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Background: The ulcerative colitis (UC) Mayo endoscopy score is a useful tool for evaluating the severity of UC in patients in clinical practice. Objectives: We aimed to develop and validate a deep learning-based approach to automatically predict the Mayo endoscopic score using UC endoscopic images. Design: A multicenter, diagnostic retrospective study. Methods: We collected 15120 colonoscopy images of 768 UC patients from two hospitals in China and developed a deep model based on a vision transformer named the UC-former. The performance of the UC-former was compared with that of six endoscopists on the internal test set. Furthermore, multicenter validation from three hospitals was also carried out to evaluate UC-former’s generalization performance. Results: On the internal test set, the areas under the curve of Mayo 0, Mayo 1, Mayo 2, and Mayo 3 achieved by the UC-former were 0.998, 0.984, 0.973, and 0.990, respectively. The accuracy (ACC) achieved by the UC-former was 90.8%, which is higher than that achieved by the best senior endoscopist. For three multicenter external validations, the ACC was 82.4%, 85.0%, and 83.6%, respectively. Conclusions: The developed UC-former could achieve high ACC, fidelity, and stability to evaluate the severity of UC, which may provide potential application in clinical practice. Registration: This clinical trial was registered at the ClinicalTrials.gov (trial registration number: NCT05336773)

Background: The community of gut microbes is a key factor controlling the intestinal barrier that communicates with the nervous system through the gut–brain axis. Based on our clinical data showing that populations of Roseburia intestinalis are dramatically decreased in the gut of patients with ulcerative colitis, we studied the efficacy of a strain belonging to this species in the context of colitis and stress using animal models. Methods: Dextran sulfate sodium was used to induce colitis in rats, which then underwent an enema with R. intestinalis as a treatment. The disease activity index, fecal changes and body weight of rats were recorded to evaluate colitis, while histological and immunohistochemical analyses were carried out to examine colon function, and 16S rRNA sequencing was performed to evaluate the gut microbiota change. Behavioral assays and immunohistochemical staining of brain were performed to assess the effect of R. intestinalis on the gut–brain axis. Results: Colitis-related symptoms in rats were significantly relieved after R. intestinalis enema, and the stool traits and colon length of rats were significantly recovered after treatment. The gut epithelial integrity and intestinal barrier were restored in treated rats, as evidenced by the higher expression of Zo-1 in colon tissues, accompanied by the restoration of gut microbiota. Meanwhile, depressive-like behaviors of rats were reduced after treatment, and laboratory experiments on neuronal cells also showed that IL-6, IL-7 and 5-HT were downregulated by R. intestinalis treatment in both serum and brain tissue, while Iba-1 expression was reduced in treated rats. Conclusions: The administration of R. intestinalis contributes to restoration of the gut microbiota, promoting colon repair and the recovery of gastrointestinal function. These alterations are accompanied by the relief of depressive-like behaviors through a process modulated by the neuronal network and the regulation of inflammation by the gut–brain axis.

MicroRNAs (miRNAs) are emerging as critical mediators in tumors, including triple-negative breast cancer (TNBC). The role of miR-518a-3p in TNBC was investigated to identify potential therapeutic target. Data from KM Plotter database ( www.kmplot.com ) showed that high miR-518a-3p expression was significantly associated with overall survival of patients with TNBC ( p = 0.04). The expression of miR-518a-3p was dysregulated in TNBC cells. Functional assays revealed that over-expression of miR-518a-3p inhibited cell invasion and migration of TNBC. Additionally, miR-518a-3p could target TMEM2 (transmembrane protein 2), and decreased protein and mRNA expression of TMEM2 in TNBC cells. Knockdown of TMEM2 suppressed cell invasion and migration through inhibiting phospho (p)-JAK1 (Janus kinase 1) and p-STAT (signal transducer and activator of transcription protein) 1/2. Moreover, over-expression of TMEM2 counteracted the suppressive effect of miR-518a-3p on TNBC invasion and migration through promoting the levels of p-JAK1 and p-STAT1/2. In conclusion, miR-518a-3p negatively regulates the JAK/STAT pathway via targeting TMEM2 and suppresses invasion and migration in TNBC, suggesting that miR-518a-3p may be a potential therapeutic target in TNBC.

