Remarkably Enhanced Methane Sensing Performance at Room Temperature via Constructing a Self-Assembled Mulberry-Like ZnO/SnO_(2) Hierarchical Structure

Development of metal oxide semiconductors-based methane sensors with good response and low power consumption is one of the major challenges to realize the real-time monitoring of methane leakage.In this work,a self-assembled mulberry-like ZnO/SnO_(2)hierarchical structure is constructed by a two-step hydrothermal method.The resultant sensor works at room temperature with excellent response of~56.1%to 2000 ppm CH_(4)at 55%relative humidity.It is found that the strain induced at the ZnO/SnO_(2)interface greatly enhances the piezoelectric polarization on the ZnO surface and that the band bending results in the accumulation of chemically adsorbed O_(2)^(-)ions close to the interface,leading to significant improvement in the sensing performance of the methane gas sensor at room temperature.

Predictive model for non-malignant portal vein thrombosis associated with cirrhosis based on inflammatory biomarkers

BACKGROUND Portal vein thrombosis(PVT),a complication of liver cirrhosis,is a major public health concern.PVT prediction is the most effective method for PVT diagnosis and treatment.AIM To develop and validate a nomogram and network calculator based on clinical indicators to predict PVT in patients with cirrhosis.METHODS Patients with cirrhosis hospitalized between January 2016 and December 2021 at the First Hospital of Lanzhou University were screened and 643 patients with cirrhosis who met the eligibility criteria were retrieved.Following a 1:1 propensity score matching 572 patients with cirrhosis were screened,and relevant clinical data were collected.PVT risk factors were identified using the least absolute shrinkage and selection operator(LASSO)and multivariate logistic regression analysis.Variance inflation factors and correlation matrix plots were used to analyze multicollinearity among the variables.A nomogram was constructed to predict the probability of PVT based on independent risk factors for PVT,and its predictive performance was verified using a receiver operating characteristic curve(ROC),calibration curves,and decision curve analysis(DCA).Finally,a network calculator was constructed based on the nomograms.RESULTS This study enrolled 286 cirrhosis patients with PVT and 286 without PVT.LASSO analysis revealed 13 variables as strongly associated with PVT occurrence.Multivariate logistic regression analysis revealed nine indicators as independent PVT risk factors,including etiology,ascites,gastroesophageal varices,platelet count,D-dimer,portal vein diameter,portal vein velocity,aspartate transaminase to neutrophil ratio index,and platelet-to-lymphocyte ratio.LASSO and correlation matrix plot results revealed no significant multicollinearity or correlation among the variables.A nomogram was constructed based on the screened independent risk factors.The nomogram had excellent predictive performance,with an area under the ROC curve of 0.821 and 0.829 in the training and testing groups,respectively.Calibration curves and DCA revealed its good clinical performance.Finally,the optimal cutoff value for the total nomogram score was 0.513.The sensitivity and specificity of the optimal cutoff values were 0.822 and 0.706,respectively.CONCLUSION A nomogram for predicting PVT occurrence was successfully developed and validated,and a network calculator was constructed.This can enable clinicians to rapidly and easily identify high PVT risk groups.

Efficacy of Juanbi capsule on ameliorating knee osteoarthritis:a network pharmacology and experimental verification-based study

Background:The purpose of the study was to investigate the active ingredients and potential biochemical mechanisms of Juanbi capsule in knee osteoarthritis based on network pharmacology,molecular docking and animal experiments.Methods:Chemical components for each drug in the Juanbi capsule were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,while the target proteins for knee osteoarthritis were retrieved from the Drugbank,GeneCards,and OMIM databases.The study compared information on knee osteoarthritis and the targets of drugs to identify common elements.The data was imported into the STRING platform to generate a protein-protein interaction network diagram.Subsequently,a“component-target”network diagram was created using the screened drug components and target information with Cytoscape software.Common targets were imported into Metascape for GO function and KEGG pathway enrichment analysis.AutoDockTools was utilized to predict the molecular docking of the primary chemical components and core targets.Ultimately,the key targets were validated through animal experiments.Results:Juanbi capsule ameliorated Knee osteoarthritis mainly by affecting tumor necrosis factor,interleukin1β,MMP9,PTGS2,VEGFA,TP53,and other cytokines through quercetin,kaempferol,andβ-sitosterol.The drug also influenced the AGE-RAGE,interleukin-17,tumor necrosis factor,Relaxin,and NF-κB signaling pathways.The network pharmacology analysis results were further validated in animal experiments.The results indicated that Juanbi capsule could decrease the levels of tumor necrosis factor-αand interleukin-1βin the serum and synovial fluid of knee osteoarthritis rats and also down-regulate the expression levels of MMP9 and PTGS2 proteins in the articular cartilage.Conclusion:Juanbi capsule may improve the knee bone microstructure and reduce the expression of inflammatory factors of knee osteoarthritis via multiple targets and multiple signaling pathways.

