ABSTRACT
Objective:To evaluate the effects of different pacing modes (unipolar/bipolar) under left bundle branch pacing(LBBP) on ventricular mechanical synchrony and myocardial work using the pressure-strain loop technique.Methods:Twenty-nine patients with LBBP due to symptomatic bradycardia were collected as LBBP group in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from December 2018 to July 2020. Another 29 matched patients with right ventricular pacing (RVP) during the same period were also included as a RVP group. Each LBBP patient was programmed to different pacing modes (uni-/bio-polar) within 1 week after the operation.Under each pacing mode, the inter- and intra-ventricular mechanical synchronization were evaluated. Meanwhile, the global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were obtained by the left ventricular pressure-strain loops technique.Results:Compared with the RVP group, the mechanical synchrony in the LBBP group was significantly improved (all P<0.05). GWI, GCW, and GWE increased, while GWW decreased, and the differences were statistically significant (all P<0.05), there were no significant differences in ventricular mechanical synchronization, GWI, GCW, GWE, and GWW between unipolar and bipolar pacing in the LBBP group (all P>0.05), there were no significant differences in these parameters when increasing output voltage (all P>0.05). Conclusions:LBBP induces better mechanical synchronization and higher myocardial work efficiency than RVP. Different LBBP pacing modes do not affect ventricular mechanical synchronization and myocardial work efficiency.
ABSTRACT
OBJECTIVE@#To identify potential mutation of PMM2 gene in an infant with congenital disorders of glycosylation type 1a (CDG-1a).@*METHODS@#Genomic DNA was extracted from peripheral blood sample of the patient. All coding exons (exons 1-8) and splicing sites of the PMM2 gene were amplified with PCR. Potential variants were detected by direct sequencing of the PCR products and comparing the results against the ESP and SNP human gene databases. A protein BLAST system was employed to analyze cross-species conservation of the variants amino acid. A PubMed BLAST CD-search system was employed to identify functional domains damaged by variants of the PMM2 gene. Impact of potential variants was analyzed using software including PolyPhen-2 SIFT and Mutation Taster. Whole exome sequencing was used to identify additional variants of the PMM2 gene which may explain the condition of the patient.@*RESULTS@#The child was found to carry compound heterozygous variants (c.458_462delTAAGA and c.395T>C) of the PMM2 gene, which were inherited respectively from his father and mother. The c.458_462delTAAGA has not been reported previously and may result in disruption of 10 functional domains within the PMM2 protein. The c.395T>C mutation has been recorded by a SNP database with frequency unknown. Both mutations were predicted as "probably damaging". Whole exome sequencing has identified no additional disease-causing variant which can explain the patient's condition.@*CONCLUSION@#The patient's condition may be attributed to the compound heterozygous variants c.458_462delTAAGA and c.395T>C of the PMM2 gene. Above results has facilitated molecular diagnosis for the patient.
Subject(s)
Humans , Infant , Congenital Disorders of Glycosylation , Genetics , Exons , Mutation , Phosphotransferases (Phosphomutases) , GeneticsABSTRACT
Accumulating evidence suggests that the small G protein Rho and its downstream effector Rho kinase may play important roles in kidney biology. The present study examined the effects of a Rho-kinase inhibitor, fasudil, on daunorubicin-induced progressive glomerulosclerosis and explored the underlying mechanism by which fasudil ameliorates glomerulosclerosis. Thirty-six male SD rats were randomly allocated into sham-operation group (sham group, n=12), unilateral nephrectomy (UNX)+daunorubicin (DRB) group (model group, n=12), UNX+DRB+Fasudil group (treatment group, n=12). Two to four weeks after the establishment of the animal model, 6 rats in each group were taken randomly for the detection of 24-h urine protein excretion. Kidney sections were examined by HE and PAS staining, immunohistochemistry and transmission electric microscopy (TEM). The expression of Rho-kinase mRNA and P27 mRNA in kidney were detected by RT-PCR. It was found that the 24-h urine protein excretion in model group was increased significantly as compared with sham group (P<0.01). But this increase was significantly suppressed by fasudil (P<0.05). At 4 week, the foot process effacement in podocytes, mesangial proliferation and ECM accumulation were observed in model group, presenting as focal segmental glomerulosclerosis. But in the treatment group, the fasudil alleviated glomerular injury, with proliferating cell nuclear antigen (PCNA)-positive cell infiltration ameliorated and the expression of P27 increased. The expression of Rho-kinase mRNA was significantly enhanced in model group and was suppressed in treatment group. Moreover, fasudil up-regulated the mRNA expression of P27. Our study demonstrated that the glomerulosclerosis was substantially ameliorated by inhibiting the expression of Rho-kinase. It is suggested that Rho-kinase pathway is involved in the renal injury and the inhibition of Rho-kinase may constitute a therapeutic strategy for the treatment of renal injury.