Epigenome-augmented eQTL-hotspots reveal genome-wide transcriptional programs in 36 human tissues.

Expression quantitative trait loci (eQTLs) are used to inform the mechanisms of transcriptional regulation in eukaryotic cells. However, the specificity of genome-wide eQTL identification is limited by stringent control for false discoveries. Here, we described a method based on the non-homogeneous Poisson process to identify 125 489 regions with highly frequent, multiple eQTL associations, or 'eQTL-hotspots', from the public database of 59 human tissues or cell types. We stratified the eQTL-hotspots into two classes with their distinct sequence and epigenomic characteristics. Based on these classifications, we developed a machine-learning model, E-SpotFinder, for augmented discovery of tissue- or cell-type-specific eQTL-hotspots. We applied this model to 36 tissues or cell types. Using augmented eQTL-hotspots, we recovered 655 402 eSNPs and reconstructed a comprehensive regulatory network of 2 725 380 cis-interactions among eQTL-hotspots. We further identified 52 012 modules representing transcriptional programs with unique functional backgrounds. In summary, our study provided a framework of epigenome-augmented eQTL analysis and thereby constructed comprehensive genome-wide networks of cis-regulations across diverse human tissues or cell types.

The role of amygdala-ventral pallidum pathway in depression-like behaviors in male mice.

The basolateral amygdala (BLA) appears to serve an important function in the pathophysiology of depression. Depressive symptoms, such as anhedonia are largely caused by dysfunction in the brain's reward system, in which the ventral pallidum (VP) participates in by controlling dopamine release. However, the role of the BLA-VP pathway in the development of depression remains poorly understood. To investigate this pathway, we employed the Chronic Unpredictable Mild Stress (CUMS) mouse model, in which we injected retroAAV expressing GFP-Cre into the VP and AAV expressing hM4Di-mCherry into the BLA. We then used CNO to activate the Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) for all behavioral tests. The CUMS procedure resulted in significant depression symptoms such as decreased sucrose preference, limited weight gain, decreased immobile latency, and increased immobile time in the forced swim and tail suspension tests. Inhibition of the BLA-VP glutamatergic projections reversed these depression-like behaviors. We found that suppressing the BLA-VP circuitry had beneficial effects on CUMS-induced depression-like behaviors such as anorexia, anhedonia, and despair. Specifically, upon suppression of glutamatergic projections in the BLA-VP circuitry, these depression-like behaviors were significantly alleviated, which highlights the vital role of this circuitry in the development of depression. Furthermore, the beneficial effects of suppressing this circuitry seem to be associated with the brain's reward system, warranting further investigation.

CDSKNNXMBD: a novel clustering framework for large-scale single-cell data based on a stable graph structure.

BACKGROUND: Accurate and efficient cell grouping is essential for analyzing single-cell transcriptome sequencing (scRNA-seq) data. However, the existing clustering techniques often struggle to provide timely and accurate cell type groupings when dealing with datasets with large-scale or imbalanced cell types. Therefore, there is a need for improved methods that can handle the increasing size of scRNA-seq datasets while maintaining high accuracy and efficiency. METHODS: We propose CDSKNNXMBD (Community Detection based on a Stable K-Nearest Neighbor Graph Structure), a novel single-cell clustering framework integrating partition clustering algorithm and community detection algorithm, which achieves accurate and fast cell type grouping by finding a stable graph structure. RESULTS: We evaluated the effectiveness of our approach by analyzing 15 tissues from the human fetal atlas. Compared to existing methods, CDSKNN effectively counteracts the high imbalance in single-cell data, enabling effective clustering. Furthermore, we conducted comparisons across multiple single-cell datasets from different studies and sequencing techniques. CDSKNN is of high applicability and robustness, and capable of balancing the complexities of across diverse types of data. Most importantly, CDSKNN exhibits higher operational efficiency on datasets at the million-cell scale, requiring an average of only 6.33 min for clustering 1.46 million single cells, saving 33.3% to 99% of running time compared to those of existing methods. CONCLUSIONS: The CDSKNN is a flexible, resilient, and promising clustering tool that is particularly suitable for clustering imbalanced data and demonstrates high efficiency on large-scale scRNA-seq datasets.