Stress granules inhibit endoplasmic reticulum stress-mediated apoptosis during hypoxia-induced injury in acute liver failure

BACKGROUND Stress granules(SGs)could be formed under different stimulation to inhibit cell injury.AIM To investigate whether SGs could protect hepatocytes from hypoxia-induced damage during acute liver failure(ALF)by reducing endoplasmic reticulum stress(ERS)mediated apoptosis.METHODS The agonist of SGs,arsenite(Ars)was used to intervene hypoxia-induced hepatocyte injury cellular model and ALF mice models.Further,the siRNA of activating transcription factor 4(ATF4)and SGs inhibitor anisomycin was then used to intervene in cell models.RESULTS With the increase of hypoxia time from 4 h to 12 h,the levels of HIF-1α,ERS and apoptosis gradually increased,and the expression of SGs marker G3BP1 and TIA-1 was increased and then decreased.Compared with the hypoxia cell model group and ALF mice model,the levels of HIF-1α,apoptosis and ERS were increased in the Ars intervention group.After siRNA-ATF4 intervention,the level of SGs in cells increased,and the levels of HIF-1α,ERS and apoptosis decreased.Compared with the siRNA-ATF4 group,the levels of G3BP1 in the siRNAATF4+anisomycin group were decreased,and the levels of HIF-1α,ERS and apoptosis were increased.Moreover,compared with the ALF group,the degree of liver injury and liver function,the levels of HIF-1α,ERS and apoptosis in the Ars intervention group were decreased,the level of SGs was increased.CONCLUSION SGs could protect hepatocytes from hypoxia-induced damage during ALF by reducing ERSmediated apoptosis.

Inhibition of Cyclin F Promotes Cellular Senescence through Cyclin-dependent Kinase 1-mediated Cell Cycle Regulation

Objective Kidney renal clear cell carcinoma(KIRC)is a common renal malignancy that has a poor prognosis.As a member of the F box family,cyclin F(CCNF)plays an important regulatory role in normal tissues and tumors.However,the underlying mechanism by which CCNF promotes KIRC proliferation still remains unclear.Methods Bioinformatics methods were used to analyze The Cancer Genome Atlas(TCGA)database to obtain gene expression and clinical prognosis data.The CCK8 assay,EdU assay,and xenograft assay were used to detect cell proliferation.The cell senescence and potential mechanism were assessed by SA-β-gal staining,Western blotting,as well as ELISA.Results Our data showed that CCNF was highly expressed in KIRC patients.Meanwhile,downregulation of CCNF inhibited cell proliferation in vivo and in vitro.Further studies showed that the reduction of CCNF promoted cell senescence by decreasing cyclin-dependent kinase 1(CDK1),increasing the proinflammatory factors interleukin(IL)-6 and IL-8,and then enhancing the expression of p21 and p53.Conclusion We propose that the high expression of CCNF in KIRC may play a key role in tumorigenesis by regulating cell senescence.Therefore,CCNF shows promise as a new biomarker to predict the clinical prognosis of KIRC patients and as an effective therapeutic target.

