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There are many risk factors for the recurrence of colorectal adenoma (CRA). The purpose of this study was to explore the predictive performance of fibrinogen-to-lymphocyte ratio (FLR) and neutrophil-to-lymphocyte ratio (NLR) on the recurrence of CRA and to construct a predictive model.This study analyzed the clinicopathological features of 421 CRA patients who underwent colonoscopy and adenectomy, and evaluated the recurrence of polyps under colonoscopy. Among them, 301 were training cohort and 120 were validation cohort. Multivariate logistic regression was used to identify independent risk factors associated with CRA recurrence. Established a nomogram model to predict the risk of recurrence in CRA patients using independent risk factors. The receiver operating characteristic (ROC) curves were used to verify the nomogram model discrimination. Calibration curves were used to verify the model calibration degree. The decision curve analysis (DCA) curves were used to verify the clinical efficacy of the nomogram model.Totally, six independent predictors, including smoking, diabetes, adenoma number, adenoma size, NLR, and FLR, were enrolled in the nomogram. In the training cohort and validation cohort, the area under the curve (AUC) of the nomogram for predicting the risk of CRA recurrence was 0.846 and 0.841, respectively. The calibration curves displayed a good agreement. DCA curves showed that this model had a high net clinical benefit.Smoking, diabetes, adenoma number, adenoma size, NLR, and FLR were influencing factors for CRA recurrence.

Emerging evidence has implicated that high-density lipoprotein cholesterol (HDL-C) as a prognostic surrogate in the context of cirrhosis. However, an exact cutoff has not been fully elucidated.We aimed to clarify optimal cutoff of HDL-C for short-term mortality based on time-to-event analysis and validated this association by performing propensity score matching (PSM) analysis.A total of 238 patients with decompensated cirrhosis were enrolled. The optimal cutoff of HDL-C was initially determined by X-tile program. Independent risk factors for 180-day mortality were identified by multiple Cox regression. The Kaplan-Meier method was implemented to generate survival curves. A 1:2 ratio PSM was performed to diminish selection bias and potential confounders.The X-tile implied that the difference in survival was most significant for HDL0.4mmol/L (16mg/dL). Circulating HDL0.4mmol/L exhibited an independent risk factor both in the entire cohort and PSM subset (HR 2.696, 95% CI 1.082-6.791, P = 0.033; HR 2.735, 95% CI 1.027-7.734, P = 0.048). Furthermore, HDL-C combined with conventional scoring systems had higher AUCs associated with poor prognosis than Child-Pugh classification or model for end-stage liver disease (MELD) in isolation (0.78 vs 0.66; 0.74 vs 0.54, P0.05 for both).HDL-C0.4 mmol/L may serve as a readily available and robust cutoff for stratifying cirrhotic patients at high 180-day mortality risk. The incorporation of HDL-C to Child-Pugh classification or MELD has the potentials to provide substantially clinical relevance without extra economic cost.

Over the last few decades, gut microbiota research has been the focus of intense research and this field has become particularly important. This research aimed to provide a quantitative evaluation of the 100 most-cited articles on gut microbiota and IBS and highlight the most important advances in this field.The database Web of Science Core Collection was used to download the bibliometric information the top 100 most-cited papers. Microsoft Excel 2021, CiteSpace, VOSviewer, R software, and an online analytical platform ( https://bibliometric.com/ ) were was applied to perform bibliometric analysis of these papers.The total citation frequency in the top 100 article ranged from 274 to 2324, with an average citation of 556.57. A total of 24 countries/regions made contributions to the top 100 cited papers, and USA, Ireland, and China were the most top three productive countries. Cryan JF was the most frequently nominated author, and of the top 100 articles, 20 listed his name. Top-cited papers mainly came from the Gastroenterology (n = 13, citations = 6373) and Gut (n = 9, citations = 3903). There was a significant citation path, indicating publications in molecular/biology/immunology primarily cited journals in molecular/biology/genetics fields. Keywords analysis suggested that the main topics on gut microbiota and IBS were mechanisms of microbiome in brain-gut axis." Behavior" was the keyword with the strongest burst strength (2.36), followed by "anxiety like behavior" (2.24), "intestinal microbiota" (2.19), and "chain fatty acid" (1.99), and "maternal separation" (1.95).This study identified and provided the bibliometric information of the top 100 cited publications related to gut microbiota and IBS. The results provided a general overview of this topic and might help researchers to better understand the evolution, Influential findings and hotspots in researching gut microbiota and IBS, thus providing new perspectives and novel research ideas in this specific area.