EMM-Promoted Pd-Catalyzed Solid State Intramolecular Heck-Type Cyclization/Boronation and Suzuki Couplings: Access to Functionalized Indolines.

EMM (electromagnetic mill)-promoted Pd-catalyzed solid state intramolecular Heck-type cyclization/boronation and Suzuki couplings are reported. Compared to previous mechanochemistry that constructed one chemical bond through a cross-coupling reaction, this strategy realizes cascade transformation along with multiple chemical bond formation. This conversion does not require organic solvents or additional heating, and it shows a good substrate scope and high functional group tolerance.

Palladium-catalyzed cascade cyclization of allenamide with 2-iodoanilines to access functionalized indoloquinolines.

A novel and efficient palladium-catalyzed cascade cyclization to indoloquinoline derivatives in one pot has been developed by using allenamide derivatives and 2-iodoanilines as the key building blocks. The process involved two cyclizations: intramolecular cyclization/π-allylic substitution and intramolecular 6-endo Heck cyclization. Furthermore, dihydrobenzofuro[2,3-b]quinoline derivatives could also be achieved via this strategy using allenyl ethers instead of allenamides. The readily available substrates, mild conditions, high efficiency and step economy make this strategy a promising method in the synthesis of polycyclic motifs.

Chinese Pedigree with Hereditary Gastrointestinal Stromal Tumors: A Case Report and Literature Review.

Familial gastrointestinal stromal tumor (GIST) is a rare autosomal dominant genetic disorder with only a few affected families reported to date. Here, we report a case of familial GISTs harboring a novel germline mutation within exon 18 of KIT. A 58-year-old male patient presented with gastric subepithelial lesions accompanied by cutaneous hyperpigmentation, which were subsequently diagnosed as multinodular GISTs. Endoscopic surgery was initially conducted to remove the larger lesions, and pathological examinations were then conducted for the diagnosis of GISTs. Family history revealed that some other family members had similar cutaneous pigmentations. Whole-exome sequencing was used to search for potential driver mutations, and Sanger sequencing was used for mutation validation. A novel primary driver mutation of KIT (c.G2485C, p.A829P) was detected in these hereditary GISTs, which has been reported in some targeted chemotherapy-resistant GISTs. Cell models were subsequently established for the rapid screening of candidate drugs and exploring potential mechanisms. This mutation could lead to cell proliferation and imatinib resistance by ligand-independent activation of KIT; however, ripretinib administration was identified as an applicable targeted therapy for this mutation. The mutation activated the JAK/STAT3 and MAPK/ERK pathways, which could be inhibited by ripretinib administration. To the best of our knowledge, this is the first report of the KIT-A829P mutation in familial GISTs, complementing the pathogenesis of familial GISTs and providing valuable information for the precision treatment of this disease.

Oncogenic potential of PIK3CD in glioblastoma is exerted through cytoskeletal proteins PAK3 and PLEK2.

The Class IA phosphoinositide-3-kinase catalytic isoforms p110α, p110ß, and p110δ have been implicated to play vital but overlapping roles in various cancers, including glioblastoma (GBM). We have previously shown that PIK3CD, encoding p110δ, is highly expressed in multiple glioma cell lines and involved in glioma cell migration and invasion. Based on the RNA sequencing data from The Cancer Genome Atlas (TCGA) database, we found the level of PIK3CD expression is significantly higher in GBM than WHO grade II and III gliomas and is closely related to poor survival. To further dissect the oncogenic roles of PIK3CD in glioma progression, we employed CRISPR/Cas9 to completely abrogate its expression in the GBM cell line U87-MG and have successfully isolated two knockout clones with different gene modifications. As expected, the knockout clones exhibited significantly lower migration and invasion capabilities when compared with their parental cells. Interestingly, knockout of PIK3CD also dramatically reduced the colony formation ability of the knockout cells. Further study revealed that PIK3CD deficiency could negate tumorigenesis in nude mice. To determine the downstream effect of PIK3CD depletion, we performed RT2 profiler PCR array of selected gene sets and found that knockout of PIK3CD impaired the activity of p-21 activated kinase 3 (PAK3) and pleckstrin 2 (PLEK2), molecules involved in cancer cell migration and proliferation. This explains why the glioma cells without the PIK3CD expression exhibited weaker oncogenic features. Further, RNAseq analysis of parent and knockout clones revealed that this interaction might happen through axonogenesis signaling pathway. Taken together, we demonstrated that PIK3CD could be a potential prognostic factor and therapeutic target for GBM patients.

