RESUMO
Polycystic kidney disease (PKD) and Alport syndrome (AS) are serious inherited disorders associated with renal disease, and thalassemia is a hereditary blood disease with a high prevalence in south China. Here, we report an exceptional PKD coincidence of thalassemia minor and AS (diagnosed genetically) in a large Chinese family. Whole genome next-generation sequencing (NGS) was performed on the proband, and all family members underwent clinical evaluation. Sanger sequencing was used to validate the mutations distinguished by NGS. The pathogenic potential of the variants were evaluated by Polymorphism Phenotyping v2 (PolyPhen-2), Sorting Intolerant From Tolerant (SIFT) algorithm, and MutationTaster. Immunohistochemical, Western blot, immunofluorescent, and TdT-mediated dUTP nick-end labeling (TUNEL) analyses were performed to investigate polycystin 1 (PC1) expression, and cell proliferation and apoptosis in kidney tissues from the proband and normal control. A novel frameshift polycystic kidney disease 1 (PKD1) mutation (c.3903delC, p.A1302Pfs) was identified to be responsible for renal disease in this family. PC1 expression, and cell proliferation and apoptosis were significantly increased in the kidney tissues of the proband. Moreover, a deletion of approximately 19.3 kb of DNA with α-globin genes (_ _SEA) was associated with thalassemia minor in the family. In addition, a collagen type IV α 5 chain (COL4A5) variant (c.2858G>T, rs78972735), annotated as a pathogenic mutation in dbSNP and human gene mutation database (HGMD), was found in four family members with no clinical traits of AS. A novel pathogenic PKD1 mutation (c.3903delC) and (_ _SEA) thalassemia deletion were found to be responsible for the clinical symptoms in this family. The reported pathogenic COL4a5 variant (c.2858G>T, rs78972735) was not pathogenic alone.
Assuntos
Colágeno Tipo IV/genética , Nefrite Hereditária/genética , Rim Policístico Autossômico Dominante/genética , Situs Inversus/genética , Talassemia beta/genética , Povo Asiático , China , Análise Mutacional de DNA , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Nefrite Hereditária/complicações , Nefrite Hereditária/diagnóstico , Linhagem , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/diagnóstico , Situs Inversus/complicações , Situs Inversus/diagnóstico , Canais de Cátion TRPP/genética , Talassemia beta/complicações , Talassemia beta/diagnósticoRESUMO
Enteral nutrition plays an irreplaceable role in the nutritional treatment of critically ill patients. In order to help clinical medical staff to manage the common complications during the implementations of enteral nutrition for critically ill patients, the consensus writing team carried out literature retrieval, literature quality evaluation, evidence synthesis. Several topics such as diarrhea, aspiration, high gastric residual volume, abdominal distension, etc. were assessed by evidence-based methodology and Delphi method. After two rounds of expert investigations, Expert consensus on prevention and management of enteral nutrition therapy complications for critically ill patients in China (2021 edition) developed, and provided guidance for clinical medical staff.
Assuntos
Estado Terminal , Nutrição Enteral , China , Consenso , Diarreia , Nutrição Enteral/efeitos adversos , HumanosRESUMO
CELSR2 is postulated to be a receptor involved in contact-mediated communication; however, its expression and function in cancer remain unknown. ING4 is a tumor suppresor encoded by the ING4 gene which inhibits cell growth. The expression of CELSR2 and ING4 in breast tumors and in benign epithelial cells have been analyzed and correlated with HER2, ER, and PR status. Immunohistochemistry was used to analyze the expression of CELSR2 and ING4 protein in breast tumors and benign epithelial cells. The differential cellular localization of both markers was analyzed and results were also correlated with HER2, ER, and PR status. CELSR2 and ING4 cytoplasmic expression was significantly stronger in tumors than in benign epithelial cells, while the nuclear expression of both markers was significantly stronger in benign epithelial cells than in tumors. When comparing the two markers in the same type of tissues, the nuclear expression of CELSR2 was significantly stronger than cytoplasmic in benign epithelial cells, while there was no significant difference in the cellular localization of CELSR2 in tumors. For ING4, the cytoplasmic expression was significantly stronger than nuclear expression in tumors, while in benign epithelial cells, ING4 was expressed at similar levels in both compartments. There was no correlation between CELSR2 expression and HER2, ER, and PR status in tumors. However, the cytoplasmic expression of ING4 was associated with HER2 positivity in tumors. Both CELSR2 and ING4 display increased cytoplasmic staining in breast cancer cells compared to benign epithelium, suggesting a possible role of both genes in the pathogenesis of human mammary neoplasia.