Genomic Characteristics of a Carbapenem-Resistant Klebsiella pneumoniae Co-Carrying bla NDM-5 and bla KPC-2 Capsular Type KL25 Recovered from a County Level Hospital in China.

Background: Hypervirulent carbapenem-resistant K. pneumoniae (hv-CRKP) has been spreading rapidly worldwide. Here, we investigated the genomic characteristics of ST11 K. pneumoniae isolate SM117 with capsular serotype KL25, co-carrying bla NDM-5, two copies of bla KPC-2 and multiple plasmid-borne virulence genes from a county level hospital in China. Methods: Antimicrobial susceptibility of K. pneumoniae SM117 was evaluated. The Illumina NovaSeq 6000 and Oxford Nanopore MinION platforms were applied to sequence the genome and then de novo assembled. The genome sequence was annotated using the NCBI Prokaryotic Genome Annotation Pipeline and further subjected to identify the sequence type (ST), capsular type, antibiotic resistance genes, plasmid replicon types and virulence genes. The phylogenetic analysis was performed based on the core genome single nucleotide polymorphisms (cgSNPs) using CSI Phylogeny 1.4, and further visualized by Interactive Tree of Life (iTOL) V5 web server. Results: The whole-genome sequence of K. pneumoniae SM117 is made up of eight contigs totaling 6,104,486 bp, contain a 5,612,620 bp single chromosome and seven plasmids. The isolate was assigned to ST11 with capsular serotype KL25, co-carrying including bla NDM-5, bla KPC-2 and multiple plasmid-borne virulence genes including rmpA2 and aerobactin genes iucABCD-iutA. The coexistence of bla KPC and bla NDM in K. pneumoniae strains exhibit a high degree of resistance to ß-lactam antibiotics. The strain SM117 also carries multiple antibiotic resistance genes, making it resistant to all antibiotics except polymyxin. The closest relative of K. pneumoniae C793 was identified in 2023 from a hospital surface sample in Zhejiang, China, with just 52 SNPs difference. Conclusion: This study reported the genomic characteristics of a multidrug-resistant ST11 K. pneumoniae with capsular serotype KL25, co-carrying bla NDM-5, two copies of bla KPC-2 genes and multiple plasmid-borne virulence genes in China. These findings will provide important knowledge of the antibiotic resistance mechanisms, genomic epidemiological characteristics and transmission dynamics of multidrug-resistant K. pneumoniae.

Tetracycline Three Times Daily Versus Four Times Daily in Bismuth-Containing Quadruple Therapy as the First-Line Treatment of Helicobacter pylori Infection: A Multicenter, Noninferiority, Randomized Controlled Trial.

BACKGROUND: Current guidelines recommend bismuth-containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth-containing quadruple therapy for first-line treatment of H. pylori infection. METHODS: This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment-naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth-containing quadruple therapies: esomeprazole 20 mg twice-daily; bismuth 220 mg twice-daily; amoxicillin 1000 mg twice-daily; and tetracycline 500 mg three times daily (TET-T) versus 500 mg four times daily (TET-F). At least 6 weeks post-treatment, a 13C-urea breath test was performed to evaluate H. pylori eradication. RESULTS: In total, 406 patients were randomly assigned to the two treatment groups. Intention-to-treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%-95.44%) versus 90.15% (183/203; 95% CI 86.05%-94.25%) (p = 0.0005) and per-protocol eradication rates were 95.34% (184/193; 95% CI 92.36%-98.31%) versus 95.72% (179/187; 95% CI 92.82%-98.62%) (p = 0.0002) for the TET-T and TET-F group, respectively. TET-T-treated patients had a lower incidence of adverse effects than TET-F-treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups. CONCLUSION: As a first-line therapy for H. pylori infection, the eradication rate of the TET-T therapy was noninferior to that of the TET-F therapy while significantly reducing the incidence of adverse reactions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05431075.

Associations between novel anthropometric indices and the prevalence of gallstones among 6,848 adults: a cross-sectional study.

