INTRODUCTION:Cancer-associated fibroblasts (CAFs) can promote gastric cancer (GC) progression through regulating the tumor microenvironment (TME). This study explored cell-to-fibroblast communication based on the single-cell data of GC, identified CAF-related genes linked to GC using high-dimensional weighted gene co-expression network analysis (hdWGCNA), and conducted functional mining, drug prediction, and molecular docking for these genes. MATERIALS AND METHODS:Single-cell data were preprocessed using the Seurat package. The communication network between cell subpopulations and fibroblasts was analyzed using CellChat. Key hub genes were initially identified through hdWGCNA, while differentially expressed genes (DEGs) between cancer and control groups were obtained using DESeq2. Subsequently, the overlapping genes between the hub genes and DEGs were subjected to LASSO regression (via the glmnet package) and SVM-RFE (implemented in e1071) to select biomarkers for GC. Immune cell infiltration was assessed using the CIBERSORT package, and functional enrichment analysis was performed on the background gene set by GSEA_4.2.2 software. Finally, drugs targeting the biomarkers were predicted by employing the DSigDB database. RESULTS:Single-cell analysis identified eight major cell subpopulations, with fibroblasts distinctly marked by DCN and LUM expression. Cell communication analysis revealed that HLA-ECD94: NKG2A and HLA-E-KLRC1 were the main interactions through which other cell clusters exerted influence on fibroblasts. COL1A1 and SERPINH1 were identified as CAF-related biomarkers that promoted GC progression through macrophage-mediated immune infiltration. High co-expression of the two genes was significantly enriched in epithelial-mesenchymal transition (EMT). DISCUSSION:COL1A1 and SERPINH1 may promote GC progression via regulating EMT and forming an immunosuppressive microenvironment through ECM remodeling and macrophage polarization. Additionally, chitosamine was screened as a potential COL1A1-targeting drug for GC treatment. CONCLUSION:These findings have deepened our current understanding of CAF-mediated mechanisms in GC, contributing to the development of precision diagnostics and therapeutics in GC.

ObjectiveCircular RNAs belong to a category of noncoding RNAs that feature a unique continuous, covalently bonded ring configuration. Recent research indicates that circular RNAs are essential for the development of metabolic dysfunction-associated steatotic liver disease. This study sought to examine the functional role and molecular mechanism of circDock6 in metabolic dysfunction-associated steatotic liver disease.MethodsQuantitative reverse transcription polymerase chain reaction was performed to determine circDock6 expression patterns in liver tissues from high-fat diet- and standard diet-fed mice in vivo. Triglyceride detection, western blot analysis, and oil red O staining were performed to evaluate the regulatory effect of circDock6 on metabolic dysfunction-associated steatotic liver disease in vitro.ResultsCircDock6 was found to be markedly overexpressed in high-fat diet liver tissues compared with that in standard diet tissues. Moreover, knockdown of circDock6 expression lowered triglyceride content and lipid droplet formation. Mechanistically, circDock6 acted as a molecular sponge for mmu-let-7g-5p, which regulated insulin-like growth factor 1 receptor expression and contributed to the progression of metabolic dysfunction-associated steatotic liver disease. CircDock6 knockdown suppressed metabolic dysfunction-associated steatotic liver disease progression by modulating insulin-like growth factor 1 receptor via mmu-let-7g-5p targeting.ConclusionOur study identified circDock6 as a novel regulator of metabolic dysfunction-associated steatotic liver disease pathogenesis through the mmu-let-7g-5p/insulin-like growth factor 1 receptor axis, indicating its potential as a therapeutic target for metabolic dysfunction-associated steatotic liver disease intervention.

