Artificial intelligence for detecting superficial esophageal squamous cell carcinoma under multiple endoscopic imaging modalities: A multicenter study.

BACKGROUND AND AIM: Diagnosis of esophageal squamous cell carcinoma (ESCC) is complicated and requires substantial expertise and experience. This study aimed to develop an artificial intelligence (AI) system for detecting superficial ESCC under multiple endoscopic imaging modalities. METHODS: Endoscopic images were retrospectively collected from West China Hospital, Sichuan University as a training dataset and an independent internal validation dataset. Images from other four hospitals were used as an external validation dataset. The AI system was compared with 11 experienced endoscopists. Furthermore, videos were collected to assess the performance of the AI system. RESULTS: A total of 53 933 images from 2621 patients and 142 videos from 19 patients were used to develop and validate the AI system. In the internal and external validation datasets, the performance of the AI system under all or different endoscopic imaging modalities was satisfactory, with sensitivity of 92.5-99.7%, specificity of 78.5-89.0%, and area under the receiver operating characteristic curves of 0.906-0.989. The AI system achieved comparable performance with experienced endoscopists. Regarding superficial ESCC confined to the epithelium, the AI system was more sensitive than experienced endoscopists on white-light imaging (90.8% vs 82.5%, P = 0.022). Moreover, the AI system exhibited good performance in videos, with sensitivity of 89.5-100% and specificity of 73.7-89.5%. CONCLUSIONS: We developed an AI system that showed comparable performance with experienced endoscopists in detecting superficial ESCC under multiple endoscopic imaging modalities and might provide valuable support for inexperienced endoscopists, despite requiring further evaluation.

Optimal pathways involved in the treatment of sevoflurane or propofol for patients undergoing coronary artery bypass graft surgery.

The cardio-protection mechanisms of sevoflurane and propofol still remain unclear in patients undergoing coronary artery bypass grafting (CABG). We designed the present study to identify the optimal pathways through integrating differential co-expressed network (DCN)-based guilt by association (GBA) principle based on the expression data of E-GEOD-4386 downloaded from EMBL-EBI. Differentially expressed genes (DEGs) were firstly identified and then DCN and sub-DCN were established. The seed pathways were predicted through GBA principle using the area under the curve (AUC) for pathway categories, and the pathway terms with AUC >0.9 were defined as the seed pathways. KEGG pathway analysis was applied to the DEGs based on DAVIA to detect significant pathways. The final optimal pathways were identified based on the traditional pathway analysis and network-based pathway inference approach. There were 83 common, 99 sevoflurane-specific and 4 propofol-specific DEGs in the expression profile of artial samples. Finally, 8 and 4 pathway terms having the AUC >0.9 were identified and determined as the seed pathways in the propofol and sevoflurane group, respectively. TNF signaling pathway, NF-κB signaling pathway, as well as NOD-like receptor signaling pathway were the common optimal ones in these two groups. Only the pathway of cytokine-cytokine receptor interaction was unique to sevoflurane, and no pathway was specific to propofol. Our results suggested that sevoflurane and propofol might synergistically possess some cardio-protective properties in patients undergoing CABG.

SARM1 deletion restrains NAFLD induced by high fat diet (HFD) through reducing inflammation, oxidative stress and lipid accumulation.

SARM1 (Sterile alpha and armadillo motif-containing protein 1) is the recently identified TIR domain-containing cytosolic protein, which is involved in toll-like receptors (TLRs) signaling transduction. In the present study, the role of SARM1 in high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) progression was explored. We found that SARM1 was expressed highly in fatty liver. And SARM1-knockout (KO) reduced steatohepatitis and metabolic disorders induced by HFD. SARM1-deletion decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in HFD-fed mice. Additionally, inflammatory response caused by HFD was alleviated by SARM1-deletion through inactivating TLR4/7/9 and nuclear factor kappa B (NF-κB) pathways. Of note, SARM1-deletion also reduced the expressions of inflammation-associated molecules in hypothalamus of HFD-fed mice. Furthermore, HFD administration led to oxidative stress in liver of mice, while being decreased in SARM1-KO mice. Moreover, SARM1-ablation improved lipid dyslipidemia by suppressing the mRNA levels of genes, linked to glycolysis, lipogenesis and transcriptional regulation. Insulin resistance was also attenuated by SARM1-deficiency through enhancing the activation of liver Akt/glycogen synthase kinase-3ß (GSK3ß) and insulin receptor substrate-1 (IRS1)/FOXO1 pathways in HFD-fed mice. Also, SARM1-knockout improved neuropeptide Y (NPY), Pro-Opiomelanocortins (POMC), Agouti-related Protein (AGRP) and Cocaine-and-Amphetamine Responsive Transcript 1 (CART1) expressions in hypothalamus of mice after HFD administration. In vitro, we found that the reduction of inflammatory response, oxidative stress and dyslipidemia induced by SARM1-knockout in primary hepatocytes after fructose stimulation was largely attributed to its suppression to TLR4/7/9. Together, the findings demonstrated that SARM1 might be an effective target for developing effective therapeutic strategies against NAFLD.

