Pepsinogen II and a no-pickled food diet are risk factors for female patients with anxiety: a cross-sectional study.

OBJECTIVES: No studies have evaluated the relationship between lifestyle and Pepsinogen (PG)I, PGII and Gastrin (G)17 in patients with anxiety. Using data from the Affiliated Hospital of Xuzhou Medical University study, we aimed to identify factors associated with anxiety. METHODS: We conducted a retrospective cross-sectional observational study involving 779 Chinese healthy checkup participants (301 males; mean age, 47.60±16.17 years) who underwent stomach-related health examinations. RESULTS: Anxiety was defined as a Hamilton Anxiety Scale (HAM-A) Scale score ≥14. The odds ratios, with 95% confidence intervals, were calculated using binary logistic analysis to assess the risk of anxiety and healthy checkup participants while adjusting for several covariates. In the HAM-A≥14 group (anxiety group), sex, PGII and pickled dishes were independent influencing factors. Binary logistic regression analysis revealed a significant difference in anxiety risk between the high PGII group and the low PGII group for females (P=0.005). There was also a significant difference in anxiety risk between the groups consuming pickled and non-pickled food for females (P=0.010). Logistic regression analysis indicated a higher risk of anxiety in females aged ≤50 years who belonged to the high PGII + no pickled foods group. CONCLUSIONS: Our study revealed that in females aged ≤50 years, high levels of PGII and no pickled foods were associated with a higher risk of anxiety.

The relationship between inflammatory cytokines and in-hospital complications of acute pancreatitis.

OBJECTIVE: Acute necrotic collection (ANC), acute peripancreatic fluid collection (APFC), pleural effusion, and ascites are common early complications of acute pancreatitis. This study aimed to investigate the relationship between 12 serum cytokines and the early complications and severity of acute pancreatitis (AP). METHODS: We retrospectively analyzed the clinical data of 307 patients with AP, and divided them into severe group and mild-to-moderate group according to the revised Atlanta classification. Propensity score matching was used to control for confounding factors. Binary logistic regression analysis was used to explore the relationship between cytokine levels and early complications of AP. RESULTS: Serum levels of interleukin (IL)-1ß, IL-5, IL-6, IL-8, IL-10, IL-17, and tumor necrosis factor-α were significantly higher in the severe acute pancreatitis (SAP) group than in the non-SAP group (p < .05). After adjusting for confounding factors, the upper quartiles of IL-6, IL-8, and IL-10 were associated with an increased risk of ANC compared with those in the lowest quartile (IL-6: quartile 3, odds ratio [OR] = 3.99, 95% confidence interval [CI] = 1.95-8.16; IL-8: quartile 4, OR = 2.47, 95% CI = 1.27-4.84; IL-10: quartile 2, OR = 2.22, 95% CI = 1.09-4.56). APFC was associated with high serum levels of IL-6 (quartile 3, OR = 1.32, 95% CI = 1.02-1.72), pleural effusions were associated with high serum levels of IL-1ß, IL-6, IL-8, and IL-10 (IL-1ß: quartile 4, OR = 2.36, 95% CI = 1.21-4.58; IL-6: quartile 3, OR = 4.67, 95% CI = 2.27-9.61; IL-8: quartile 3, OR = 2.95, 95% CI = 1.51-5.79; IL-10: quartile 4, OR = 3.20, 95% CI = 1.61-6.36), and high serum levels of IL-6 and IL-10 were associated with an increased risk of ascites (IL-6: quartile 3, OR = 3.01, 95% CI = 1.42-6.37; IL-10: quartile 3, OR = 2.57, 95% CI = 1.23-5.37). CONCLUSION: Serum cytokine levels, including IL-1ß, IL-6, IL-8, and IL-10 may be associated with the occurrence of early complications of AP. In daily clinical practice, IL-6 may be the most worthwhile cytokine to be detected.

The value of machine learning approaches in the diagnosis of early gastric cancer: a systematic review and meta-analysis.