Background Gastric adenocarcinoma (GA) is a heterogeneous malignancy with high invasion and metastasis. We aimed to explore the metastatic characteristics of GA using single-cell RNA-sequencing (scRNA-seq) analysis. Methods The scRNA-seq dataset was downloaded from the GEO database and the “Seurat” package was used to perform the scRNA-seq analysis. The CellMarker2.0 database provided gene markers. Subsequently, differentially expressed genes (DEGs) were identified using the FindMarkers function and subjected to enrichment analysis with the “ClusterProlifer”. “GseaVis” package was used for visualizing the gene levels. Finally, the SCENIC analysis was performed for identifying key regulons. The expression level and functionality of the key genes were verified by quantitative real-time PCR (qRT-PCR), wound healing and transwell assays. Results A total of 7697 cells were divided into 8 cell subsets, in which the Cytotoxic NK/T cells, Myeloid cells and Myofibroblasts had higher proportion in the metastatic tissues. Further screening of DEGs and enrichment analysis revealed that in the metastatic tissues, NK cells, monocytes and inflammatory fibroblasts with low immune levels contributed to GA metastasis. In addition, this study identified a series of key immune-related regulons that mediated the lower immune activity of immune cells. Further in vitro experiment verified that CXCL8 was a key factor mediating the proliferation and migration of GA cells. Conclusion The scRNA-seq analysis showed that high infiltration of immune cells with lower immune activity mediated heterogeneity to contribute to GA metastasis.

A 48-year-old man developed sudden-onset haematemesis and melena after decompensated posthepatitic cirrhosis. Endoscopic variceal injectional sclerotherapy was emergently performed. However, the patient developed esophago-pleural fistula, empyema, and liver failure. He thus received symptomatic treatments and nasojejunal feedings, which failed to restore the nutrition as the gastroesophageal reflux exacerbated the hydrothorax. Percutaneous endoscopic gastro-jejunal (PEG-J) was therefore carefully performed for enteral nutrition support. The patient had recovered from the fistula at a six-month follow-up, which allowed the resumption of an oral diet. Our literature review revealed that PEG-J is a feasible approach to treating esophago-pleural fistula, a rare but lethal complication of endoscopic sclerotherapy.

Background Circular RNA (circRNA) is a kind of endogenous non-coding RNAs and has shown diagnostic values in various cancers. This study aimed to explore whether hsa_circ_0001789 could be a novel biomarker for gastric cancer (GC). Methods Quantitative reverse transcriptase PCR was used to detect the expression of hsa_circ_0001789 in 108 paired GC and paracancerous tissues as well as in 24 paired plasma specimens. Possible associations between hsa_circ_0001789 expression and clinicopathologic factors of GC patients were examined using one-way ANOVA. A receiver operating characteristic (ROC) curve was established to investigate the diagnostic value of hsa_circ_0001789 in GC. Results GC tissues and plasma samples showed down-regulated hsa_circ_0001789 levels than their counterparts, which were closely correlated with the malignant characteristics of GC. The area under the ROC curve (AUC) of hsa_circ_0001789 in GC tissues was 0.82, while the cut-off value was 9.5, indicating a favorable diagnostic value. Compared with the traditional tumor biomarkers, hsa_circ_0001789 had preferred AUCs that reached 0.786 for predicting the stage of invasion, 0.603 for predicting the stage of lymphatic metastasis, 0.722 for predicting the stage of distant metastasis, and 0.786 for predicting TNM stage. Conclusions Hsa_circ_0001789 may be a novel biomarker for the diagnosis of gastric carcinoma.

Objective:Mendelian randomization was used to explore whether there is a causal relationship between gastroesophageal reflux disease (GERD) and chronic cough.Methods:We extracted independent genetic variants strongly associated with chronic cough from two published genome-wide association studies (GWAS) and summary statistics for GERD from a GWAS analysis in the European Molecular Biology Laboratory. The causal relationship between chronic cough and GERD was assessed using inverse variance weighted (IVW) as main estimation.Results:GERD was observed for causal association with increased risk for chronic cough for IVW analysis for applying two GWAS data (P=1.70×10?7 and P=2.42×10?5, respectively). However, there was no association of genetically predicted chronic cough with GERD (all P>0.05). None evidence of significant pleiotropy and heterogeneity was observed.Conclusion:There was a causal relationship between GERD and increased risk of chronic cough.

