Diagnostic Value of Ultrasound Endoscopy-Guided Fine-Needle Aspiration for Peritoneal Lesions.

Background: Peritoneal lesions present diagnostic challenges, necessitating precise imaging techniques. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) offers a promising approach for accurate diagnosis, aiding in optimal patient management and treatment planning. Objective: This study aims to assess the diagnostic efficacy of EUS-FNA in peritoneal lesions to offer insight in guiding optimal patient management. Methods: A prospective observational study was conducted, and a total of 58 patients who underwent EUS-FNA of the peritoneum at our hospital between October 2021 and November 2021 were included. The ultrasound diagnostic instrument facilitated puncture guidance, with 2-5 punctures performed in various parts of the selected peritoneal lesion areas. The analysis encompassed evaluating the sensitivity, specificity, positive predictive value, and negative predictive value of biopsy for diagnosing peritoneal-associated lesions, alongside assessing the number of punctures, puncture satisfaction, and incidence of postoperative complications. Results: The included patients undergoing EUS-FNA revealed that 41 (70.69%) had malignant lesions, while 17 (29.31%) presented with benign lesions. The diagnostic accuracy of EUS-FNA for peritoneal lesions was determined to be 94.83%, with a diagnostic sensitivity of 97.30% for malignant tumors, specificity of 90.48%, positive predictive value of 94.74%, and negative predictive value of 95%. Lesions exhibited a size range of 2.5cm × 2.9cm to 15.2cm × 9.8cm. Each patient underwent 2-5 punctures (3.3 ± 1.4), with a puncture satisfaction rate of 96.55%. The incidence of postoperative complications following EUS-FNA was found to be 3.45%. Conclusion: EUS-FNA exhibits substantial diagnostic utility for peritoneal-related lesions, marked by exceptional accuracy, sensitivity, specificity, and favorable safety. Its clinical adoption is warranted, promising improved patient care and management.

A modified dual-knife fistulotomy for achieving challenging biliary cannulation in type 3 papilla.

Video 1A modified dual-knife fistulotomy for achieving challenging biliary cannulation in type 3 papilla.

Comparison of endoscopic resection therapies for rectal neuroendocrine tumors.

AIMS: This study was to evaluate and compare the efficacy and safety of endoscopic mucosal resection (EMR), clip-and-snare assisted endoscopic mucosal resection (CS-EMR), and endoscopic submucosal dissection (ESD) for the endoscopic resection of rectal NETs. MATERIAL AND METHODS: A retrospective analysis was performed on 47 patients with rectal NETs who underwent endoscopic treatment in The Second Affiliated Hospital of Soochow University. Manifestations of clinic pathological characteristics, complications, procedure time and hospitalization costs were studied. RESULTS: The complete resection rates with CS-EMR and ESD were significantly higher than those with EMR (CS-EMR vs. EMR, p = 0.038; ESD vs. EMR, p = 0.04), but no significant difference was found between the CS-EMR and ESD groups (p = 0.383). The lateral margin was less distant in the CS-EMR group than in the ESD group and there was no difference with regard to vertical margin (lateral margin distance, 1500 ± 3125 vs.3000 ± 3000 µm; vertical margin distance, 400 ± 275 vs.500 ± 500 µm). Compared to ESD, CS-EMR required less operation time (p < 0.01) and money (p < 0.01) and reduced the length of hospital stays (p < 0.01). CONCLUSIONS: The CS-EMR technique is more effective and efficient than EMR for small rectal NETs. In addition, CS-EMR reduces procedure time, duration of post-procedure hospitalization and decreases patients' cost compared to ESD while ensuring sufficient vertical margin distances.

Thiol-Based Modification of MarR Protein VnrR Regulates Resistance Toward Nitrofuran in Vibrio cholerae By Promoting the Expression of a Novel Nitroreductase VnrA and of NO-Detoxifying Enzyme HmpA.

