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Background: With the number of critically ill patients increasing in gastroenterology departments (GEDs), infections associated with Carbapenem-resistant Gram-negative bacteria (CR-GNB) are of great concern in GED. However, no CR-GNB bloodstream infection (BSI) risk prediction model has been established for GED patients. Almost universally, CR-GNB colonization precedes or occurs concurrently with CR-GNB BSI. The objective of this study was to develop a nomogram that could predict the risk of acquiring secondary CR-GNB BSI in GED patients who are carriers of CR-GNB. Methods: We conducted a single-center retrospective case–control study from January 2020 to March 2022. Univariate and multivariable logistic regression analysis was used to identify independent risk factors of secondary CR-GNB bloodstream infections among CR-GNB carriers in the gastroenterology department. A nomogram was constructed according to a multivariable regression model. Various aspects of the established predicting nomogram were evaluated, including discrimination, calibration, and clinical utility. We assessed internal validation using bootstrapping. Results: The prediction nomogram includes the following predictors: high ECOG PS, severe acute pancreatitis, diabetes mellitus, neutropenia, a long stay in hospital, and parenteral nutrition. The model demonstrated good discrimination and good calibration. Conclusions: With an estimate of individual risk using the nomogram developed in this study, clinicians and nurses can identify patients with a high risk of secondary CR-GNB BSI early. [ABSTRACT FROM AUTHOR]