Introduction Using real-world data, we compared the quality of bowel preparation instructed by the digestive and non-digestive physicians in outpatients for colonoscopy and identified potential risk factors. Methods This was a retrospective study based on real-world data, which were collected from the Ningbo First Hospital in China from December 2019 to October 2020. Outpatients included were classified into the digestive and the non-digestive physician groups according to the referring physician. The primary outcome was adequate bowel preparation measured by the Boston Bowel Preparation Scale (BBPS), namely, a BBPS score of 2 or higher in any colonic segment and a total score ≥ 6. Secondary outcomes included the total mean BBPS scores and possible risk factors associated with poor bowel preparation. Results There were 671 outpatients included, with 392 in the digestive physician group and 279 in the non-digestive physician group. Adequate bowel preparation was 84.2% in the digestive physician group and 71.0% in the non-digestive physician group (odds ratio [OR]: 1.50, p < 0.001), and the latter had lower total mean BBPS scores (6.12 ± 1.33 vs. 6.66 ± 1.29, p < 0.001). The non-digestive physician was an independent risk factor according to the multivariate logistic regression analysis (OR: 0.45, p < 0.001). Conclusion The quality of bowel preparations instructed by non-digestive physicians was inferior to digestive physicians, which was a factor potentially associated with poor bowel preparation (ClinicalTrials.gov number: NCT04738578).

BACKGROUND Asymptomatic infections and mild symptoms are common in patients infected with the Omicron variant, and data on liver test abnormalities are rare. AIM To evaluated the clinical characteristics of asymptomatic and mild coronavirus disease 2019 (COVID-19) patients with abnormal liver test results. METHODS This retrospective study included 661 laboratory-confirmed asymptomatic and mild COVID-19 patients who were treated in two makeshift hospitals in Ningbo from April 5, 2022 to April 29, 2022. Clinical information and viral shedding time were collected, and univariate and multivariate logistic regression models were performed in statistical analyses. RESULTS Of the 661 patients, 83 (12.6%) had liver test abnormalities, and 6 (0.9%) had liver injuries. Abnormal liver tests revealed a reliable correlation with a history of liver disease (P < 0.001) and a potential correlation with male sex and obesity (P < 0.05). Elevated alanine aminotransferase was reliably associated with obesity (P < 0.05) and a history of liver disease (P < 0.001). Elevated aspartate transaminase (AST) was reliably correlated with a history of liver disease (P < 0.001), and potentially correlated with age over 30 years (P < 0.05). There was a reliable correlation between AST & GE; 2x the upper limit of normal and a longer viral shedding time, especially in mild cases. CONCLUSION Obesity and a history of liver disease are risk factors for liver test abnormalities. Being male and an older age are potential risk factors. Attention should be given to liver tests in asymptomatic and mild COVID-19 patients, which has crucial clinical significance for evaluating the viral shedding time.

Objectives: Colorectal cancer in the right side of the colon is supposed to harder to detect by colonoscopy. The aim of this study was to evaluate whether a second forward-view examination of the right side of the colon could increase adenoma detection rate (ADR) and polyp detection rate (PDR). Methods: This was a single-centre randomized controlled trial. Patients undergoing colonoscopy were recruited and randomly assigned to the second forward-view examination (SFE) group, in which the right side of the colon was examined twice and a traditional colonoscopy (TC) group in which the colonoscopy was performed in a standard manner. The primary outcomes were the proximal PDR and ADR. The overall PDR and ADR, and advanced lesion detection rate were also recorded and compared.. Results: A total of 392 patients were included in the study (SFE group 197 vs. TC group 195). The proximal PDR and ADR in the SFE group were significantly higher than those in the TC group (PDR 17.8% vs. 9.7%, P = 0.021; ADR 14.2% vs.7.2%, P = 0.024). No significant difference was found for overall PDR/ADR, or advanced lesion detection rate between the two groups. Conclusions : This prospective study revealed that a second forward-view examination of the right side of the colon could result in a modest improvement in proximal ADR and PDR. This simple and time-effective technique might be recommended for routine colonoscopy. Trial registration: Clinical Trials.gov, NCT03619122. Registered on 7/8/2018.

