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Background: In this prospective cohort study, we evaluated features of "adult‐onset megacolon with focal hypoganglionosis." Methods: We assessed the radiologic, endoscopic, and histopathologic phenotyping and treatment outcomes of 29 patients between 2017 and 2020. Data from community controls, consisting of 19,948 adults undergoing health screenings, were analyzed to identify risk factors. Experts reviewed clinical features and pathological specimens according to the London Classification for gastrointestinal neuromuscular pathology. Key results: The median age of the patients with adult‐onset megacolon with focal hypoganglionosis at symptom onset was 59 years (range, 32.0–74.9 years), with mean symptom onset only 1 year before diagnosis. All patients had focal stenotic regions with proximal bowel dilatation (mean diameter, 78.8 mm; 95% confidence interval [CI], 72–86). The comparison with community controls showed no obvious risk factors. Ten patients underwent surgery, and all exhibited significant hypoganglionosis: 5.4 myenteric ganglion cells/cm (interquartile range [IQR], 3.7–16.4) in the stenotic regions compared to 278 cells/cm (IQR, 190–338) in the proximal and 95 cells/cm (IQR, 45–213) in the distal colon. Hypoganglionosis was associated with CD3+ T cells along the myenteric plexus. Colectomy was associated with significant symptom improvement compared to medical treatment [change in the Global Bowel Satisfaction score, −5.4 points (surgery) vs. ‐0.3 points (medical treatment); p < 0.001]. Conclusions and inferences: Adult‐onset megacolon with focal hypoganglionosis has distinct features characterized by hypoganglionosis due to inflammation. Bowel resection appears to benefit these patients. [ABSTRACT FROM AUTHOR]

Alcoholic liver disease (ALD), a liver function disorder caused by excessive alcohol intake, is a serious threat to global public health and social development. Toxic metabolites and reactive oxygen species produced during the metabolism of alcohol can alter the epigenetic state including DNA methylation, histone modifications, and expression of microRNAs. Epigenetic alterations can conversely involve various signaling pathways, which could contribute to the initiation and progression of ALD. To elucidate the relationship between epigenetic alterations and alcohol damage not only reinforces our understanding on pathogenesis of ALD, but also provides novel targets for clinical diagnosis, treatment, and drug research of ALD. In this review, we have summarized the research progress of epigenetic alterations and related mechanisms caused by alcohol in the pathogenesis of ALD. Considering the invertibility of epigenetic alterations, treatment of ALD through epigenetic modification with common less harmful compounds is also related. [ABSTRACT FROM AUTHOR]

Aims Neuroimaging studies have demonstrated both structural and functional abnormalities in widespread brain regions in patients with subcortical vascular mild cognitive impairment (sv MCI). However, whether and how these changes alter functional brain network organization remains largely unknown. Methods We recruited 21 patients with sv MCI and 26 healthy control ( HC) subjects who underwent resting-state functional magnetic resonance imaging scans. Graph theory-based network analyses were used to investigate alterations in the topological organization of functional brain networks. Results Compared with the HC individuals, the patients with sv MCI showed disrupted global network topology with significantly increased path length and modularity. Modular structure was also impaired in the sv MCI patients with a notable rearrangement of the executive control module, where the parietal regions were split out and grouped as a separate module. The sv MCI patients also revealed deficits in the intra- and/or intermodule connectivity of several brain regions. Specifically, the within-module degree was decreased in the middle cingulate gyrus while it was increased in the left anterior insula, medial prefrontal cortex and cuneus. Additionally, increased intermodule connectivity was observed in the inferior and superior parietal gyrus, which was associated with worse cognitive performance in the sv MCI patients. Conclusion Together, our results indicate that sv MCI patients exhibit dysregulation of the topological organization of functional brain networks, which has important implications for understanding the pathophysiological mechanism of sv MCI. [ABSTRACT FROM AUTHOR]