On the Innovation,Design,Construction,and Experiments of OMEGA-Based SSPS Prototype:The Sun-Chasing Project

This study systematically introduces the development of the world’s first full-link and full-system ground demonstration and verification system for the OMEGA space solar power satellite(SSPS).First,the OMEGA 2.0 innovation design was proposed.Second,field-coupling theoretical models of sunlight concentration,photoelectric conversion,and transmitting antennas were established,and a systematic optimization design method was proposed.Third,a beam waveform optimization methodology considering both a high beam collection efficiency and a circular stepped beam shape was proposed.Fourth,a control strategy was developed to control the condenser pointing toward the sun while maintaining the transmitting antenna toward the rectenna.Fifth,a high-efficiency heat radiator design method based on bionics and topology optimization was proposed.Sixth,a method for improving the rectenna array’s reception,rectification,and direct current(DC)power synthesis efficiencies is presented.Seventh,high-precision measurement technology for high-accuracy beam-pointing control was developed.Eighth,a smart mechanical structure was designed and developed.Finally,the developed SSPS ground demonstration and verification system has the capacity for sun tracking,a high concentration ratio,photoelectric conversion,microwave conversion and emission,microwave reception,and rectification,and thus satisfactory results were obtained.

Chinese herbal medicine for the treatment of endocrine therapyrelated osteoporosis among patients with breast cancer:A systematic review and meta-analysis

Objective:To assess the efficacy and safety of combining traditional Chinese medicine(TCM),specifically Chinese herbal medicine(CHM),with Western medicine(WM),compared to WM alone to treat breast cancer endocrine therapy-related osteoporosis(BCET-OP)by meta-analysis.Methods:Thirty-eight randomized controlled trials involving 2170 participants were analyzed.Eight databases were searched for articles published between inception and December 2023.Quality assessment was performed using the Risk of Bias 2 tool.Results:Significant increases were observed in the TCM-WM group in lumbar vertebrae bone mineral density(BMD)(P<.001,mean difference(MD)=0.07,95%confidence interval(CI):0.06 to 0.08),lumbar vertebrae T-score(P=.0005,MD=0.21,95%CI:0.09 to 0.33)and collum femoris BMD(P=.01,MD=0.10,95%CI:0.02 to 0.19).No significant difference was observed between the groups in the collum femoris T-score and estradiol levels.Bone gla-protein levels were significantly increased in the TCM-WM group(P=.0002,MD=0.52,95%CI:0.25 to 0.79).Beta-CrossLaps decreased significantly in the TCM-WM group(P=.0008,MD=−0.10,95%CI:−0.16 to−0.04).No significant difference was observed between the TCM-WM and WM groups in alkaline phosphatase,in procollagen type I N-terminal propeptide,and in the Kupperman index.The visual analog score(VAS)was decreased in the TCM-WM group compared to the WM group(P<.001,MD=−1.40,95%CI:−1.94 to−0.87).No significant difference in adverse events was observed between the two groups.Conclusion:Combining CHM with WM in patients with BCET-OP significantly improved BMD,T-score,and certain bone turnover markers and reduced the VAS score,indicating potential benefits for bone health and related pain.Adverse event analysis revealed no differences between the groups,supporting the feasibility of the combination therapy.However,further research,particularly in diverse populations,is required.

Relationship between intestinal microbial dysbiosis and primary liver cancer

Background: Intestinal microbial dysbiosis is involved in liver disease pathogenesis. However, its role in primary liver cancer(PLC), particularly in hepatocarcinogenesis remains unclear. The present study aimed to study the changes in intestinal flora at various stages of PLC and clarify the relationship between intestinal microbes and PLC. Methods: Twenty-four patients with PLC(PLC group), 24 patients with liver cirrhosis(LC group), and 23 healthy control individuals(HC group) were enrolled from October 2016 to October 2017. Stool specimens of the participants were collected and the genomic DNA of fecal bacteria was isolated. High-throughput pyrosequencing of 16 S r DNA was used to identify differences in gut bacterial diversity among HC, LC, and PLC groups. We also analyzed the relationship between clinical factors and intestinal microorganisms in LC and PLC groups. Results: Diversity of Firmicutes tended to decrease from the HC to LC and PLC groups at the phylum level. Among species, Enterobacter ludwigii displayed an increasing trend in the PLC group, wherein the relative abundance of Enterobacter ludwigii in the PLC group was 100 times greater than that in the HC and LC groups. The ratio of Firmicutes/Bacteroidetes was significantly decreased with the disease progression. In addition, the linear discriminant analysis effect size method indicated that Clostridia were predominant in the gut microbiota of the HC group, whereas Enterococcaceae, Lactobacillales, Bacilli and Gammaproteobacteria may be used as diagnostic markers of PLC. Redundancy analysis showed a correlation between intestinal microbial diversity and clinical factors AST, ALT, and AFP. Veillonella showed a significant positive correlation with AFP in the PLC group, whereas Subdoligranulum showed a negative correlation with AFP. Conclusions: This study indicates that dysbiosis of the gut microbiota might be involved in PLC development and progression.

