Discovery of pyrazolone spirocyclohexadienone derivatives with potent antitumor activity.

Starting from easy accessible pyrazoletetrahydropyran acetals, a series of new pyrazolone spirocyclohexadienone derivatives were synthesized and assayed for antitumor activity. Compound 10s was identified to possess good antitumor activity. It could induce MDA-MB-231 cancer cell apoptosis in a concentration dependent manner and arrest the cell cycle progression mainly at the G1 phase.

Giant Goos-Hänchen Shifts in Au-ITO-TMDCs-Graphene Heterostructure and Its Potential for High Performance Sensor.

In order to improve the performance of surface plasmon resonance (SPR) biosensor, the structure based on two-dimensional (2D) of graphene and transition metal dichalcogenides (TMDCs) are proposed to greatly enhance the Goos-Hänchen (GH) shift. It is theoretically proved that GH shift can be significantly enhanced in SPR structure coated with gold (Au)-indium tin oxide (ITO)-TMDCs-graphene heterostructure. In order to realize high GH shifts, the number of TMDCs and graphene layer are optimized. The highest GH shift (-801.7 λ) is obtained by Au-ITO-MoSe2-graphene hybrid structure with MoSe2 monolayer and graphene bilayer, respectively. By analyzing the GH variation, the index sensitivity of such configuration can reach as high as 8.02 × 105 λ/RIU, which is 293.24 times of the Au-ITO structure and 177.43 times of the Au-ITO-graphene structure. The proposed SPR biosensor can be widely used in the precision metrology and optical sensing.

Analysis and prediction of single-stranded and double-stranded DNA binding proteins based on protein sequences.

BACKGROUND: DNA-binding proteins perform important functions in a great number of biological activities. DNA-binding proteins can interact with ssDNA (single-stranded DNA) or dsDNA (double-stranded DNA), and DNA-binding proteins can be categorized as single-stranded DNA-binding proteins (SSBs) and double-stranded DNA-binding proteins (DSBs). The identification of DNA-binding proteins from amino acid sequences can help to annotate protein functions and understand the binding specificity. In this study, we systematically consider a variety of schemes to represent protein sequences: OAAC (overall amino acid composition) features, dipeptide compositions, PSSM (position-specific scoring matrix profiles) and split amino acid composition (SAA), and then we adopt SVM (support vector machine) and RF (random forest) classification model to distinguish SSBs from DSBs. RESULTS: Our results suggest that some sequence features can significantly differentiate DSBs and SSBs. Evaluated by 10 fold cross-validation on the benchmark datasets, our prediction method can achieve the accuracy of 88.7% and AUC (area under the curve) of 0.919. Moreover, our method has good performance in independent testing. CONCLUSIONS: Using various sequence-derived features, a novel method is proposed to distinguish DSBs and SSBs accurately. The method also explores novel features, which could be helpful to discover the binding specificity of DNA-binding proteins.

Recognition of the Duration and Prediction of Insect Prevalence of Stored Rough Rice Infested by the Red Flour Beetle (Tribolium castaneum Herbst) Using an Electronic Nose.

The purpose of this research is to explore the feasibility of applying an electronic nose for the intelligent monitoring of injurious insects in a stored grain environment. In this study, we employed an electronic nose to sample rough rice that contained three degrees of red flour beetle (Tribolium castaneum Herbst) infestation for different durations-light degree (LD), middle degree (MD), and heavy degree (HD)-and manually investigated the insect situation at the same time. Manual insect situation investigation shows that, in all three rice treatments, the insect amounts gradually decreased after infestation. When the insect population of stored rough rice was under 13 insects per 60 g of rough rice, the natural speed of decrease of the insect population became very slow and reached the best artificial insect killing period. Linear discriminant analysis (LDA) provided good performance for MD and HD insect harm duration identification, but performed poorly for LD insect harm duration identification. Both k-means clustering analysis (K-means) and fuzzy c-means analysis (FCM) effectively identified the insect harm duration for stored rough rice. The results from the back-propagation artificial neural network (BPNN) insect prevalence prediction for the three degrees of rough rice infestation demonstrated that the electronic nose could effectively predict insect prevalence in stored grain (fitting coefficients were larger than 0.89). The predictive ability was best for LD, second best for MD, and least accurate for HD. This experiment demonstrates the feasibility of electronic noses for detecting both the duration and prevalence of an insect infestation in stored grain and provides a reference for the intelligent monitoring of an insect infestation in stored grains.