Background: We performed a systematic review and pooled analysis to assess the effectiveness and safety of different endoscopic resection methods for 10- to 20-mm nonpedunculated colorectal polyps. Methods: Articles in PubMed, EMBASE, and the Cochrane Library related to the common endoscopic treatment of 10- to 20-mm nonpedunculated polyps published as of April 2020 were searched. Primary outcomes were the R0 resection rate and en bloc resection rate. Secondary outcomes were safety and the recurrence rate. Meta-regression and subgroup analysis were also performed. Results: A total of 36 studies involving 3212 polyps were included in the final analysis. Overall, the effectiveness of resection methods with a submucosal uplifting effect, including endoscopic mucosal resection (EMR), cold EMR and underwater EMR (UEMR), was better than that of methods without a nonsubmucosal uplifting effect [R0 resection rate, 90% (95% confidence interval (CI) 0.81–0.94, I2 = 84%) vs 82% (95% CI 0.78–0.85, I2 = 0%); en bloc resection rate 85% (95% CI 0.79–0.91, I2 = 83%) vs 74% (95% CI 0.47–0.94, I2 = 94%)]. Regarding safety, the pooled data showed that hot resection [hot snare polypectomy, UEMR and EMR] had a higher risk of intraprocedural bleeding than cold resection [3% (95% CI 0.01–0.05, I2 = 68%) vs 0% (95% CI 0–0.01, I2 = 0%)], while the incidences of delayed bleeding, perforation and post-polypectomy syndrome were all low. Conclusions: Methods with submucosal uplifting effects are more effective than those without for resecting 10- to 20-mm nonpedunculated colorectal polyps, and cold EMR is associated with a lower risk of intraprocedural bleeding than other methods. Additional research is needed to verify the advantages of these methods, especially cold EMR.

Background Poor bowel preparation (BP) is commonly observed in inpatients undergoing colonoscopy, particularly those with a higher risk for inadequate BP. The objective of this study was to determine whether face-to-face instruction (FFI) and personalized BP regimens could improve the quality of BP for inpatient colonoscopy procedures. Methods In this endoscopist-blinded, randomized controlled trial, 320 inpatients were enrolled and randomly allocated at a ratio of 1:1 to the control and intervention groups. The intervention group received FFI and personalized BP regimes, while the control group received the standard education and BP regimes. The primary outcome was an adequate BP rate. Secondary outcomes included rates of procedure-related adverse events, incorrect diet restriction and laxative intake, quality of sleep before colonoscopy and willingness to repeat the BP. Results Demographic characteristics were comparable between the control and intervention groups. Notably, the adequate BP rate in the FFI group was significantly higher compared to the control group [intention-to-treat (ITT) analysis: 70.0% vs. 51.3%, P < 0.001; per-protocol (PP) analysis: 79.4% vs. 58.6%, P < 0.001; (IDDF2021-ABS-0120 Figure 1. The rate of adequate BP between the FFI and control groups for inpatients following ITT and PP analyses). Bowel cleanliness was significantly improved in response to the intervention in high-risk inpatients (ITT analysis: 65% vs. 44.6%, P = 0.004; PP analysis: 73.0% vs. 51.7%, P = 0.004) and in low-risk inpatients (ITT analysis: 80% vs. 62.7%, P = 0.037; PP analysis: 92.3% vs. 69.8% P = 0.003). There were no significant differences between the control and intervention groups regarding secondary outcomes. Conclusions FFI and personalized BP regimens improve the rate of adequate BP, especially in patients with a higher risk for inadequate BP. As such, inpatients would benefit from this novel approach for better BP to ultimately improve the quality of colonoscopies.

Objectives Colorectal cancer on the right side of the colon has been suggested to be harder to detect by colonoscopy. The aim of this study was to evaluate whether a second forward-view examination of the right side of the colon could increase the adenoma detection rate (ADR) and/or polyp detection rate (PDR). Methods This was a single-centre randomized controlled trial. Patients undergoing colonoscopy were recruited and randomly assigned to the second forward-view examination (SFE) group, in which the right side of the colon was examined twice or the traditional colonoscopy (TC) group in which the colonoscopy was performed in a standard manner. The primary outcome was the ADR of right colon. The overall PDR and ADR, PDR of the right colon, per-adenoma miss rate of the right colon, and advanced lesion detection rate were also recorded and compared. Results A total of 392 patients were included in the study (SFE group 197 vs. TC group 195). The ADR and PDR of the right colon in the SFE group were significantly higher than those in the TC group (ADR 10.7% vs. 5.1%; P = 0.042); PDR 17.8% vs. 9.7%, P = 0.021). No significant difference was found in overall PDR/ADR, or advanced lesion detection rate between the two groups. Conclusions This prospective controlled study revealed that a second forward-view examination could modestly increase the ADR and PDR of the right colon during unsedated colonoscopies. This simple, safe and time-effective technique might be recommended for routine unsedated colonoscopy. Trial registration: Clinical Trials.gov, NCT03619122. Registered on 7/8/2018.