Background: With the increasing number of critically ill patients in the gastroenterology department (GED), infections associated with Carbapenem resistant gram-negative bacteria (CR-GNB) are of great concern in GED. As the turn-around time (TAT) for a positive screening culture result is slow, contact precaution and pre-emptive isolation, cohorting methods should be undertaken immediately on admission for high-risk patients. Accurate prediction tools for CR-GNB colonization in GED can help determine target populations upon admission. And thus, clinicians and nurses can implement preventive measures more timely and effectively. Objective: The purpose of the current study was to develop and internally validate a CR-GNB carrier risk predictive nomogram for a Chinese population in GED. Methods: Based on a training dataset of 400 GED patients collected between January 2020 and December 2021, we developed a model to predict CR-GNB carrier risk. A rectal swab was used to evaluate the patients' CR-GNB colonization status microbiologically. We optimized features selection using the least absolute shrinkage and selection operator regression model (LASSO). In order to develop a predicting model, multivariable logistic regression analysis was then undertaken. Various aspects of the predicting model were evaluated, including discrimination, calibration, and clinical utility. We assessed internal validation using bootstrapping. Results: The prediction nomogram includes the following predictors: Transfer from another hospital (Odds ratio [OR] 3.48), High Eastern Cooperative Oncology Group (ECOG) performance status (OR 2.61), Longterm in healthcare facility (OR 10.94), ICU admission history (OR 9.03), Blood stream infection history (OR 3.31), Liver cirrhosis (OR 4.05) and Carbapenem usage history within 3 month (OR 2.71). The model demonstrated good discrimination and good calibration. Conclusion: With an estimate of individual risk using the nomogram developed in this study, clinicians and nurses can take more timely infection preventive measures on isolation, cohorting and medical interventions. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is the leading cause of cancer-related deaths worldwide, with limited treatment options and low long-term survival rates. The complex and variable signal regulation networks are one of the important reasons why it is difficult for pancreatic cancer to develop precise targeted therapy drugs. Numerous studies have associated feedback loop regulation with the development and therapeutic response of cancers including pancreatic cancer. Therefore, we review researches on the role of feedback loops in the progression of pancreatic cancer, and summarize the connection between feedback loops and several signaling pathways in pancreatic cancer, as well as recent advances in the intervention of feedback loops in pancreatic cancer treatment, highlighting the potential of capitalizing on feedback loops modulation in targeted therapy for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the diagnostic value of gastrin-17 (G-17) and pepsinogen (PG) in gastric cancer (GC) screening in China, especially eastern China, and to determine the best diagnostic combination and threshold (cutoff values) to screen out patients who need gastroscopy. Methods. The serum concentrations of G-17 and pepsinogen I and II (PGI and PGII) in 834 patients were analyzed, and the PGI/PGII ratio (PGR) was calculated. According to pathological results, patients can be divided into chronic nonatrophic gastritis (NAG)/chronic atrophic gastritis (CAG)/intraepithelial neoplasia (IN)/GC groups. The differences in G-17, PG, and PGR in each group were analyzed, and their values in GC diagnosis were evaluated separately and in combination. Results. There were differences in serum G-17, PGII, and PGR among the four groups (NAG/CAG/IN/GC) (P ≤ 0.001). In total, 54 GC cases were diagnosed, of which 50% were early GC. There was no significant difference in the PGI levels among the four groups (P = 0.377). NAG and CAG composed the chronic gastritis (CG) group. The G-17 and PGII levels in the IN and GC groups were higher than those in the CG group (both P ≤ oth C), while the PGR levels were lower (P ≤ lower). When distinguishing NAG from CAG, the best cutoff value for G-17 was 9.25 pmol/L, PGII was 7.06 μg/L, and PGR was 12.07. When distinguishing CG from IN, the best cutoff value for G-17 was 3.86 pmol/L, PGII was 11.92 μg/L, and PGR was 8.26. When distinguishing CG from GC, the best cutoff value for G-17 was 3.89 pmol/L, PGII was 9.16 μg/L, and PGR was 14.14. The sensitivity, specificity, accuracy, and positive and negative predictive values of G-17/PGII/PGR for GC diagnosis were 83.3%/70.4%/79.6%, 51.8%/56.3%/47.8%, 53.8%/57.2%/49.9%, 10.7%/10.9%/9.6%, and 97.8%/96.5%/97.1%, respectively. The sensitivity, specificity, accuracy, and positive predictive and negative predictive values of PGII/G-17 vs. PGR/G-17 vs. PGR/PGII in the diagnosis of GC were 63.0% vs. 70.4% vs. 64.8%, 70.5% vs. 70.1% vs. 60.4%, 70.0% vs. 70.1% vs. 60.7%, 12.9% vs. 14.0% vs. 10.2%, and 96.5% vs. 97.2% vs. 96.1%, respectively. Conclusion. The PGII and G-17 levels in patients with gastric IN and GC were significantly increased, while the serum PGR level was significantly decreased. Serological detection is effective for screening GC. The combination of different markers can improve the diagnostic efficiency. The highest diagnostic accuracy was G-17 combined with PGR, and the best cutoff values were G − 17 > 3.89 pmol / L and PGR < 14.14. [ABSTRACT FROM AUTHOR]

The biliary microbiota is related to the pathogenesis of human bile duct stones. However, the extent to which a history of invasive endoscopic sphincterotomy (EST) affects the biliary bacterial community remains largely unknown. We collected bile samples from the common bile duct of 100 choledocholithiasis patients. We performed 16S rRNA sequencing to investigate and compare the biliary microbial community. The patients without antibiotic treatment (AT) were grouped into three clusters based on their biliary microbial compositions. The patients with a history of EST were significantly enriched in one cluster mainly consisting of gastrointestinal bacteria compared with the other two clusters consisting of oral and environmental bacteria. The β-diversities of patients with and without EST were also significantly different, whereas the α-diversities were comparable. The only significantly enriched bacterial genus associated with a history of EST was Pyramidobacter , while eight other genera were significantly decreased. For patients with AT, seven of these genera maintained their association with EST, including Pyramidobacter. However, after AT, the difference in β-diversities was diminished. EST induced a marked shift in the biliary microbial composition. A cluster of biliary bacteria was associated with a history of EST, and Pyramidobacter was specific to EST. [ABSTRACT FROM AUTHOR]