The necessarity of treatment for small gastric subepithelial tumors (1-2 cm) originating from muscularis propria: an analysis of 972 tumors.

BACKGROUND AND OBJECTIVES: Up till now, there are still controversies about the specific indication of endoscopic resection for small gastric subepithelial tumors (gSETs) originating from muscularis propria. We aimed to investigate the safety of endoscopic resection and postoperative pathology analysis. METHOD: The patients with primary small gSETs originating from muscularis propria, treated by endoscopic resection in the endoscopic center of Shengjing Hospital between January, 2011 and September, 2019 were enrolled. The complete resection rate, adverse events and clinicopathological features were recorded. RESULT: A total of 936 patients with 972 gastric SETs ≤ 2 cm originating from muscularis propria were included in our study. All the lesions were successfully treated by endoscopic resection. Nearly half of lesions were proved to be gastrointestinal stromal tumor (GIST) [n = 411 (42.3%)] according to postoperative pathology. All the objects were further subdivided into 2 groups, ≤ 1 cm, > 1 and ≤ 2 cm gSETs. The risk of gastric GIST of intermediate/high risk in the group (> 1 and ≤ 2 cm gSETs) is 8.41 times as that of gastric GIST in the group (the size of gastric ≤ 1 cm gSETs) (P < 0.05). CONCLUSION: Endoscopic resection is a safe and effective treatment for small gSETs. gSETs (1-2 cm) is more risky than gSETs (≤ 1 cm) and should be resected. This should be evaluated by further studies.

Double anchor lock fixing method to prevent stent displacement in endoscopic ultrasound-guided gastroenterostomy: a porcine study.

BACKGROUND: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is widely used in patients with gastric outlet obstruction (GOO). Recurrence of obstruction symptoms caused by stent migration is the major reason for reintervention in EUS-GE. To solve this problem, we proposed developing a double anchor lock (DAL) fixing stent method for EUS-GE. The safety and efficacy of the DAL fixing stent method were evaluated in this study. METHODS: Sixteen Bama miniature pigs were randomly divided into an experimental group (n = 8) and a control group (n = 8). A gastric outlet obstruction model was established for all the pigs. The experimental group was treated with the DAL fixing stent method for EUS-GE, while the control group was treated with EUS-GE. Three-month stent migration rate, remission rate of GOO, re-occlusion intervention rate, weight change, and incidence of procedure-related complications of EUS-GE were analyzed and estimated in the two groups. RESULTS: EUS-GE was successfully completed in every subject in both groups. Symptoms of digestive tract obstruction can be relieved in all animals. The stent existence rate in the 3 months was higher in the experimental group than in the control group (87.5% vs. 12.5%, P = 0.012). Except for one animal in the experimental group in which there was pneumoperitoneum due to a stent insertion failure, no animal experienced bleeding or perforation. CONCLUSION: The DAL fixing stent method, which can effectively prevent stent migration, is safe and simple. EUS-GE can effectively relieve the symptoms of digestive tract obstruction.

Stent placement to prevent strictures after esophageal endoscopic submucosal dissection: a systematic review and meta-analysis.