Aims: Epidemiological investigations have indicated low resistance toward nitrofuran in clinical isolates, suggesting its potential application in the treatment of multidrug-resistant bacteria. Therefore, it is valuable to explore the mechanism of bacterial resistance to nitrofuran. Results: Through phenotypic screening of ten multiple antibiotic resistance regulator (MarR) proteins in Vibrio cholerae, we discovered that the regulator VnrR (VCA1058) plays a crucial role in defending against nitrofuran, specifically furazolidone (FZ). Our findings demonstrate that VnrR responds to FZ metabolites, such as hydroxylamine, methylglyoxal, hydrogen peroxide (H2O2), ß-hydroxyethylhydrazine. Notably, VnrR exhibits reversible responses to the addition of H2O2 through three cysteine residues (Cys180, Cys223, Cys247), leading to the derepression of its upstream gene, vnrA (vca1057). Gene vnrA encodes a novel nitroreductase, which directly contributes to the degradation of FZ. Our study reveals that V. cholerae metabolizes FZ via the vnrR-vnrA system and achieves resistance to FZ with the assistance of the classical reactive oxygen/nitrogen species scavenging pathway. Innovation and Conclusion: This study represents a significant advancement in understanding the antibiotic resistance mechanisms of V. cholerae and other pathogens. Our findings demonstrate that the MarR family regulator, VnrR, responds to the FZ metabolite H2O2, facilitating the degradation and detoxification of this antibiotic in a thiol-dependent manner. These insights not only enrich our knowledge of antibiotic resistance but also provide new perspectives for the control and prevention of multidrug-resistant bacteria.

The Influence of Soil Erodibility and Saturated Hydraulic Conductivity on Soil Nutrients in the Pingshuo Opencast Coalmine, China.

Soil erodibility (K factor) and saturated hydraulic conductivity (Ks) are essential indicators for the estimation of erosion intensity and can potentially influence soil nutrient losses, making them essential parameters for the evaluation of land reclamation quality. In this study, 132 soil samples from 22 soil profiles were collected to measure soil physicochemical properties (e.g., particle size distribution, bulk density and soil nutrient content) and calculate the K factor and Ks of reclaimed soils across the South Dump of the Pingshuo opencast coalmine in the Loess Plateau, China. Geostatistical analysis and the kriging interpolation were employed to quantify the spatial variations in the K factor and Ks in different layers. The results show that the K factor at 0−10 cm is obviously lower than that of other soil layers due to the external input of organic matter, while the Ks tends to decrease along with soil depth. Horizontally, the K factor at 0−10 cm and 50−60 cm shows a decreasing tendency from west to east, while that of other soil layers seems not to show any spatial distribution pattern along latitude or longitude. Meanwhile, the Ks at 0−10 cm presents a striped distribution pattern, while that of other soil layers shows a patchy pattern. On the other hand, the independent-sample t-test and Spearman's correlation analysis were carried out to determine the effects of soil erodibility on total nitrogen (TN), soil organic matter (SOM), available phosphorus (AP) and potassium (AK). Overall, the K factor is negatively correlated with TN (r = −0.362, p < 0.01) and SOM contents (r = −0.380, p < 0.01), while AP and AK contents are mainly controlled by Ks. This study provides insight on the optimization of reclamation measures and the conservation of soil nutrients in reclaimed land of similar ecosystems.

The correlation between postoperative complications of ERCP and quality of life after discharge in patients with choledocholithiasis.

