LMNA is one of the leading causative genes of genetically inherited dilated cardiomyopathy (DCM). Unlike most DCM-causative genes, which encode sarcomeric or sarcomere-related proteins, LMNA encodes nuclear envelope proteins, lamin A and C, and does not directly associate with contractile function. However, a mutation in this gene could lead to the development of DCM. The molecular mechanism of how LMNA mutation contributes to DCM development remains largely unclear and yet to be elucidated. The objective of this study was to clarify the mechanism of developing DCM caused by LMNA mutation. Methods and Results We assessed cardiomyocyte phenotypes and characteristics focusing on cell cycle activity in mice with Lmna mutation. Both cell number and cell size were reduced, cardiomyocytes were immature, and cell cycle activity was retarded in Lmna mutant mice at both 5 weeks and 2 years of age. RNA-sequencing and pathway analysis revealed "proliferation of cells" had the most substantial impact on Lmna mutant mice. Cdkn1a, which encodes the cell cycle regulating protein p21, was strongly upregulated in Lmna mutants, and upregulation of p21 was confirmed by Western blot and immunostaining. DNA damage, which is known to upregulate Cdkn1a, was more abundantly detected in Lmna mutant mice. To assess the proliferative capacity of cardiomyocytes, the apex of the neonate mouse heart was resected, and recovery from the insult was observed. A restricted cardiomyocyte proliferating capacity after resecting the apex of the heart was observed in Lmna mutant mice. Conclusions Our results strongly suggest that loss of lamin function contributes to impaired cell proliferation through cell cycle defects. The inadequate inborn or responsive cell proliferation capacity plays an essential role in developing DCM with LMNA mutation.Background and aim Hyperhomocysteinemia (Hhcy) has been recognized as a risk factor of several chronic diseases. There is accumulating evidence that both genetic and dietary factors had a notable impact on the risk of Hhcy. The present study aims to investigate the interaction effect on Hhcy between methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and dietary intake. Methods Data were collected in a cross-sectional survey conducted in China; 3,966 participants with complete information on sociodemographic characteristics, anthropometric measurements, and dietary intake were included in the analyses. Dietary patterns were identified by factor analysis combined with cluster analysis. Blood samples were collected and MTHFR C677T genotypes were tested. Both the multiplicative statistical model and the additive model were conducted to investigate the interactive effects. Results Proportions of MTHFR C677T genotypes among participants were 29.2% for TT, 47.4% for CT, and 23.4% for CC. Three dietary patterns were identified, namely, the balanced pattern, the snack pattern, and the high-meat pattern. Compared with the balanced pattern, the other two patterns were associated with an elevated risk of Hhcy [the snack pattern odds ratio (OR) 1.2, 95% confidence interval (CI) 1.0-1.5; the high-meat pattern OR 1.3, 95% CI 1.1-1.6] after adjustment for age group, gender, residential region, and MTHFR C677T genotypes. A multiplicative interaction between the high-meat pattern and MTHFR 677TT genotype was observed, and synergistic effects between both the snack pattern and the high-meat pattern with MTHFR 677TT were identified. Conclusion Our results indicated that MTHFR C677T polymorphism and dietary patterns had interactive effects on Hhcy among the Chinese population. Subsequent targeted and appropriate dietary guidelines should be recommended for high-risk populations or patients of Hhcy carrying specific genotypes.Aims To evaluate the interrelation between neutrophil to lymphocyte ratio (NLR) coupled with gene signatures, inflammation, and diastolic dysfunction in patients with heart failure (HF) with preserved ejection fraction (HFpEF). Methods The clinical profile of 172 patients with HFpEF (EF ≥ 50%) and 173 non-HF control individuals was analyzed retrospectively. The association between NLR and HFpEF and the predictive performance of NLR for HFpEF were assessed by the binary logistic regression analysis and the receiver operating characteristic curve (ROC). click here Multivariate linear regression models further examined the associations between NLR and high-sensitivity C-reactive protein (hs-CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and average septal-lateral E/e', respectively. The freshly isolated neutrophils from 30 HFpEF patients and 42 non-HF controls were subjected to transcriptomic profiling. The biomarkers related to neutrophil activation and inflammation were detected in serum samples. RFpEF patients, which may suggest a causative role of neutrophils in the pathogenesis of the disease.Renal involvement occurs in approximately 5% of patients with Sjögren's syndrome (SS). We reported the case of a 20-year-old African woman who was received for paralysis of 4 limbs secondary to hypokalemia. The diagnosis of renal tubular acidosis type 1 complicated by hypokalemia was retained. In the etiologic research of renal tubular acidosis type 1, primary SS was retained. The patient received symptomatic treatment based on potassium chloride, sodium bicarbonate, hydration, and a low protein diet. In terms of etiological treatment, she was put on corticosteroid and hydroxychloroquine. The outcome was favorable with correction of acidosis and hypokalemia.A 70-year-old woman underwent a renal biopsy due to nephrotic syndrome. She had suffered from nontuberculous mycobacterial infection (NTM) for 14 years. The patient was diagnosed as having membranoproliferative glomerulonephritis (MPGN) type 3 and immunoglobulin (Ig)-associated MPGN based upon LM/erythromycin and IF findings, respectively. In high-magnification imaging, electron-dense deposits showed immunotactoid glomerulopathy (ITG). There was no evidence of hematological cancer, and the patient improved after receiving treatments for NTM. To the best of our knowledge, this patient is the first to show an association between ITG and NTM. Although ITG is generally considered as related to lymphoproliferative disease, it is suggested that ITG is driven by bacterial infection and is a potential outcome of Ig-associated MPGN.