Endoscopic submucosal dissection (ESD) is an important method for the treatment of early esophageal cancer. However, post-procedure stenosis is one of the most common long-term complications. This meta-analysis aimed to investigate whether stent placement is effective in the stenosis prevention, and which type of stent would be more effective. A systematic and electronic search of clinical trials and observational studies conducted before March 2020 on the efficacy of stent placement in preventing esophageal stricture after ESD was performed. Search terms included "ESD," "esophageal stenosis," "esophageal stricture," and "stents." We conducted a bias risk assessment of the eligible reports and a meta-analysis of the data using Revman 5.3 software. We included two randomized controlled trials (RCTs) and a prospective cohort study involving 163 patients with esophageal mucosal defects encompassing at least three-quarters of the esophagus circumference after ESD. The meta-analysis results showed that post-ESD stenosis rates (RR, 0.37; 95% CI, 0.22-0.64; P = 0.0003) and the number of endoscopic balloon dilations (EBDs) (MD, -1.74; 95% CI, -2.46 to -1.01; P < 0.00001) were reduced in the pooled analysis of three studies, indicating that stent placement was effective for stenosis prevention, especially a polyglycolic acid (PGA) sheet combined with stent placement can prevent stenosis (RR, 0.41; 95% CI, 0.23-0.74; P = 0.003) and reduce the number of EBDs (MD, -1.65; 95% CI, -2.40 to -0.90; P < 0.0001) significantly. Stent placement can reduce the rate of esophageal stenosis after ESD, especially when stents are covered with PGA sheets. However, more high-quality, low-bias RCTs with a sufficient sample size are needed to demonstrate its effectiveness.

Retrieval anchor-assisted endoscopic ultrasound-guided gastroenterostomy for gastric outlet obstruction.

OBJECTIVES: Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is an emerging procedure for gastric outlet obstruction (GOO) as an alternative to endoscopic stent placement in the duodenum or surgery; however, it is technically challenging. This study aimed to evaluate the safety, success rate, and adverse events rate associated with retrieval anchor-assisted EUS-GE. METHODS: Data from patients who underwent retrieval anchor-assisted EUS-GE for malignant and benign GOO were retrospectively analyzed. Patients' clinical and demographic characteristics, procedure time, and success and adverse event rates were recorded. RESULTS: A total of 10 patients (6 females; mean age 63.2 ± 5.8 years) were included in our study. Nine cases were malignant and one case was benign GOO. Nine patients received retrievable anchor-assisted EUS-GE for GOO. One patient received retrievable anchor-assisted EUS-GE and concurrent EUS-guided hepatogastrostomy due to the biliary obstruction. There were no complications during any of the procedures. The rate of technical and clinical success was 100%. CONCLUSIONS: EUS-GE is a safe and effective procedure for GOO. The retrieval anchor can make EUS-GE easier to perform successfully.

Endoscopic diagnosis of gastrointestinal melanoma.

Background: Gastrointestinal (GI) melanoma can be diagnosed by endoscopy combined with biopsy and subsequent pathological examination. However, the disease may be misdiagnosed due to the limited awareness of GI melanoma.Objective: We aimed to describe characteristics of GI melanoma that can be detected by endoscopy and endoscopic ultrasound (EUS).Methods: We retrospectively analyzed patients with GI melanoma diagnosed by endoscopic biopsy or postoperative pathology between August 2008 and January 2017. Images of endoscopic examinations, including endoscopy and EUS, were reviewed to characterize GI melanomas.Results: A total of 21 patients (9 males, 12 females) with GI melanoma were enrolled in this study. Several types of melanoma were identified: anorectal melanoma (n = 15), esophageal melanoma (n = 3), gastric melanoma (n = 2), and melanoma of the small intestine (n = 1). EUS was performed for one case of esophageal melanoma, one case of gastric melanoma, and seven cases of anorectal melanoma.Conclusions: GI melanoma is a rare disease. Most GI melanomas showed typical endoscopic manifestations, including black plaques. EUS is a reliable tool for evaluating the depth of infiltration of GI melanoma.

Direct endoscopic full-thickness resection for submucosal tumors with an intraluminal growth pattern originating from the muscularis propria layer in the gastric fundus.

