, and so on. RESULTS: Of 106 CM patients enrolled, 16 were identified as persistent cases. Among all variables, persistent CM patients were more like to be human immunodeficiency viruses (HIV) infection (P < 0.05), stiff neck (P < 0.01), a serum hemoglobin < 90 g/L (P < 0.01), a serum potassium concentration <2.7 mg/L (P < 0.01), an intracranial pressure (ICP) >400 mmH2 O (P < 0.01), and a latex agglutination cryptococcal antigen titer of cerebrospinal fluid (CSF LACT) >1:1024 (P < 0.01) than nonpersistent ones. A multivariate analysis showed that HIV infection (OR 7.49), stiff neck (OR 11.7), a serum potassium <2.7 mmol/L (OR 9.45), and an ICP >400 mmH2 O (OR 6.83) were closely correlated with persistent CM. CONCLUSIONS: Although it is difficult to deal with persistent CM nowadays, some cases could be predicted early enough in the future, so as to be treated appropriately and have relatively good outcomes.

Disseminated cryptococcal lymphadenitis with negative latex agglutination test.

We reported an unusual case of disseminated cryptococcal lymphadenitis in an immunocompetent host who presented with fever and lymphadenopathy, which were the only two symptoms and signs. Latex agglutination test of serum and cerebrospinal fluid (CSF) were negative, while lymph node biopsy showed Cryptococcus neoformans. A diagnosis of disseminated cryptococcal lymphadenitis was made. Then the patient was treated with amphotericin B for 15 days as initial therapy and itraconazole for 6 months as maintenance therapy respectively. The patient received re-examination per 6 months and was followed up for 2 years. Swollen lymph nodes diminished gradually, and no fever or other symptoms were found. Latex agglutination test of serum and CSF were negative throughout the follow-up period, and anti-HIV, syphilis and tuberculosis antibody were all negative.

Xiaoyin recipe ( ) for psoriasis induces a Th1/Th2 balance drift toward Th2 in peripheral blood mononuclear cells of experimental autoimmune thyroiditis rats.

OBJECTIVE: To explore the regulatory mechanism of Xiaoyin Recipe () on the T helper 1/T helper 2 (Th1/Th2) immune balance. METHODS: Thirty-six experimental animals were divided into three groups, 12 rats in each group: blank control group (B group), negative control group (N group), and Xiaoyin Recipe treatment group (T group). The latter two groups received immunization of experimental autoimmune thyroiditis (EAT), and T group were treated with Xiaoyin Recipe for a month. Then, the expression of Th1-Th2-related genes in peripheral blood mononuclear cells (PBMCs) were screened with Oligo GEArray Rat Th1-Th2-Th3 Microarray. The expressions of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), T-box expressed in T-cells (T-bet), and GATA-binding protein-3 (GATA-3) were detected by real-time polymerase chain reaction (RT-PCR). RESULTS: Gene array screening showed that compared to N group, in T group after Xiaoyin Recipe treatment, 3 genes were upregulated in EAT rats, including interleukin-27 receptor alpha (IL-27rα), glomulin (Glmn), and GATA-3, while 38 genes were downregulated, such as CD28, IL-18, signal transducer, and activator of transcription 1 (STAT1), T-bet, TNF receptor superfamily member 4 (TNFRSF4), TNF ligand superfamily member 5 (TNFSF5), and TNF receptor superfamily member 5 (TNFRSF5). While RT-PCR showed that there was an increased level of TNF-α mRNA (P<0.01), an elevated ratio of T-bet/GATA-3, and a decreased level of IL-10 mRNA in PBMC of N and T group compared to B group (P <0.01); and after treatment with Xiaoyin Recipe, IL-10 mRNA level increased (P <0.01), while TNF-α mRNA level and T-bet/GATA-3 ratio decreased in T group compared to N group (P <0.01). CONCLUSION: Xiaoyin Recipe for psoriasis could induce a Th1/Th2 balance drift toward Th2 in PBMC of EAT rats and thus improve the conditions.

[Effect of arotinoid trometamol on the expression of genes in human keratinocytes].

OBJECTIVE: To investigate the gene expression pattern of human keratinocytes (KCs) after arotinoid trometamol (AT) treatment. METHODS: Human keratinocytes (KCs) of the line HaCat were cultured. AT (10(-6) mol/L) was added in the culture fluid for 24 h. A gene chip containing 4000 cDNA clones was used to identify the differentially expressed genes in the HaCat cells, and then the results were verified by real-time PCR. RESULTS: Gene chip hybridization showed that 580 of the 4000 full-length human cDNA exhibited differential expression (>or= 2-fold); 253 genes with complete annotation were identified, including 143 genes up-regulated and 110 genes down-regulated. The differentially expressed genes mainly participated into the processes of cell cycle and immunology. CONCLUSION: Microarry technology helps study the third generation of retinoid acid induced gene expression pattern in human KCs in a high through-put way. AT can be used to treat psoriasis by regulating some processes, such as the cell cycle, inflammation, etc.