BACKGROUND: The application of machine learning (ML) for identifying early gastric cancer (EGC) has drawn increasing attention. However, there lacks evidence-based support for its specific diagnostic performance. Hence, this systematic review and meta-analysis was implemented to assess the performance of image-based ML in EGC diagnosis. METHODS: We performed a comprehensive electronic search in PubMed, Embase, Cochrane Library, and Web of Science up to September 25, 2022. QUADAS-2 was selected to judge the risk of bias of included articles. We did the meta-analysis using a bivariant mixed-effect model. Sensitivity analysis and heterogeneity test were performed. RESULTS: Twenty-one articles were enrolled. The sensitivity (SEN), specificity (SPE), and SROC of ML-based models were 0.91 (95% CI: 0.87-0.94), 0.85 (95% CI: 0.81-0.89), and 0.94 (95% CI: 0.39-1.00) in the training set and 0.90 (95% CI: 0.86-0.93), 0.90 (95% CI: 0.86-0.92), and 0.96 (95% CI: 0.19-1.00) in the validation set. The SEN, SPE, and SROC of EGC diagnosis by non-specialist clinicians were 0.64 (95% CI: 0.56-0.71), 0.84 (95% CI: 0.77-0.89), and 0.80 (95% CI: 0.29-0.97), and those by specialist clinicians were 0.80 (95% CI: 0.74-0.85), 0.88 (95% CI: 0.85-0.91), and 0.91 (95% CI: 0.37-0.99). With the assistance of ML models, the SEN of non-specialist physicians in the diagnosis of EGC was significantly improved (0.76 vs 0.64). CONCLUSION: ML-based diagnostic models have greater performance in the identification of EGC. The diagnostic accuracy of non-specialist clinicians can be improved to the level of the specialists with the assistance of ML models. The results suggest that ML models can better assist less experienced clinicians in diagnosing EGC under endoscopy and have broad clinical application value.

The efficacy and safety of fexuprazan in treating erosive esophagitis: a phase III, randomized, double-blind, multicenter study.

BACKGROUND AND AIM: Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in treating erosive esophagitis (EE). METHODS: This was a phase III, randomized, double-blind multicenter study. Patients with endoscopically confirmed EE were randomized to receive fexuprazan 40 mg or esomeprazole 40 mg once a daily for 4-8 weeks. The healing rates of EE, symptom response, GERD-health-related quality life (GERD-HRQL), and treatment-emergent adverse events (TEAEs) were compared between fexuprazan group and esomeprazole group. RESULTS: A total of 332 subjects were included in full analysis set (FAS) and 311 in per-protocol set (PPS). The healing rates of fexuprazan and esomeprazole groups at 8 weeks were 88.5% (146/165) and 89.0% (145/163), respectively, in FAS and 97.3% (145/149) and 97.9% (143/146), respectively, in PPS. Noninferiority of fexuprazan compared with esomeprazole according to EE healing rates at 8 weeks was demonstrated in both FAS and PPS analysis. No significant difference was found between groups in EE healing rates at 4 weeks, symptom responses, and changes of GERD-HRQL. The incidence of drug-related AEs was 19.4% (32/165) in fexuprazan arm and 19.6% (32/163) in esomeprazole arm. CONCLUSION: This study demonstrated noninferior efficacy of fexuprazan to esomeprazole in treating EE. The incidence of TEAEs was similar between fexuprazan and esomeprazole. Trial registration number NCT05813561.

A sensitive and robust plasma-based DNA methylation panel for early detection of target gastrointestinal cancers.

BACKGROUND: Target gastrointestinal cancers (GICs), encompassing esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC), originate within a single readily accessible luminal organ system and are diagnosable using endoscopy. However, endoscopy is an invasive procedure with low compliance and no plasma-based DNA methylation assay for the early detection of GICs. METHODS: Nine potential DNA methylation markers were identified and evaluated in tissue (n=60) and plasma (n=155) cohorts to select the most suitable markers. A training cohort (n=244) and a validation cohort (n=199), including GICs patients, benign tumors, gastrointestinal polyps, and controls, were enrolled to develop and validate a DNA methylation panel. An independent prospective cohort (n=158) was used to validate the panel's performance and compare it with blood protein tumor markers. RESULTS: Six out of nine candidate methylation markers with excellent discrimination abilities in both tissue and plasma cohorts were selected for the DNA methylation panel. The panel demonstrated high AUC values of 0.937 (EC), 0.968 (GC), and 0.987 (CRC) in training cohort, and achieved AUC values of 0.921 (EC), 0.921 (GC), and 0.959 (CRC) in validation cohort. Notably, it achieved impressive AUC values of 0.971 and 0.843 for identifying stage I GICs in the training and validation cohorts, respectively. In the prospective cohort, the six-marker panel showed comparable AUC values to CEA, AFP, and CA19-9 (0.935, 0.769, 0.663, and 0.668, respectively). CONCLUSION: This study successfully developed and validated a novel, robust, sensitive, and specific plasma-based DNA methylation panel, offering a promising strategy for the early detection of GICs.

