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Gastroscopic biopsy provides the only effective method for gastric cancer diagnosis, but the gold standard histopathology is time-consuming and incompatible with gastroscopy. Conventional stimulated Raman scattering (SRS) microscopy has shown promise in label-free diagnosis on human tissues, yet it requires the tuning of picosecond lasers to achieve chemical specificity at the cost of time and complexity. Here, we demonstrate that single-shot femtosecond SRS (femto-SRS) reaches the maximum speed and sensitivity with preserved chemical resolution by integrating with U-Net. Fresh gastroscopic biopsy is imaged in <60 s, revealing essential histoarchitectural hallmarks perfectly agreed with standard histopathology. Moreover, a diagnostic neural network (CNN) is constructed based on images from 279 patients that predicts gastric cancer with accuracy >96%. We further demonstrate semantic segmentation of intratumor heterogeneity and evaluation of resection margins of endoscopic submucosal dissection (ESD) tissues to simulate rapid and automated intraoperative diagnosis. Our method holds potential for synchronizing gastroscopy and histopathological diagnosis. Diagnosis of gastric cancer currently requires gastroscopic biopsy, which requires time and expertize to perform. Here, the authors demonstrate a femto-SRS imaging method which showed high accuracy in diagnosing gastric cancer without the need for pathologistbased diagnosis.

All the recommendations in this document were evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, which categorizes evidence quality into four levels (A, B, C, and D) [Supplementary Table 1, http://links.lww.com/CM9/C553] and classifies the recommendations as either strong or weak. Endoscopic therapy alone may result in noncurative resections, particularly for large or deeply invasive tumors. [...]complications such as perforation and bleeding associated with endoscopic therapy can pose substantial challenges to management. For patients receiving neoadjuvant therapy, preoperative endoscopic marking of the lesion enhances tumor localization and facilitates precise resection planning. Effective techniques include submucosal injection of contrast agents, preoperative titanium clip placement for marking, and intraoperative endoscopic verification (Quality of evidence: B; strength of recommendation: strong; level of consensus: 100% agreement).

Esophageal squamous cell carcinoma (ESCC) is malignant while the carcinogenesis is still unclear. Here, we perform a comprehensive multi-omics analysis of 786 trace-tumor-samples from 154 ESCC patients, covering 9 histopathological stages and 3 phases. Proteogenomics elucidates cancer-driving waves in ESCC progression, and reveals the molecular characterization of alcohol drinking habit associated signatures. We discover chromosome 3q gain functions in the transmit from nontumor to intraepithelial neoplasia phases, and find TP53 mutation enhances DNA replication in intraepithelial neoplasia phase. The mutations of AKAP9 and MCAF1 upregulate glycolysis and Wnt signaling, respectively, in advanced-stage ESCC phase. Six major tracks related to different clinical features during ESCC progression are identified, which is validated by an independent cohort with another 256 samples. Hyperphosphorylated phosphoglycerate kinase 1 (PGK1, S203) is considered as a drug target in ESCC progression. This study provides insight into the understanding of ESCC molecular mechanism and the development of therapeutic targets. The progression of oesophageal squamous cell carcinoma (ESCC) from early to advanced stages requires comprehensive molecular characterisation. Here, the authors perform a proteogenomics analysis of ESCC patient samples across nine histopathological stages and three phases, identifying key alterations and paths for progression.