Background: Traditional anthropometric measures, including body mass index (BMI), are insufficient for evaluating gallstone risk. This study investigated the association between novel anthropometric indices and gallstone risk among 6,848 participants from the National Health and Nutrition Examination Survey in the United States. Methods: Measures calculated included weight (WT), BMI, waist circumference (WC), waist-to-height ratio (WtHR), conicity index (CI), A Body Shape Index (ABSI), Body Roundness Index (BRI), Abdominal Volume Index (AVI), and Weight-adjusted Waist Index (WWI). Logistic regression and smooth curve fitting assessed the relationships between these indices and gallstones, complemented by receiver operating characteristic (ROC) curve analysis to evaluate their discriminative power. Results: The results indicated significant differences between study groups, with a positive and independent correlation identified between gallstones and all measures except ABSI. Specifically, per 1 SD increase in WC, WT, BMI, WtHR, and AVI was associated with a 57%, 59%, 52%, 53%, and 53% increased risk of gallstones, respectively. Dose-response analysis confirmed a positive correlation between these indices and gallstone risk. ROC analysis highlighted WtHR and BRI as having superior discriminative abilities (AUC = 0.6703). Further, among participants with a BMI < 30 kg/m2, elevated levels of WT, WtHR, CI, BRI, and WWI significantly increased the risk of gallstones (P < 0.001). Likewise, elevated BMI heightened the risk at low levels of WT, WC, WtHR, BRI, AVI, and CI (P < 0.001). Conclusion: This study supports the positive association between various anthropometric indicators and gallstones, recommending that newer anthropometric indices be considered more extensively to enhance gallstone prevention and treatment strategies.

Effect of Rab18 on liver injury and lipid accumulation by regulating perilipin 2 and peroxisome proliferator-activated receptor gamma in non-alcoholic fatty liver disease.

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) is currently one of the most common chronic liver diseases worldwide, characterized by the presence of lipid droplets. Rab18 is an important lipid droplet protein; however, its effects and mechanisms of action on NAFLD remain unclear. METHODS: Free fatty acid-stimulated AML-12 cells and high-fat diet (HFD)-fed mice were used as NAFLD models. Lentiviruses overexpressing Rab18 (Rab18-OE) or knockdown (Rab18-KD) were used to generate stable cell lines for genetic analysis. Blood serum levels of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, glucose, and leptin were measured using a biochemical autoanalyzer. Hematoxylin and eosin staining was performed to detect pathological damage to the liver. Lipid accumulation in the cells was assessed by Oil Red O staining. Target expression was measured using qPCR, western blotting, and immunocytochemistry. RESULTS: Rab18 mRNA and protein expression levels increased in free fatty acid-stimulated AML-12 cells and the livers of HFD-fed mice. Rab18-OE increased lipid accumulation in vitro, which was attenuated by Rab18-KD. In vivo, Rab18-OE augmented liver pathological damage, serum alanine aminotransferase/aspartate aminotransferase activity, and triglyceride, total cholesterol, and low-density lipoprotein levels, whereas Rab18-KD decreased these indicators. Rab18-KD also downregulated blood glucose levels in HFD-fed mice. Mechanistically, Rab18-OE and Rab18-KD regulated the mRNA and protein expression levels of perilipin 2 (PLIN2) and peroxisome proliferator-activated receptor gamma (PPARγ) in vitro and in vivo, respectively. Immunocytochemistry revealed that Rab18 colocalized with PLIN2 and PPARγ in AML-12 cells. CONCLUSION: Rab18 expression was elevated in vitro and in vivo in the NAFLD mouse model. Rab18 regulates PLIN2 and PPARγ expression to exaggerate liver injury and lipid accumulation in patients with NAFLD. Thus, Rab18 may be a crucial protein in this disease and a potential therapeutic target.

Associations of life's essential 8 with MAFLD and liver fibrosis among US adults: a nationwide cross-section study.

Background: Life's essential' 8 (LE8) is a newly updated cardiovascular health (CVH) metrics from the American Heart Association, with close relevance to metabolism. Our objective is to explore the association between LE8 scores and incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) and advanced liver fibrosis in American adults. Methods: This population-based cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2005 and 2018, encompassing adults aged 20 years or older. Validated non-invasive scoring systems were employed to define liver steatosis and advanced liver fibrosis. Multivariable logistic regression and smooth curve fitting techniques were applied to evaluate the associations. All analyses were adjusted for the survey' complex design parameters and accounted for sample weights. Results: A total of 11,820 participants were included. A higher LE8 score was found to be inversely associated with the incidence of MAFLD and advanced liver fibrosis, with odds ratios (OR) of 0.64 (95% CI: 0.57-0.71) for MAFLD and 0.75 (95% CI: 0.61-0.92) for advanced liver fibrosis per 1 standard deviation (SD) increase in LE8 score. Similar patterns were found in the relationship between health behaviors/factors score and incidence of MAFLD and advanced liver fibrosis. In subgroup analyses, the interaction test showed that age, education level, marital status, CVD, hypertension and diabetes had a significant impact on the association between LE8 score and MAFLD (all P for interaction < 0.05). Among male, elderly, wealthy, other race, CVD, diabetes and depression participants, the correlation between LE8 score and advanced liver fibrosis was not statistically significant (P > 0.05). Younger participants exhibited a more pronounced negative association between the CVH metric and both MAFLD and advanced life fibrosis. Conclusion: LE8 and its subscales score were inversely associated with the presence of MAFLD and advanced liver fibrosis in non-linear patterns. Optimal LE8 score may significantly reduce the risk of liver steatosis and fibrosis.