A Cuproptosis-Related LncRNA Risk Model for Predicting Prognosis and Immunotherapeutic Efficacy in Patients with Hepatocellular Carcinoma.

Cuproptosis is a novel programmed cell death pathway that is initiated by direct binding of copper to lipoylated tricarboxylic acid (TCA) cycle proteins. Recent studies have demonstrated that cuproptosis-related genes regulate tumorigenesis. However, the potential role and clinical significance of cuproptosis-related long noncoding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) have not been established. We performed a bioinformatics analyses of RNA-sequencing data of HCC patients extracted from The Cancer Genome Atlas (TCGA) dataset to identify and validate a cuproptosis-related lncRNA prognostic signature. Furthermore, we analyzed the clinical significance of the prognostic signature of cuproptosis-related lncRNA in predicting the immunotherapeutic efficacy and the status of the tumor immune microenvironment. The RNA-sequencing data, genomic mutations, and clinical information were downloaded for 374 HCC samples and 50 normal liver samples from TCGA-Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset. Co-expression analysis of Gene-lncRNA pairs with 49 known cuproptosis-related prognostic genes was used to define cuproptosis-related prognostic lncRNAs. We performed the LASSO algorithm and univariate and multivariate Cox regression analysis, respectively, to gradually identify the prognostic risk models of cuproptosis-related lncRNA based on the TCGA-LIHC dataset. Subsequently, the predictive performance of the model was evaluated using receiver operation characteristic (ROC) curves, Kaplan-Meier survival curves, and prognostic nomogram. The analysis of gene-lncRNA co-expression with 49 known cuproptosis-related genes identified 1359 cuproptosis-related lncRNAs in the TCGA-LIHC data set. A prognostic model was constructed with nine cuproptosis-related prognostic lncRNAs (AC007998.3, AC003086.1, AC009974.2, IQCH-AS1, LINC0256 1, AC105345.1, ZFPM2-AS1, AL353708.1 and WAC-AS1) using LASSO regression and Cox regression analyses. Risk scores were calculated for all HCC patient samples based on the four cuproptosis-related lncRNA prognostic models. All HCC patients were divided into high-risk and low-risk subgroups according to a 1:1 ratio column. The Kaplan-Meier survival curve analysis showed that the overall survival rate (OS) of the high-risk group patients was significantly lower than that of the low-risk group. The principal component analysis (PCA) confirmed that the prognostic lncRNA model accurately distinguished between high- and low-risk HCC patients. Furthermore, regression analysis as well as ROC curves confirmed the prognostic value of the risk score. A nomogram with risk scores and other clinicopathological characteristics was constructed. The nomogram accurately predicted the probability of 1-, 3-, and 5-year OS in HCC patients. Tumor mutation burden (TMB) scores were higher for high-risk patients than for low-risk patients. HCC patients in the low-risk group showed lower TIDE scores and greater sensitivity to antitumor drugs than those in the high-risk group. Tumor immune responses and tumor immune cell infiltration were significantly different between the high-risk and low-risk groups of patients with HCC. Our study identified a 9-cuproptosis-related lncRNA signature that accurately predicted prognosis, immunotherapeutic efficacy, and the status of the tumor immune microenvironment in HCC patients. Therefore, this cuproptosis-related lncRNA risk model is a potential prognostic biometric feature in HCC and shows high clinical value in identifying HCC patients who are potentially responsive to immunotherapy.

Construction and validation of a prognostic nomogram for predicting cancer-specific survival in patients with intermediate and advanced colon cancer after receiving surgery and chemotherapy.