BACKGROUND: The treatment of choledocholithiasis by endoscopic retrograde cholangiopancreatography (ERCP) is a difficult endoscopic procedure involving a complicated surgical process. During and after ERCP, surgery-related complications may occur, and serious complications can threaten the life of the patient. This study aims to evaluate the correlation between the possible complications of ERCP treatment of choledocholithiasis and the quality of life of patients, and to provide a basis for formulating corresponding intervention measures. METHODS: Using the Gastrointestinal Quality of Life Index (GIQLI) and the MOS item short from health survey (SF-36), we conducted random telephone follow-ups of 194 patients admitted to The Second Affiliated Hospital of Soochow University who underwent ERCP for the treatment of choledocholithiasis from October 2017 to December 2020. The patients' complications symptoms and quality of life were recorded, and a comparative analysis was performed. RESULTS: During the hospitalization of the included 194 patients, complications occurred in 38 cases (19.6%), including 18 cases (9.3%) of hyperamylase, 11 cases (5.7%) of acute pancreatitis, and 5 cases (2.6%) of cholecystitis. There were 4 cases (2.1%) of gastrointestinal bleeding. The SF-36 scores in the complication group were significantly lower than those in the non-complication group across various dimensions, including bodily pain (BP), general health (GH), vitality (VT), social functioning (SE), and mental health (MH). Furthermore, the GIQLI scores in the complication group were lower than those in the non-complication group across various dimensions, including symptoms, subjective symptoms, physical function status, social activity status, as well as mental and psychological status. Multiple regression analysis showed that dimensions such as PF, BP, and subjective symptoms were more likely to be affected by hyperamylaseemia, acute pancreatitis, and cholecystitis, and the difference was statistically significant (P<0.05). CONCLUSIONS: Complications after ERCP result in a poor quality of life after discharge in choledocholithiasis patients, suggesting that nurses need to take effective measures to prevent and actively treat hyperamylase, acute pancreatitis, and acute pancreatitis during the hospitalization of holedocholithiasis patients after ERCP. Common complications, such as cholecystitis, promote the recovery of patients and reduce the impact of the disease on quality of life.

Optogenetic Modification of Pseudomonas aeruginosa Enables Controllable Twitching Motility and Host Infection.

Cyclic adenosine monophosphate (cAMP) is an important secondary messenger that controls carbon metabolism, type IVa pili biogenesis, and virulence in Pseudomonas aeruginosa. Precise manipulation of bacterial intracellular cAMP levels may enable tunable control of twitching motility or virulence, and optogenetic tools are attractive because they afford excellent spatiotemporal resolution and are easy to operate. Here, we developed an engineered P. aeruginosa strain (termed pactm) with light-dependent intracellular cAMP levels through introducing a photoactivated adenylate cyclase gene (bPAC) into bacteria. On blue light illumination, pactm displayed a 15-fold increase in the expression of the cAMP responsive promoter and an 8-fold increase in its twitching activity. The skin lesion area of nude mouse in a subcutaneous infection model after 2-day pactm inoculation was increased 14-fold by blue light, making pactm suitable for applications in controllable bacterial host infection. In addition, we achieved directional twitching motility of pactm colonies through localized light illumination, which will facilitate the studies of contact-dependent interactions between microbial species.

Enhancement of Proliferation and Invasion of Gastric Cancer Cell by KDM5C Via Decrease in p53 Expression.

Gastric cancer is a malignancy with high incidence and the second leading cause of cancer death worldwide. Development of efficient therapies against gastric cancer is urgent. Until now, the mechanisms of gastric cancer genesis remain elusive. The KDM5C is a histone demethylase that promotes cancer cell growth and is enriched in drug-resistant cancer cells. But the pathogenic breadth and mechanistic aspects of this effect relative to gastric cancer have not been defined. In present study, we found that KDM5C was overexpressed in gastric cancer cell lines and gastric cancer tissues but not in normal gastric tissues. The proliferation and invasive potential of gastric cancer cells was significantly increased by ectopic expression of KDM5C. Contrarily, RNA interference targeting KDM5C in gastric cancer cells significantly decreased the proliferation and invasive potential of cells. Moreover, we also found that the expression of p53 was modulated by KDM5C. Cells with overexpression of KDM5C exhibited greatly decreased p53 expression, whereas silencing of KDM5C expression dramatically increased p53 expression at both the messenger RNA and protein levels. Inhibition of p53 by small-interfering RNA reversed the shKDM5C-induced proliferation and invasion. Our results collectively suggested that KDM5C played a role in gastric cancer cells proliferation and invasion, which may be partly associated with the p53 expression.