Gastrointestinal stromal tumour (GIST) lesions are mesenchymal neoplasms commonly found in the upper gastrointestinal tract, but non-invasive GIST detection during an endoscopy remains challenging because their ultrasonic images resemble several benign lesions. Techniques for automatic GIST detection and other lesions from endoscopic ultrasound (EUS) images offer great potential to advance the precision and automation of traditional endoscopy and treatment procedures. However, GIST recognition faces several intrinsic challenges, including the input restriction of a single image modality and the mismatch between tasks and models. To address these challenges, we propose a novel Query

Insulin (INS) is easily degraded when administered orally and loading it into polylactic acid/glycolic acid (PLGA) polymer nanoparticles can enhance the efficacy of the drug. The W/O/W double emulsion solvent volatilization method was adopted to prepare INS-loaded PLGA nanoparticles. The preparation formula of nanoparticles was determined according to the type, concentration, and PLGA concentration of the emulsifier. Then, the morphology, particle size, and drug encapsulation efficiency of nanoparticles were characterized. Phosphate buffered solution (PBS) with pH = 7.4 was utilized as the release medium, and the prepared nanoparticles were analyzed for in vitro release performance. In addition, the rat diabetes model was constructed, and subcutaneous injection of nanoparticle in vitro release solution was performed to observe its hypoglycemic effect, which was used for the treatment of diabetic patients. Patients were rolled into experimental group and control group. The changes of the patients’ HbA1c, blood lipids (total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)), C peptide, and aminopeptidase N (APN) were observed before and after treatment. Through the test, the appearance of the prepared nanoparticles was round, the average particle size was 416.7 nm, and the INS encapsulation efficiency was (36.82±2.26)%. After 36 h, the cumulative release of INS reached (60.58 ±1.45)%, and then the release rate gradually slowed down. The drug release tended to be balanced after 72 h, and the best hypoglycemic effect was achieved after subcutaneous administration 3 h (P < 0.01). The blood glucose level of the rat diabetes model was greatly decreased after 3 h injection of 36.8 IU/kg PLGA polymer nanoparticles (P < 0.05), and the blood glucose dropped to the lowest at 8 h (P < 0.01), which was only (38.8 ± 3.72)% of the initial blood glucose. HbA1C of diabetic patients increased remarkably after treatment (P < 0.05), TG, TC, and LDL-C in blood lipids decreased, and HDL-C increased, without statistically considerable differences (P > 0.05). The serum APN level increased greatly (P < 0.01). In short, the prepared PLGA polymer nanoparticles can effectively reduce blood glucose, help diabetic patients to relieve the toxicity of high glucose in the body, and improve the secretion function of INS.

MicroRNAs (miRNAs) critically impact a wide array of eukaryotic developmental and physiologic processes through post-transcriptional gene silencing. In this study, we employed miRNA array and investigated in vitro the miRNA profile of immature dendritic cells (iDCs) derived from monocytes isolated from human venous blood. Our results showed that there were 379 miRNAs which were detectable in both monocytes and iDCs among the 856 miRNAs assayed, of which 155 miRNAs were detectable in monocytes while 224 miRNAs were detectable in iDCs. There were 103 miRNAs differentially expressed which could be relevant to the differentiation of iDCs from human monocytes. Sixty-two out of 103 miRNAs were upregulated whereas 41 miRNAs were downregulated. Of particular interest were the tremendous upregulation of miR122a and the downregulation of miR200c in iDCs. In addition, it was found that the strikingly downregulated miRNAs in iDCs also included miR-335, miR-514, miR-509, miR-31, miR-442b, miR-1, miR-199a, miR-203, miR-363 and miR-489 whereas the upregulation of miR-210, miR-155, miR-126, miR-139, miR-452, miR-19a, miR-25 and miR-181d were remarkable. Our results revealed a profile change of miRNAs when human iDCs were differentiated from monocytes as a result of in vitro stimulation with relevant cytokines.