Effects of Hydrostatic Pressure and Cation Type on the Chloride Ion Transport Rate in Marine Concrete: An Experimental Study.

The effect of hydrostatic pressure and cation type on chloride ion transport in marine underwater concrete cannot be ignored. The study of the chloride ion transport behavior of concrete under the effect of hydrostatic pressure and cation type coupling can provide a basis for durability design and the protection of marine concrete. In this work, the chloride ion transport behavior of marine concrete in four common chloride salt solutions under different hydrostatic pressures is studied by a hydrostatic pressure test device developed by the authors. The results show that hydrostatic pressure and its action time significantly influence the chloride ion transport behavior in marine concrete; the higher the hydrostatic pressure of concrete, the faster the chloride ion transport rate. The longer the time, the more chloride ions accumulated in the same position, and the farther the chloride ion transport distance. Cation type has a certain influence on the transport process of chloride ions. Under the same test conditions, the chloride ion transport rate in a divalent cation solution is about 5% higher than that in a monovalent cation solution. The results also show that the chloride ion binding capacity under hydrostatic pressure is only 10~20% of that under natural diffusion. Using the test results, a predictive model of a chloride ion apparent transport coefficient based on the hydrostatic pressure and hydrostatic pressure action time corrected by a cation type influence coefficient is established.

Preparation and Properties of Porous Concrete Based on Geopolymer of Red Mud and Yellow River Sediment.

Red mud (RM) and Yellow River sediment (YRS) are challenging to handle as waste materials. In this study, RM with geopolymer and heavy metal adsorption characteristics was combined with YRS and ground granulated blast furnace slag (GGBS) to develop a porous geopolymer with high strength and high adsorption performance. A geopolymer cementitious material with high strength was prepared using high temperature water bath curing of 90 °C and different dosages of YRS, and a porous geopolymer concrete was further prepared. The compressive strength, fluidity and setting time of geopolymer cementitious materials were tested, and the compressive strength, porosity and permeability of porous geopolymer concrete were also tested. The environmental impact assessment of geopolymer cementitious materials was further conducted. The hydration products and microstructure of geopolymer gel materials were analyzed by XRD, SEM and FT-IR tests. The results show that the addition of YRS can effectively prolong the setting time of the geopolymer cementitious material, and the enhancement rate is as high as 150% compared with the geopolymer cementitious materials without the addition of YRS. An appropriate amount of YRS can improve the compressive strength of the geopolymer cementitious materials, and its early compressive strength can be further improved under the high temperature water bath curing of 90 °C, and the compressive strength at an age of 3 d can be up to 86.7 MPa. Meanwhile, the compressive strength of porous geopolymer concrete at an age of 28 d is up to 28.1 MPa. YRS can participate in geopolymer reactions, and high temperature water bath curing can promote the reaction degree. Curing method and YRS dosages have little effect on the porosity and permeability of the porous geopolymer concrete. The porous geopolymer has a good heavy metal adsorption effect, and the alkaline pH values can be gradually diluted to neutral.

Study on the Reactivity Activation of Coal Gangue for Efficient Utilization.

In this study, the research aim is to enhance the activity index of activated coal gangue and study its activation mechanism. The activation process of coal gangue was optimized through orthogonal tests, and the Back-Propagation (BP) neural network model was improved using a genetic algorithm. With the effects of grinding duration, calcination temperature, and calcination duration, the morphological changes and phase transformation processes of coal gangue were studied at the micro and meso levels to clarify the activation mechanism. The results indicated that the effect of calcination temperature on the strength activity index of coal gangue was most significant, followed by grinding duration and calcination duration. The potential activity of coal gangue can be effectively stimulated through mechanical and thermal activation, and the content of potential active minerals in coal gangue powders was also increased. The activation process of coal gangue for the optimal scheme was obtained as grinding at 76 min first and thermal treatment at 54 min at 749 °C. As the thermal activation under 950 °C, some unstable external hydroxyls, and internal hydroxyls in kaolinite from coal gangue were removed, the AlⅥ-O octahedron was destroyed, and kaolinite was transformed into spatially disordered metakaolinite with very high activity.

