Adipose-derived stem cells promote glycolysis and peritoneal metastasis via TGF-ß1/SMAD3/ANGPTL4 axis in colorectal cancer.

Peritoneal metastasis, the third most common metastasis in colorectal cancer (CRC), has a poor prognosis for the rapid progression and limited therapeutic strategy. However, the molecular characteristics and pathogenesis of CRC peritoneal metastasis are poorly understood. Here, we aimed to elucidate the action and mechanism of adipose-derived stem cells (ADSCs), a prominent component of the peritoneal microenvironment, in CRC peritoneal metastasis formation. Database analysis indicated that ADSCs infiltration was increased in CRC peritoneal metastases, and high expression levels of ADSCs marker genes predicted a poor prognosis. Then we investigated the effect of ADSCs on CRC cells in vitro and in vivo. The results revealed that CRC cells co-cultured with ADSCs exhibited stronger metastatic property and anoikis resistance, and ADSCs boosted the intraperitoneal seeding of CRC cells. Furthermore, RNA sequencing was carried out to identify the key target gene, angiopoietin like 4 (ANGPTL4), which was upregulated in CRC specimens, especially in peritoneal metastases. Mechanistically, TGF-ß1 secreted by ADSCs activated SMAD3 in CRC cells, and chromatin immunoprecipitation assay showed that SMAD3 facilitated ANGPTL4 transcription by directly binding to ANGPTL4 promoter. The ANGPTL4 upregulation was essential for ADSCs to promote glycolysis and anoikis resistance in CRC. Importantly, simultaneously targeting TGF-ß signaling and ANGPTL4 efficiently reduced intraperitoneal seeding in vivo. In conclusion, this study indicates that tumor-infiltrating ADSCs promote glycolysis and anoikis resistance in CRC cells and ultimately facilitate peritoneal metastasis via the TGF-ß1/SMAD3/ANGPTL4 axis. The dual-targeting of TGF-ß signaling and ANGPTL4 may be a feasible therapeutic strategy for CRC peritoneal metastasis.

A Deep Learning Application of Capsule Endoscopic Gastric Structure Recognition Based on a Transformer Model.

BACKGROUND: Gastric structure recognition systems have become increasingly necessary for the accurate diagnosis of gastric lesions in capsule endoscopy. Deep learning, especially using transformer models, has shown great potential in the recognition of gastrointestinal (GI) images according to self-attention. This study aims to establish an identification model of capsule endoscopy gastric structures to improve the clinical applicability of deep learning to endoscopic image recognition. METHODS: A total of 3343 wireless capsule endoscopy videos collected at Nanfang Hospital between 2011 and 2021 were used for unsupervised pretraining, while 2433 were for training and 118 were for validation. Fifteen upper GI structures were selected for quantifying the examination quality. We also conducted a comparison of the classification performance between the artificial intelligence model and endoscopists by the accuracy, sensitivity, specificity, and positive and negative predictive values. RESULTS: The transformer-based AI model reached a relatively high level of diagnostic accuracy in gastric structure recognition. Regarding the performance of identifying 15 upper GI structures, the AI model achieved a macroaverage accuracy of 99.6% (95% CI: 99.5-99.7), a macroaverage sensitivity of 96.4% (95% CI: 95.3-97.5), and a macroaverage specificity of 99.8% (95% CI: 99.7-99.9) and achieved a high level of interobserver agreement with endoscopists. CONCLUSIONS: The transformer-based AI model can accurately evaluate the gastric structure information of capsule endoscopy with the same performance as that of endoscopists, which will provide tremendous help for doctors in making a diagnosis from a large number of images and improve the efficiency of examination.

Selection of Site for Harvesting Dermal Grafts as a Spacer in the Correction of Eyelid Retraction.

BACKGROUND: Several materials can serve as spacer grafts in the repair of retracted lower eyelids. However, previous studies did not reveal any of these to be superior to the others. From our perspective, autologous dermal grafts are ideal because they are biologically compatible and abundantly available. However, the absorption of these grafts is an issue, and the thickness of the dermal grafts is crucial. We evaluated the dermal thickness at five potential donor sites using ultrasonography and the efficacy and safety of the posterior neck dermis as a spacer graft in the correction of retracted lower eyelids. METHODS: In 20 healthy volunteers, the dermal thickness was assessed using ultrasonography and compared between the posterior neck, upper arm, inguinal area, intergluteal cleft, and gluteal sulcus. Between January 2018 and June 2021, eight retracted lower eyelids in eight patients were repaired using a posterior neck dermal graft. The surgical results of these grafts were also evaluated. RESULTS: The mean age of the volunteers was 37.8 years, and the mean body mass index was 24.45 kg/m2. The intergluteal cleft provided the thickest dermis followed by the posterior neck and gluteal sulcus, which were not significantly different. The upper arm and inguinal area had the thinnest dermis without significant differences between them. The mean marginal reflex distance 2/iris ratio decreased by 0.15 (p=0.008). The mean cosmetic score (0-10) for evaluation of lower eyelid reconstruction increased by 3.38 (p=0.011). The mean Vancouver Scar Scale score for evaluation of donor site scarring was 3.21. CONCLUSIONS: Although the posterior neck dermis is the second thickest, it is an ideal spacer graft in the reconstruction of retracted lower eyelids. Adequate thickness, uncomplicated methods, and a closer surgical field are its advantages. Additionally, donor site morbidity is minimal, with acceptable scarring. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Diminishing Role of Pelvic Stability Evaluation in the Era of Computed Tomographic Scanning.

Pelvic fractures can result in life-threatening hemorrhages or other associated injuries. Therefore, computed tomography (CT) scanning plays a key role in the management of pelvic fracture patients. However, CT scanning is utilized as an adjunct in secondary survey according to traditional Advanced Trauma Life Support (ATLS) guidelines, whereas pelvic x-ray is used as a primary tool to evaluate pelvic stability and the necessity of further CT scanning. In the current study, we attempted to evaluate the role of CT scanning in the era of advanced technology. The significance of pelvic stability was also analyzed. From January 2012 to December 2014, the trauma registry and medical records of pelvic fracture patients were retrospectively reviewed. A 64-slice multidetector CT scanner was used in our emergency department as a standard diagnostic tool for evaluating trauma patients. Pelvic x-ray was used as a primary tool for screening pelvic fractures, and pelvic stability was evaluated accordingly. CT scans were performed in patients with unstable pelvic fractures, suspected associated intra-abdominal injuries (IAIs), or other conditions based on the physicians' clinical judgment. The clinical features of patients with stable and unstable pelvic fractures were compared. The patients with stable pelvic fractures were analyzed to determine the characteristics associated with retroperitoneal hemorrhage (RH) or IAIs. Patients with stable pelvic fractures were also compared based on whether they underwent a CT scan. A total of 716 patients were enrolled in this study. There were 533 (74.4%) patients with stable pelvic fractures. Of these patients, there were 66 (12.4%) and 50 (9.4%) patients with associated RH and IAI, respectively. There were no significant differences between the patients with associated RH based on their primary evaluation (vital signs, volume of blood transfusion, and hemoglobin level). Similarly, the demographics and the primary evaluation results (symptoms, coma scale, and white blood cell counts) of the patients with associated IAIs were also not significantly different from the patients without associated IAIs. Furthermore, the time to definitive hemostasis (surgery or angioembolization) was not significantly different between the unstable patients who underwent a CT scan or those who did not.In the management of pelvic fracture patients, the role of pelvic stability is not significant in the evaluation of associated RH or IAI. Routine CT scanning is suggested for pelvic fracture patients because of the rapid scanning time and sufficient information produced.