Intramural esophageal bronchogenic cysts (EBCs) are rare congenital malformations. Differences in reports on the clinical features of intramural EBCs and some controversies about the treatment strategy for intramural EBCs exist.To investigate the clinical characteristics of intramural EBCs and evaluate the safety and efficacy of endoscopic resection.The clinical and endoscopic features, endoscopic resection treatment, postoperative adverse events, and follow-up results of 17 patients with intramural EBCs were retrospectively studied.Intramural EBCs exhibited male predominance with a male/female ratio of 58.8% (10/7) and were predominantly found in the distal esophagus. Approximately 94.1% of patients presented with gastrointestinal symptoms. All lesions were protruding masses covered by intact mucosal epithelium. The morphologies of intramural EBCs were diverse under white light endoscopy. On endoscopic ultrasonography, intramural EBCs presented as homogeneous or inhomogeneous hypoechoic or anechoic lesions. Eleven lesions originated from the muscularis propria, which underwent submucosal tunnel endoscopic resection (STER), and six lesions were from the submucosa, which underwent endoscopic submucosal dissection (ESD). Approximately 88.2% of patients underwent complete endoscopic resection. No serious pneumothorax, bleeding, pleural effusion, esophagotracheal fistula, or other adverse events occurred in all patients after endoscopic resection, and no cyst recurrence, metastasis, or esophageal scar stenosis was observed during the follow-up period.Intramural EBCs can be treated by digestive endoscopic surgery. STER and ESD are safe, effective, and minimally invasive resection methods.

Diagnosis and complete resection of esophageal granular cell tumors (GCTs) is an area of concern. However, articles on endoscopic ultrasound (EUS) and endoscopic resection of esophageal granular cell tumors are few. To evaluate the role of endoscopic ultrasound and endoscopic resection in the diagnosis and treatment of esophageal granular cell tumors.A retrospective analysis of 15 patients with esophageal granular cell tumors who underwent endoscopic ultrasound examination and endoscopic resection in our hospital was conducted. The clinical data, endoscopic ultrasound images, endoscopic treatment, pathological characteristics, postoperative complications and follow-up status of all patients were evaluated. Ten board-certified endoscopists independently evaluated the white light endoscopic images of the 15 patients (Test 1) and the endoscopic ultrasound images together with white light endoscopic images of the same patient set (Test 2).Female patients accounted for 53.4% of the participants. The average age at the time of diagnosis was 49.13 ± 9.31 years old. Ten lesions (66.67%) showed hypoechoic signal, four lesions (26.67%) showed hyperechoic signal and one lesion showed medium signal. The diagnostic accuracy was significantly higher with Test 2(65.3% vs. 92.0%,The endoscopic ultrasound images of esophageal granular cell tumors have certain characteristics that help diagnose esophageal granular cell tumors. Endoscopic resection of esophageal granular cell tumors is an effective, safe and feasible treatment method.

To control the emergence and transmission of CRE, it is important to perform retrospective genomic investigations. It is important to evaluate the plasmid diversity, genetic environment, and evolutionary relationships of the bla NDM -positive clinical strains in the early transmission stages.

Background. To analyze the time trends in cardia cancer detection rates using endoscopic surveillance from 1999 to 2019 in a high-volume Chinese hospital. Methods. In this retrospective, single-center study, data were collected from the Endoscopy Center of the Department of Gastroenterology, Tianjin Medical University General Hospital, from 1999 to 2019. Cases of cardia cancer ( n = 1567 ) were extracted from a database of patients who underwent endoscopy. Clinical and epidemiological characteristics of patients with cardia cancer were analyzed, including sex, age, and proportion of early gastric cancer and degree of tumor differentiation. The joinpoint regression method was used to identify change points in incidence trends. Annual percent change (APC) values, with 95% confidence intervals (CI), were calculated for time periods before and after change points. Results. Of the 343942 patients who underwent endoscopy during 1999–2009, 1567 (4.6%) were identified with cardia cancer. The overall cardia adenocarcinoma detection rate decreased significantly from 1999 to 2004 ( APC = − 37.3 , 95% CI: -20.9, -6.4), followed by a relatively slower decline rate from 2004 to 2019 ( APC = − 7.7 , 95% CI: -4.4, -7.6). The crude rate of detection of early cardia cancer could not be determined by joinpoint analysis. Rates of detection reduced significantly in patients aged 60–69 and 70-79 years ( APC = − 8.3 , 95% CI: -9.8, -6.8 and APC = − 7.3 , 95% CI: -8.8, -5.8, respectively). The detection rate in males decreased rapidly from 1999 to 2004 ( APC = − 35.9 , 95% CI: -18.2, 5.6, P < 0.05 ), while the decline rate was relatively slow from 2005 to 2019 ( APC = − 6.9 , 95% CI: -3.4, -6.1, P < 0.05 ). Among females, the detection rates also decreased from 1999 to 2004 ( APC = − 21.2 , 95% CI: -28.1, -13.7), but remained stable from 2007 to 2019 ( APC = − 3.8 , 95% CI: -7.9, -0.5). Detection of poorly differentiated cardia cancer also declined from 2009 to 2019 ( APC = − 12.8 , 95% CI: -15.3, -10.0). Conclusions. The detection rate of cardia cancer among gastric cancers has been stable from 2008 to 2019. The trend of detection rate of early cardia cancer showed no significant statistical meaning; hence, it remains necessary to carefully observe the cardia area during endoscopy examination.