Irigenin sensitizes TRAIL-induced apoptosis via enhancing pro-apoptotic molecules in gastric cancer cells.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) holds promising value for cancer therapy due to its capacity to induce apoptosis in cancer cells. Nevertheless, TRAIL therapy is greatly hampered by its resistance. Irigenin (Iri), isoflavonoids, can be isolated from the rhizome of Belamcanda chinensis, and has been shown anti-cancer properties. In this study, we explored if Iri could enhance TRAIL-regulated apoptosis in TRAIL resistant gastric cancer cells. Iri significantly potentiated TRAIL-triggered cytotoxicity. Iri alone and TRAIL alone showed no effective role in apoptosis induction, whereas combined treatment with Iri and TRAIL markedly induced apoptosis in cancer cells, as evidenced by the up-regulation of cleaved Caspase-8/-9/-3 and PARP. Additionally, the sensitization to TRAIL was along with the enhancement of pro-apoptotic proteins, including FAS-associated protein with death domain (FADD), death receptor 5 (DR5) and Bax. And suppressing FADD, DR5 and Bax by si RNA significantly reduced the apoptosis and enhanced the cell viability induced by the co-application of Iri and TRAIL. Moreover, the sensitization to TRAIL was accompanied by the decrease of Cellular-FLICE inhibitory protein (c-FLIP), Bcl-2 and Survivin. Additionally, Iri could sensitize TRAIL to produce reactive oxygen species (ROS). Pre-treatment of N-acetyl-cysteine (NAC), ROS scavenger, attenuated Iri plus TRAIL-induced apoptosis and improved cell viability. Finally, combination of Iri and TRAIL inhibited tumor growth in the xenograft model. Collectively, our present study gave new insights into the effects of Iri on potentiating TRAIL-sensitivity, and suggested that Iri could be a potential candidate for sensitizer of TRAIL-resistant cancer cell treatment.

Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: simplified criteria may be effective in the diagnosis in Chinese patients.

OBJECTIVE: To evaluate the Paris criteria, the revised diagnostic criteria and the simplified diagnostic scoring system in the diagnosis of primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome in Chinese patients. METHODS: Medical records of the patients who were diagnosed with PBC at the Union Hospital and Tongji Hospital, Tongji Medical University, Huazhong University of Science and Technology (Wuhan, Hubei Province, China) from 2003 to 2012 were retrospectively reviewed. The overlap syndrome was diagnosed based on the Paris criteria, the revised criteria and the simplified criteria, respectively. Patients' clinical characteristics, laboratory examination results and histological findings were collected. The sensitivity and specificity of the three criteria for diagnosing PBC-AIH overlap syndrome were calculated. RESULTS: PBC-AIH overlap syndrome was diagnosed in 2, 13 and 10 patients with PBC based on the Paris, the revised and the simplified criteria, respectively. The sensitivity and specificity of the simplified criteria in diagnosing the overlap syndrome was 90.0% and 98.2%, which were the highest among the three criteria, followed by the revised criteria. The Paris criteria showed a high specificity (100%) but a relatively low sensitivity (20.0%). In addition, some patients who did not fulfil the Paris criteria still benefited from the immunosuppressive agents. CONCLUSIONS: For Chinese patients with the PBC-AIH overlap syndrome, the simplified criteria appear to be the most efficacious compared with the Paris criteria and the revised criteria. Further studies should be performed to confirm these observations with respect to long-term outcomes and therapeutic implications.

[Limb preservation surgery combined with perioperative rehabilitation for the treatment of 7 patients with stage II to III giant cell tumor of bone in the proximal humerus].

OBJECTIVE: To study the effects of the extensive resection of the tumor-loading segment and artificial humerus head replacement combined with perioperative rehabilitation for the treatment of stage II to III giant cell tumor of bone in the proximal humerus. METHODS: From March 2007 to March 2010, 7 patients with stage II to III giant cell tumor of bone in the proximal humerus were treated. Among the patients, 3 patients were male and 4 patients were female with a mean age of 34.6 years (ranged, 18 to 49 years). The mean course of disease was 19 months (ranged, 6 to 35 months). All the patients were confirmed to suffer stage II to III giant cell tumor of bone in the proximal humerus by pathology and X-ray examinations. Clinical manifestations of the patients included persistence aggravated pain of the shoulder, swelling in the proximate arm with obviously tenderness, activity limited of the joint. All the patients were treated with extensive resection of the tumor-loading segment and artificial humerus head replacement combined with perioperative rehabilitation. CMS and OSIS score system were used to evaluate shoulder function and shoulder stability. RESULTS: All the patients were followed up, and the duration ranged from 14 to 35 months, with an average of 17 months. There were no serious complications or recurrence in all cases. One year after the surgery CMS and OSIS score system were 70.7 scores (ranged,63 to 82 scores) and 25.1 scores (ranged, 18 to 29 scores) respectively. According to evaluation for shoulder function, 2 patients got an excellent result and 5 good. According to evaluation of shoulder stability, 1 patient got an excellent result and 6 good. CONCLUSION: Extensive resection of the tumor-loading segment and artificial humerus head replacement combined with perioperative rehabilitation for the treatment of stage II to III giant cell tumor of bone in the proximal humerus would not only preserve the upper extremity but also preserve the function of upper extremity.