The value of artificial intelligence techniques in predicting pancreatic ductal adenocarcinoma with EUS images: A meta-analysis and systematic review.

Conventional EUS plays an important role in identifying pancreatic cancer. However, the accuracy of EUS is strongly influenced by the operator's experience in performing EUS. Artificial intelligence (AI) is increasingly being used in various clinical diagnoses, especially in terms of image classification. This study aimed to evaluate the diagnostic test accuracy of AI for the prediction of pancreatic cancer using EUS images. We searched the Embase, PubMed, and Cochrane Library databases to identify studies that used endoscopic ultrasound images of pancreatic cancer and AI to predict the diagnostic accuracy of pancreatic cancer. Two reviewers extracted the data independently. The risk of bias of eligible studies was assessed using a Deek funnel plot. The quality of the included studies was measured by the QUDAS-2 tool. Seven studies involving 1110 participants were included: 634 participants with pancreatic cancer and 476 participants with nonpancreatic cancer. The accuracy of the AI for the prediction of pancreatic cancer (area under the curve) was 0.95 (95% confidence interval [CI], 0.93-0.97), with a corresponding pooled sensitivity of 93% (95% CI, 0.90-0.95), specificity of 90% (95% CI, 0.8-0.95), positive likelihood ratio 9.1 (95% CI 4.4-18.6), negative likelihood ratio 0.08 (95% CI 0.06-0.11), and diagnostic odds ratio 114 (95% CI 56-236). The methodological quality in each study was found to be the source of heterogeneity in the meta-regression combined model, which was statistically significant (P = 0.01). There was no evidence of publication bias. The accuracy of AI in diagnosing pancreatic cancer appears to be reliable. Further research and investment in AI could lead to substantial improvements in screening and early diagnosis.

Effects of Butylphthalide Sodium Chloride Injection Combined with Edaravone Dexborneol on Neurological Function and Serum Inflammatory Factor Levels in Sufferers Having Acute Ischemic Stroke.

For investigating an influence on butylphthalide sodium chloride injection combined with edaravone dexborneol on neurological function and serum inflammatory factor levels in sufferers having acute ischemic stroke, 120 sufferers having acute ischemic stroke from September 2020 to September 2021 are chosen for the study subjects. In line with the diverse therapies, they took part in a control group and the study group, with 60 examples in each group. The control group is treated with edaravone dexborneol, and the study group is treated with butylphthalide sodium chloride injection, based on the control group. The posttreatment curative efficacy on the two groups is recorded, and treatment of both the two groups is compared. Before and after neurological function indexes (NIHSS and mRS), inflammatory factor indexes (IL-6, CRP, and TNF-α), life quality index (Barthel index), hemorheological indexes (plasma-specific viscosity), and neurological levels of NSE are logged and contrasted between the two groups of adverse reactions during therapy. Postcure, the overall response rate and Barthel index of the study group obviously overtop those of the control group (p < 0.05). IL-6, CRP, TNF-α, NSE, plasma specific viscosity, and NIHSS and mRS scores obviously hypodown those of the control group (p < 0.05), and untoward effects on the two groups during curing are lower, and the discrepancy is not obvious(p > 0.05). Butylphthalide sodium chloride injection combined with edaravone dexborneol can enhance curative efficacy on sufferers having acute ischemic stroke, improve neurological function, blood rheology, and quality of life, and decrease the secretion of cytokine, having a better effect and high medication safety.

P2X7R antagonist protects against renal injury in mice with adriamycin nephropathy.