Background and Aims: Proton pump inhibitor (PPI) was widely used in cirrhotic patients with variceal bleeding empirically rather than evidence-based practice. We aimed to evaluate the plausible indication of PPI use in variceal bleeding cirrhotic patients and figure out whether it can decrease the re-bleeding rate after endoscopic therapy. Furthermore, we also investigated the association between PPI and bleeding-related mortality in these patients. Methods: We have searched in PubMed, Medline, Web of Science, Google Scholar, Cochrane and Embase prior to May 2019. Pooled OR and 95% CI were calculated by random-effects model. Results: A total of 11 original articles including 1,818 cirrhotic patients were analyzed. The overall meta-analysis highlighted that PPI use may decrease the re-bleeding rate after endoscopic therapy (OR 0.52, 95% CI 0.35–0.77). The conclusion was irrespective of study methods, endoscopic purpose and hemorrhage sites. However, the conclusion speculated that PPI should be prescribed >1 month. Meanwhile, PPI use may not impact the bleeding-related mortality. Conclusions: PPI, used for >1 month, can decrease re-bleeding rate after endoscopic therapy in cirrhotic patients for prophylaxis or emergency treatment purpose. No matter how long it takes, PPI use is not associated with bleeding-related mortality.

Saccharomyces boulardii (S. boulardii) is a probiotic yeast that has been elucidated to be efficacious in fighting various gastrointestinal diseases in preclinical as well as clinical studies. Its general mechanisms of probiotic action in the treatment of gastrointestinal conditions cover multifaceted aspects, including immune regulation, production of antimicrobial substances, pathogen competitive elimination, gut barrier integrity maintenance, intestinal trophic effect and antioxidant potency. In this review, basic knowledge with regard to the gut-liver axis, available probiotics remedies and mechanistic insights of S. boulardii as probiotics will be elucidated. In addition, we summarize the therapeutic potential of S. boulardii in several liver diseases evident from both bench and bedside information, such as acute liver injury/failure, fibrosis, hepatic damages due to metabolic disturbance or infection and obstructive jaundice. Future prospects in relation to medicinal effects of S. boulardii are also exploited and discussed on the basis of novel and attractive therapeutic concept in the latest scientific literature.

The prevalence of colorectal cancer (CRC) has markedly increased worldwide in the last decade. Alterations of bile acid metabolism and gut microbiota have been reported to play vital roles in intestinal carcinogenesis. About trillions of bacteria have inhabited in the human gut and maintained the balance of host metabolism. Bile acids are one of numerous metabolites that are synthesized in the liver and further metabolized by the gut microbiota, and are essential in maintaining the normal gut microbiota and lipid digestion. Multiple receptors such as FXR, GPBAR1, PXR, CAR and VDR act as sensors of bile acids have been reported. In this review, we mainly discussed interplay between bile acid metabolism and gut microbiota in intestinal carcinogenesis. We then summarized the critical role of bile acids receptors involving in CRC, and also addressed the rationale of multiple interventions for CRC management by regulating bile acids-microbiota axis such as probiotics, metformin, ursodeoxycholic acid and fecal microbiota transplantation. Thus, by targeting the bile acids-microbiota axis may provide novel therapeutic modalities in CRC prevention and treatment.

Background: Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune inflammatory and fibrotic condition. The disease is characterized by tissue infiltration with dense lymphoplasmacytes and IgG4-positive plasma cells. Summary: The aim of this study was to provide gastroenterologists with novel insights into evaluating the gastroesophageal involvement with IgG4-RD or mimickers of this condition and to give special attention to clinicopathological features. A literature review was performed using the PubMed database. A total of 39 studies presenting cases in the form of isolated, typical, and nontypical gastroesophageal involvement with IgG4-RD published between 2010 and 2018 were included. These studies were thoroughly reviewed for symptoms, lesion location, lesion type, lesion size, immune-histopathology, associated diseases, treatment, and follow-up. Of the 39 studies reviewed, 9 were esophageal IgG4-RD lesions, isolated esophageal IgG4-RD 66.66% (6/9), a typical form of esophageal IgG4-RD 11.11% (1/9), and nontypical form esophageal IgG4-RD 22.22% (2/9). The 30 gastric IgG4-RD that include isolated gastric IgG4-RD 46.66% (14/30), typical gastric IgG4-RD 40% (12/30), and nontypical gastric IgG4-RD 13.33% (4/30). The majority of lesions were inflammatory tumors, ulceration, nodular lesions, chronic gastritis, and malignant lesions. Key Messages: IgG4-RD may be manifested by isolated, typical and nontypical forms of gastroesophageal lesions and should be taken into consideration in the differential diagnosis. Corticosteroids may be the sole diagnostic treatment for this condition.