Efficacy of Tetracycline Three Times Daily was Comparable to That of Four Times Daily for Helicobacter pylori Rescue Treatment: A Multicenter, Noninferiority, Randomized Controlled Trial.

BACKGROUND: The optimal dosage of tetracycline remains unclear for Helicobacter pylori eradication. Frequent dosing requirements may decrease patient adherence and increase the incidence of adverse events, potentially reducing treatment efficacy. This study aimed to compare the efficacy of different tetracycline dosages in rescue treatment for H. pylori infection. METHODS: A total of 406 patients needing H. pylori rescue treatment were enrolled. Patients were randomized into two groups and received bismuth-containing quadruple therapies as follows: esomeprazole 40 mg twice daily, bismuth 220 mg twice daily, amoxicillin 1000 mg twice daily, and tetracycline 500 mg either three (TET-T group) or four (TET-F group) times daily. At least 6 weeks after treatment completion, a 13C-urea breath test was performed to evaluate H. pylori eradication. RESULTS: The intention-to-treat (ITT) eradication rates were 91.13% (185/203) and 90.15% (183/203) (p = 0.733), the modified ITT (MITT) eradication rates were 94.87% (185/195) and 95.31% (183/192) (p = 0.841), and the per-protocol (PP) eradication rates were 94.79% (182/192) and 95.21% (179/188) (p = 0.851) in the TET-T group and TET-F group, respectively. The eradication rates for the TET-T group were not inferior to those of the TET-F group in ITT, MITT, and PP analyses. The incidence of adverse effects was significantly lower in the TET-T group than in the TET-F group (23.65% vs. 33.50%, p = 0.028). No significant differences were observed in treatment compliance between the groups. CONCLUSIONS: The dose of tetracycline administered three times daily showed comparable efficacy to that administered four times daily, while significantly reducing the incidence of adverse events. The combination of tetracycline and amoxicillin in bismuth-containing quadruple therapy achieved a high eradication rate in H. pylori rescue treatment.

Fourteen-Day Tegoprazan-Amoxicillin Dual Therapy as the First-Line Treatment of Helicobacter pylori Infection (SHARE2301): A Multicenter, Noninferiority, Randomized Clinical Trial.

BACKGROUND: Potassium-competitive acid blockers have demonstrated enormous potential in the eradication treatment of Helicobacter pylori infection, with tegoprazan being one of the representatives. The available data on the safety and efficacy of tegoprazan in dual therapy are limited. MATERIALS AND METHODS: The multicenter, noninferiority, randomized-controlled trial was conducted from May 2023 to March 2024. Treatment-naive subjects were randomly assigned (1:1) to enter either the tegoprazan-amoxicillin (TA) group (tegoprazan 50 mg twice daily and amoxicillin 750 mg four times daily) or the esomeprazole-amoxicillin (EA) group (esomeprazole 20 mg and amoxicillin 750 mg all four times daily), with a duration for 14 days. The primary outcome was eradication rate as determined by 13C-urea breath test, including per-protocol (PP) analysis and intention-to-treat (ITT) analysis. Secondary outcomes were adverse events and compliance. RESULTS: A total of 368 individuals were included in the randomization. The eradication rates in the EA group and the TA group were 84.2% and 85.8%, respectively, according to an ITT analysis (p = 0.77), and 88.5% and 88.2%, respectively, according to PP analysis (p = 1.00). The eradication rates for the TA group were not inferior to those of the EA group in both PP (p = 0.0023) and ITT analyses (p = 0.0009). There were no significant statistical differences in the incidence of adverse events and compliance between the two groups. The multivariate logistic regression analysis revealed that poor compliance increased the risk of eradication failure (p < 0.001). CONCLUSIONS: Dual therapy containing tegoprazan is safe and effective to be considered as a clinical first-line treatment option, but further optimization involving antimicrobial susceptibility testing and adjustments in dosage and frequency is warranted. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05870683.

