Objective:To investigate the genomic profiles and immune microenvironment of olfactory neuroblastoma (ONB).Methods:Nineteen ONB cases diagnosed in the Beijing Tongren Hospital from May 2018 to October 2022 were divided into low-grade and high-grade groups according to the Hyams grading system, including 7 low-grade and 12 high-grade ONB. Whole exome sequencing and multiplex immunofluorescence analyses were performed on tissue samples of these ONB.Results:A total of 929 nonsynonymous alterations were identified in 18 of the 19 ONB (18/19) cases. The most commonly altered cancer-related genes were CTNNB1 (3/19) and ZNRF3 (3/19). The most mutated oncogenic pathways were the WNT and RAS pathways. The median tumor mutation burden (TMB) was 0.45/Mb, ranging from 0 to 3.25. The median tumor neoantigen load (TNB) was 9.39 neoantigens/Mb, ranging from 0 to 38.30. The median allelic mutation tumor heterogeneity (MATH) score was 16.95, ranging from 3.05 to 117.47. Only one of the 19 cases expressed PD-L1 (composite positive score, CPS>1) in the tumor cells. The median percentage of CD8 + tumor-infiltrating lymphocyte (TIL) in the tumor region was 1.08%. No significant differences were observed between the low-and high-grade groups for mutant genes, mutant pathways, TMB, TNB, MATH, PD-L1 expression levels, or CD8 + TILs percentage( P>0.05). However, the low-grade group showed significantly more CD68 + macrophages in both the tumor and total region than the high-grade group. Notably, CD68 +CD163 - macrophages accounted for an average of 80.52% of CD68 + macrophages. Conclusions:CTNNB1 and ZNRF3 are the most commonly altered cancer-related genes. The low expression of PD-L1 and the low percentage of CD8 + TIL indicate that ONB might not be sensitive to immunotherapy. The percentage of M1-type macrophages in low-grade ONB is significantly higher than that in high-grade ONB, suggesting that M1-type macrophages may be involved in the progression of ONB from low-grade to high-grade.

Idiopathic inflammatory myopathy(IIM)is a heterogeneous autoimmune disease of unknown etiology characterized by proximal limb muscle involvement and chronic inflammation.Multiple systems may be involved,with interstitial lung disease(ILD)being the most common manifestation of respiratory system involvement in IIM.This article summarizes the current methods of myositis animal models and myositis-associated ILD model construction methods,so as to provide reference for the subsequent construction and research of IIM-ILD models.

Objective:To evaluate the safety and efficacy of percutaneous transhepatic papillary balloon dilation (PTPBD) combined with flexible ureteroscopy-guided dual-frequency double-pulse ND:YAG (FREDDY) laser lithotripsy (PTPBD-FREDDY) for the treatment of giant (>1.5 cm diameter) common bile duct stones.Methods:A retrospective analysis was conducted on 26 patients with large-diameter difficult choledocholithiasis admitted to two medical centers from December 2017 to October 2021. Among these patients, four could not tolerate surgery or endoscopic treatment, six experienced failure of endoscopic treatment, and 16 refused to undergo endoscopic or surgical treatment. All patients underwent the PTPBD-FREDDY procedure. The FREDDY laser lithotripsy was performed under ureteroscopic guidance, followed by a balloon to push the stones into the duodenum. The primary endpoint was the technical success rate, and the secondary endpoints included the rate of stone recurrence and related complications.Results:All 26 patients successfully completed the operation, achieving a technical success rate of 100%. The average lithotripsy frequency and operation time for bilirubin stones were significantly higher than those of mixed stones and cholesterol stones ( P<0.01). The main postoperative complications included mild fever ( n=3), abdominal pain ( n=3), nausea ( n=2) and vomiting ( n=1). One patient experienced biliary tract bleeding, which improved after conservative treatment. No serious complications such as pancreatitis, sepsis, or biliary perforation were observed. After 2 years of follow-up, no cases of stone recurrence were observed. Conclusions:PTPBD-FREDDY is a safe and effective treatment for patients with giant common bile duct stones. It provides a new therapeutic option for patients with giant choledocholithiasis who can not tolerate surgery or have failed endoscopic treatment, demonstrating promising prospects.