BACKGROUND AND AIMS: Endoscopic full-thickness resection (EFTR) is difficult to perform in a retroflexed fashion in the gastric fundus. The present study aims at exploring whether direct EFTR can be a simple, effective and safe procedure to treat intraluminal-growth submucosal tumors originating from the muscularis propria. METHODS: The patients with intraluminal-growth submucosal tumors originating from the muscularis propria in gastric fundus treated by direct EFTR between 01 January 2017 and 01 September 2018 were retrospectively reviewed. In addition, we analyzed the patients with intraluminal-growth submucosal tumors originating from the muscularis propria in gastric fundus treated by traditional EFTR. The differences in tumor resection time, cost-effectiveness, and complication rate were evaluated. RESULTS: Forty patients were enrolled in the present study, 20 patients of which were in the direct EFTR group and 20 patients of which were in the traditional EFTR group. En-bloc resections of gastric tumors were successfully performed in all 40 cases. There was no significant difference in the average tumor size of the two groups (24.3 ± 2.9 mm in direct EFTR group verus 24.0 ± 2.6 mm in the traditional group, p = 0.731), but significant difference existed in the operative time between two groups (35.0 ± 8.2 min in direct EFTR group verus 130.6 ± 51.9 min in the traditional group, p<0.05). No complications, such as postoperative bleeding and perforation, occurred in any groups. CONCLUSIONS: Direct EFTR is a safe, simple and cost-effective procedure for SMTs with an intraluminal growth pattern originating from the muscularis propria layer in the gastric fundus.

Diagnostic efficacy of double-balloon enteroscopy in patients with suspected isolated small bowel Crohn's disease.

BACKGROUND: Owing to the development of double-balloon enteroscopy (DBE) and video capsule endoscopy (VCE) in recent years, direct visualization of the entire small intestinal mucosa has become possible. Because of the nonspecific symptoms and the anatomic location of the small bowel, diagnosis of isolated small bowel Crohn's disease (CD) remains a challenge. The aim of this research was to explore the value of DBE for isolated small bowel CD in situations where routine tests cannot confirm the diagnosis. METHODS: This study included patients with suspected isolated small bowel CD who were hospitalized in Shengjing Hospital from April 2014 to June 2018. We included patients presenting with chronic diarrhea, abdominal pain, abdominal mass, perianal lesions, and systemic symptoms including weight loss, fever, and anemia after excluding infection factors. Patients with purely colonic CD were excluded from this cohort. Patients with suspected isolated small bowel CD underwent DBE. RESULTS: In 16/18 patients, pathological findings were detected by DBE. In 12 of the cases, small bowel CD was confirmed. The remaining four patients were diagnosed with small bowel inflammation, duodenal carcinoma, ileum inflammation and small bowel ulcers. However, the diagnosis of CD was confirmed in 14/18 (78%) patients by taking into account the clinical presentation, endoscopic and histological results as well as the experimental treatment. DBE assisted in the diagnosis in 86% (12/14) of the patients. CONCLUSIONS: In the diagnosis of small bowel CD, DBE is a helpful tool. Before assessment with DBE, clinical features, colonoscopy, and CT were used to initially assess the intestine. According to the lesions indicated by CT, we chose the most appropriate endoscope insertion route, and combined the endoscopic characteristics and pathological results of DBE to confirm the diagnosis.

Evaluation of ultrasound-guided Freka-Trelumina enteral nutrition tube placement in the treatment of acute pancreatitis.

BACKGROUND: Enteral nutrition should be implemented as early as possible in patients with moderate or severe acute pancreatitis. This study was designed to evaluate the feasibility and Deffectiveness of ultrasound-guided Freka-Trelumina tube placement for enteral nutrition in acute pancreatitis. METHODS: Patients with severe acute pancreatitis admitted to Shengjing Hospital of China Medical University who needed Freka-Trelumina tube placement for enteral nutrition and gastrointestinal decompression were included in the current study. The relevant evaluation indicators of tube placement included the success rate of tube placement, tube placement time, tube shift rate, and blocking rate. In addition, the evaluation indicators of ultrasound-guided tube placement (from 1 January 2018 to 31 July 2019) were compared with those of previous endoscope-guided placement (from 1 January 2015 to 31 December 2017) by analysing the data from the electronic medical record system. RESULTS: The success rate of ultrasound-guided tube placement was 90.7% (49/54). All 49 patients tolerated the Freka-Trelumina feeding tube. The average ultrasound-guided tube placement time for the 49 patients was 18.4 ± 12.8 min (range, 5-36 min). The Freka-Trelumina feeding tube had a shift rate of 10.2% (5/49). The blocking rate of the Freka-Trelumina feeding tube was 12.2% (6/49). The success rate of tube placement, tube shift rate and blocking rate for endoscope-guided tube placement were 100% (62/62), 11.3% (7/62), and 12.9% (8/62), respectively. The average endoscope-guided tube placement time for the 62 patients was 16.5 ± 5.7 min (range, 12-31 min). The comparison between the ultrasound-guided group and the endoscope-guided group showed that the success rate of tube placement, tube placement time, tube shift rate and blocking rate were similar. CONCLUSION: The ultrasound-guided method can be done non-invasively at the bedside, which is safe and convenient, and the Freka-Trelumina feeding tube can be placed in time to achieve the goal of early enteral nutrition and gastrointestinal decompression.