Optical enhancement mode 2 improves the detection rate of gastric neoplastic lesion in high-risk populations: A multicenter randomized controlled clinical study.

OBJECTIVES: Detection of early neoplastic lesions is crucial for improving the survival rates of patients with gastric cancer. Optical enhancement mode 2 is a new image-enhanced endoscopic technique that offers bright images and can improve the visibility of neoplastic lesions. This study aimed to compare the detection of neoplastic lesions with optical enhancement mode 2 and white-light imaging (WLI) in a high-risk population. METHODS: In this prospective multicenter randomized controlled trial, patients were randomly assigned to optical enhancement mode 2 or WLI groups. Detection of suspicious neoplastic lesions during the examinations was recorded, and pathological diagnoses served as the gold standard. RESULTS: A total of 1211 and 1219 individuals were included in the optical enhancement mode 2 and WLI groups, respectively. The detection rate of neoplastic lesions was significantly higher in the optical enhancement mode 2 group (5.1% vs. 1.9%; risk ratio, 2.656 [95% confidence interval, 1.630-4.330]; p < 0.001). The detection rate of neoplastic lesions with an atrophic gastritis background was significantly higher in the optical enhancement mode 2 group (8.6% vs. 2.6%, p < 0.001). The optical enhancement mode 2 group also had a higher detection rate among endoscopists with different experiences. CONCLUSIONS: Optical enhancement mode 2 was more effective than WLI for detecting neoplastic lesions in the stomach, and can serve as a new method for screening early gastric cancer in clinical practice. CLINICAL REGISTRY: United States National Library of Medicine (https://www. CLINICALTRIALS: gov), ID: NCT040720521.

Extracorporeal membrane oxygenation combined with minimally invasive surgery for acute respiratory failure and sudden cardiac arrest: A case report.

Acute respiratory failure and sudden cardiac arrest caused by acute intrathoracic infection is a fatal clinical condition with a low resuscitation success rate. The present study describes the case of a patient with acute empyema secondary to an acute lung abscess rupture, complicated by acute respiratory failure and sudden cardiac arrest caused by severe hypoxemia. The patient recovered well through the administration of multiple therapeutic measures, including medication and closed chest drainage, cardiopulmonary resuscitation, extracorporeal membrane oxygenation combined with continuous renal replacement therapy, and minimally invasive surgical resection of the lung lesion with persistent alveolar fistula as the clinical manifestation. To the best of our knowledge, the treatment of such a severe condition combined with thoracoscopic surgery has rarely been reported before, and the present study may provide insight regarding therapeutic schedules for acute respiratory failure by intrathoracic infection, and excision of ruptured lung abscess.

Systematic pan-cancer analysis identifies cuproptosis-related gene DLAT as an immunological and prognostic biomarker.

Lipoylated dihydrolipoamide S-acetyltransferase (DLAT), the component E2 of the multi-enzyme pyruvate dehydrogenase complex, is one of the key molecules of cuproptosis. However, the prognostic value and immunological role of DLAT in pan-cancer are still unclear. Using a series of bioinformatics approaches, we studied combined data from different databases, including the Cancer Genome Atlas, Genotype Tissue-Expression, the Cancer Cell Line Encyclopedia, Human Protein Atlas, and cBioPortal to investigate the role of DLAT expression in prognosis and tumor immunity response. We also reveal the potential correlations between DLAT expression and gene alterations, DNA methylation, copy number variation (CNV), tumor mutational burden (TMB), microsatellite instability (MSI), tumor microenvironment (TME), immune infiltration levels, and various immune-related genes across different cancers. The results show that DLAT displays abnormal expression within most malignant tumors. Through gene set enrichment analysis (GSEA), we found that DLAT was significantly associated with immune-related pathways. Further, the expression of DLAT was also confirmed to be correlated with the tumor microenvironment and diverse infiltration of immune cells, especially tumor-associated macrophages (TAMs). In addition, we found that DLAT is co-expressed with genes encoding major histocompatibility complex (MHC), immunostimulators, immune inhibitors, chemokines, and chemokine receptors. Meanwhile, we demonstrate that DLAT expression is correlated with TMB in 10 cancers and MSI in 11 cancers. Our study reveals that DLAT plays an essential role in tumorigenesis and cancer immunity, which may be used to function as a prognostic biomarker and potential target for cancer immunotherapy.

