ABSTRACT
Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Subject(s)
Female , Animals , Mice , Humans , Child, Preschool , Intellectual Disability/genetics , Heart Defects, Congenital/genetics , Facies , Cleft Palate , Muscle HypotoniaABSTRACT
Objective:To explore the application of standardized treatment process for early enteral nutrition combined with gastric retention after operation in patients with esophageal cancer.Methods:Using convenience sampling, 84 patients with gastric retention complicated by early enteral nutrition support after esophagectomy in Department of Thoracic Surgery, Third People′s Hospital of Dalian from July 2015 to June 2020 were selected as the subjects. They were divided into control group and experimental group according to admission time with 42 cases in each group. The control group received routine nursing, while the experimental group received early enteral nutrition and gastric retention standardized treatment process nursing. The differences between the two groups in nutritional status and immune indexes before and 7 days after operation, the standard feeding rate within 7 days after operation, incidence of postoperative complications and enteral nutrition-related complications, length of hospitalization time and hospitalization expenses were compared.Results:In the control group, 2 cases were lost to follow-up. There was no statistically significant difference in preoperative nutritional status and immune indexes between the two groups ( P<0.05); 7 days after operation, the body mass index, serum total protein, prealbumin, nitrogen balance, IgM, CD3, CD4, and CD4/CD8 of the experimental group were all higher than those of the control group, and the differences between the two groups were statistically significant ( t values were 2.228-5.332, P<0.05 or 0.01).The standard feeding rate within 7 days was (68.93±8.12)% in the experimental group and (51.19±6.96)% in the control group, respectively, and the difference between the two groups was statistically significant ( t value was -4.38, P<0.01). The incidence of postoperative nausea and vomiting, Ⅱ B healing, anastomotic fistula and aspiration was 2.38% (1/42), 2.38% (1/42) and 0 (0/42), 2.38% (1/42) in the experimental group and 15.00%(6/40), 7.50% (3/40) and 5.00% (2/40) and 10.00% (4/40) in the control group, respectively, and the differences were statistically significant ( χ2 values were 5.99 - 9.88, P< 0.05 or 0.01). The length of hospitalization time in the experimental group was (10.18±1.69) d, and the hospitalization cost was (53 268.46 ±3 651.56) yuan, both lower than (13.66 ± 2.18) d and (64 972.39 ± 4 029.81) yuan in the control group, and the difference was statistically significant ( t values were 2.14, 2.89, P< 0.05). Conclusions:The standardized treatment process of enteral nutrition combined with gastric retention can improve the feeding rate, nutritional index and immune index within 7 days after operation, reduce postoperative complications and incidence of enteral nutrition related complications, reduce the hospitalization time and reduce hospitalization expenses.
ABSTRACT
Alcoholic dementia is increasingly becoming both a severe medical issue and a social problem;the unknown overall mecha-nism is the bottleneck for effective intervention and treatment of alcoholic brain injury. As the primary structure for the release, transmission of neurotransmitter and information integration between neurons, synapse plays a significant role in performing the advanced function of brain, such as learning and memory. Based on the neurobiological principles of synaptic structure and function, the changes in process and efficiency of synaptic transmission and information integration stressed by alcoholic molecular were reviewed in comparison with the nor-mal process. The molecular mechanisms for alcoholic brain damage in learning and memory abilities were systematically discussed from the levels of synaptic morphology, material components, and signal transduction, respectively, and the repairing strategies for the damaged syn-aptic structure were proposed accordingly. Hopefully, this review could provide a deep insight into understanding the molecular mechanism of alcoholic brain damage, and draw ideas for the memory-enhancing peptides development.