Whole transcriptome sequencing for revealing the pathogenesis of sporotrichosis caused by Sporothrix globosa.

This study aimed to investigate the molecular mechanism of sporotrichosis and identify possible novel therapeutic targets. Total RNA was extracted from skin lesion samples from sporotrichosis patients and used to construct a long-chain RNA transcriptome library and miRNA transcriptome library for whole transcriptome sequencing. The differentially expressed genes (DEGs) between the groups were identified, and then Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis enrichment analyses were performed based on the DEGs. An lncRNA-miRNA-mRNA ceRNA network was constructed. The expressions of JAK/STAT pathway-related proteins were detected in the patient and control tissues using RT-qPCR and Western blot analysis. Enrichment analysis showed that the DEGs were mainly enriched in various infectious diseases and immune response-related signaling pathways. Competing endogenous RNA network analysis was performed and identified the hub lncRNAs, miRNAs, and mRNAs. Compared with the control group, the mRNA expressions of SOCS3, IL-6, and JAK3 were significantly upregulated, while the expression of STAT3 did not change significantly. Also, the protein expressions of SOCS3, IL-6, JAK3, and STAT3, as well as phosphorylated JAK3 and STAT3, were significantly upregulated. We identified 671 lncRNA DEGs, 3281 mRNA DEGs, and 214 miRNA DEGs to be involved in Sporothrix globosa infection. The study findings suggest that the JAK/STAT pathway may be a therapeutic target for sporotrichosis.

Efficacy and safety of vagus nerve stimulation in the treatment of refractory epilepsy. / è¿·èµ°ç¥žç»åˆºæ¿€æœ¯æ²»ç–—éš¾æ²»æ€§ç™«ç—«çš„ç–—æ•ˆå’Œå®‰å ¨æ€§.

OBJECTIVES: Vagus nerve stimulation (VNS) is a neuromodulative therapeutic technique for patients with drug-resistant epilepsy who are not suitable for resection or who have experienced a failed resection. This study aims to explore the efficacy and safety of VNS in patients with refractory epilepsy, and to analyze the influential factors for the efficacy. METHODS: A retrospective review of clinical data were conducted for 35 patients, who were treated for refractory epilepsy through VNS surgery in the Department of Neurosurgery, Xiangya Hospital, Central South University from April 2016 to August 2019. All patients were analyzed in terms of the clinical and follow-up data. RESULTS: After a mean follow-up of 26 months (6-47 months), outcome was as follows: 7 patients were MuHugh class I, 13 patients were MuHugh class II, 8 patients were MuHugh class III, and 7 patients were MuHugh class IV-V. The total efficacy rate in the short duration group was significantly higher than that in the long duration group (77.8% vs 50.0%, P=0.013), whereas different ages (P=0.382), gender (P=0.824), types of seizure (P=0.829), and MRI features (P=0.791) showed no correlation with efficacy. None patients developed permanent complication postoperatively. CONCLUSIONS: VNS is a safe and effective option in treating patients with refractory epilepsy, especially for those with short duration.

A huge malignant phyllodes tumor of the breast with osteoclast-like giant cells: a case report.

The malignant phyllodes tumor (PT) of the breasts is a rare type of fibroepithelial neoplasm. Osteoclast-like giant cells (OLGCs) exist in many types of tumors. But malignant PTs with OLGCs were rarely reported. Here, we presented a case of a 49-year-old woman who had a 23 cm ×21 cm ×6 cm mass which was growing for 2 years in her left breast. The patient had moderate anemia due to the hemorrhage and exudation on the surface of the tumor. The imaging examinations such as PET-CT found no lymphatic involvement and distant metastasis. We performed mastectomy with a 2 cm surgical margin and free skin flap transplantation to restore the big wound. The vacuum assisted closure (VAC) system was used to promote wound healing. Histological examination of the surgical specimen showed atypical spindle-like stroma cells, marked nuclear pleomorphism, focal necrosis, and mitotic activity. Typical leaf-like architectures of PTs were observed in some regions. OLGCs were found in many sections of the tumor with a number of vascular proliferations. The final diagnosis was malignant PT with OLGCs. After a three-month follow-up, no local recurrence or metastasis was found. Autogenous skin grafts with VAC are available for large area skin defect after excising a huge breast tumor. The presence of OLGCs in malignant tumors may be related to necrosis and hemorrhage of the tumor. These findings also provide opportunities for understanding the mechanisms of tumor formation and development.

Factors associated with prognosis of dysembryoplastic neuroepithelial tumors patients after surgical resection: a retrospective observational study.