The emergence and dissemination of metallo-β-lactamases (MBLs) producing Enterobacterales is a great concern for public health due to the limited therapeutic options. No MBL inhibitors are currently available in clinical practice. Herein, we synthesized a series of H

Background. Patients with prolonged inflammatory bowel disease (IBD) can develop into colorectal cancer (CRC), also called colitis-associated cancer (CAC). Studies have shown the association between gut dysbiosis, abnormal bile acid metabolism, and inflammation process. Here, we aimed to investigate these two factors in the CAC model. Methods. C57BL/6 mice were randomly allocated to two groups: azoxymethane/dextran sodium sulfate (AOM/DSS) and control. The AOM/DSS group received AOM injection followed by DSS drinking water. Intestinal inflammation, mucosal barrier, and bile acid receptors were determined by real-time PCR and immunohistochemistry. Fecal microbiome and bile acids were detected via 16S rRNA sequencing and liquid chromatography-mass spectrometry. Results. The AOM/DSS group exhibited severe mucosal barrier impairment, inflammatory response, and tumor formation. In the CAC model, the richness and biodiversity of gut microbiota were decreased, along with significant alteration of composition. The abundance of pathogens was increased, while the short-chain fatty acids producing bacteria were reduced. Interestingly, Clostridium XlV and Lactobacillus, which might be involved in the bile acid deconjugation, transformation, and desulfation, were significantly decreased. Accordingly, fecal bile acids were decreased, accompanied by reduced transformation of primary to secondary bile acids. Given bile acid receptors, the ileum farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) axis was downregulated, while Takeda G-protein receptor 5 (TGR5) was overexpressed in colonic tumor tissues. Conclusion. Gut dysbiosis might alter the metabolism of bile acids and promote CAC, which would provide a potential preventive strategy of CAC by regulating gut microbiota and bile acid metabolism.

Carbapenem-resistant Enterobacterales (CRE) pose a serious threat to clinical management and public health. We investigated the molecular characteristics of 12 IMP-4 metallo-β-lactamase-producing strains, namely, 5 Enterobacter cloacae, 3 Escherichia coli, 2 Klebsiella pneumoniae, and 2 Citrobacter freundii. These strains were collected from a tertiary teaching hospital in Zhengzhou from 2013 to 2015. The minimum inhibitory concentration (MIC) results showed that each blaIMP–4-positive isolate was multidrug-resistant (MDR) but susceptible to colistin. All of the E. coli belonged to ST167, two C. freundii isolates belonged to ST396, and diverse ST types were identified in E. cloacae and K. pneumoniae. S1-PFGE, Southern blotting, and PCR-based replicon typing assays showed that the blaIMP–4-carrying plasmids ranged from ∼52 to ∼360 kb and belonged to FII, FIB, HI2/HI2A, and N types. N plasmids were the predominant type (8/12, 66.7%). Plasmid stability testing indicated that the blaIMP–4-carrying N-type plasmid is more stable than the other types of plasmids. Conjugative assays revealed that three of the blaIMP–4-carrying N plasmids were transferrable. Complete sequence analysis of a representative N type (pIMP-ECL14–57) revealed that it was nearly identical to pIMP-FJ1503 (KU051710) (99% nucleotide identity and query coverage), an N-type blaIMP–4-carrying epidemic plasmid in a C. freundii strain. PCR mapping indicated that a transposon-like structure [IS6100-mobC-intron (K1.pn.I3)-blaIMP–4-IntI1-IS26] was highly conserved in all of the N plasmids. IS26 involved recombination events that resulted in variable structures of this transposon-like module in FII and FIB plasmids. The blaIMP–4 gene was captured by a sul1-type integron In1589 on HI2/HI2A plasmid pIMP-ECL-13–46.