Background Poor bowel preparation is commonly observed in inpatients undergoing colonoscopy, particularly those with higher risks for inadequate bowel preparation. Aims The objective of this study was to determine whether personalized bowel preparation regimens combined with face-to-face instruction (FFI) could improve the quality of bowel preparation for inpatient. Methods In this endoscopist-blinded, randomized controlled trial, 320 inpatients were enrolled and randomly allocated (1:1) to the control and intervention groups. The intervention group received FFI and personalized bowel preparation regimens, while the control group received the routine bowel preparation regimen and education. The primary outcome was adequate bowel preparation rate. Secondary outcomes included rates of procedure-related adverse events, incorrect diet restriction and laxative intake, etc. Results The adequate bowel preparation rate in the intervention group was significantly higher compared to control group [intention-to-treat (ITT) analysis: 70.0% vs 51.3%, P < 0.001; per-protocol (PP) analysis: 79.4% vs 58.6%, P < 0.001]. Bowel cleanliness was significantly improved in high-risk inpatients (ITT analysis: 65% vs 44.6%, P = 0.004; PP analysis: 73.0% vs 51.7%, P = 0.004) and in low-risk inpatients (ITT analysis: 80% vs 62.7%, P = 0.037; PP analysis: 92.3% vs 69.8%, P = 0.003). There were no significant differences between two groups regarding procedure-related adverse events. Conclusions Personalized bowel preparation regimens combined with FFI improve the rate of adequate bowel preparation, especially for patients with high-risk factors. As such, inpatients could benefit from this novel approach for better bowel preparation to ultimately improve the quality of colonoscopies.

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BACKGROUND:We aimed to compare the accuracy of individuals' wrist and forehead temperatures with their tympanic temperature under different circumstances.METHODS:We performed a prospective observational study in a real-life population in Ningbo First Hospital in China. We consecutively recorded individuals' wrist and forehead temperatures in Celsius (°C) using a non-contact infrared thermometer (NCIT). We also measured individuals' tympanic temperature using a tympanic thermometer (IRTT) and defined fever as a tympanic temperature of ≥37.3 °C.RESULTS:We enrolled 528 participants, including 261 indoor and 267 outdoor participants. We grouped the outdoor participants into four groups according to their means of transportation to the hospital: by foot, by bicycle/electric vehicle, by car, or as a passenger in a car. Under different circumstances, the mean difference in the forehead measurement ranged from -1.72 to -0.56 °C across groups, and that in the wrist measurement ranged from -0.96 to -0.61°C. Both measurements had high fever screening abilities in indoor patients. (Wrist: AUC 0.790; 95% CI: 0.725-0.854, P<0.001; forehead: AUC 0.816; 95% CI: 0.757-0.876, P <0.001). The cut-off value of the wrist measurement for detecting a tympanic temperature of ≥37.3 °C was 36.2 °C, with 86.4% sensitivity and 67.0% specificity, and the best threshold for the forehead measurement was 36.2 °C, with 93.2% sensitivity and 60.0% specificity.CONCLUSION:Wrist measurements are more stable than forehead measurements under different circumstances. Both measurements have favorable fever screening abilities in indoor patients. The cut-off values were both 36.2 °C.