OBJECTIVE: To explore factors that might be associated with prognosis of dysembryoplastic neuroepithelial tumors (DNTs). METHODS: DNTs patients who were admitted to the Department of Neurosurgery of Xiangya Hospital between 1 January 2010 and 31 December 2018 and underwent surgical resection were retrospectively analyzed. Clinical, neuroimaging, and pathological features of DNTs were compared among patients with different outcomes and analyzed using the Kaplan-Meier curves and univariable Cox regression analysis. RESULTS: Thirty-three DNTs patients were included finally, of which the average age at seizure onset was 11.59 ± 7.46 years old and the average duration of seizures prior to surgical resection was 3.00 ± 4.68 years. After surgical resection, the patients were followed up for 2.39 ± 1.97 years, and 28 patients (84.85%) were seizure-free (class I of the Engel Outcome Scale) while five patients (15.15%) were seizure-continuous (class II or III of the Engel Outcome Scale). When compared with seizure-free patients, seizure-continuous patients had greater age at seizure onset and longer duration of seizures before surgical resection (p < .05). No variables were found to be statistically significantly associated with prognosis in univariable Cox regression analysis, but patients with extra-temporal DNTs were found to have better prognosis than those with temporal DNTs (log-rank test p = .048). CONCLUSIONS: Elder seizure onset age, longer duration of seizures prior to surgical resection, and a temporal location may be risk factors of poor prognosis for DNTs patients after surgical resection.

Side of Lesions Predicts Surgical Outcomes in Patients With Drug-Resistant Temporal Lobe Epilepsy Secondary to Focal Cortical Dysplasia Type IIIa.

Objective: This study aims to evaluate the surgical outcomes and analyze the predictors of surgical outcomes in patients undergoing anterior temporal lobectomy (ATL) for drug-resistant temporal lobe epilepsy (TLE) secondary to focal cortical dysplasia (FCD) type IIIa. Methods: Data on patients with drug-resistant TLE secondary to FCD type IIIa who had undergone ATL at Xiangya Hospital, Central South University from January 2014 to April 2018, were collected retrospectively. International League Against Epilepsy (ILAE) classification was used to evaluate postoperative seizure outcomes. Predictors of surgical outcomes were identified by using univariate and multivariate analyses. Results: A total of 43 patients with drug-resistant TLE secondary to FCD type IIIa who had undergone ATL were included in this study. Twenty patients had right ATL, and 23 patients had left ATL. With a follow-up of 2-6 years, 76.7% (33 of 43) of patients were seizure-free. Univariate and multivariate analysis results indicated that lesions on the right side independently predict postoperative seizure freedom (OR, 0.08; 95% CI, 0.01-0.72; P = 0.024). Conclusion: ATL is an effective therapy for patients with drug-resistant TLE secondary to FCD type IIIa. Patients with lesions on the right side are more likely to achieve postoperative seizure freedom.

IL-1α and IL-1ß promote NOD2-induced immune responses by enhancing MAPK signaling.

Both toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) induce a tightly regulated inflammatory response at risk of causing tissue damage, depending on the effectiveness of ensuing negative feedback regulatory mechanisms. Cross-regulation between TLRs, NLRs, and cytokine receptors has been observed. However, the cross-regulation between interleukin-1 (IL-1) receptors and NOD2 is not completely understood. In this study, we found that IL-1α/ß increased NOD2-induced inflammatory response in human monocytic THP1 cells, peripheral blood mononuclear cells (PBMCs), mouse macrophage RWA264.7 cells and spleen cells, and in an in vivo experiment. IL-1α/ß pre-treatment induced the production of CXC chemokines, including growth-regulated oncogene (GRO)-α, GRO-ß, and IL-8, and proinflammatory cytokines, including IL-1ß, IL-6, and TNFα, which are induced by the activation of NOD2, in a dose- and time-dependent manner. However, pre-treatment with the NOD2 ligand muramyl dipeptide (MDP) did not up-regulate the expression of cytokines induced by IL-1α/ß re-treatment. IL-1ß treatment increased the expression of A20, which is an important inhibitor of the innate immune response. However, the overexpression of A20 failed to inhibit MDP-induced cytokine production, suggesting that A20 had no effects on the NOD2-induced immune response. In addition, IL-1α/ß increased the expression of NOD2 and its downstream adaptor RIP2, and IL-1α/ß pre-treatment increased MDP-induced activation of mitogen-activated protein kinases (MAPKs), including ERK, JNK, and P38, which contributed to MDP-induced cytokine production. Based on these results, IL-1α/ß promote the NOD2-induced immune responses by enhancing MDP-induced activation of MAPK signaling pathways.