Preserving global and local structures during projection learning is very important for feature extraction, they commonly introduce an extra graph regularization term, If this initial graph construction is of low quality then the resulting projection may also be of low quality. Moreover, conventional projection methods simply use Euclidean distance to measure the similarity of samples, ignoring the dynamic structure information of data. Meanwhile, recent studies have shown that a probabilistically motivated distance measurement (called effective distance) can model the dynamic structure information of data. In this paper, we propose an effective distance based Low-Rank Preserving Projection method (EDLRPP), EDLRPP imposes the effective distance based graph constraint on the reconstruction error of data instead of introducing the extra regularization term to capture the global and local structure of data, which can greatly reduce the complexity of the model. We evaluate our method on datasets in the task of image classification, with results demonstrating the effectiveness of the method.

Autism spectrum disorder (ASD) refers to a syndrome of social deficits and repetitive behaviors. It remains a behaviorally defined syndrome with no reliable biomarkers. Although many studies have been devoted to detecting clinically useful biomarkers based on resting-state functional magnetic resonance imaging (rs-fMRI), they fail to take the strong group relationships in the feature selection process, thus leading to significant information loss. To address this issue, we propose an automatic method for ASD diagnosis based on elastic net with rs-fMRI data. The advantage of the elastic network method is that it does not need to make feature selection in advance, which greatly saves time and improves the efficiency of the algorithm. Experimental results on the public database ABIDE demonstrate the effectiveness and usefulness of the proposed method.

Background Accumulating evidence points to a close relationship between gut dysbiosis and colorectal cancer (CRC). As >90% of CRC develop from adenoma, we aimed to investigate the crucial role of imbalanced gut microbiota on the progression of intestinal adenoma. Methods The Apcmin/+ mice gavage with phosphate-buffered saline (PBS), feces from healthy controls or CRC patients after antibiotic cocktails. The intestinal tissues were isolated for histopathology, western blotting, and RNA-seq. The microbiota of feces and short-chain fatty acids (SCFAs) were analysed by 16S rDNA Amplicon Sequencing and gas chromatography. Findings The Apcmin/+mice gavaged by feces from CRC patients had more intestinal tumours compared with those fed with feces from healthy controls or PBS. Administration of feces from CRC patients increased tumour proliferation and decreased apoptosis in tumour cells, accompanied by impairment of gut barrier function and up-regulation the pro-inflammatory cytokines profile. The up-regulated the expression of β-catenin and cyclinD1 further indicating the activation of Wnt signalling pathway. The abundance of pathogenic bacteria was increased after FMT, while producing SCFAs bacteria and SCFAs production were decreased. Interpretation Gut microbiota of CRC patients disrupted intestinal barrier, induced low-grade inflammation and dysbiosis. The altered gut microbiota enhanced the progression of intestinal adenomas in Apcmin/+mice, suggesting that a new strategy to target gut microbiota against CRC could be noted. Fund The study was supported by the National Natural Science Foundation of China, Tianjin Research Programme of Application Foundation and Advanced Technology of China, and China Postdoctoral Science Foundation.

Background. To assess the role of endoscopic ultrasound (EUS) in the diagnosis of upper gastrointestinal subepithelial lesions (SELs) and to investigate EUS combined with a grayscale histogram analysis for the differentiation of leiomyomas and gastrointestinal stromal tumors (GISTs). Methods. A retrospective study of 709 patients with upper gastrointestinal SELs was conducted by EUS before endoscopic resection. The EUS findings of SELs and pathological results after endoscopic resection were compared. The EUS images of SELs, particularly, leiomyoma and GIST, were further analyzed via a grayscale histogram to differentiate between the two tumors. Results. Of the 709 patients, 47 cases were pathologically undetermined. The diagnostic consistency of EUS with endoscopic resection was 88.2% (584/662), including 185 muscularis mucosa, 61 submucosa, and 338 muscularis propria, respectively. The diagnostic consistency of EUS with pathology was 80.1% (530/662). The gray value of GISTs was significantly higher than that of leiomyomas (58.9±8.3 vs. 39.5±5.9, t=57.0, P<0.0001). The standard deviation of leiomyomas was significantly lower than that of GISTs (20.6±7.0 vs. 39.8±9.3, t=23.7, P<0.0001). The grayscale histogram analysis of GISTs showed higher echo ultrasound, and the echo of leiomyoma was more uniform. Conclusion. EUS is the preferred procedure for the evaluation of upper gastrointestinal SELs. EUS combined with a grayscale histogram analysis is an effective method for the differentiation of leiomyomas and GISTs.

