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We also report that combined inactivation of Mri/Paxx results in live-born mice with modest phenotype, and combined inactivation of Mri/Dna-pkcs results in embryonic lethality. Therefore, we conclude that XLF is functionally redundant with MRI and PAXX during lymphocyte development in vivo. Moreover, Mri genetically interacts with Dna-pkcs and Paxx.Dementia is a progressive cognitive syndrome, with few effective pharmacological treatments that can slow its progress. Hence, non-pharmacological treatments (NPTs) play an important role in improving patient symptoms and quality of life. Designing the optimal personalised NPT strategy relies on objectively and quantitatively predicting the treatment outcome. Magnetoencephalography (MEG) findings can reflect the cognitive status of patients with dementia, and thus potentially predict NPT outcome. In the present study, 16 participants with cognitive impairment underwent NPT for several months. Their cognitive performance was evaluated based on the Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale - Cognitive at the beginning and end of the NPT period, while resting-state brain activity was evaluated using MEG during the NPT period. Our results showed that the spectral properties of MEG signals predicted the changes in cognitive performance scores. High frequency oscillatory intensity at the right superior frontal gyrus medial segment, opercular part of the inferior frontal gyrus, triangular part of the inferior frontal gyrus, post central gyrus, and angular gyrus predicted the changes in cognitive performance scores. Thus, resting-state brain activity may be a powerful tool in designing personalised NPT.Hepatocellular carcinoma (HCC) is one of the leading malignant diseases worldwide, but therapeutic targets for HCC are lacking. Here, we characterized a significant upregulation of Small Nuclear Ribonucleoprotein Polypeptides B and B1 (SNRPB) in HCC via qRT-PCR, western blotting, tissue microarray and public database analyses. Increased SNRPB expression was positively associated with adjacent organ invasion, tumor size, serum AFP level and poor HCC patient survival. Next, we transfected SNRPB into HCC cells to construct SNRPB-overexpressing cell lines, and short hairpin RNA targeting SNRPB was used to silence SNRPB in HCC cells. Functional studies showed that SNRPB overexpression could promote HCC cell malignant proliferation and stemness maintenance. Inversely, SNRPB knockdown in HCC cells caused inverse effects. Importantly, analysis of alternative splicing by RNA sequencing revealed that SNRPB promoted the formation of AKT3-204 and LDHA-220 splice variants, which activated the Akt pathway and aerobic glycolysis in HCC cells. In conclusion, SNRPB could serve as a prognostic predictor for patients with HCC, and it promotes HCC progression by inducing metabolic reprogramming.The relationship between autophagy and immunity has been thoroughly investigated. However, little is known about the role of autophagy in shaping the immune-microenvironment of periodontitis. Thus, we aim to explore the impact of autophagy on the immune-microenvironment of periodontitis. The expression distinctions of autophagy genes between healthy and periodontitis samples have been investigated. The connections between autophagy and immune characteristics including infiltrating immunocyte, immune reaction and human leukocyte antigen (HLA) gene were evaluated. The distinct autophagy-mediated expression patterns were identified and immune characteristics under distinct patterns were revealed. Autophagy phenotype-related genes were identified. 16 autophagy genes were dysregulated and a ten-autophagy classifier was constructed that can well distinguish periodontitis and healthy samples. Immune characteristics were closely related to autophagy higher expression of EDEM1 positively relates to infiltrating activated B cell; NCKAP1 negatively relates to monocyte; CXCR4 enhances BCR Signaling Pathway and PEX3 decreases the activity of TNF Family Members Receptors; positive expression correlation of EDEM1-HLADOB and negative correlation of RAB11A-HLADOB were observed. Selleck PLX5622 Two distinct autophagy expression patterns were identified which demonstrated different immune characteristics. 4309 autophagy phenotype-related genes were identified, and 219 of them were related to immunity, whose biological functions were found to be involved in immunocyte regulations. Our study revealed the strong impact of autophagy on the immune-microenvironment of periodontitis and brought new insights into the understanding of the pathogenesis of periodontitis.The characteristics of COVID-19 patients with autoimmune rheumatic diseases (AIRD) have rarely been reported. Patients with AIRD have suppressed immune defense function, which may increase their susceptibility to COVID-19. However, the immunosuppressive agents AIRD patients routinely used may be beneficial for protecting the cytokine storm caused by SARS-CoV-2. In this retrospective study, we included all confirmed cases in Huoshenshan Hospital from February 4 to April 9. Data were extracted from electronic medical records and were analyzed for clinical and laboratory features using SPSS (version 25.0). Of 3059 patients, 21 had the comorbidities with systematic lupus erythematosus (SLE) and/or rheumatoid arthritis (RA), including 5 with SLE, 15 with RA, and 1 with Rhupus. The proportion was 57.1% for severe cases, 61.9% for either severe or critical cases, and 4.8% for critical cases. The main manifestations, ARDS and ICU admission rate, as well as the mortality and length of hospital stay of COVID-19 in AIRD patients were similar to COVID-19 patients in the general population. Our preliminary experience shows that patients with AIRD tend to have a higher risk of SARS-CoV-2 infection, and may be at risk for a severe but less likely critical disease course. Further investigation is needed to understand the immunological features of these diseases.
To evaluate whether presurgical treatment using long-acting somatostatin receptor ligands (SRL) may change pituitary tumor consistency and improve surgical outcome in GH-secreting pituitary macroadenomas.
Retrospective study of 40 patients with GH-secreting pituitary macroadenomas operated for the first time by endoscopic transsphenoidal approach. Tumor consistency was evaluated intraoperatively and then correlated with histopathological fibrosis parameters and surgical outcomes. Surgical remission was reported based on the 2010 criteria.
The mean tumor size of GH-secreting macroadenomas was of 16.9 ± 8.2 mm and 25 were invasive pituitary adenomas (PAs). Presurgical treatment with long-acting SRL was performed in 17 patients (11 lanreotide, 6 octreotide). The cure rate was higher in those patients pre-treated with monthly doses ≥30 mg of octreotide or ≥90 mg of lanreotide than in those treated with lower doses or untreated (8/11 (72.7%) vs 11/29 (37.9%), P = 0.049). However, although the proportion of soft tumors increased as higher doses of SRL were considered in the pre-treated group, no statistical significance was reached, even when the highest approved monthly doses were used (6/6 (100%) vs 23/34 (67.