Biliary bacteria have been implicated in gallstone pathogenesis, though a clear understanding of their composition and source is lacking. Moreover, the effects of the biliary environment, which is known to be generally hostile to most bacteria, on biliary bacteria are unclear. Here, we investigated the bacterial communities of the biliary tract, duodenum, stomach, and oral cavity from six gallstone patients by using 16S rRNA amplicon sequencing. We found that all observed biliary bacteria were detectable in the upper digestive tract. The biliary microbiota had a comparatively higher similarity with the duodenal microbiota, versus those of the other regions, but with a reduced diversity. Although the majority of identified bacteria were greatly diminished in bile samples, three Enterobacteriaceae genera (Escherichia, Klebsiella, and an unclassified genus) and Pyramidobacter were abundant in bile. Predictive functional analysis indicated enhanced abilities of environmental information processing and cell motility of biliary bacteria. Our study provides evidence for the potential source of biliary bacteria, and illustrates the influence of the biliary system on biliary bacterial communities. [ABSTRACT FROM AUTHOR]

Introduction: Although the 9-minute mean withdrawal time (m-WT) is often reported to be associated with the optimal adenoma detection rate (ADR), no randomized trials of screening colonoscopy have confirmed the impact of a 9-minute m-WT on adenoma miss rate (AMR) and ADR., Methods: A multicenter tandem trial was conducted in 11 centers. Seven hundred thirty-three asymptomatic participants were randomized to receive segmental tandem screening colonoscopy with a 9-minute withdrawal, followed by a 6-minute withdrawal (9-minute-first group, 9MF, n = 366) or vice versa (6-minute-first group, 6MF, n = 367). The primary outcome was the lesion-level AMR., Results: The intention-to-treat analysis revealed that 9MF significantly reduced the lesion-level (14.5% vs 36.6%, P < 0.001) and participant-level AMR (10.9% vs 25.9%, P < 0.001), advanced adenoma miss rate (AAMR, 5.3% vs 46.9%, P = 0.002), multiple adenomas miss rate (20.7% vs 56.5%, P = 0.01), and high-risk adenomas miss rate (14.6% vs 39.5%, P = 0.01) of 6MF without compromising detection efficiency ( P = 0.79). In addition, a lower false-negative rate for adenomas ( P = 0.002) and high-risk adenomas ( P < 0.05), and a lower rate of shortening surveillance schedule ( P < 0.001) were also found in 9MF, accompanying with an improved ADR in the 9-minute vs 6-minute m-WT (42.3% vs 33.5%, P = 0.02). The independent inverse association between m-WT and AMR remained significant even after adjusting ADR, and meanwhile, 9-minute m-WT was identified as an independent protector for AMR and AAMR., Discussion: In addition to increasing ADR, 9-minute m-WT also significantly reduces the AMR and AAMR of screening colonoscopy without compromising detection efficiency., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: Acute pancreatitis (AP) is an inflammatory disease with very poor outcomes. However, the order of induction and coordinated interactions of systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS) and the potential mechanisms in AP are still unclear., Methods: An integrative analysis was performed based on transcripts of blood from patients with different severity levels of AP (GSE194331), as well as impaired lung (GSE151572), liver (GSE151927) and pancreas (GSE65146) samples from an AP experimental model to identify inflammatory signals and immune response-associated susceptibility genes. An AP animal model was established in wild-type (WT) mice and Tlr2-deficient mice by repeated intraperitoneal injection of cerulein. Serum lipase and amylase, pancreas impairment and neutrophil infiltration were evaluated to assess the effects of Tlr2 in vivo ., Results: The numbers of anti-inflammatory response-related cells, such as M2 macrophages ( P = 3.2 × 10 -3 ), were increased with worsening AP progression, while the numbers of pro-inflammatory response-related cells, such as neutrophils ( P = 3.0 × 10 -8 ), also increased. Then, 10 immune-related AP susceptibility genes (SOSC3, ITGAM, CAMP, FPR1, IL1R1, TLR2, S100A8/9, HK3 and MMP9) were identified. Finally, compared with WT mice, Tlr2-deficient mice exhibited not only significantly reduced serum lipase and amylase levels after cerulein induction but also alleviated pancreatic inflammation and neutrophil accumulation., Discussion: In summary, we discovered SIRS and CARS were stimulated in parallel, not activated consecutively. In addition, among the novel susceptibility genes, TLR2 might be a novel therapeutic target that mediates dysregulation of inflammatory responses during AP progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Li, Xu, Zhu, Huang, Yang, Cheng, Gu, Zheng, Zhang and Shen.)