Objective:To construct an intelligent endoscopic image analysis system that could monitor the blind spot of the upper gastrointestinal tract, and to test its performance.Methods:A total of 87 167 upper gastrointestinal endoscopy images (dataset 1) including 75 551 for training and 11 616 for testing, and a total of 2 414 pharyngeal images (dataset 2) including 2 233 for training and 181 for testing were retrospectively collected from the Digestive Endoscopy Center of Renmin Hospital of Wuhan University between 2016 to 2020. A 27-category-classification model for blind spot monitoring in the upper gastrointestinal tract (model 1, which distinguished 27 anatomical sites such as the pharynx, esophagus, and stomach) and a 5-category-classification model for blind spot monitoring in the pharynx (model 2, which distinguished palate, posterior pharyngeal wall, larynx, left and right pyriform sinuses) were constructed. The above models were trained and tested based on dataset 1 and 2, respectively, and trained based on the EfficientNet-B4, ResNet50 and VGG16 models of the keras framework. Thirty complete upper gastrointestinal endoscopy videos were retrospectively collected from the Digestive Endoscopy Center of Renmin Hospital of Wuhan University in 2021 to test model 2 blind spot monitoring performance.Results:The cross-sectional comparison results of the accuracy of model 1 in identifying 27 anatomical sites of the upper gastrointestinal tract in images showed that the mean accuracy of EfficientNet-B4, ResNet50, and VGG16 were 90.90%, 90.24%, and 89.22%, respectively, with the EfficientNet-B4 model performance the best, and the accuracy of EfficientNet-B4 model for each site ranged from 80.49% to 97.80%. The cross-sectional comparison results of the accuracy of model 2 in identifying the 5 anatomical sites of the pharynx in the images showed that the mean accuracy of EfficientNet-B4, ResNet50, and VGG16 were 99.40%, 98.56%, and 97.01%, respectively, in which the EfficientNet-B4 model had the best performance, and the accuracy of EfficientNet-B4 model for each site ranged from 96.15% to 100.00%. The overall accuracy of model 2 in identifying the 5 anatomical sites of the pharynx in the video was 97.33% (146/150).Conclusion:The intelligent endoscopic image analysis system based on deep learning can monitor blind spots in the upper gastrointestinal tract, coupled with pharyngeal blind spot monitoring and esophagogastroduodenal blind spot monitoring functions. The system shows high accuracy in both images and videos, which is expected to have a potential role in clinical practice and assisting endoscopists to achieve full observation of the upper gastrointestinal tract.

Objective:To analyze the cost-effectiveness of a relatively mature artificial intelligence (AI)-assisted diagnosis and treatment system (ENDOANGEL) for gastrointestinal endoscopy in China, and to provide objective and effective data support for hospital acquisition decision.Methods:The number of gastrointestinal endoscopy procedures at the Endoscopy Center of Renmin Hospital of Wuhan University from January 2017 to December 2019 were collected to predict the procedures of gastrointestinal endoscopy during the service life (10 years) of ENDOANGEL. The net present value, payback period and average rate of return were used to analyze the cost-effectiveness of ENDOANGEL.Results:The net present value of an ENDOANGEL in the expected service life (10 years) was 6 724 100 yuan, the payback period was 1.10 years, and the average rate of return reached 147.84%.Conclusion:ENDOANGEL shows significant economic benefits, and it is reasonable for hospitals to acquire mature AI-assisted diagnosis and treatment system for gastrointestinal endoscopy.

Objective:To construct a real-time artificial intelligence (AI)-assisted endoscepic diagnosis system based on YOLO v3 algorithm, and to evaluate its ability of detecting focal gastric lesions in gastroscopy.Methods:A total of 5 488 white light gastroscopic images (2 733 images with gastric focal lesions and 2 755 images without gastric focal lesions) from June to November 2019 and videos of 92 cases (288 168 clear stomach frames) from May to June 2020 at the Digestive Endoscopy Center of Renmin Hospital of Wuhan University were retrospectively collected for AI System test. A total of 3 997 prospective consecutive patients undergoing gastroscopy at the Digestive Endoscopy Center of Renmin Hospital of Wuhan University from July 6, 2020 to November 27, 2020 and May 6, 2021 to August 2, 2021 were enrolled to assess the clinical applicability of AI System. When AI System recognized an abnormal lesion, it marked the lesion with a blue box as a warning. The ability to identify focal gastric lesions and the frequency and causes of false positives and false negatives of AI System were statistically analyzed.Results:In the image test set, the accuracy, the sensitivity, the specificity, the positive predictive value and the negative predictive value of AI System were 92.3% (5 064/5 488), 95.0% (2 597/2 733), 89.5% (2 467/ 2 755), 90.0% (2 597/2 885) and 94.8% (2 467/2 603), respectively. In the video test set, the accuracy, the sensitivity, the specificity, the positive predictive value and the negative predictive value of AI System were 95.4% (274 792/288 168), 95.2% (109 727/115 287), 95.5% (165 065/172 881), 93.4% (109 727/117 543) and 96.7% (165 065/170 625), respectively. In clinical application, the detection rate of local gastric lesions by AI System was 93.0% (6 830/7 344). A total of 514 focal gastric lesions were missed by AI System. The main reasons were punctate erosions (48.8%, 251/514), diminutive xanthomas (22.8%, 117/514) and diminutive polyps (21.4%, 110/514). The mean number of false positives per gastroscopy was 2 (1, 4), most of which were due to normal mucosa folds (50.2%, 5 635/11 225), bubbles and mucus (35.0%, 3 928/11 225), and liquid deposited in the fundus (9.1%, 1 021/11 225).Conclusion:The application of AI System can increase the detection rate of focal gastric lesions.

