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Coffin-Siris syndrome (CSS) (OMIM #135900) involves multiple congenital malformations, including hypotonia, short stature, sparse scalp hair, a coarse face, prominent eyebrows, a wide mouth, delayed bone age, and hypoplastic or absent fifth fingers/toes or nails, together with developmental delay. The cause of CSS is suggested to be related to alterations in the BRG- or HRBM-associated factor (BAF) pathway in humans. In this gene family, pathogenic variations in the AT-rich interactive domain-containing protein 1B (ARID1B) gene are revealed to be a significant element causing neurodevelopmental disability in patients with CSS. Herein, we describe the clinical features and gene variations in four Chinese patients with CSS. All the patients shared common features of short fifth fingers/toes or hypoplastic nails, coarse facial features, thick eyebrows, long cilia, a flat nasal bridge, a broad nose, a wide mouth, a high palate, and hypotonia. Besides, they had an intellectual disability, language, and motor developmental delay. Candidate genes were screened for variations using polymerase chain reaction (PCR) and sequencing. The variations were sequenced by next-generation sequencing and confirmed by first-generation sequencing. Exome sequencing suggested four de novo variations in the ARID1B gene in four unrelated patients. These included two frameshift variations (c.3581delC, c.6661_6662insG) and two nonsense variations (c.1936C>T, c.2248C>T). Of the four variations, three variations were novel. The results in our present study broaden the understanding of the disease and further interpret the molecular genetic mechanism of these rare variations in CSS. [ABSTRACT FROM AUTHOR]

Background: In China, there were few studies about the pathogens of acute viral encephalitis and meningitis in children in recent years. The aims of this study were to characterize the etiology and prognosis of acute viral encephalitis and meningitis in Chinese children.Methods: This was a multicentre prospective study. Two hundred and sixty one viral encephalitis patients and 285 viral meningitis patients were enrolled. The mean age of viral encephalitis and meningitis were 5.88 ± 3.60 years and 6.39 ± 3.57 years, respectively. Real-time reverse transcription PCR and multiplex PCR were used to detect human enteroviruses and herpes viruses in cerebrospinal fluid (CSF) of patients with encephalitis or meningitis. The enzyme-linked immune absorbent assay (ELISA) was used for detecting IgM antibody against Japanese encephalitis virus (JEV) in CSF and against mumps virus, tick-borne encephalitis virus (TBEV), dengue virus and rubella virus in acute serum. The clinical and outcome data were collected during patients' hospitalization.Results: The etiology of viral encephalitis was confirmed in 52.5% patients. The primary pathogen was human enteroviruses (27.7%) in viral encephalitis. The incidence of sequelae and the fatality rate of viral encephalitis with confirmed etiology were 7.5% and 0.8%, respectively. The etiology of viral meningitis was identified in 42.8% cases. The leading pathogen was also human enteroviruses (37.7%) in viral meningitis. The prognosis of viral meningitis was favorable with only 0.7% patients had neurological sequelae.Conclusions: Human enteroviruses were the leading cause both in acute viral encephalitis and viral meningitis in children. The incidence of sequelae and fatality rate of viral encephalitis with confirmed etiology were 7.5% and 0.8%, respectively. The prognosis of viral meningitis was favorable compared to viral encephalitis. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is one of the primary pathological factors that contributes to aging-related cognitive impairments, but the underlying mechanisms remain unclear. We recently reported that old DM rats exhibited impaired myogenic responses of the cerebral arteries and arterioles, poor cerebral blood flow autoregulation, enhanced blood-brain barrier (BBB) leakage, and cognitive impairments. These changes were associated with diminished vascular smooth muscle cell contractile capability linked to elevated reactive oxygen species (ROS) and reduced ATP production. In the present study, using a nonobese T2DN DM rat, we isolated parenchymal arterioles (PAs), cultured cerebral microvascular pericytes, and examined whether cerebrovascular pericyte in DM is damaged and whether pericyte dysfunction may play a role in the regulation of cerebral hemodynamics and BBB integrity. We found that ROS and mitochondrial superoxide production were elevated in PAs isolated from old DM rats and in high glucose (HG)-treated α-smooth muscle actin-positive pericytes. HG-treated pericytes displayed decreased contractile capability in association with diminished mitochondrial respiration and ATP production. Additionally, the expression of advanced glycation end products, transforming growth factor-β, vascular endothelial growth factor, and fibronectin were enhanced, but claudin 5 and integrin β1 was reduced in the brain of old DM rats and HG-treated pericytes. Further, endothelial tight junction and pericyte coverage on microvessels were reduced in the cortex of old DM rats. These results demonstrate our previous findings that the impaired cerebral hemodynamics and BBB leakage and cognitive impairments in the same old DM model are associated with hyperglycemia-induced cerebrovascular pericyte dysfunction. NEW & NOTEWORTHY This study demonstrates that the loss of contractile capability in pericytes in diabetes is associated with enhanced ROS and reduced ATP production. Enhanced advanced glycation end products (AGEs) in diabetes accompany with reduced pericyte and endothelial tight junction coverage in the cortical capillaries of old diabetic rats. These results suggest our previous findings that the impaired cerebral hemodynamics, BBB leakage, and cognitive impairments in old DM model are associated with hyperglycemia-induced cerebrovascular pericyte dysfunction.