Leukocyte CH25H is a potential diagnostic and prognostic marker for lung adenocarcinoma.

Metastasis, a major challenge during the treatment of lung cancer, causes deterioration in patient health outcomes. Thus, to address this problem, this study aimed to explore the role and contribution of Cholesterol 25-Hydroxylase (CH25H) as a potential diagnostic and prognostic marker in lung cancer. Online public databases were used to analyze the expression level, prognostic value, gene-pathway enrichment, and immune infiltration of CH25H in lung cancer patients. The Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to analyze and detect the CH25H expression levels in leukocytes from lung cancer patients. The expression level of CH25H was significantly reduced in lung adenocarcinoma (LUAD), which is associated with a higher disease stage, but not in lung squamous cell carcinoma (LUSC). Kaplan-Meier survival analysis indicated that LUAD patients with low CH25H expression had a worse prognosis. Mechanistically, our results showed that in LUAD, CH25H may be a regulatory factor affecting the immune cell infiltration level, and the resultant tumor development. Experimental data showed that low expression of CH25H in leukocytes was significantly associated with LUAD metastasis (P < 0.01). Our study suggests that CH25H may function as a prognostic and risk stratification biomarker for LUAD.

KDM5A regulates the growth and gefitinib drug resistance against human lung adenocarcinoma cells.

KDM5A, a histone demethylase, has been shown to be involved in several cancer-related process. The present study was undertaken to explore the role and therapeutic potential of KDM5A in human lung adenocarcinoma. The results of the qRT-PCR, immunohistochemistry, and western blotting showed significant upregulation of KDM5A expression in lung adenocarcinoma tissues and cell lines. The RNA interference-mediated silencing of KDM5A in lung adenocarcinoma cell line SK-LU-1 led to significant inhibition of in vitro cell proliferation via induction of apoptosis. The induction of apoptosis in SK-LU-1 lung adenocarcinoma cells was concomitant with upregulation of Bax and downregulation of Bcl-2 expression. In contrary, overexpression of KDM5A prompted the proliferation of SK-LU-1 lung adenocarcinoma cells. Interestingly, the SK-LU-1 cancer cells showed remarkably higher sensitivity to gefitinib under KDM5A transcriptional knockdown. Taken together, KDM5A is significantly upregulated in human lung adenocarcinoma and regulates the proliferation of the lung adenocarcinoma cells. These findings suggest potential of KDM5A to act as a therapeutic target for the management of human lung adenocarcinoma.

Value of Magnifying Chromoendoscopy and Magnifying Optical Enhancement Technology in Classifying Colorectal Polyps: A Prospective Controlled Study.

BACKGROUND AND AIMS: Magnifying chromoendoscopy (ME-CE) through the observation of pit patterns is a productive way to distinguish between neoplastic and nonneoplastic polyps. Magnifying optical enhancement technology (ME-OE) is an emerging virtual chromoendoscopy imaging technology and appeared to be a promising approach. However, this information is currently not available. This study is aimed at comparing the differential diagnostic value of ME-CE and OE for neoplastic and nonneoplastic polyps. Patients and Methods. Consecutive patients undergoing colonoscopy were randomized (1 : 1) into examination by ME-OE or ME-CE. Histopathological findings were utilized as the reference standard. Accuracy, sensitivity, specificity, and positive and negative predictive values of two endoscopy methods were compared using ME-OE (were classified according to the JNET classification) and ME-CE (were classified according to the Kudo pit pattern classification), respectively, and the time to predict the histological polyp type was compared. And the agreements between the pathological and clinical diagnosis by ME-OE or ME-CE were analyzed. RESULTS: A total of 365 polyps were found in the 220 patients included (ME-OE: 185; ME-CE: 180.202 had nonneoplastic polyps, 163 had neoplastic polyps). The diagnostic accuracy of ME-OE was higher than that of ME-CE (93% vs. 92%, p > 0.05). The average diagnosis time was lower in ME-OE than ME-CE (83 ± 26.4 s vs. 194 ± 17.7 s, p < 0.001). The agreements between the pathological and clinical diagnosis were at least substantial in both groups. CONCLUSION: ME-OE was superlative to ME-CE in predicting the histology of polyps. OE devoted classification would possibly similarly enhance the endoscopist performance. The trial is registered with ChiCT2000032075.

Histone demethylase KDM5A enhances cell proliferation, induces EMT in lung adenocarcinoma cells, and have a strong causal association with paclitaxel resistance.