BACKGROUND: Existing predictive models often focus solely on overall survival (OS), neglecting the bias that other causes of death might introduce into survival rate predictions. To date, there is no strict predictive model established for cancer-specific survival (CSS) in patients with intermediate and advanced colon cancer after receiving surgery and chemotherapy. METHODS: We extracted the data from the Surveillance, Epidemiology, and End Results (SEER) database on patients with stage-III and -IV colon cancer treated with surgery and chemotherapy between 2010 and 2015. The cancer-specific survival (CSS) was assessed using a competitive risk model, and the associated risk factors were identified via univariate and multivariate analyses. A nomogram predicting 1-, 3-, and 5-year CSS was constructed. The c-index, area under the curve (AUC), and calibration curve were adopted to assess the predictive performance of the model. Additionally, the model was externally validated. RESULTS: A total of 18 risk factors were identified by univariate and multivariate analyses for constructing the nomogram. The AUC values of the nomogram for the 1-, 3-, and 5-year CSS prediction were 0.831, 0.842, and 0.848 in the training set; 0.842, 0.853, and 0.849 in the internal validation set; and 0.815, 0.823, and 0.839 in the external validation set. The C-index were 0.826 (se: 0.001), 0.836 (se: 0.002) and 0.763 (se: 0.013), respectively. Moreover, the calibration curve showed great calibration. CONCLUSION: The model we have constructed is of great accuracy and reliability, and can help physicians develop treatment and follow-up strategies that are beneficial to the survival of the patients.

Effect of COP1 in Promoting the Tumorigenesis of Gastric Cancer by Down-Regulation of CDH18 via PI3K/AKT Signal Pathway.

In recent years, the involvement of E3 ubiquitin ligase constitutive photomorphogenesis 1 (COP1) in the tumorigenesis of gastric cancer (GC) has been elucidated. However, the exact underlying mechanism remains to be clarified. In the present study, the expression profiles of COP1 in GC were derived from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases, followed by verification via immunohistochemical staining (IHC), Western blotting (WB), and quantitative real-time polymerase chain reaction (qRT-PCR) reaction assays on clinical samples. In vitro, the gain- and loss-of-function experiments of COP1 protein were conducted to explore its role in GC cell lines HGC-27 and SGC-7901. Furthermore, we screened the interaction protein of COP1 by yeast two-hybrid experiment and verified their combination by co-immunoprecipitation (co-IP). We preliminary explored the possible underlying mechanisms of COP1 protein in GC cell lines via WB. COP1 was upregulated in GC tissues compared with the corresponding non-carcinoma tissues. In vitro, the upregulation of COP1 protein promoted the proliferation and migration of GC cells. The yeast two-hybrid experiment and co-IP indicated that Cadherin 18 (CDH18) could constitute a complex with COP1. Moreover, cells with COP1 over-expression showed low levels of CDH18 expression, with the intracellular PI3K/AKT pathway activated and the malignancy of GC cell lines enhanced. Our findings demonstrated that COP1 promoted the GC tumorigenesis by downregulated CDH18 with the involvement of PI3K/AKT signaling pathway in cell lines, suggesting the potential of COP1 as a prognostic biomarker and therapeutic target for GC.

PUS7 promotes the proliferation of colorectal cancer cells by directly stabilizing SIRT1 to activate the Wnt/ß-catenin pathway.

Pseudouridine synthase 7 (PUS7) may play key roles in cancer development. However, few studies have been conducted in this area. In the present study, we explored the function and potential mechanisms of PUS7 in colorectal cancer (CRC) progression. We found that PUS7 had higher expression in CRC tissues and cell lines. Clinically, high expression of PUS7 was associated with an unfavorable prognosis for CRC patients. Functionally, knockdown of PUS7 suppressed the proliferation of CRC cells in vitro and inhibited tumorigenicity in vivo. Mechanistically, RNA sequencing and coimmunoprecipitation (Co-IP) indicated that PUS7 exhibited oncogenic functions through the interaction of Sirtuin 1 (SIRT1) and activated the Wnt/ß-catenin signaling pathway. Thus, our findings suggest that PUS7 promotes the proliferation of CRC cells by directly stabilizing SIRT1 to activate the Wnt/ß-catenin pathway.

A Novel Plasma-Based Methylation Panel for Upper Gastrointestinal Cancer Early Detection.