Spinal cord injury (SCI) remains among the most challenging pathologies worldwide and has limited therapeutic possibilities and a very bleak prognosis. Biomaterials and stem cell transplantation are promising treatments for functional recovery in SCI. Seven patients with acute complete SCI diagnosed by a combination of methods were included in the study, and different lengths (2.0–6.0 cm) of necrotic spinal cord tissue were surgically cleaned under intraoperative neurophysiological monitoring. Subsequently, NeuroRegen scaffolds loaded with autologous bone marrow mononuclear cells (BMMCs) were implanted into the cleaned site. All patients participated in 6 months of rehabilitation and at least 3 years of clinical follow-up. No adverse symptoms associated with stem cell or functional scaffold implantation were observed during the 3-year follow-up period. Additionally, partial shallow sensory and autonomic nervous functional improvements were observed in some patients, but no motor function recovery was observed. Magnetic resonance imaging suggested that NeuroRegen scaffold implantation supported injured spinal cord continuity after treatment. These findings indicate that implantation of NeuroRegen scaffolds combined with stem cells may serve as a safe and promising clinical treatment for patients with acute complete SCI. However, determining the therapeutic effects and exact application methods still requires further study.

Deep sea oil resources worldwide possess great potential for exploration; however, multiphase medium technology requires urgent development. The multiphase pump has achieved great success as one of the most advanced machinery in underwater oil and gas exploration. Tip clearance is inevitable between the rotating and stationary components of the multiphase pump. In this study, tip clearance sizes of 0.0, 0.2, 0.5, and 0.8 mm are selected to investigate the effect of tip clearance on energy performance and flow characteristics of a multiphase pump. Results show that pressure rises decrease by 10.72%, 24.96%, and 41.39% with gas volume fraction = 0% under different tip clearance sizes, while the pressure rises decrease by 17.10%, 25.35%, and 38.11% with gas volume fraction = 10%. The dominant frequencies and maximum amplitudes of pressure fluctuation rise with the increase in tip clearance. The entrainment effect between the tip leakage flow and main flow in the impeller strengthens with the increase in tip clearance size; the induced vortex area and leakage flow rate also increase.

Stem cells and biomaterials transplantation hold a promising treatment for functional recovery in spinal cord injury (SCI) animal models. However, the functional recovery of complete SCI patients was still a huge challenge in clinic. Additionally, there is no clinical standard procedure available to diagnose precisely an acute patient as complete SCI. Here, two acute SCI patients, with injury at thoracic 11 (T11) and cervical 4 (C4) level respectively, were judged as complete injury by a stricter method combined with American Spinal Injury Association (ASIA) Impairment Scale, magnetic resonance imaging (MRI) and nerve electrophysiology. Collagen scaffolds, named NeuroRegen scaffolds, with human umbilical cord mesenchymal stem cells (MSCs) were transplanted into the injury site. During 1 year follow up, no obvious adverse symptoms related to the functional scaffolds implantation were found after treatment. The recovery of the sensory and motor functions was observed in the two patients. The sensory level expanded below the injury level, and the patients regained the sense function in bowel and bladder. The thoracic SCI patient could walk voluntary with the hip under the help of brace. The cervical SCI patient could raise his lower legs against the gravity in the wheelchair and shake his toes under control. The injury status of the two patients was improved from ASIA A complete injury to ASIA C incomplete injury. Furthermore, the improvement of sensory and motor functions was accompanied with the recovery of the interrupted neural conduction. These results showed that the supraspinal control of movements below the injury was regained by functional scaffolds implantation in the two patients who were judged as the complete injury with combined criteria, it suggested that functional scaffolds transplantation could serve as an effective treatment for acute complete SCI patients.

Regeneration of damaged neurons and recovery of sensation and motor function after complete spinal cord injury (SCI) are challenging. We previously developed a collagen scaffold, NeuroRegen, to promote axonal growth along collagen fibers and inhibit glial scar formation after SCI. When functionalized with multiple biomolecules, this scaffold promoted neurological regeneration and functional recovery in animals with SCI. In this study, eight patients with chronic complete SCI were enrolled to examine the safety and efficacy of implanting NeuroRegen scaffold with human umbilical cord mesenchymal stem cells (hUCB-MSCs). Using intraoperative neurophysiological monitoring, we identified and surgically resected scar tissues to eliminate the inhibitory effect of glial scarring on nerve regeneration. We then implanted NeuroRegen scaffold loaded with hUCB-MSCs into the resection sites. No adverse events (infection, fever, headache, allergic reaction, shock, perioperative complications, aggravation of neurological status, or cancer) were observed during 1 year of follow-up. Primary efficacy outcomes, including expansion of sensation level and motor-evoked potential (MEP)-responsive area, increased finger activity, enhanced trunk stability, defecation sensation, and autonomic neural function recovery, were observed in some patients. Our findings suggest that combined application of NeuroRegen scaffold and hUCB-MSCs is safe and feasible for clinical therapy in patients with chronic SCI. Our study suggests that construction of a regenerative microenvironment using a scaffold-based strategy may be a possible future approach to SCI repair.