Activation of the purinergic P2X7 receptor (P2X7R) has been associated with the development of experimental nephritis. Therefore, the current study aimed to explore the mechanism of P2X7R in renal injured mice with adriamycin (ADR) nephropathy. The protective effect of a P2X7R antagonist on the kidneys of mice with ADR nephropathy was also evaluated. Nephropathy was induced by a single intravenous injection of ADR (10.5 mg/kg). A total of 6 h before the model was established, the P2X7R antagonist A438079 (100, 200 and 300 µmol/kg) was injected into the mice, which was subsequently administered daily for 1 week by intraperitoneal injection. Subsequently, all mice were sacrificed, after which blood, 24 h-urine and the kidneys were collected. The levels of albumin (ALB) and total cholesterol (TC) in the serum, along with urine protein content at 24 h were determined using an automatic biochemical analyzer. The levels of IL-1ß and IL-18 were additionally detected in the renal tissues by ELISA. Moreover, the expression of P2X7R, oxidized (ox)-low density lipoprotein (LDL), C-X-C motif chemokine ligand 16 (CXCL16), Bax, caspase-3 and NLRP3 in renal tissues was detected by immunohistochemistry. Apoptosis in the renal tissues was observed using the TUNEL assay. The results demonstrated that compared with the control group, decreased weight, increased proteinuria, decreased serum ALB and increased serum TC was observed in the ADR group. The expression of IL-1ß, IL-18, P2X7R, ox-LDL, CXCL16, Bax, caspase-3 and NLRP3, as well as cellular apoptosis in the renal tissues of the ADR group, was significantly increased in the ADR group compared with the control. However, compared with the ADR group, the changes in all indices in the ADR + A438079 groups were attenuated. Overall, P2X7R, ox-LDL and CXCL16 may be associated with ADR nephropathy, while inhibition of P2X7R may reduce the expression of ox-LDL by downregulating the CXCL16 pathway to alleviate kidney injury in mice with ADR nephropathy. Furthermore, activated P2X7R may promote the release of inflammatory cytokines IL-1ß and IL-18 through the downstream P2X7R/NLRP3 pathway and upregulate the expression of Bax and caspase-3 to promote apoptosis, which participates in the process of ADR nephropathy. Inhibiting P2X7R may also reduce the release of IL-1ß and IL-18 by downregulating the P2X7R/NLRP3 pathway, downregulating the expression of Bax and caspase-3, and reducing apoptosis, thereby alleviating kidney injury in mice with ADR nephropathy.

Methods of a New Chronic Pancreatitis and Spontaneous Pancreatic Cancer Mouse Model Using Retrograde Pancreatic Duct Injection of Dibutyltin Dichloride.

The current study aimed to develop a new chronic pancreatitis and spontaneous pancreatic cancer model on C57/BL6 mouse through retrograde pancreatic duct injection of dibutyltin dichloride (DBTC) and explore its basic pathological changes as compared to the previous published chronic pancreatitis model through tail vein injection of DBTC with alcohol drinking. C57/BL6 mice were randomly divided into 3 groups: CG (control group; n = 15), VG (tail vein injection of DBTC (8 mg/kg) with 10% alcohol drinking group; n = 20), and PG (retrograde pancreatic duct injection of DBTC group (1 mg/kg); n = 30). Five mice in each group were sacrificed at a specific time point after the first treatment. The pathological section was observed. The activities of amylase, bilirubin, and hyaluronic acid in serum were determined. The expression of fibronectin, COL1A1, α-SMA, MMP-1, and TIMP-1 in the pancreas was assayed. Severe fibrosis of the pancreas with inflammatory cell infiltration could be observed on day 21 in the PG. In the VG, slight fibrosis of the pancreas with inflammatory cell infiltration was observed on day 28. There were significant differences in serum amylase, bilirubin, and hyaluronic acid levels between the PG and VG. The protein level of COL1A1 and α-SMA significantly increased in the PG. The mRNA expression of TIMP-1 is upregulated and the MMP-1 mRNA level is downregulated in the PG. Finally, typical neoplastic pathological change is significantly obvious in the PG. In conclusion, we established and validated a new chronic pancreatitis (CP) and spontaneous pancreatic cancer mouse model through retrograde injection of DBTC into the pancreatic duct. Previously reported mouse model through tail vein injection of DBTC with alcohol drinking could not cause obvious CP and neoplastic pathological change in mice.

Evodiamine-Inspired Topoisomerase-Histone Deacetylase Dual Inhibitors: Novel Orally Active Antitumor Agents for Leukemia Therapy.