BACKGROUND: Upper gastrointestinal cancer (UGC) is an important cause of cancer death in China, with low five-year survival rates due to the majority of UGC patients being diagnosed at an advanced stage. Therefore, there is an urgent need to develop cost-effective, reliable and non-invasive methods for the early detection of UGC. METHODS: A novel plasma-based methylation panel combining simultaneous detection of three methylated biomarkers (ELMO1, ZNF582 and TFPI2) and an internal control gene were developed and used to examine plasma samples from 186 UGC patients and 190 control subjects. RESULTS: The results indicated excellent PCR amplification efficiency and reproducibility of ELMO1, ZNF582 and TFPI2 in the range of 10-100,000 copies per PCR reaction of fully methylated genomic DNA. The methylation levels of ELMO1, ZNF582 and TFPI2 were significantly higher in UGC samples than those in control subjects. The sensitivities of ELMO1, ZNF582 and TFPI2 alone for UGC detection were 32.3%, 61.3% and 30.6%, respectively; when three markers were combined, the sensitivity was improved to 71.0%, with a specificity of 90.0%, and the area under the curve (AUC) was 0.870 (95% CI: 0.832-0.902). CONCLUSION: Methylated ELMO1, ZNF582 and TFPI2 were specific for UGC and the three-methylated gene panel provided an alternative non-invasive choice for UGC early detection.

A simplified multiplex methylated DNA testing for early detection of colorectal cancer in stool DNA.

BACKGROUND: ColoDefense1.0 assay has demonstrated its excellent sensitivity and specificity for early detection of colorectal cancer (CRC) by detecting the methylation levels of SDC2 and SEPT9, while exhibited limitations on relatively large sample capacity required and limited detection throughput by applying triplicate PCR reactions for each sample. In this study, ColoDefense1.0 was simplified and optimized into ColoDefense2.0 in a single PCR reaction. METHODS: A total 529 stool specimens were collected, and 244 CRC patients, 34 patients with advanced adenomas (AA), 64 with small polyps (SP) and 187 control subjects were divided in training and validation cohorts. Methylation levels of SEPT9 and SDC2 were examined by qPCR reactions in triplicate or single. RESULTS: The stool DNA quantity stored in preservative buffer at 37 °C up to 7 days exhibited no significant decrease. In the training cohort, when the number of replicates reduced from 3 to 1, the overall performance of ColoDefense2.0 was identical to that of ColoDefense1.0, showing sensitivities of 71.4% for AA and 90.8% for all stage CRC with a specificity of 92.9%. In the validation cohort, sensitivities of SP, AA and CRC using ColoDefense2.0 were 25.0%, 55.0% and 88.2%, increased from 14.1% (20.3%), 40.0% (40.0%) and 79.4% (67.6%) using SDC2 (SEPT9) alone; along with an overall specificity of 90.2%, decreased from 94.1% (95.1%) using SDC2 (SEPT9) alone. CONCLUSION: The simplified ColoDefense test maintained the overall performance while reduced the number of PCR reactions to 1/3, and provided an effective and convenient tool to detect early CRC and precancerous lesions and potentially improve the compliance of screening.

Feasibility and reproducibility of a plasma-based multiplex DNA methylation assay for early detection of gastric cancer.

BACKGROUND: Gastric cancer (GC) is a leading cause of cancer death and an important barrier to increasing life expectancy in China. Early detection of GC can significantly reduce its mortality rate. METHODS: A new plasma-based multiplex DNA methylation assay combining simultaneous detection of three biomarkers (KCNQ5, C9orf50 and CLIP4) and one control gene (ACTB) was developed. It was used to examine 12 paired tissue samples and a training cohort of 151 plasma samples. Its performance was subsequently confirmed in validation cohort 1 (n = 105) and validation cohort 2 (n = 139). RESULTS: Three methylation markers showed significantly higher methylation levels in GC tissues than in paired adjacent tissues. The assay showed a sensitivity of 67.9 % with a specificity of 86.6 % for GC detection in the training cohort, and the AUC was 0.786 (95 % CI: 0.701-0.855). The methylation levels in GC patients were significantly higher than those in benign gastric tumors and in control group. Meanwhile, the assay achieved a sensitivity of 65.5 % with a specificity of 90.0 % in the validation cohort 1, and the AUC was 0.805 (95 % CI: 0.716-0.876). In the validation cohort 2, its sensitivity and specificity were 73.7 % and 84.1 %, respectively, and the AUC was 0.851 (95 % CI: 0.776-0.909). CONCLUSION: The plasma-based multiplex DNA methylation assay was highly specific for GC early detection. It has the potential to become an alternative approach to improve diagnosis of GC in the clinics.

The involvement of Pellino-1 downregulation in the modulation of visceral hypersensitivity via the TLR4/NF-κB pathway in the rat fastigial nucleus.