Objective:To compare the cost-effectiveness before and after using an artificial intelligence gastroscopy-assisted system for early gastric cancer screening.Methods:The gastroscopy cases before (non-AI group) and after (AI group) the use of artificial intelligence gastroscopy-assisted system were retrospectively collected in Renmin Hospital of Wuhan University from January 1, 2017 to February 28, 2022. The proportion of early gastric cancer among all gastric cancer was analyzed. Costs were estimated based on the standards of Renmin Hospital of Wuhan University and the 2021 edition of Wuhan Disease Diagnosis-related Group Payment Standards. Cost-effectiveness analysis was conducted per 100 thousand cases with and without the system. And the incremental cost-effectiveness ratio was calculated.Results:For the non-AI group, the proportion of early gastric cancer among all gastric cancer was 28.81% (70/243). The cost of gastroscopy screening per 100 thousand was 54 598.0 thousand yuan, early gastric treatment cost was 221.8 thousand yuan, and a total cost was 54 819.8 thousand yuan. The direct effectiveness was 894.2 thousand yuan, the indirect effectiveness was 1 828.2 thousand yuan and the total effectiveness was 2 722.4 thousand yuan per 100 thousand cases. For the AI group, the early gastric cancer diagnositic rate was 36.56%(366/1 001), where gastroscopy cost was 53 440.0 thousand yuan, early gastric treatment cost 315.8 thousand yuan, the total cost 53 755.8 thousand yuan. The direct effectiveness was 1 273.5 thousand yuan, indirect effectiveness 2 603.1 thousand yuan and the total effectiveness 3 876.6 thousand yuan per 100 thousand cases. The use of the system reduced the cost of early gastric cancer screening by 1 064.0 thousand yuan, and increased the benefit by 1 154.2 thousand yuan per 100 thousand cases. The incremental cost-effectiveness ratio was -0.92.Conclusion:The use of artificial intelligence gastroscopy-assisted system for gastric early cancer screening can reduce medical costs as well as improve the efficiency of screening, and it is recommended for gastroscopy screening .

Stapled peptides with significantly enhanced pharmacological profiles have emerged as promising therapeutic molecules due to their remarkable resistance to proteolysis and performance to penetrate cells. The all-hydrocarbon peptide stapling technique has already widely adopted with great success, yielding numerous potent peptide-based molecules. Based on our prior efforts, we conceived and prepared a double-stapled peptide in this study, termed FRNC-1, which effectively attenuated the bone resorption capacity of mature osteoclasts in vitro through specific inhibition of phosphorylated GSK-3β. The double-stapled peptide FRNC-1 displayed notably improved helical contents and resistance to proteolysis than its linear form. Additionally, FRNC-1 effectively prevented osteoclast activation and improved bone density for ovariectomized (OVX) mice after intravenous injection and importantly, after oral (intragastric) administration. The double-stapled peptide FRNC-1 is the first orally effective peptide that has been validated to date as a therapeutic candidate for postmenopausal osteoporosis (PMOP).

Autophagy is a cellular process in which proteins and organelles are engulfed in autophagosomal vesicles and transported to the lysosome/vacuole for degradation. Protein-protein interactions (PPIs) play a crucial role at many stages of autophagy, which present formidable but attainable targets for autophagy regulation. Moreover, selective regulation of PPIs tends to have a lower risk in causing undesired off-target effects in the context of a complicated biological network. Thus, small-molecule regulators, including peptides and peptidomimetics, targeting the critical PPIs involved in autophagy provide a new opportunity for innovative drug discovery. This article provides general background knowledge of the critical PPIs involved in autophagy and reviews a range of successful attempts on discovering regulators targeting those PPIs. Successful strategies and existing limitations in this field are also discussed.

Objective:To investigate the preoperative risk factors affecting early extremity blood supply after repair of major arterial injury so as to provide clues for prevention of limb ischemia.Methods:The clinical data were retrospectively analyzed of the 139 patients (140 extremities) with major extremity arterial injury who had been admitted to Department of Microsurgery, Orthopaedic Trauma and Hand Surgery, The First Hospital Affiliated to Sun Yat-sen University from January 2003 to December 2019. There were 112 males and 27 females, with a mean age of 30 (20, 44) years. The primary outcome was the early status of blood supply to the injured extremity (48 hours after surgery). Univariate analysis was conducted of such factors as gender, age, ischemia time, injury mechanism, injury site, fracture, soft tissue lesion, and duration of surgery. The significant factors ( P<0.1) were then analyzed by logistic regression, and P<0.05 was considered statistically significant. Results:Ischemia happened in 44 (31.4%, 44/140) extremities within 48 hours after surgery. There were significant differences in injury mechanism, ischemia time, fracture, and soft tissue lesion between patients with and without postoperative extremity ischemia ( P<0.05). Logistic regression analysis indicated that blunt injury ( OR=5.639, 95% CI: 1.068 to 29.761, P=0.042) and soft tissue lesion ( OR=12.568, 95% CI: 3.402 to 46.431, P<0.001) were significant preoperative risk factors affecting the early blood supply after repair of major extremity arterial injury. Conclusion:As blunt injury and soft tissue defect are preoperative risk factors for early extremity ischemia after repair of major extremity arterial injury, surgeons should pay more attention to them when assessing patients and making repair protocols.