Simple risk factors to predict urgent endoscopy in nonvariceal upper gastrointestinal bleeding pre-endoscopically.

The goal of this study is to evaluate how to predict high-risk nonvariceal upper gastrointestinal bleeding (NVUGIB) pre-endoscopically. A total of 569 NVUGIB patients between Match 2011 and January 2015 were retrospectively studied. The clinical characteristics and laboratory data were statistically analyzed. The severity of NVUGIB was based on high-risk NVUGIB (Forrest I-IIb), and low-risk NVUGIB (Forrest IIc and III). By logistic regression and receiver-operating characteristic curve, simple risk score systems were derived which predicted patients' risks of potentially needing endoscopic intervention to control bleeding. Risk score systems combined of patients' serum hemoglobin (Hb) ≤75 g/L, red hematemesis, red stool, shock, and blood urine nitrogen ≥8.5 mmol/L within 24 hours after admission were derived. As for each one of these clinical signs, the relatively high specificity was 97.9% for shock, 96.4% for red stool, 85.5% for red hematemesis, 76.7% for Hb ≤75 g/L, and the sensitivity was 50.8% for red hematemesis, 47.5% for Hb ≤75 g/L, 14.2% for red stool, and 10.9% for shock. When these 5 clinical signs were presented as a risk score system, the highest area of receiver-operating characteristic curve was 0.746, with sensitivity 0.675 and specificity 0.733, which discriminated well with high-risk NVUGIB. These simple risk factors identified patients with high-risk NVUGIB of needing treatment to manage their bleeding pre-endoscopically. Further validation in the clinic was required.

Improved autophagic flux is correlated with mTOR activation in the later recovery stage of experimental acute pancreatitis.

BACKGROUND/OBJECTIVES: Lysosomal/autophagic pathway plays important role in the early onset of acute pancreatitis (AP). However, its role in the later recovery phase of AP is unknown. This study aims to investigate the role of lysosomal/autophagic pathway in the self-limited program of AP and elucidate the underlying mechanisms. METHODS: AP was induced in the rat by 3% sodium taurocholate injection in the pancreaticobiliary duct. Serum amylase activity assay, histological examination, and cell death detection were used to assess the time course of AP severity. Meanwhile, the expression of LC3-II, p62 and Lamp-2 was measured to evaluate the status of autophagic flux. S6RP phosphorylation was detected to determine the time course of mTOR activation. Rapamycin was administered to block mTOR activity. RESULTS: AP developed in the rats to the most severe at 24 h but tended to self-restore at 36 and 48 h. The impairment of autophagic flux characterized by the accumulation of LC3-II and p62 and the depletion of Lamp-2 occurred at 24 h after AP induction followed by the restoration over the following 24 h. Furthermore, the phosphorylation of S6RP was increased at 36 and 48 h after AP induction despite the initial inhibition. Rapamycin treatment reduced the level of phospho-S6RP and inhibited the restoration of autophagic homeostasis and pancreatic tissue injury. CONCLUSIONS: Activation of mTOR is correlated with the improvement of autophagic flux and pancreatic injury, suggesting that mTOR activation plays a potential protective role in the later recovery of AP.

MHC2MIL: a novel multiple instance learning based method for MHC-II peptide binding prediction by considering peptide flanking region and residue positions.