Irritable bowel syndrome (IBS) is a common functional bowel disorder whose key characteristics include chronic visceral hypersensitivity (CVH) and abnormal brain-gut interactions. Pellino-1 is an E3 ubiquitin ligase, mediating the degradation or modification of targeted proteins. Some brain regions, such as the fastigial nucleus (FN), may play important roles in CVH; however, the molecular mechanism underlying this phenomenon is not clear. In this study, we assessed the roles of Pellino-1 within the FN in modulating VH by generating a colorectal distention (CRD) model in male Sprague-Dawley rats. Our results showed that the downregulation of Pellino-1 in the fastigial nucleus (FN) was involved in the modulation of visceral hypersensitivity. The expression of Pellino-1 was downregulated in the FN of adult CRD rats compared with control rats, whereas TLR4 and NF-κB were upregulated in the CRD model. To overexpress Pellino-1, a lentivirus specifically expressing Pellino-1 and green fluorescent protein was administered into the FN. The overexpression of Pellino-1 increased the visceral sensitivity of CRD rats, and the expression of TLR4 and NF-κB increased further. After administration of TAK-242 (a specific TLR4 inhibitor), the visceral response to overexpression of Pellino-1 was reversed. Overall, the findings indicated the involvement of the FN in the development of CVH; the downregulation of Pellino-1 in the FN acted through the TLR4/NF-κB pathway to protect against CVH in a CRD rat model.

Low serum pepsinogen II levels are closely linked with a risk of metabolic syndrome among healthy individuals with asymptomatic Helicobacter pylori infection: a cross-sectional study.

Aim:Helicobacter pylori (Hp) infection has a connection with metabolic syndrome (MetS). Pepsinogen II (PGII) is a marker for gastric epithelial function. The present research was aimed at determining the associations among serum PGII levels, Hp infection and MetS in healthy subjects. Methods: This cross-sectional study enrolled 1242 healthy people, including 545 subjects with asymptomatic Hp infection and 697 subjects without Hp infection. Based on the number of MetS components present, subjects with Hp infection were assigned to the following groups: group 1, no component (126 subjects); group 2, one or two components (260 subjects); and group 3, three or more components (159 subjects). Physical measurements and biochemical indices were recorded. Serum PGII levels were recorded using ELISA. SPSS and GraphPad Prism were used for statistical analyses. Results: Among subjects with Hp infection, serum PGII was evidently downregulated in group 3 compared with group 1 (14.95 ± 8.24 vs 17.97 ± 9.08 µg/l; p = 0.015). Serum PGII levels were correlated with an increased risk of MetS (odds ratio: 0.867; 95% CI: 0.772-0.974; p = 0.016), as indicated by the multivariate logistic regression analysis. Grouping subjects with Hp infection according to quartiles of serum PGII levels identified an evident difference in MetS prevalence among the four quartile-based groups (p = 0.047). Conclusions: Among healthy subjects with asymptomatic Hp infection, serum PGII levels were lower in those with MetS than in those without MetS. Serum PGII levels showed an independent and negative correlation with the risk of MetS in healthy subjects with Hp infection.

The Effect of Linked Color Imaging for Adenoma Detection. A Meta-analysis of Randomized Controlled Studies.

BACKGROUND AND AIMS: The effect of linked color imaging (LCI) compared with white light imaging (WLI) is conflicting. The aim of this meta-analysis is to compare the efficacy of LCI versus WLI for the adenoma detection. METHODS: PubMed, Embase, Google Scholar and Cochrane Library were searched up to the end of Aug 18, 2021. All randomized controlled trials (RCTs) comparing LCI with WLI were included. Dichotomous data were pooled to obtain the relative risk (RR) with a 95% confidence interval (CI), whereas continuous data were pooled using a mean difference (MD) with 95%CI. RESULTS: A total of 10 RCTs involving 5,510 patients were included. The use of LCI was associated with a statistically significant improvement in adenoma detection rate (ADR), polyp detection rate (PDR), mean adenomas per patient (MAP) and mean polyp per patient (MPP) when compared to WLI (ADR: RR=1.15, 95%CI: 1.07-1.23, p=0.0001, PDR: RR=1.15, 95%CI: 1.08-1.22, p<0.0001; MAP: MD=0.18, 95%CI: 0.09- 0.28, p=0.0002; MPP: MD=0.13, 95%CI: 0.01, 0.25, p=0.03). When stratified by size, LCI group had a higher detection rate of small adenomas (<10 mm) than the WLI group. Besides, LCI showed a significant decrease in adenoma miss rate (AMR) when compared to WLI. There were no statistically significant differences between the two groups in advanced ADR (AADR), sessile serrated lesion detection rate (SDR), cecal intubation rate, insertion time, and withdrawal time. CONCLUSIONS: The pooled evidence suggests that LCI can significantly improve the detection of ADR, especially for small adenomas (<10 mm). Moreover, the AMR were significantly lower using LCI compared with WLI.