Recent reports suggest that histone demethylase KDM5A emerges as a new player in the development of drug resistance and thus increases the challenges of chemotherapy. Here, we explore the role of KDM5A in cell proliferation, epithelial-mesenchymal transition (EMT)and its causal association with paclitaxel resistance in lung adenocarcinoma. Paclitaxel-resistant lung adenocarcinoma PTX-Calu-3 cells showed significantly higher IC50 value (7±0.176 µM) upon paclitaxel treatment than lung adenocarcinoma SK-LI-1 (3.6±0.005 nM), Calu-3 (4.3±0.015 nM), and A549 (4.5±0.106 nM) cells. We found that expression of KDM5A and P-glycoprotein (P-gp), which plays a critical role in the development of paclitaxel resistance, were significantly higher in PTX-Calu-3 cells compared to SK-LI-1, Calu-3, and A549 cells.. We observed a significant increase in the expression of mesenchymal markers N-cadherin and vimentin, and a concomitant decrease in expression of E-cadherin and α-catenin in PTX-Calu-3 compared to SK-LI-1, Calu-3, and A549 lung cancer cell lines. Transwell Boyden chamber and wound healing assays further demonstrated that a significantly higher number of PTX-Calu-3 cells were invasive and motile compared to SK-LI-1, Calu-3, and A549 cells, thus supporting the role of KDM5A in metastasis-associated processes. Additionally, a significantly higher expression of KDM5A was observed in lung adenocarcinoma patients' samples compared with adjacent normal tissues as well as in PTX-Calu-3 cells compared toSK-LI-1, Calu-3, and A549 cells, as shown both with histochemistry and real time-polymerase chain reaction (RT-PCR). In summary, these results suggest that KDM5A plays a key role in lung adenocarcinoma by promoting proliferation, EMT, and drug resistance to paclitaxel treatment.

Comparison of white-light endoscopy, optical-enhanced and acetic-acid magnifying endoscopy for detecting gastric intestinal metaplasia: A randomized trial.

BACKGROUND: Gastric intestinal metaplasia (GIM) is a precancerous lesion of the stomach, which severely affects human life and health. Currently, a variety of endoscopic techniques are used to screen/evaluate GIM. Traditional white-light endoscopy (WLE) and acetic-acid chromoendoscopy combined with magnifying endoscopy (ME-AAC) are the interventions of choice due to their diagnostic efficacy for GIM. Optical-enhanced magnifying endoscopy (ME-OE) is a new virtual chromoendoscopy technique to identify GIM, which combines bandwidth-limited light and image enhancement processing technology to enhance the detection of mucosal and vascular details. We hypothesized that ME-OE is superior to WLE and ME-AAC in the evaluation of GIM. AIM: To directly compare the diagnostic value of WLE, ME-AAC, and ME-OE for detection of GIM. METHODS: A total of 156 patients were subjected to consecutive upper gastrointestinal endoscopy examinations using WLE, ME-AAC, and ME-OE. Histopathological findings were utilized as the reference standard. Accuracy, sensitivity, specificity, and positive and negative predictive values of the three endoscopy methods in the diagnosis of GIM were evaluated. Moreover, the time to diagnosis with ME-AAC and ME-OE was analyzed. Two experts and two non-experts evaluated the GIM images diagnosed using ME-OE, and diagnostic accuracy and intra- and inter-observer agreement were analyzed. RESULTS: GIM was detected in 68 of 156 patients (43.6%). The accuracy of ME-OE was highest (91.7%), followed by ME-AAC (86.5%), while that of WLE (51.9%) was lowest. Per-site analysis showed that the overall diagnostic accuracy of ME-OE was higher than that of ME-AAC (P = 0.011) and WLE (P < 0.001). The average diagnosis time was lower in ME-OE than in ME-AAC (64 ± 7 s vs 151 ± 30 s, P < 0.001). Finally, the inter-observer agreement was strong for both experts (k = 0.862) and non-experts (k = 0.800). The internal consistency was strong for experts (k = 0.713, k = 0.724) and moderate for non-experts (k = 0.667, k = 0.598). CONCLUSION: For endoscopists, especially experienced endoscopists, ME-OE is an efficient, convenient, and time-saving endoscopic technique that should be used for the diagnosis of GIM.

circ-NRIP1 Promotes Glycolysis and Tumor Progression by Regulating miR-186-5p/MYH9 Axis in Gastric Cancer.