Multivariate analysis of the factors affecting the prognosis of walled-off pancreatic necrosis after endoscopic ultrasound-guided drainage.

BACKGROUND AND AIMS: Endoscopic ultrasound (EUS)-guided drainage has become the treatment of choice for walled-off pancreatic necrosis (WOPN). However, no consensus exists on the most significant patient- and procedure-related factors that affect prognosis. The aim of the study is to investigate the correlation between patient- and procedure-related factors and post-procedure complications after EUS-guided drainage. METHODS: A retrospective analysis of the clinical characteristics of patients with WOPN who underwent EUS-guided drainage at our endoscopy center between November 2011 and August 2017 was performed. Chi-square analysis and binary logistic regression statistical methods were used to analyze the correlation between influencing factors and prognosis. RESULTS: A total of 85 patients (male/female, 50/35) with WOPN were included in the study. The average age was 44.95 years. The cyst diameter was 10.58 ± 4.78 cm. Multivariate analysis showed that WOPN with higher solid content (> 30%) increased the probability of endoscopic necrosectomy (OR 6.798; 95% CI 1.423, 32.470; p = 0.016). The use of a metal stent increased the probability of endoscopic necrosectomy (OR 3.503; 95% CI 1.251, 9.810; p = 0.017) and the length of hospitalization (OR 3.315; 95% CI 1.192, 9.215; p = 0.022). Female patients had a higher probability of requiring endoscopic necrosectomy (OR 2.683; 95% CI 1.027, 7.007; p = 0.044) and prolonged hospitalization (OR 2.675; 95% CI 1.065, 6.721; p = 0.036). CONCLUSION: The solid content of WOPN, type of stent, and sex of patients were associated with increased probability of endoscopic necrosectomy.

Long-term assessment of over-the-scope clip (OTSC) behavior after gastric application.

Background: The aim of this study was to assess the long-term behavior of the over-the-scope clip (OTSC) after gastric application.Material and methods: A database of all patients who had OTSC placement with regular follow-up at a tertiary hospital between November 2013 and September 2016 was retrospectively analyzed. The incidence, time, and related adverse events of clip attachment and detachment were recorded. The relationship between the position of the clip and detachment was assessed by Fisher's exact test.Results: Seventy-two patients who had gastric OTSC placement due to iatrogenic perforations by endoscopic interventions were included in the study. The overall incidence of clip detachment was 27.8% (20/72). Fisher's exact test confirmed a significant association between clip detachment rate and clip position (p = .005): cardia 50% (3/6); gastric fundus 13.2% (5/38); gastric body 75% (9/16); and gastric antrum 25% (3/12). Except for one patient (5%; 1/20) who experienced minor gastric hemorrhage, there were no complications related to spontaneous clip detachment. There was no delayed bleeding, perforation, or obstruction due to clips staying in place in the long-term.Conclusions: Long-term gastric clip attachment appears to be safe even if spontaneous detachment occurs.

Germline and somatic variations influence the somatic mutational signatures of esophageal squamous cell carcinomas in a Chinese population.