BACKGROUND: Computational prediction of major histocompatibility complex class II (MHC-II) binding peptides can assist researchers in understanding the mechanism of immune systems and developing peptide based vaccines. Although many computational methods have been proposed, the performance of these methods are far from satisfactory. The difficulty of MHC-II peptide binding prediction comes mainly from the large length variation of binding peptides. METHODS: We develop a novel multiple instance learning based method called MHC2MIL, in order to predict MHC-II binding peptides. We deem each peptide in MHC2MIL as a bag, and some substrings of the peptide as the instances in the bag. Unlike previous multiple instance learning based methods that consider only instances of fixed length 9 (9 amino acids), MHC2MIL is able to deal with instances of both lengths of 9 and 11 (11 amino acids), simultaneously. As such, MHC2MIL incorporates important information in the peptide flanking region. For measuring the distances between different instances, furthermore, MHC2MIL explicitly highlights the amino acids in some important positions. RESULTS: Experimental results on a benchmark dataset have shown that, the performance of MHC2MIL is significantly improved by considering the instances of both 9 and 11 amino acids, as well as by emphasizing amino acids at key positions in the instance. The results are consistent with those reported in the literature on MHC-II peptide binding. In addition to five important positions (1, 4, 6, 7 and 9) for HLA(human leukocyte antigen, the name of MHC in Humans) DR peptide binding, we also find that position 2 may play some roles in the binding process. By using 5-fold cross validation on the benchmark dataset, MHC2MIL outperforms two state-of-the-art methods of MHC2SK and NN-align with being statistically significant, on 12 HLA DP and DQ molecules. In addition, it achieves comparable performance with MHC2SK and NN-align on 14 HLA DR molecules. MHC2MIL is freely available at http://datamining-iip.fudan.edu.cn/service/MHC2MIL/index.html.

[Protective effects and possible mechanism of lipoxin A(4) analogue in rats with acute pancreatitis].

OBJECTIVE: To explore the protective effects and possible mechanism of lipoxin A(4)-methyl ester (LXA(4)-ME) in rats with acute pancreatitis (AP). METHODS: A total of 120 male SD rats were randomly divided into 3 groups: Sham operation (n = 40), AP (n = 40) and LXA(4)-ME (n = 40). Sham operation group received normal saline after sham operation. AP was induced by a retrograde infusion of 5% sodium taurocholate into pancreatobiliary duct. AP group received normal saline after modeling. In the LXA(4)-ME group, LXA(4)-ME was administered (87.5 µg/kg) intravenously after the onset of AP. The rats were sacrificed at 12 h and 24 h post-induction. Their serum levels of amylase were detected. The amount of ascites was calculated and histological changes of pancreas were observed. The activities of myeloperoxidase (MPO) and levels of malonaldehyde (MDA) in pancreas were determined. The mRNA levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-10, intercellular adhesion molecule (ICAM-1), E-selectin and nuclear factor (NF)-κB p65 in pancreas were measured by reverse transcription-polymerase chain reaction (RT-PCR). The expression of NF-κB p65 protein was also measured by immunohistochemistry. RESULTS: Compared with the AP group, the pathological scores of the LXA(4)-ME group improved (12 h: 8.7 ± 1.3 vs 11.3 ± 1.5, 24 h: 7.8 ± 1.1 vs 11.7 ± 0.8) and the amount of ascites was lower(12 h: (6.88 ± 1.23) ml vs (12.32 ± 1.94) ml, 24 h: (6.53 ± 0.91) ml vs (14.15 ± 1.68) ml, all P < 0.01). The serum levels of amylase in the LXA(4)-ME group were significantly lower than those in the AP group respectively at 12 h and 24 h post-operation (all P < 0.01). The activity of MPO and the level of MDA in pancreas in the LXA(4)-ME group were significantly lower than those in the AP group (all P < 0.01). The pancreatic expressions of TNF-α mRNA, IL-1ß mRNA, ICAM-1 mRNA, E-selectin mRNA and NF-κB p65 mRNA at 12 h and 24 h decreased in the LXA(4)-ME group versus the AP group at the corresponding time points (all P < 0.01)while the expression of IL-10 mRNA increased versus the AP group at the corresponding time points (all P < 0.01). Compared with that in the AP group, the pancreatic expression of NF-κB p65 protein decreased in the LXA(4)-ME group (12 h: 24.8% ± 3.0% vs 45.3% ± 3.4%, 24 h: 31.6% ± 3.0% vs 48.1% ± 4.6%, both P < 0.01). CONCLUSION: LXA(4)-ME exerts protective effects in AP rats. And its mechanism may be due to the suppression of NF-κB activation.