On the basis of the synergism of topoisomerase (Top) and histone deacetylase (HDAC) inhibitors in antitumor therapy, a series of novel Top/HDAC dual inhibitors were designed and synthesized by the pharmacophore fusion strategy. After systematic structure-activity relationship studies, lead compound 16j was identified to simultaneously inhibit both Top and HDAC with good potency, which showed potent antiproliferative activities with a broad spectrum. Mechanistic studies indicated that compound 16j efficiently induced apoptosis with S cell-cycle arrest in HEL cancer cells. It was orally active in HEL xenograft models and exhibited excellent in vivo antitumor efficacy (TGI = 68.5%; 10 mg/kg). Altogether, this work highlights the therapeutic potential of evodiamine-inspired Top/HDAC dual inhibitors and provides a valuable lead compound for the development of novel antitumor agents for leukemia therapy.

The Global Status and Trends of Enteropeptidase: A Bibliometric Study.

BACKGROUND: Enteropeptidase (EP) is a type II transmembrane serine protease and a physiological activator of trypsinogen. Extensive studies related to EP have been conducted to date. However, no bibliometric analysis has systematically investigated this theme. Our study aimed to visualize the current landscape and frontier trends of scientific achievements on EP, provide an overview of the past 120 years and insights for researchers and clinicians to facilitate future collaborative research and clinical intervention. METHODS: Quantitative analysis of publications relating to EP from 1900 to 2020 was interpreted and graphed through the Science Citation Index Expanded of Web of Science Core Collection (limited to SCIE). Microsoft office 2019, GraphPad Prism 8, VOSviewer, and R-bibliometrix were used to conduct the bibliometric analysis. RESULTS: From 1900 to 2020, a total of 1,034 publications were retrieved. The USA had the largest number of publications, making the greatest contribution to the topic (n = 260, 25.15%). Active collaborations between countries/regions were also enrolled. Grant and Hermontaylor were perhaps the most impactful researchers in the landscape of EP. Protein Expression and Purification and the Journal of Biological Chemistry were the most prevalent (79/1,034, 7.64%) and cited journals (n = 2,626), respectively. Using the top 15 citations and co-citations achievements clarified the theoretical basis of the EP research field. Important topics mainly include the structure of EP, the affective factors for activating substrates by EP, EP-related disorders, and inhibitors of EP. CONCLUSION: Based on the bibliometric analysis, we have gained a comprehensive analysis of the global status and research frontiers of studies investigating EP, which provides some guidance and reference for researchers and clinicians engaged in EP research.

Bibliometric Analysis of Cathepsin B Research From 2011 to 2021.

Cathepsin B (CTSB) is a lysosomal protease implicated in the progression of various diseases. A large number of CTSB-related studies have been conducted to date. However, there is no comprehensive bibliometric analysis on this subject. In our study, we performed quantitative analysis of CTSB-related publications retrieved from the Science Citation Index Expanded (SCIE) of the Web of Science Core Collection (reference period: 2011-2021). A total of 3,062 original articles and reviews were retrieved. The largest number of publications were from USA (n = 847, 27.66%). The research output of each country showed positive correlation with gross domestic product (GDP) (r = 0.9745, P < 0.0001). Active collaborations between countries/regions were also observed. Reinheckel T and Sloane BF were perhaps the most impactful researchers in the research landscape of CTSB. Plos ONE was the most prevalent (119/3,062, 3.89%) and cited journal (3,021 citations). Comprehensive analysis of the top citations, co-citations, and keywords was performed to acquire the theoretical basis and hotspots of CTSB-related research. The main topics included CTSB-related cancers and inflammatory diseases, CTSB-associated cell death pattern, and the applications of CTSB. These results provide comprehensive insights into the current status of global CTSB-related research especially in pancreas, which is worthy of continued follow-up by practitioners and clinicians in this field.

Novel insight on marker genes and pathogenic peripheral neutrophil subtypes in acute pancreatitis.

Acute pancreatitis is a common critical and acute gastrointestinal disease worldwide, with an increasing percentage of morbidity. However, the gene expression pattern in peripheral blood has not been fully analyzed. In addition, the mechanism of coronavirus disease 2019 (COVID-19)-induced acute pancreatitis has not been investigated. Here, after bioinformatic analysis with machine-learning methods of the expression data of peripheral blood cells and validation in local patients, two functional gene modules in peripheral blood cells of acute pancreatitis were identified, and S100A6, S100A9, and S100A12 were validated as predictors of severe pancreatitis. Additionally, through a combination analysis of bulk sequencing and single-cell sequencing data of COVID-19 patients, a pivotal subtype of neutrophils with strong activation of the interferon-related pathway was identified as a pivotal peripheral blood cell subtype for COVID-19-induced acute pancreatitis. These results could facilitate the prognostic prediction of acute pancreatitis and research on COVID-19-induced acute pancreatitis.