BACKGROUND: Gastric cancer (GC) is a severe threat to human life, with high incidence and mortality. Circular RNAs (circRNAs) play crucial roles in the progression of GC. This study attempted to investigate the potential role of circ-NRIP1 and associated action mechanisms in GC cells. METHODS: The expression of circ-NRIP1 and miR-186-5p was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, apoptosis, and migration were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flow cytometry assay, and transwell assay, respectively. Cellular glycolysis, including cellular glucose uptake, lactate, and ATP/ADP ratios, was also detected by commercial assay kits. The protein levels of hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2) were quantified by Western blot. The relationship between miR-186-5p and circ-NRIP1 or myosin heavy chain 9 (MYH9) was predicted by the online bioinformatics tool, starBase, and verified by dual-luciferase reporter assay. Xenograft tumor model was used to evaluate biological function in vivo. RESULTS: The expression of circ-NRIP1 was up-regulated in tissues of GC patients and cells, as well as negatively associated with that of miR-186-5p in tissues. circ-NRIP1 knockdown inhibited cell proliferation, migration, and glycolysis, but induced apoptosis in HGC-27 and AGS cells. circ-NRIP1 competitively targeted miR-186-5p, and MYH9 was a target of miR-186-5p. miR-186-5p knockdown inverted the bio-function effects and glycolytic activation from circ-NRIP1 silencing in HGC-27 and AGS cells. Meanwhile, MYH9 overexpression could rescue the effects of miR-186-5p. Besides, miR-186-5p knockdown inverted the expression pattern of si-circ-NRIP1 transfection in GC cells. Additionally, in vivo experiments confirmed that sh-circ-NRIP1 inhibited tumor growth. CONCLUSION: circ-NRIP1 accelerated the glycolysis and GC progression by modulating MYH9 via miR-186-5p, suggesting that circ-NRIP1 was a promising biomarker for the treatment of GC.

Circ_0032821 acts as an oncogene in cell proliferation, metastasis and autophagy in human gastric cancer cells in vitro and in vivo through activating MEK1/ERK1/2 signaling pathway.

BACKGROUND: Circular RNA (circRNA) is increasingly attracting attention in gastric cancer (GC). Hsa_circ_0032821 (circ_0032821) has been declared to be upregulated in human GC tissues. However, the biological role of circ_0032821 remains undisclosed in GC cells. METHODS: Expression of circ_0032821 was measured by real-time quantitative PCR. Cell proliferation, autophagy, Epithelial-mesenchymal transition (EMT), migration, and invasion were evaluated by Cell counting kit-8 assay, western blotting or transwell assays. Expression of proliferating cell nuclear antigen (PCNA), Matrix metalloproteinase 2 (MMP2), MMP9, Light chain 3 (LC3), p62, total and phosphorylated Extracellular signal-regulated kinase 1/2 (ERK1/2) and Mitogen-activated protein kinase's kinase 1 (MEK1) was evaluated by western blotting. Xenograft tumor model was established to measure tumor growth in vivo. RESULTS: Circ_0032821 was significantly upregulated in human GC tumors and cells. Moreover, circ_0032821 might be a biomarker for the advanced Tumor node metastasis (TNM) stage, lymphoid node metastasis and poor prognosis in gastric cancer. Knockdown of circ_0032821 by transfection induced decrease of cell proliferation, EMT, migration and invasion, but increase of autophagy of AGS and HGC-27 cells in vitro, as well as induced tumor growth inhibition in vivo. Besides, overexpression of circ_0032821 by transfection functioned the opposite effects in human GC cells. Mechanically, the MEK1/ERK1/2 signaling pathway was activated when circ_0032821 upregulation, whereas inhibited when circ_0032821 silencing. CONCLUSION: Circ_0032821 expression induced cell proliferation, EMT, migration, invasion, and autophagy inhibition in human GC cells in vitro and in vivo through activating MEK1/ERK1/2 signaling pathway, suggesting circ_0032821 as an oncogenic role in GC.

Sarcopenia and Short-Term Outcomes After Esophagectomy: A Meta-analysis.