Aims: Temperature screening is important in the population during the outbreak of 2019 Novel Coronavirus (COVID-19). This study aimed to compare the accuracy and precision of wrist and forehead temperature with tympanic temperature under different circumstances. Methods: We performed a prospective observational study in a real-life population. We consecutively collected wrist and forehead temperatures in Celsius (C) using a non-contact infrared thermometer (NCIT). We also measured the tympanic temperature using a tympanic thermometers (IRTT) and defined fever as a tympanic temperature ≥37.3C. Results: We enrolled a total of 528 participants including 261 indoor and 267 outdoor participants. We divided outdoor participants into four types according to their means of transportation to the hospital as walk, bicycle, electric vehicle, car, and inside the car. Under different circumstance, the mean difference ranged from -1.72 to -0.56C in different groups for the forehead measurements, and -0.96 to -0.61C for the wrist measurements. Both measurements had high fever screening abilities in inpatients (wrist: AUC 0.790; 95% CI: 0.725-0.854, P <0.001; forehead: AUC 0.816; 95% CI: 0.757-0.876, P <0.001). The cut-off value of wrist measurement for detecting tympanic temperature ≥37.3C was 36.2C with a 86.4% sensitivity and a 67.0% specificity, and the best threshold of forehead measurement was also 36.2C with a 93.2% sensitivity and a 60.0% specificity. Conclusions: Wrist measurement is more stable than forehead measurement under different circumstance. Both measurements have great fever screening abilities for indoor patients. The cut-off value of both measurements was 36.2C.

Background We performed this systematic review and pooled analysis to assess the effectiveness and safety of different endoscopic resection methods for 10- to 20-mm non-pedunculated colorectal polyps. Methods Articles in PubMed, EMBASE, and the Cochrane Library related to the common endoscopic treatment of 10- to 20-mm non-pedunculated polyps published as of April 2020 were searched. Primary outcomes were the complete resection rate (CRR) and the en bloc resection rate (EBRR). Secondary outcomes were safety and the recurrence rate. Meta-regression and subgroup analysis were also performed. Results A total of 36 studies, including 3212 polyps were included in the final analysis. Overall, the efficacy of resection methods with a submucosal uplifting effect, including endoscopic mucosal resection (EMR), cold EMR and underwater EMR, was better than that of non-submucosal uplifting methods [CRR 90% (95% CI 0.81–0.94, I2=84%) vs 82% (95% CI 0.78–0.85, I2=0%); EBRR 85% (95% CI 0.79–0.91, I2=83%) vs 74% (95% CI 0.47–0.94, I2=94%)] (figure 1). In terms of safety, the pooled data showed that hot resection (hot snare polypectomy and EMR) had a higher risk of early bleeding compared to cold resection [3% (95% CI 0.01–0.05, I2=68%) vs 0% (95% CI 0–0.01, I2=0%)], while the incidence of perforation and polypectomy were both low. Critical heterogeneity was observed in the main outcomes. Conclusions Methods with submucosal uplifting effects for 10- to 20-mm non-pedunculated colorectal polyps are more effective, and cold resection may be safer. Additional research is needed to prove the advantages of these methods, especially cold EMR, in this area.

Background: Recent studies have shown that microRNA-99a(miR-99a)plays a key role in the development of virious malignancies; however, its relationship with gastric cancer remains unclear. In this study, we investigated the functions and potential mechanisms of miR-99a in gastric cancer. Methods: Real-time qRT-PCR was used to assess the expression levels of miR-99a in gastric cancer tissue samples and cell lines compared to their matched adjacent normal tissues and a normal gastric mucosa epithelial cell line, respectively. SGC-7901 cells were transfected with miR-99a mimics and negative controls to determine the effects of miR-99a overexpression on cell proliferation, cell cycle transition, migration and invasion of gastric cancer cells in vitro . The role of miR-99a in endogenous c-Src expression in gastric cancer cells was also investigated by qRT-PCR and Western blotting. Results: Our results showed a significant increase in miR-99a expression in both gastric cancer tissues and cells compared to normal tissues and cells. Overexpression of miR-99a significantly promoted the cell proliferation, migration and invasion of gastric cancer cells compared to normal cells, with a concurrent increase in the S+G2 phases of the cell cycle. Further investigations found that miR-99a overexpression led to significant upregulation of endogenous c-Src. Conclusion: Taken together, our findings suggest that miR-99a may act as a tumour promoter in the pathogenesis of gastric cancer by indirectly modulating c-Src expression.