BACKGROUND: Esophageal squamous cell carcinomas (ESCC) is the fourth most lethal cancer in China. Previous studies reveal several highly conserved mutational processes in ESCC. However, it remains unclear what are the true regulators of the mutational processes. RESULTS: We analyzed the somatic mutational signatures in 302 paired whole-exome sequencing data of ESCC in a Chinese population for potential regulators of the mutational processes. We identified three conserved subtypes based on the mutational signatures with significantly different clinical outcomes. Our results show that patients of different subpopulations of Chinese differ significantly in the activity of the "NpCpG" signature (FDR = 0.00188). In addition, we report ZNF750 and CDC27, of which the somatic statuses and the genetic burdens consistently influence the activities of specific mutational signatures in ESCC: the somatic ZNF750 status is associated with the AID/APOBEC-related mutational process (FDR = 0.0637); the somatic CDC27 copy-number is associated with the "NpCpG" (FDR = 0.00615) and the AID/APOBEC-related mutational processes (FDR = 8.69 × 10- 4). The burdens of germline variants in the two genes also significantly influence the activities of the same somatic mutational signatures (FDR < 0.1). CONCLUSIONS: We report multiple factors that influence the mutational processes in ESCC including: the subpopulations of Chinese; the germline and somatic statuses of ZNF750 and CDC27 and exposure to alcohol and tobacco. Our findings based on the evidences from both germline and somatic levels reveal potential genetic regulators of the somatic mutational processes and provide insights into the biology of esophageal carcinogenesis.

Retrievable puncture anchor traction method for EUS-guided gallbladder drainage: a porcine study.

BACKGROUND AND AIMS: EUS-guided gallbladder drainage (EUS-GBD) is a challenging technique for endoscopists that requires a high level of skill. EUS-GBD is challenging because the gallbladder can be easily collapsed. To resolve this issue, we aimed to develop a retrievable puncture anchor traction (RPAT) method for EUS-GBD. We evaluated and compared the success rate, safety, and outcomes of the RPAT method for EUS-GBD against EUS-GBD without RPAT using a porcine model. METHODS: In total, 16 Bama mini pigs (weighing 15-20 kg) were randomly divided into an experimental group (n = 8) and a control group (n = 8). The RPAT method was performed in the experimental group and EUS-GBD without retrievable puncture anchor was performed in the control group. Incidence of operative adverse events, wound healing, and success rates of EUS-GBD were compared and analyzed between the experimental group and the control group. RESULTS: All EUS-GBD procedures were successfully performed in all 8 animals in the experimental group (100%). However, in the control group, EUS-GBD was successfully performed only on 4 pigs (50%); the remaining 4 pigs died because of EUS-GBD failure caused by gallbladder collapse leading to unsuccessful frontal stent release. CONCLUSIONS: RPAT helped increase the success rate of EUS-GBD and could reduce gallbladder collapse. Therefore, we believe this method can be applied to EUS-GBD in the near future. Furthermore, RPAT will enhance the safety of EUS-GBD.

Preliminary opinion on assessment categories of stomach ultrasound report and data system (Su-RADS).

OBJECTIVE: Transabdominal ultrasound after oral administration of an echoic cellulose-based gastric ultrasound contrast agent (TUS-OCCA) has recently been suggested as a valuable mass-screening tool for gastric cancer. The aim of this study was to propose a producible stomach ultrasound reporting and data system (Su-RADS) using TUS-OCCA for gastric cancer screening. PATIENTS: The study includes information of 2738 patients who underwent both gastroscopy and TUS-OCCA examinations recorded in software system. Gastroscopy examination with pathological diagnosis was considered as gold standard. Various gastric lesions were classified into category 1-5 based on gastric wall thicknesses of them (especially the mucosa layer). RESULTS: The total malignant ratios of patients enrolled in this study were 17.1% (469/2738). The malignant ratios for category 1-5 were, respectively, 1.1, 1.7, 12.2, 34.2 and 78.1%. Category 2 indicated mild thickening of gastric wall at low risk for malignancy (1.7%); category 3 indicated moderate thickening at moderate risk for malignancy (12.2%); category 4 indicated severe thickening at high risk for malignancy (34.2%); category 5 indicated extremely severe thickening at extremely high risk for malignancy (78.1%). If category 2 was identified as cut-off point distinguishing between benign and malignant, the sensitivity and specificity by Su-RADS are 95.1 and 78.6%, respectively. CONCLUSION: The Su-RADS system could inform the physicians about key findings, indicating the risk for malignancy and necessity of additional gastroscopy examination. Prospectively randomly controlled study design with larger clinical trial is needed for further investigations.