The emergence and dissemination of metallo-β-lactamases (MBLs) producing Enterobacterales is a great concern for public health due to the limited therapeutic options. No MBL inhibitors are currently available in clinical practice. Herein, we synthesized a series of H2dpa derivatives containing pentadentate-chelating ligands and evaluated their inhibitory activity against MBLs. Related compounds inhibited clinically relevant MBLs (Imipenemase, New Delhi metallo-β-lactamase (NDM) and Verona integron-encoded metallo-β-lactamase) with IC50 values of 1–4.9 μM. In vitro, the most promising compounds, 5b and 5c, which had a chiral methyl at the acid adjacent to 5a, demonstrated potent synergistic activity against engineered strains, with fractional inhibitory concentration index values as low as 0.07–0.18. The addition of 5b and 5c restored meropenem efficacy against 42 MBL-producing Enterobacterales and Pseudomonas aeruginosa to satisfactory clinical levels. In addition, safety tests revealed that 5b/5c showed no toxicity in red blood cells, cell lines or mouse model. Further studies demonstrated that compounds 5b and 5c were non-competitive MBL inhibitors. In vivo compounds 5b and 5c potentiated meropenem efficacy and increased the survival rate from 0 to at least 83% in mice with sepsis caused by an NDM-1-positive clinical strain. The activity of the compounds exhibited consistency at the molecular, cellular, and in vivo levels. These data indicated that H2dpa derivatives 5b and 5c containing pentadentate-chelating ligands may be worthy of further study.

Baicalin is the main bioactive component extracted from the traditional Chinese medicine Baical Skullcap Root, and its anti-tumor activity has been studied in previous studies. PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a serine/threonine protein kinase, is highly expressed in many cancer cells and stimulates the tumorigenic properties, and so, it is a pivotal target for agent to cure cancers. We reported for the first time that baicalin suppressed PBK/TOPK activities by directly binding with PBK/TOPK in vitro and in vivo. Ex vivo studies showed that baicalin suppressed PBK/TOPK activity in JB6 Cl41 cells and H441 lung cancer cells. Moreover, knockdown of PBK/TOPK in H441 cells decreased their sensitivity to baicalin. In vivo study indicated that injection of baicalin in H441 tumor-bearing mice effectively suppressed cancer growth. The PBK/TOPK downstream signaling molecules Histone H3 and ERK2 in tumor tissues were also decreased after baicalin treatment. Taken together, baicalin can inhibit proliferation of lung cancer cells as a PBK/TOPK inhibitor both in vitro and in vivo.

Background: Accumulating evidence points to a close relationship between gut dysbiosis and colorectal cancer (CRC). As more than 90% of CRC develop from adenoma, we aimed to investigate the crucial role of imbalanced gut microbiota on the progression of intestinal adenoma. Methods: The Apcmin/+ mice gavage with phosphate-buffered saline (PBS), feces from healthy controls or CRC patients after antibiotic cocktails. The intestinal tissues were isolated for histopathology, western blotting, and RNA-seq. The microbiota of feces and short-chain fatty acids (SCFAs) were analyzed by 16S rDNA Amplicon Sequencing and gas chromatography. Results: The Apcmin/+ mice gavaged by feces from CRC patients had more intestinal tumors compared with those fed with feces from healthy controls or PBS. Administration of fecal from CRC patients increased tumor proliferation and decreased apoptosis in tumor cells, accompanied by impairment of gut barrier function and up-regulation the pro-inflammatory cytokines profile. Abnormal expression of genes related to Wnt-protein binding and lipid metabolic process was observed. The upregulated the expression of β-catenin and cyclinD1 further indicating the activation of Wnt signaling pathway. The abundance of pathogenic bacteria was increased after FMT, while SCFAs producing bacteria and SCFAs production were decreased. Conclusion: Gut microbiota of CRC patients disrupted intestinal barrier, induced low-grade inflammation and dysbiosis. The altered gut microbiota enhanced the progression of intestinal adenomas in Apcmin/+ mice, suggesting that a new strategy to target gut microbiota against CRC could be noted. Funding Statement: This study is supported by the grants (81741075, 81570478, and 81700456) from the National Natural Science Foundation of China, the grants (17JCYBJC24900, 17ZXMFSY00210) from Tianjin Research Program of Application Foundation and Advanced Technology of China, the grant (2019M651049) from China Postdoctoral Science Foundation. Declaration of Interests: The authors state: "No potential conflicts of interest." Ethics Approval Statement: All experimental procedures have been approved by the Ethics Committee of Tianjin Medical University.