BACKGROUND: This meta-analysis aimed to investigate the value of preoperative sarcopenia in predicting complications after esophagectomy. Clinicopathologic characteristics of sarcopenia patients, which may support sarcopenia management, also were studied. METHODS: This study searched for articles describing an association between sarcopenia and short-term outcomes after esophagectomy using PubMed, EMBASE, and the Cochrane Library. Mantel-Haenszel and inverse variance models were used for the meta-analyses of end points. RESULTS: The meta-analysis included 14 studies comprising a total of 2387 patients. Sarcopenia was significantly associated with advanced age (weighted mean difference [WMD], 3.48; 95% confidence interval [CI], 2.22-4.74), lower body mass index (WMD - 2.22; 95% CI - 2.65 to - 1.79), squamous cell carcinoma (odds ratio [OR], 2.78; 95% CI 1.72-4.47), advanced clinical tumor stage (OR 1.65; 95% CI 1.28-2.15), and neoadjuvant therapy (OR 1.87; 95% CI 1.38-2.53). The sarcopenia patients showed lower preoperative albumin levels (WMD - 0.11; 95% CI - 0.19 to - 0.04) than the nonsarcopenia patients. Sarcopenia was significantly predictive of pneumonia (OR 2.58; 95% CI 1.75-3.81) and overall complications (OR 1.52; 95% CI 1.07-2.15) after esophagectomy. The sarcopenia patients also showed nonsignificant increases in the risks of anastomotic leakage (OR 1.29; 95% CI 0.99-1.67), vocal cord palsy (OR 2.03; 95% CI 0.89-4.64), and major complications (≥ Clavien-Dindo grade III; OR 1.30; 95% CI 0.95-1.79) but not increased operation time, blood loss, or mortality. CONCLUSIONS: Preoperative sarcopenia assessment showed considerable potential for predicting postoperative complications for esophageal cancer patients. To realize this potential, more effective diagnostic criteria and severity classifications for sarcopenia are warranted.

Genetic dissection of top three leaf traits in rice using progenies from a japonica × indica cross.

The size of the top three leaves of rice plants is strongly associated with yield; thus, it is important to consider quantitative traits representing leaf size (e.g., length and width) when breeding novel rice varieties. It is challenging to measure such traits on a large scale in the field, and little is known about the genetic factors that determine the size of the top three leaves. In the present study, a population of recombinant inbred lines (RILs) and reciprocal single chromosomal segment substitution lines (SSSLs) derived from the progeny of a japonica Asominori × indica IR24 cross were grown under four diverse environmental conditions. Six morphological traits associated with leaf size were measured, namely length and flag leaf, length and flag, second and third leaves. In the RIL population, 49 QTLs were identified that clustered in 30 genomic region. Twenty-three of these QTLs were confirmed in the SSSL population. A comparison with previously reported genes/QTLs revealed eight novel genomic regions that contained uncharacterized ORFs associated with leaf size. The QTLs identified in this study can be used for marker-assisted breeding and for fine mapping of novel genetic elements controlling leaf size in rice.

Probe-based endomicroscopy for in vivo detection of gastric intestinal metaplasia and neoplasia: a multicenter randomized controlled trial.

Background and study aims Owing to the indistinctive endoscopic appearance of gastric intestinal metaplasia (GIM), gastric intraepithelial neoplasia (GIN), and early gastric cancer (EGC), a significant number of such lesions may be missed during surveillance endoscopy. The aim of this clinical trial was to assess the value of combined computed virtual chromoendoscopy (flexible spectral imaging color enhancement [FICE]) and probe-based confocal laser endomicroscopy (pCLE) for in vivo detection of GIM, GIN, and EGC. Patients and methods This was a multicenter, randomized controlled trial performed in 238 patients at four tertiary centers. Patients were randomized to FICE-guided pCLE with targeted biopsies (group A) or FICE with standard biopsies (group B). The diagnostic yield of GIM, GIN, or EGC was compared between the two groups. Results On a per-patient assessment, the diagnostic yield for GIM/GIN/EGC was 73.3 % (88/120) in group A and 63.6 % (75/118) in group B (P = 0.09). On a per-biopsy analysis, FICE-guided pCLE with targeted biopsies significantly increased the diagnostic yield of GIM/GIN/EGC vs. FICE with standard biopsies, from 31.5 % (252/800) to 75.1 % (313/417) (P < 0.001). In addition, pCLE-guided targeted biopsies led to a significant 48.5 % decrease in the number of biopsies per patient vs. FICE with standard biopsies (P < 0.001). Conclusions Real-time pCLE and targeted biopsies after FICE improved the diagnostic yield for the detection of GIM, GIN, and EGC, and only required about half the number of biopsies vs. FICE with standard biopsies. This may allow a better regimen for endoscopic surveillance and subsequent treatment of patients with premalignant and malignant gastric abnormalities.Trial registered at ClinicalTrials.gov (NCT02515721).