The Efficacy of Simethicone With Polyethylene Glycol for Bowel Preparation: A Systematic Review and Meta-Analysis.

BACKGROUND: Simethicone (SIM) is a commonly used antifoaming agent in the clinic. However, it has not been clarified whether SIM can improve the quality of intestinal preparation and the detection rates of adenomas (ADR) and polyps (PDR). This systematic review and meta-analysis were carried out to mainly evaluate the effect of SIM in bowel preparation for colonoscopy. MATERIALS AND METHODS: An electronic and a manual search of the literature for studies was conducted in PubMed, EMBASE, and Web of Science in all published data before February 1, 2020. The primary outcomes were the quality of bowel preparation and the ADR and PDR. All the data were calculated using a pooled estimate of risk ratio with 95% confidence intervals, and a random-effect model was used for the calculation. RESULTS: Eighteen randomized controlled trials with 7187 patients were included in this meta-analysis. Polyethylene glycol (PEG) with SIM improved colon cleansing (P<0.00001), PDR (P=0.006) and the detection rate of lesions in the right colon (P<0.00001) when compared with PEG alone. There was no difference in the ADR (P=0.68), withdrawal time (P=0.06), cecal intubation rate (P=0.98), and cecal intubation time (P=0.65) between 2 groups. The rate of abdominal bloating rate was higher in the PEG group, but there was no significant difference in vomiting (P=0.65), and abdominal pain (P=0.25). CONCLUSIONS: SIM improves the quality of bowel cleanliness and PDR but not ADR. Besides, SIM improves the detection rate of lesions in the right colon and decreased abdominal bloating, but do not affect vomiting and abdominal pain or cramping.

Protective effect of HCN2-induced SON sensitization on chronic visceral hypersensitivity in neonatal-CRD rat model.

Abnormal brain-gut interactions contribute to the development of chronic visceral hypersensitivity (CVH), which is the pivotal feature of irritable bowel syndrome (IBS). Despite the consensus with respect to the vital role of hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) channels in promoting painful symptoms in the peripheral nervous system, we identified that the upregulation of HCN2 in supraoptic nucleus (SON) was involved in the modulation of CVH in rat model of neonatal colorectal distention (n-CRD). Specifically, colorectal distention (CRD) upregulated the expression of c-Fos in SON in adult CVH rats, indicating the involvement of SON sensitazation in visceral sensation. Moreover, the administration of ZD7288 (the pan-HCN channel inhibitor) rather than 8-Br-cAMP (the non-specific HCN channel agonist) aggravated the CVH symptoms and reduced the phosphorylation level of CaMKII-CREB cascade. Together, the findings indicated that the upregulation of supraoptic HCN2 contributed to the sensitization of SON, which had protective effects on the modulation of CVH with the involvement of CaMKII-CREB cascade in n-CRD rat model.

Feasibility of Methylated CLIP4 in Stool for Early Detection of Colorectal Cancer: A Training Study in Chinese Population.

BACKGROUND: Early detection of colorectal cancer (CRC) and precancerous lesion is vitally important for mitigating CRC morbidity and mortality. Aberrant DNA methylations in certain promoter regions have been identified to be closely associated with CRC development and progression, suggesting their potential as diagnostic biomarkers for early detection. In this study, we evaluated the performance of methylated CLIP4 in stool specimens as a potential biomarker for CRC detection. METHODS: A total of 321 subjects out of 365 enrolled participants were included in the final analysis, including 154 CRC patients, 23 advanced adenoma (AA) patients, 49 small polyp (SP) patients, and 95 healthy controls. CLIP4 methylation level was examined by qPCR with bisulfite converted DNA purified from approximately 5 g stool specimen. RESULTS: Methylated CLIP4 test showed high sensitivities of 78.3% (95% CI: 55.8%-91.7%) and 90.3% (95% CI: 84.2%-94.3%) for detecting AA and CRC, respectively, with a specificity of 88.4% (95% CI: 79.8%-93.8%). CLIP4 methylation level discriminated AA and CRC patients from control subjects with area under the curve values of 0.892 (95% CI: 0.795-0.988) and 0.961 (95% CI: 0.938-0.983). Further analysis indicated no significant difference in sensitivities among different ages, genders, stages, locations, sides, tumor sizes and differentiation statuses. CONCLUSIONS: Methylated CLIP4 showed a strong potential as a noninvasive biomarker for early CRC detection.