Brachytherapy is a targeted type of radiotherapy utilized in the treatment of cancers. Elastin-like polypeptides are a unique class of genetically engineered peptide polymers that have several attractive properties for brachytherapy.To explore the feasibility and application of brachytherapy for VX2 liver tumor using elastin-like polypeptides with (131)I so as to provide reliable experimental evidence for a new promising treatment of liver cancer.Elastin-like polypeptide as carrier was labeled with (131)I using the iodogen method. Ten eligible rabbits with VX2 liver tumor were randomly divided into the treatment group (n = 5) and control group (n = 5). The treatment group received brachytherapy using elastin-like polypeptide with (131)I, and in the control group, elastin-like polypeptide was injected into the VX2 liver tumor as a control. Periodic biochemical and imaging surveillances were required to assess treatment efficacy.The stability of elastin-like polypeptide with (131)I in vitro was maintained at over 96.8 % for 96 h. Biochemistry and imaging indicated brachytherapy using elastin-like polypeptide with (131)I for liver tumor can improve liver function and inhibit tumor growth (P 0.05).Elastin-like polypeptide can be an ideal carrier of (131)I and have high labeling efficiency, radiochemical purity and stability. Brachytherapy using elastin-like polypeptide with (131)I for liver tumor is a useful therapy that possesses high antitumor efficacy advantages.

Introduction: Co-existence of both virulence and multidrug-resistant (MDR) determinants on a self-transmissible plasmid facilitates simultaneous transfer of virulence and resistance in a single event and rapid emergence of virulent and MDR Klebsiella pneumoniae clones. Method: This study identified extensively drug-resistant ST15 strains, KP17-15 and KP17-16, from clinical cases with microbiological and genomical approaches. Results: The chromosomes of KP17-15 and KP17-16 were highly homologous with 12 SNP differences, indicating that the two strains were derived from the same clone. Multiple plasmids existed in the isolates, including novel virulence plasmids p17-15-vir (479 kb) and p17-16-vir (290 kb) for KP17-15 and KP17-16, respectively. Notably, the plasmid p17-15-vir (479 kb) was a hybrid plasmid that might be formed by recombination of two homologous regions encoding group II intron reverse transcriptase and mobile element ISShes11 shared by p17-16-vir (290 kb) and a conjugative MDR plasmid p17-16-CTX (188 kb). p17-15-vir was readily transferable to ST11 Klebsiella pneumoniae by conjugation. Moreover, p17-16-vir, a non-conjugative virulence plasmid lacking the transfer (tra) operon, was also transferable by conjugation under the help of p17-16-CTX or p17-16-KPC. Fusion of p17-16-vir with p17-16-CTX into a p17-15-vir-like plasmid was also observed in the transconjugant. Conclusion: The findings uncover the evolutionary pathway of a novel hybrid virulence MDR plasmid and transfer mechanism of a non-conjugative virulence plasmid. Systematic surveillance of such hybrid virulence MDR plasmids in clinical Klebsiella pneumoniae should be performed.

A group of stimulus-responsive biopolymers developed from the hydrophobic domain of tropoelastin is collectively known as elastin-like polypeptides (ELPs). These peptides generally consist of repeated pentapeptide units of the form (VPGXG)n, where X can be any amino acid with the exception of proline. ELPs present wide-ranging possibilities in biomedicine due to their many beneficial characteristics, including tunable phase transition behavior and biological compatibility, along with the absence of immunogenic and pyrogenic characteristics. The present paper reviews the physicochemical characteristics of ELPs and outlines a range of applications in biotechnology and medicine.

BACKGROUND Currently, non-invasive methods for screening pancreatic cancer are lacking. There is little information regarding whether endoscopic ultrasound (EUS) imaging has a discriminatory ability for detecting benign and malignant pancreatic neoplasms. In this study, we retrospectively analyzed the demographic, clinicopathologic, and EUS features and follow-up information. MATERIAL AND METHODS A total of 58 patients with pancreatic neoplasms who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) over a 7-year period (2009-2016) at our Department of Digestive Diseases were enrolled in our study. RESULTS Of the 58 patients, 38 (65.5%) were diagnosed with malignant pancreatic neoplasms and 20 (34.5%) were benign ones. Of all the EUS findings, size of neoplasm (P=0.037) and regularity of margin (P=0.011) were significantly different between malignant and benign pancreatic neoplasms. However, age, sex, location, echo pattern, and dilation of main pancreatic duct did not show any significant difference (P>0.05). Size combined with regularity to detect malignant pancreatic neoplasms showed the following diagnostic values: sensitivity, 73.68%; specificity, 90%; positive predictive value, 76.60%; negative predictive value 81.82%; and area under the receiver operating characteristic curve, 0.887 (95% CI: 0.777-0.955, P