Endoscopic resection of upper gastrointestinal lymphangioma: A single-center experience.

Objective: Lymphagioma, which in most cases as benign tumors, occurs in head, neck, axilla, and mediastinum. Lymphangioma is exceedingly rare in the upper gastrointestinal tract including esophagus, stomach, and duodenum. However, the clinical characteristics, natural history, and recurrence rate after endoscopic resection remain unclear. This study aims to evaluate the characteristic findings and assess the efficacy of endoscopic techniques in the management of this disease. Methods: In this systematic retrospective analysis, we evaluated all 24 cases of upper gastrointestinal lymphangioma resected by endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) and diagnosed by histopathology at our hospital from January 2012 to May 2021. We analyzed the results of endoscopy, endoscopic ultrasonography (EUS), CT, histologic examination, and follow-up assessments. Results: 9 male and 15 female patients with esophageal lymphangioma were enrolled in this study, with a mean age of 54.17 ± 11.60 years (range 30-71 years). The lesions' size varied from 2.20 to 40.10 mm, with the median size of 7.83 mm. All patients were evaluated preoperatively, whose endoscopic appearance typically appears as dilated lymphatic channels beneath the surface epithelium of the protrude mucosal or sub-mucosal lesion. Endoscopic ultrasonography revealed the presence of a honeycomb-like or grid-like mass with a heterogeneous echo pattern, and a clear boundary between the lesion and the muscularis propria layer may be helpful for the primary diagnosis of this disease. 22 patients underwent EMR and 2 patient were treated with ESD. Histologic examination revealed that the lesions contained many dilated lymphatic vessels, which confirmed the initial diagnosis of lymphangioma in all patients. No major adverse events were found during the operation or a median follow-up of 43 months (range 13-92). Conclusions: Endoscopic ultrasonography has important clinical value for the primary diagnosis of lymphangioma in the upper gastrointestinal tract. This study also suggests that endoscopic resection should be considered as a more minimally invasive, safe, feasible, and effective therapeutic option comparing to laparoscopic surgery.

Cryo-EM structures reveal the activation and substrate recognition mechanism of human enteropeptidase.

Enteropeptidase (EP) initiates intestinal digestion by proteolytically processing trypsinogen, generating catalytically active trypsin. EP dysfunction causes a series of pancreatic diseases including acute necrotizing pancreatitis. However, the molecular mechanisms of EP activation and substrate recognition remain elusive, due to the lack of structural information on the EP heavy chain. Here, we report cryo-EM structures of human EP in inactive, active, and substrate-bound states at resolutions from 2.7 to 4.9 Å. The EP heavy chain was observed to clamp the light chain with CUB2 domain for substrate recognition. The EP light chain N-terminus induced a rearrangement of surface-loops from inactive to active conformations, resulting in activated EP. The heavy chain then served as a hinge for light-chain conformational changes to recruit and subsequently cleave substrate. Our study provides structural insights into rearrangements of EP surface-loops and heavy chain dynamics in the EP catalytic cycle, advancing our understanding of EP-associated pancreatitis.

Establishing and validating an ADCP-related prognostic signature in pancreatic ductal adenocarcinoma.

