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Abstract Background Clinically, a large part of inflammatory bowel disease (IBD) patients is complicated by oral lesions. Although previous studies proved oral microbial dysbiosis in IBD patients, the bacterial community in the gastrointestinal (GI) tract of those IBD patients combined with oral ulcers has not been profiled yet. Methods In this study, we enrolled four groups of subjects, including healthy controls (CON), oral ulcer patients (OU), and ulcerative colitis patients with (UC_OU) and without (UC) oral ulcers. Bio-samples from three GI niches containing salivary, buccal, and fecal samples, were collected for 16S rRNA V3-V4 region sequencing. Bacterial abundance and related bio-functions were compared, and data showed that the fecal microbiota was more potent than salivary and buccal microbes in shaping the host immune system. ~ 22 UC and 10 UC_OU 5-aminosalicylate (5-ASA) routine treated patients were followed-up for six months; according to their treatment response (a decrease in the endoscopic Mayo score), they were further sub-grouped as responding and non-responding patients. Results We found those UC patients complicated with oral ulcers presented weaker treatment response, and three oral bacterial genera, i.e., Fusobacterium, Oribacterium, and Campylobacter, might be connected with treatment responding. Additionally, the salivary microbiome could be an indicator of treatment responding in 5-ASA routine treatment rather than buccal or fecal ones. Conclusions The fecal microbiota had a strong effect on the host’s immune indices, while the oral bacterial microbiota could help stratification for ulcerative colitis patients with oral ulcers. Additionally, the oral microbiota had the potential role in reflecting the treatment response of UC patients. Three oral bacteria genera (Fusobacterium, Oribacterium, and Campylobacter) might be involved in UC patients with oral ulcers lacking treatment responses, and monitoring oral microbiota may be meaningful in assessing the therapeutic response in UC patients.

Large cardiovascular outcome trials have reported favorable effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on heart failure. To study the potential mechanism of the SGLT2 inhibition in heart failure, we used the murine doxorubicin-induced cardiomyopathy model and identified the toll-like receptor 9 (TLR9), NAD-dependent deacetylase sirtuin-3 (SIRT3), and Beclin 1, acting in a complex together in response to empagliflozin treatment. The interactions and implications in mitochondrial function were evaluated with TLR9 deficient, SIRT3 deficient, Beclin 1 haplodeficient, and autophagy reporter mice and confirmed in a patient with SIRT3 point mutation and reduced enzymatic activity. The SGLT2 inhibitor, empagliflozin, protects the heart from doxorubicin cardiomyopathy in mice, by acting through a novel Beclin 1-toll-like receptor (TLR) 9-sirtuin-(SIRT) 3 axis. TLR9 and SIRT3 were both essential for the protective effects of empagliflozin. The dilated cardiomyopathy patient with SIRT3 point mutation and reduced enzymatic activity is associated with reduced TLR9 activation and the absence of mitochondrial responses in the heart after the SGLT2 inhibitor treatment. Our data indicate a dynamic communication between autophagy and Beclin 1-TLR9-SIRT3 complexes in the mitochondria in response to empagliflozin that may serve as a potential treatment strategy for heart failure.

Background and objectivesThe objective of this study is to investigate the outcomes of concurrent platinum-based chemoradiation therapy (CCRT), laparoscopic nerve-sparing ultra-radical hysterectomy (LNSURH), and open radical hysterectomy (ORH) on patients with locally advanced cervical carcinoma (LACC).MethodsA single-center retrospective study was conducted on LACC patients who received CCRT, ORH, or LNSURH from January 2011 to December 2019. Data on age, tumor size, overall survival (OS), disease-free survival (DFS), and early and late morbidities were collected. After 24 months of treatment, patients were asked a series of questions about their urinary, bowel, and sexual activities. Early morbidities were defined as those occurring during or within a month of treatment, whereas late morbidities and complications were defined as those occurring a month after treatment. The postoperative complications were classified with reference to the Clavien–Dindo classification (CD) system.ResultsThe Kaplan–Meier curves revealed no significant differences in OS and DFS among the three groups (P = 0.106 for DFS and P = 0.190 for OS). The rates of early complications in the CCRT group were comparable with those in the operated groups (P = 0.46). However, late complications were significantly lower in the ORH and LNSURH groups relative to those in the CCRT group. The scores of urinary and bowel functions were restored to the pretreatment state, although the sexual function scores were not satisfactory.ConclusionsThe treatments of CCRT, ORH, and LNSURH can be considered options for patients with LACC, as their OS and DFS showed no significant difference. In addition, LNSURH exhibited a lower incidence of late complications and high sexual function scores.