Linderalactone is one of the main extracts of Linderae Radix, which is widely used in traditional Chinese medicine. There have been few studies on the antitumor effect of linderalactone in the past. In this study, we explored the anti-pancreatic cancer activity of linderalactone in vitro and in vivo . The  results showed that linderalactone inhibited the proliferation of pancreatic cancer cells in a time- and dose-dependent manner. Cell migration and invasion were significantly inhibited by linderalactone. The cell cycle was arrested in the G2/M phase, and the expression levels of cell cycle-associated proteins changed significantly with linderalactone treatment. In addition, linderalactone induced cell apoptosis and altered the expression of apoptotic markers, such as caspase 3 and PARP1. Mechanistically, linderalactone suppressed the PI3K/AKT  signaling pathway by downregulating the phosphorylation of PI3K and AKT. The xenograft study results were consistent with the in vitro results, and there was no obvious chemical toxicity. Thus, our research demonstrated that linderalactone exhibits antitumor activity against pancreatic cancer and may be developed as a potential anti-pancreatic cancer agent in the future., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Dongchao Xu et al.)

Background: The optimal timing of enteral nutrition (EN) initiation in predicted severe acute gallstone pancreatitis (SAGP) and its influence on disease outcomes are not well known., Methods: We conducted a retrospective study of patients with predicted SAGP treated with endoscopic retrograde cholangiopancreatography and EN. The patients were classified into two groups according to the timing of EN initiation after admission: within 48 h, and more than 48 h. The primary outcome was in-hospital mortality. The secondary outcomes were length of hospital stay, need for intensive care admission, need for surgical intervention, improvements in blood test results after 7-10 days of EN, incidence of pancreatic necrosis and infection, and hospital care costs. The microbiological profiles of infectious complications were also evaluated., Results: Of the 98 patients, 31 and 67 started EN within 48 h, and more than 48 h after admission, respectively. Early EN was associated with a decrease in in-hospital mortality (0 vs. 11.9%; p=0.045), length of hospital stay (median:18 vs . 27 days; p=0.001), need for intensive care admission (3.2% vs . 20.9%; p=0.032), and hospital care costs (median:9,289 vs . 13,518 US$; p=0.007), compared to delayed EN. Moreover, early EN for 7-10 days had more beneficial effects on blood test results than delayed EN, including total protein (p=0.03) and CRP (p=0.006) levels. However, the need for surgical intervention and incidence of pancreatic necrosis did not differ between the two groups. In our study, Gram-negative bacteria were the main responsible pathogens (50.5%). Infection with multidrug-resistant organisms (MDRO) was found in 19.4% of the patients. The most common MDRO was MDR Enterococcus faecium . Early EN was not superior in reducing incidence of infected pancreatic necrosis, bacteremia, polymicrobial infection, or MDROs., Conclusions: In patients with predicted SAGP, early EN is associated with a decrease in in-hospital mortality, length of hospital stay, need of intensive care admission, and hospital care costs, compared to delayed EN. There are no significant benefits of early EN in reducing the rate of infection-related complications. Further studies with larger sample sizes are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jin, Wei, Hu, Sun, Fang, Shen, Yang, Zhang and Jin.)