With the progress of precision medicine treatment in pancreatic ductal adenocarcinoma (PDAC), individualized cancer-related examination and prediction is of great importance in this high malignant tumor, and antibody-dependent cell phagocytosis (ADCP) with changed pathways highly enrolled in the carcinogenesis of PDAC. High-throughput data of pancreatic ductal adenocarcinoma were downloaded and 160 differentially expressed ADCP-related genes (ARGs) were obtained. Secondly, GO and KEGG enrichment analyses show that ADCP is a pivotal biologic process in pancreatic carcinogenesis. Next, CALB2, NLGN2, NCAPG and SERTAD2 are identified through multivariate Cox regression. These 4 genes are confirmed with significant prognostic value in PDAC. Then, a risk score formula is constructed and tested in PDAC samples. Finally, the correlation between these 4 genes and M2 macrophage polarization was screened. Some pivotal differentially expressed ADCP-related genes and biologic processes, four pivotal subgroup was among identified in the protein-protein network, and hub genes was found in these sub group. Then, an ADCP-related formula was set: CALB2* 0.355526 + NLGN2* -0.86862 + NCAPG* 0.932348 + SERTAD2* 1.153568. Additionally, the significant correlation between M2 macrophage-infiltration and the expression of each genes in PDAC samples was identified. Finally, the somatic mutation landscape and sensitive chemotherapy drug between high risk group and low risk group was explored. This study provides a potential prognostic signature for predicting prognosis of PDAC patients and molecular insights of ADCP in PDAC, and the formula focusing on the prognosis of PDAC can be effective. These findings will contribute to the precision medicine of pancreatic ductal adenocarcinoma treatment.

Combination of a negative pressure suction device and endoscope can accurately locate the bleeding site of refractory epistaxis.

BACKGROUND: Selective endoscopic coagulation of a nasal bleeding vessel is an effective means of treating epistaxis. Precisely locating the bleeding site(s) is critical. OBJECTIVE: To investigate the utility of combining a negative pressure suction device and endoscope in locating bleeding sites of refractory epistaxis. METHODS: A total of 116 patients with refractory epistaxis, who underwent systematic endoscopic exploration under local anesthesia in the absence of identifiable sites of bleeding were randomizely divided into two groups via negative pressure group (NPG) and control group (CG): The negative pressure suction device combined with an endoscope was used to re-explore the epistaxis. Nasal bleeding was induced using this method to help the operator locate the site of epistaxis accurately; the bleeding was then stopped using electrocoagulation with the suction electrode. The CG was treated with endoscopic re-exploration and selective tamponade. RESULTS: Compared with the CG, there were statistically significant differences in length of hospital stay, rebleeding, and postoperative pain and complications (all p < .05). CONCLUSION AND SIGNIFICANCE: Combining a negative pressure suction device and endoscope was a safe and effective technique for accurately locating bleeding sites in patients with refractory epistaxis.

Exosomes Released From Human Bone Marrow-Derived Mesenchymal Stem Cell Attenuate Acute Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation in Mice.

OBJECTIVE: Mesenchymal stromal cell-derived exosomes have been applied for the treatment of several immune diseases. This study aimed to explore the effect of human bone marrow-derived mesenchymal stem cell (hBMSC)-derived exosomes on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: hBMSC were cultured, and the culture supernatants were then collected to prepare exosomes using total exosome isolation reagent from Invitrogen. Mouse aGVHD model was established by allogeneic cell transplantation and injected with hBMSC-derived exosomes (Msc-exo) via tail vein. Exosomes from human fibroblast (Fib-exo) were used as the treatment control. The effects of Msc-exo on dendritic cells, CD4+, and CD8+ T cells in aGVHD mice were analyzed through flow cytometry. The impact on inflammatory cytokines was tested by ELISA. Besides, the body weight, survival rate, and clinical score of treated mice were monitored. RESULTS: Msc-exo were successfully prepared. aGVHD mice injected with Msc-exo led to 7-8-fold increase of the CD8α+ conventional dendritic cells (cDCs) and CD11b+ cDCs compared with the controls. In addition, Msc-exo altered the T help and Treg subpopulation, and decreased the cytotoxicity and proliferation of cytotoxic T cells to favor inflammatory inhibition in aGVHD mice. Mice that received Msc-exo exhibited decreased weight loss and reduced aGVHD clinical score in a time-dependent manner as well as reduced lethality compared with Fib-exo treated or untreated control. Furthermore, the levels of IL-2, TNF-α, and IFN-γ were decreased, as well as the level of IL-10 was increased after Msc-exo treatment in vivo and in vitro. CONCLUSION: hBMSC-derived exosomes could attenuate aGVHD damage and promote the survival of aGVHD mice by regulating the DC and T-cell subpopulation and function, and lead to inhibited inflammatory response in aGVHD mice.