Irinotecan (CPT11) chemotherapy-induced diarrhea affects a substantial cancer population due to β-glucuronidase (Gus) converting 10-O-glucuronyl-7-ethyl-10-hydroxycamptothecin (SN38G) to toxic 7-ethyl-10-hydroxycamptothecin (SN38). Existing interventions primarily address inflammation and Gus enzyme inhibition, neglecting epithelial repair and Gus-expressing bacteria. Herein, we discovered that dehydrodiisoeugenol (DDIE), isolated from nutmeg, alleviates CPT11-induced intestinal mucositis alongside a synergistic antitumor effect with CPT11 by improving weight loss, colon shortening, epithelial barrier dysfunction, goblet cells and intestinal stem cells (ISCs) loss, and wound-healing. The anti-mucositis effect of DDIE is gut microbiota-dependent. Analysis of microbiome profiling data from clinical patients and CPT11-induced mucositis mice reveals a strong correlation between CPT11 chemotoxicity and Gus-expressing bacteria, particularly Enterococcus faecalis (E. faecalis). DDIE counters CPT11-induced augmentation of E. faecalis, leading to decreased intestinal Gus and SN38 levels. The Partial Least Squares Path Model (PLS-PM) algorithm initially links E. faecalis to dysregulated epithelial renovation. This is further validated in a 3D intestinal organoid model, in which both SN38 and E. faecalis hinder the formation and differentiation of organoids. Interestingly, colonization of E. faecalis exacerbates CPT11-induced mucositis and disturbs epithelial differentiation. Our study unveils a microbiota-driven, epithelial reconstruction-mediated action of DDIE against mucositis, proposing the 'Gus bacteria-host-irinotecan axis' as a promising target for mitigating CPT11 chemotoxicity.

Objective:To investigate the effect of aspirin on the outcomes in adult patients with ischemic moyamoya disease treated with encephaloduroarteriosynangiosis (EDAS).Methods:Adult patients with ischemic moyamoya disease treated EDAS in the Department of Neurosurgery, the Fifth Medical Center, PLA General Hospital from January 2015 to September 2018 were enrolled retrospectively. The control group only received EDAS treatment, and the aspirin group received EDAS and aspirin antiplatelet treatment. The data of the both groups were analyzed retrospectively and the effective rate of operation, the incidence of perioperative intracerebral hemorrhage, the incidence of recurrent cerebrovascular events at 6 months after operation and the improvement rate of the modified Rankin Scale (mRS) score were compared.Results:A total of 120 adult patients with ischemic moyamoya disease were enrolled, including 60 in the aspirin group and 60 in the control group. EDAS was performed on 107 cerebral hemispheres in both groups. The operative effective rate in the aspirin group was significantly higher than that in the control group (82.24% vs. 65.42%; χ2=7.836, P=0.005). There was no perioperative cerebral hemorrhage event in the aspirin group and the control group. There was no significant difference in the incidence of cerebral infarction within 6 months after operation, but the incidence of transient ischemic attack in the aspirin group was significantly lower than that in the control group (15% vs. 40%; χ2=9.404, P=0.002). In addition, the improvement rate of mRS score in the aspirin group at 6 months after operation was significantly higher than that in the control group (85% vs. 63.33%; χ2=7.350, P=0.007). Conclusions:The combination of EDAS and aspirin can effectively improve the outcomes of adult patients with ischemic moyamoya disease without increasing the risk of perioperative intracerebral hemorrhage.

Objective:To investigate the correlation between RNF213 gene p. R4810K polymorphism and posterior cerebral artery involvement in Chinese children with familial moyamoya disease.Methods:Children with familial moyamoya disease admitted to the Department of Neurosurgery, the Fifth Medical Center of PLA General Hospital from August 2004 to June 2018 were enrolled, and they were divided into posterior cerebral artery involved group and posterior cerebral artery uninvolved group. RNF213 gene p. R4810K single nucleotide polymorphism was detected. Multivariate logistic regression analysis was used to determine the independent risk factors for posterior cerebral artery involvement. Results:A total of 65 children with familial moyamoya disease were enrolled. Their age was 6.98±4.46 years and 37 (56.9%) were male. The first symptom of 55 children (84.6%) was cerebral ischemia, and 37 (56.9%) involved posterior cerebral artery. There were 3 (4.6%) children with p. R4810K AA genotype, 26 (40.0%) with GA genotype, and 36 (55.4%) with GG genotype. The p. R4810K genotype distribution in the posterior cerebral artery involved group was statistically different from that in the uninvolved group (GA+ AA genotype: 56.8% vs. 28.6%; χ2=5.124, P=0.024), and there were no statistical difference in gender, age, first symptom, and genetic pattern. Multivariate logistic regression analysis showed that after adjusting the first onset age and gender, p. R4810K G>A mutation was the only independent risk factor for posterior cerebral artery involvement (odds ratio 3.240, 95% confidence interval 1.082-9.705; P=0.020). Conclusion:The p. R4810K polymorphism of RNF213 gene is associated with posterior cerebral artery involvement in Chinese children with familial moyamoya disease.

Coronavirus disease 2019 (COVID-19), caused by the 2019 novel coronavirus (2019-nCoV), is spreading on a large scale in China. COVID-19 mainly affects the respiratory system and cause symptoms such as severe hypoxemia and high fever. At present, there is no specific treatment drug, and patients' autoimmunity is closely related to disease prognosis. The brain tissue of patients with moyamoya disease is in a state of ischemia and hypoxia for a long time. Hypoxemia and high fever will aggravate the cerebral ischemia and hypoxia in patients with moyamoya disease, and patients with moyamoya disease may also have autoimmune abnormalities. Because people with moyamoya disease are also likely to have COVID-19 and COVID-19 can cause many conditions that may aggravate the symptoms of patients with moyamoya disease, which brings new problems and challenges to the clinical diagnosis and treatment of moyamoya disease. In this article, the diagnosis and treatment process and prevention and control measures of patients with moyamoya disease under the current epidemic situation are thought, and the key issues in the treatment of patients with moyamoya disease after suffering from COVID-19 are sorted out. It is hoped to provide reference for the diagnosis and treatment of moyamoya disease under the COVID-19 epidemic situation.