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Recently, LRP10 has been identified as a causative gene for Parkinson's disease (PD). However, subsequent studies showed inconsistent conclusions. To explore its relevance to PD, we systematically analyzed LRP10 rare mutations in a large Han Chinese familial PD cohort of 385 unrelated probands using segregation analysis, transcriptional effect analysis, and burden test. Lomeguatrib supplier As a result, 3 missense variants and 1 splicing region variant in LRP10 were identified in 4 probands. Segregation analysis revealed 1 variant p.Arg66His cosegregating with PD status, 1 variant p.Ala613Ser not, and the other variant p.Gln581His unknown. The variant c.406+5G>T located at the splicing region has no effect on splicing, suggesting it is likely a rare neutral intronic variant. The burden test suggested no significant over-representation of rare variants in PD probands. Therefore, more robust independent studies are warranted to explore the pathogenicity of LRP10 mutations.Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are 2 monogenic cerebral small vessel diseases sharing several common clinical features including young stroke, migraine, and cognitive dysfunction. The aim of this study was to understand the role of MELAS in patients with CADASIL-like manifestations. We screened 429 unrelated patients with genetically unassigned CADASIL-like syndrome for mitochondrial DNA m.3243A>G mutation. None of them were found to have the mutation. Our finding suggests that m.3243A>G rarely causes CADASIL-like phenotype. It may be not necessary to consider MELAS as a differential diagnosis of CADASIL. Screening m.3243A>G in patients with CADASIL-like phenotype is of limited value.

Prostate cancer (PCa) is the second most common male cancer in the world. Its incidence is estimated to grow to 1.7 million new cases and 499,000 new deaths by 2030. Treatment of OCPC can affect patients physically and mentally, as well as their close relationships and their job or career, which conditions health-related quality of life (QoL).

Evaluate the impact on QoL attributable to the treatment for Organ Confined Prostate Cancer (OCPC).

Prospective multicenter observational study of 406 patients with OCPC treated from January 2015 to June 2018. The sample was divided into four study groups, according to the type of treatment radical prostatectomy (RP) (GA), external radiotherapy (ERT) (GB), brachytherapy (BT) (GC) and other treatments different from monotherapy with RP, ERT or BT (GD).

The age in GC was lower, the mean Prostate Specific Antigen (PSA) of all patients was 8.13ng/ml, the group with the highest mean PSA was GB with a mean of 10.43ng/dL, the mean Tumor Stage (TNM) was 3.82, and GD had the lowest post treatment quality of life.

OCPC treatment affects QoL. Curative monotherapies, specifically RP and BT, have less effect on QoL than external radiotherapy or other therapeutic alternatives. Urinary incontinence and fistulas secondary to OCPC have the highest impact on QOL impairment. The internationally validated SF 36 questionnaire is a useful cross-sectional measure of QOL to compare the impact of OCPC treatment modalities.

OCPC treatment affects QoL. Curative monotherapies, specifically RP and BT, have less effect on QoL than external radiotherapy or other therapeutic alternatives. Urinary incontinence and fistulas secondary to OCPC have the highest impact on QOL impairment. The internationally validated SF 36 questionnaire is a useful cross-sectional measure of QOL to compare the impact of OCPC treatment modalities.Pre-mRNA splicing is a fundamental process in mammalian gene expression, and alternative splicing plays an extensive role in generating protein diversity. Because the majority of genes undergo pre-mRNA splicing, most cellular processes depend on proper spliceosome function. We focus on the cell cycle and describe its dependence on pre-mRNA splicing and accurate alternative splicing. We outline the key cell-cycle factors and their known alternative splicing isoforms. We discuss different levels of pre-mRNA splicing regulation such as post-translational modifications and changes in the expression of splicing factors. We describe the effect of chromatin dynamics on pre-mRNA splicing during the cell cycle. In addition, we focus on spliceosome component SF3B1, which is mutated in many types of cancer, and describe the link between SF3B1 and its inhibitors and the cell cycle.To discover immune factors that can predict the progression of COVID-19, we evaluated circulating immune cells and plasma cytokines in COVID-19 patients. We found that T cells, including CD4+ T cells and CD8+ T cells, were significantly decreased in severe COVID-19 symptoms but not in mild symptoms, in comparison with healthy people. T cells remained at a low level after recovery from severe COVID-19. CD4+CD25+CD127low Treg-enriched cells were significantly increased in either mild or severe COVID-19 patients, regardless of recovery or not. Moreover, in either mild or severe COVID-19 patients, Treg-enriched cells up-regulated CD25 and down-regulated CD127. After recovery, CD25 was partially down-regulated but still higher than the normal level, while CD127 returned to the normal level in mild patients but not severe patients. B cells were decreased in mild patients and further decreased in severe patients, and remained low after recovery. NK cells were decreased only in severe COVID-19, with a tendency to return to the normal level after recovery. Plasma IL-6 and IL-10 were both elevated in severe patients but not in mild patients. After recovery, IL-6 remained higher than its normal level, while IL-10 returned to the normal level. Binary logistic regression analysis indicated that CD4+ T cells, B cells, IL-6, and IL-10 were significantly associated with COVID-19 severity. Therefore, these parameters are indicators of COVID-19 severity. Dynamic monitoring of these parameters would benefit therapy planning and prognosis evaluation.Common or dominant, T-cell receptor (TCR), V and J usage, in combination with particular human leukocyte antigen (HLA) alleles, has been associated with differing outcomes in viral infections, autoimmunity, and more recently, in cancer. Cervical cancer in particular represents the most dramatic series of distinctions of outcomes associated with differing combinations of dominant V or J usage and HLA alleles, possibly because of the strong association of cervical cancer with human papilloma virus (HPV), in turn leading to a likely molecular consistency in the mechanism of HPV antigen presentation. Thus, we considered assessing TRB V and J usage, HLA allele combinations, for their associations with survival rates and related data, in the cancer genome atlas head and neck cancer dataset. We obtained the TRB VDJ recombination reads from both the blood and tumor exome files and determined the V and J identities. We then established case ID (patient) subsets of V or J usage, HLA alleles, and determined, for example, that the TRBJ2-7, HLA-B*4001 combination was associated with a better disease free survival rate than were either the TRBJ1-3, HLA-DPB1*0301 or the TRBJ2-1, HLA-DPB1*0201 combinations.