Mesenchymal stem cells (MSCs) transplantation is a promising antifibrotic strategy but facing clinical controversies. Inspired by advances in nanomedicine, we aimed to bypass these clinical barriers of MSCs by identifying the key antifibrotic molecule of MSCs and developing a specific liver-targeting nanocarrier. : Cytokines secreted by MSCs were examined with serum stimulation of cirrhotic patients. Immunohistochemistry, microarray, immunoblotting, and quantitative real-time PCR (qRT-PCR) were applied to identify the critical antifibrotic cytokine and to discover its role in modulating antifibrotic effects. Biomineralization method was used to prepare calcium phosphate nanoparticles (NPs). The targeting and therapeutic efficiency of NPs were evaluated by imaging and biochemical studies on fibrotic mice induced by CCl . : The stimulated MSCs exhibited high-level expression of Tumor necrosis factor (TNF)-stimulated gene 6 (TSG-6). On animal study, exogenous administration of TSG-6 alone can ameliorate liver fibrosis while TSG-6 knocked MSCs (Lv-TSG-6 MSCs) lost antifibrotic effects. Further studies verified the importance of TSG-6 and identified its antifibrotic mechanism by modulating M2 macrophages and increasing matrix metalloproteinase 12 (MMP12) expression. Additionally, we found a feedback loop between TSG-6, MMP12 and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), which may improve our understanding of the aggravating process of cirrhosis and antifibrotic mechanisms of TSG-6 and MSCs. Based on these findings, we developed calcium phosphate nanoparticles (CaP@BSA NPs) by biomineralization method using bovine serum albumin (BSA) as the biotemplate. Imaging tracking and drug loading studies showed specific liver targeting and high TSG-6 loading efficacy of as-prepared CaP@BSA NPs. therapeutic study further demonstrated the improved therapeutic effects of TSG-6 loaded CaP@BSA. : TSG-6 was a major antifibrotic cytokine of MSCs, TSG-6 loaded CaP@BSA NPs showed specific liver accumulation and improved therapeutic effects, which indicated translational potentials of CaP@BSA as a promising drug carrier for the liver disease management.

AimTo investigate the risk factors for delayed bleeding following endoscopic submucosal dissection (ESD) for colorectal neoplasms.MethodsWe retrospectively reviewed the medical records of 991 consecutive patients who underwent ESD for colorectal neoplasms at our hospital from January 2007 to November 2016. Delayed post-ESD bleeding was defined as bleeding within 6 h to 30 days after ESD that resulted in either of the three situations: overt hematochezia, bleeding spots confirmed by repeat colonoscopy, or the requirement of a blood transfusion. Delayed bleeding was furtherly separated into early and late delayed bleeding by the end of post-ESD day 2. We analyzed the relationship between delayed bleeding and candidate factors including patient-, lesion-, and treatment-related details.ResultsDelayed post-ESD bleeding was found in 47 patients (4.7%), of which 18 cases were late delayed bleeding. Among all patients, 14 patients required a second colonoscopy, and 2 other patients were transferred to surgery. Univariate analysis revealed that patients with hypertension (p = 0.017) and using hot biopsy forceps for wound management (p = 0.028) were significantly associated with late delayed bleeding. Both risk factors remained significant after multivariate analysis: hypertension (OR 2.829, 95% CI 1.101–7.265, p = 0.031), hot biopsy forceps (OR 2.873, 95% CI 1.013–8.147, p = 0.047). Using hot biopsy forceps was also the significant risk factor for late delayed bleeding compared with early delayed bleeding.ConclusionPatient with hypertension and using hot biopsy forceps for wound management during procedure call for attention on high risk of delayed post-ESD bleeding. Therefore, additional perioperative treatment is recommended in patients with these risk factors.

Background The aim of this study was to investigate the management and treatment for complications during and after peroral endoscopic myotomy (POEM) for patients suffering from esophageal achalasia (EA). Methods The data of 119 cases of EA patients who underwent POEM from October 2010 to July 2011 and the complications that arose during the operation, after the operation, and during follow-up were analyzed. Results Complications that occurred during the operation included cutaneous emphysema (22.7 %, 27/119) and pneumothorax (2.5 %, 3/119). Postoperative complications included pneumothorax (25.2 %, 30/119), subcutaneous emphysema (55.5 %, 66/119), mediastinal emphysema (29.4 %, 35/119), delayed hemorrhage (0.8 %, 1/119), pleural effusion (48.7 %, 58/119), minor inflammation or segmental atelectasis of the lungs (49.6 %, 59/119), and gas under diaphragm or aeroperitoneum (39.5 %, 47/119). Complications that occurred during follow-up included one case of difficulty eating caused by the stricture of mucosa and one case of dehiscence at the mouth of the tunnel created during surgery, with food retention. No deaths occurred. All complications were resolved through traditional treatment. No additional surgery was needed. Conclusion Complications arising during and after POEM should be treated quickly and can be resolved by using traditional treatment. POEM can be expected to become the preferred treatment for EA.