Pancreatic cancer is one of the most aggressive solid malignancies, as it has a 5-year survival rate of less than 10%. The growth and invasion of pancreatic cancer cells into normal tissues and organs make resection and treatment difficult. Finding an effective chemotherapy drug for this disease is crucial. In this study, we selected the tetracyclic triterpenoid compound cucurbitacin I, which may be used as a potential therapeutic drug for treating pancreatic cancer. First, we found that cucurbitacin I inhibited pancreatic cancer proliferation in a dose-time dependent manner. Further studies have shown that cucurbitacin I blocks the cell cycle of pancreatic cancer in the G2/M phase and induces cell apoptosis. In addition, under the action of the compound, the invasion ability of cells was greatly reduced and markedly impaired the growth of pancreatic tumour xenografts in nude mice. Furthermore, the decrease in pancreatic cancer cell proliferation caused by cucurbitacin I appeared to involve JAK2/STAT3 signalling pathway inhibition, and the use of JAK2/STAT3 activators effectively restored the inhibition. In conclusion, our research may provide a basis for the further development of pancreatic cancer treatment drugs., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Backgroud: At present, therapeutic endoscopic retrograde cholangiopancreatography (ERCP) has gradually been used in the diagnosis and treatment of biliary and pancreatic diseases in children, but reports on and the application of ERCP in children, especially in infants, are still highly limited. Case Presentation: This case report describes a 99-day-old infant with choledocholithiasis who successfully underwent ERCP to relieve an obstruction. The infant developed obstructive jaundice during chemotherapy for a malignant tumor, and a routine blood examination showed signs of infection. Liver damage also occurred. B-ultrasound suggested stones in the lower segment of the common bile duct (CBD). After sufficient communication and preparation, biliary drainage was successfully carried out in the infant using adult duodenoscope (JF240) and related instruments with cooperation from the Department of Anesthesiology. Conclusions: This paper preliminarily introduces our experience with adult duodenoscope in children, providing a good example for hospitals without a special duodenoscope for children to carry out pediatric ERCP. Clinicians should pay close attention to the need of careful use of ERCP in infants., (Copyright © 2020 Lou, Sun, Zhang and Shen.)

Elevated levels of C-reactive protein (CRP) have been described as a prognostic factor in various types of human malignancy. In the present study, the prognostic potency of CRP was validated for patients with colorectal cancer (CRC) in order to guide patient management and define high-risk populations for follow-up or for therapeutic purposes. The association between the high sensitivity-CRP (hs-CRP) levels of a total of 123 patients with CRC and their clinicopathological characteristics was explored. Subsequently, univariate and multivariate analyses were performed to investigate the survival impact of pre-treatment hs-CRP levels in this cohort study. Statistically significant correlations between the serum levels of hs-CRP and lymph node and distant metastasis (P<0.001 and P=0.012, respectively), vascular and perineural invasion (P<0.001 and P<0.001), grades (P=0.022) and clinical stages (P=0.001), but not age and gender (P=0.616 and 0.676, respectively), were found. The five-year survival rate of patients with elevated (>5.0 mg/l) hs-CRP levels was demonstrated to be significantly less than that of those in the normal group (≥5.0 mg/l) by applying the Kaplan-Meier method (13.3 versus 57.0%, log-rank test P<0.001). Furthermore, following identification as a prognostic factor through using univariate analysis, high levels of hs-CRP (P<0.001) were validated as an independent prognosticator in CRC in the present study through using multivariate analysis. Pre-treatment serum CRP levels were associated with advanced and progressed CRC patients, therefore these levels may serve as a potential prognostic marker for CRC patients.

Multiple myeloma (MM) is an uncommon type of malignant hematological neoplasm which, besides primarily involving the bone marrow, has a potent tendency to involve other organs and to present with various clinical manifestations. Involvement of the gastrointestinal (GI) system, particularly presenting with GI hemorrhage, in the course of MM is extremely rare. In the present study, we report a case of a middle-aged male who initially demonstrated GI bleeding and was finally diagnosed with MM. Further laboratory examinations, including analysis of globulin in the blood, bone marrow aspiration and radiogram, supported this diagnosis. This case may promote the possible involvement of plasma cell myeloma in the differential diagnosis of patients with unexplained and refractory GI bleeding. In this study we also present a thorough review of the literature with regard to the association between MM and GI hemorrhage.