Blood leukocytes methylation levels analysis indicate methylated plasma test is a promising tool for colorectal cancer early detection.

Background: A number of plasma methylated DNA biomarkers related to colorectal cancer (CRC) have been identified. However, the effect of methylation level in leukocytes on plasma-based methylation test was rarely reported. Methods: Blood samples from 213 individuals including 91 CRC patients were collected and separated into 3.5 mL of plasma and paired leukocyte fractions. DNA were extracted from plasma and leukocytes and bisulfite converted, followed by ColoDefense test that detects methylated SEPT9 (mSEPT9) and methylated SDC2 (mSDC2) simultaneously in a single qPCR reaction. Results: Both mSEPT9 and mSDC2 levels in leukocytes exhibited no significant difference among CRC, benign tumors and healthy controls. However, mSEPT9 and mSDC2 levels in plasma were significantly higher in CRC group than those in other groups. The sensitivities of mSEPT9 and mSDC2 alone for detecting CRC with plasma samples were 75.8% and 60.4% with specificities of 94.7% and 86.8%, respectively. These two markers in combination exhibited an improved sensitivity of 85.7% for CRC detection with a specificity of 86.8%, mostly attributable to increased sensitivity of 81.8% for detecting stage 0-II CRC. AUC values for mSEPT9 and mSDC2 alone were 0.864 (95% CI: 0.798 - 0.929) and 0.796 (95% CI: 0.719 - 0.874), respectively, but improved to 0.972 (95% CI: 0.949 - 0.996) when combined for ColoDefense test. Conclusions: The leukocytes gDNA will not affect the performance of plasma ColoDefense test, and plasma ColoDefense test exhibited high sensitivity and specificity in a validation set, demonstrating its potential as a non-invasive and cost-effective method for CRC early detection.

Methylated SFRP2 and SDC2 in stool specimens for Colorectal Cancer early detection: A cost-effective strategy for Chinese population.

Background: The aim of this study was to evaluate the feasibility of combination of methylated SFRP2 and methylated SDC2 (SpecColon test) in stool specimens for colorectal cancer (CRC) early detection and to optimize the cut-off value of methylated SFRP2 and methylated SDC2. Methods: Approximately 5 g of stool specimen each was collected from 420 subjects (291 in the training cohort and 129 in the validation cohort). Stool DNA was extracted and bisulfite-converted, followed by detection of methylated level of SFRP2 and SDC2. Youden index was employed to determine the cut-off value. Results: The whole operating time for stool SpecColon test takes less than 5 hours. The limit of detection of combination of methylated SFRP2 and methylated SDC2 was as low as 5 pg per reaction. The optimized cut-off value was methylated SFRP2 analyzed by 3/3 rule and methylated SDC2 analyzed by 2/3 rule. In the training cohort, the sensitivities of stool SpecColon test for detecting AA and early stage CRC (stage 0-II) were 53.8% (95% CI: 26.1%-79.6%) and 89.1% (95% CI: 77.1%-95.5%) with a specificity of 93.5% (95% CI: 87.2%-96.9%), and the AUC for CRC diagnosis was 0.879 (95% CI: 0.830-0.928). Similar performance was achieved by SpecColon test also in the validation cohort, where its sensitivities for detecting AA and early stage CRC (stage 0-II) were 61.5% (95% CI: 32.3-84.9%) and 88.5% (95% CI: 68.5%-97.0%) with a specificity of 89.5% (95% CI: 74.3-96.7%). Conclusion: Combined detections of methylated SFRP2 and methylated SDC2 in stool samples demonstrated high sensitivities and specificity for the detection of AA and early stage CRC. Therefore, this combination has the potential to become an accurate and cost-effective tool for CRC early detection.