According to an analysis of 138 hospitalized COVID-19 patients in Wuhan, 41% patients were highly suspicious of nosocomial infection (5). [...]this causes delay in treating life-threatening situations. [...]how to carry out necessary endoscopic procedures with both endoscopy staff and patients well protected is a question of high priority at the present. [...]although GI endoscopy is a “high-risk” procedure during COVID-19 pandemic, it is irrational to stop all endoscopic procedures.

Aberrant de novo lipogenesis (DNL) results in excessive hepatic lipid accumulation and liver steatosis, the causative factors of many liver diseases, such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC). However, the underlying mechanism of DNL dysregulation remains largely unknown. Ubiquitination of proteins in hepatocytes has been shown to be widely involved in lipid metabolism of liver. Here, we revealed that Ubiquitin-specific peptidase 7 (USP7), a deubiquitinase (DUB), played key roles in DNL through regulation of zinc finger protein 638 (ZNF638) in hepatocytes. USP7 has been shown not only to interact with and deubiquitylate ZNF638, but also to facilitate the transcription of ZNF638 via the stabilization of cAMP responsive element binding protein (CREB). USP7/ZNF638 axis selectively increased the cleavage of sterol regulatory element binding protein (SREBP1C) through AKT/mTORC1/S6K signaling, and formed USP7/ZNF638/SREBP1C nuclear complex to regulate lipogenesis-associated enzymes, including acetyl-CoA carboxylase (ACACA), fatty acid synthase (FASN), and Stearoyl-CoA desaturase (SCD). In the mice liver steatosis model induced by fructose, USP7 or ZNF638 abrogation significantly ameliorated disease progression. Furthermore, USP7/ZNF638 axis participated in the progression of lipogenesis-associated HCC. Our results have uncovered a novel mechanism of hepatic DNL, which might be beneficial to the development of new therapeutic targets for hepatic lipogenesis-associated diseases.

BackgroundThe improved submucosal tunneling endoscopic resection (STER) with slant tunnel was created by our group innovatively for submucosal tumors (SMTs) in the proximal esophagus. This study aimed to provide the preliminary results of the improved STER from our center.MethodsThe key step of the improved STER is establishing a slant tunnel instead of a vertical tunnel. After a longitudinal incision was made proximally in the inclined top to the tumor, a submucosal tunnel was established from the incision to the SMT slantingly. 28 patients undergoing STER with slant tunnel were enrolled in the retrospective study. Clinical results including en bloc resection, curative resection and complication were collected.ResultsAll the submucous tumors located at proximal esophagus originated from muscularis propria were successfully resected by the innovative STER. Tumor size ranged from 18-43 mm, with 96.4% (27/28) en bloc resection rate and 92.9% (26/28) curative rate. Three patients suffered complication, 1 patient with mild pleural effusion and another 2 patients with fever for one day. All of the complications were cured by conservative treatment.ConclusionsSTER with slant tunnel seems to provide an optional treatment for tumors in proximal esophagus.

Background Peroral endoscopic myotomy (POEM) has shown excellent results for the treatment of achalasia in adults, but studies for children are limited. The study was aimed to analyze outcomes of peroral endoscopic myotomy (POEM) in children and compared with those in adults in a large multi-center study.MethodsRecords of consecutive patients with achalasia who underwent POEM at three tertiary centers were reviewed. A total of 130 children were included in this study. The primary outcomes of perioperative outcomes and clinical follow-up data were analyzed.ResultsOne child (0.8%) experienced technical failure. Five children (3.8%) had major adverse events, including one with pneumothorax requiring drainage, two with delayed mucosa barrier failure, one with readmission, and one with vital-sign instability. Both post-POEM Eckardt score and median LES pressure were significantly lower than their pre-POEM reference values in children (0.7 vs 7.4; 7.0 vs 27.1 mmHg; both P < 0.001). During a median follow-up time of 40 months, clinical reflux rate was 27.0% and clinical failure rates at 1, 3, and 5 years were 1.8%, 3.5%, and 4.4% for children. The technical failure, major adverse events, and postoperative clinical reflux were comparable between children and adults (all P > 0.05). Kaplan–Meier analysis showed that the risk of clinical failure was lower in children than adults (log-rank test, hazard ratio = 0.37, 95% confidence interval 0.15–0.91, P = 0.023).ConclusionsPOEM can be safely performed in children with achalasia, and produce a better clinical response during long-term follow-up compared with that in adults.