Ethyl pyruvate protects against experimental acute-on-chronic liver failure in rats

AIM： To investigate the protective effects of ethyl py- ruvate （EP） on acute-on-chronic liver failure （ACLF） in rats. METHODS： An ACLF model was established in rats, and animals were randomly divided into normal, mod- el and EP treatment groups. The rats in EP treatment group received EP （40 mg/kg） at 3 h, 6 h, 12 h and 24 h after induction of ACLF. Serum endotoxin, high mobility group box-1 （HMGB1）, alanine transaminase （ALT）, tumor necrosis factor-α （TNF-α）, interferon-α （IFN-γ）, interleukin （IL）-10 and IL-18 levels, changes of liver histology and HMGB1 expressions in liver tis- sues were detected at 48 h after induction of ACLF. The effects of EP on the survival of ACLF rats were also observed.RESULTS： Serum levels of endotoxin （0.394 ± 0.066 EU/mL vs 0.086±0.017 EU/mL, P 〈 0.001）, HMGB1 （35.42±10,86 μg/L vs 2.14 ± 0.27 μg/L, P 〈 0.001）, ALT （8415.87 ± 3567.54 IU/L vs 38.64 ± 8.82 IU/L, P 〈 0.001）, TNF-α （190.77 ± 12.34 ng/L vs 124.40 ± 4.12 ng/L, P 〈 0.001）, IFN-γ （715.38 ± 86.03 ng/L vs 398.66 ± 32.91 ng/L, P 〈 0.001）, IL-10 （6.85 ± 0.64 ng/L vs 3.49 ± 0.24 ng/L, P 〈 0.001） and IL-18 （85.19 ±3.49 ng/L vs 55.38 ±1.25 ng/L, P 〈 0.001） were significantly increased, and liver tissues presented se- vere pathological injury in the model group compared with the normal group, Howeverr EP administration significantly improved hepatic histopathology and re- duced the serum levels of endotoxin （0.155±0.045 EU/mL vs 0.394 ± 0.066 EU/mL vs P 〈 0.001） and in- flammatory cytokines （11.13 ± 2.58 μg/L vs 35.42 ± 10.86 μg/L for HMGB1, 3512.86 ± 972.67 IU/L vs 8415.87 ± 3567.54 IU/L for ALT, 128.55 ± 5.76 ng/L vs 190.77 ± 12.34 ng/L for TNF-α 438.16 ± 38.10 ng/L vs 715.38 ± 86.03 ng/L for IFN-γ 3.55 ± 0.36 ng/L vs 6.85 ± 0.64 ng/L for IL-10, and 60.35 ± 1.63 ng/L vs 85.19 ± 3.49 ng/L for IL-18, respectively, P 〈 0.001）, and the levels of HMGB1 in liver tissues re- gardless of treatment time after induction of ACLF. EP treatment at the four time points prolonged the me- dian survival time of ACLF rats （60 h） to 162 h, 120 h, 102 h and 78 h, respectively （χ2 = 41.17, P 〈 0.0001）. CONCLUSION： EP administration can protect against ACLF in rats, and is a potential and novel therapeutic agent for severe liver injury.

SHEL模式下医疗安全教学与学生临床思维能力提升研究

目的:探索SHEL模式在医疗安全教学和提升学生临床思维能力的应用效果。方法:将46名大三全日制护理本科生随机分为观察组和对照组各23人。对照组按常规安全管理培训,观察组采用SHEL模式,从软件、硬件、环境和人员四个方面进行综合培训。比较两组学生的安全知识得分和患者满意度来评估培训效果。结果:观察组在护理内容、安全意识和生活细节得分显著高于对照组(P<0.01),患者满意度有显著提高(P<0.01)。结论:SHEL模式有效提升了学生的医疗安全知识和临床思维能力,增强了其安全意识,提高了其护理安全管理水平,从而增进了患者的满意度。

Ethyl pyruvate prevents inflammatory factors release and decreases intestinal permeability in rats with D-galactosamine-induced acute liver failure

BACKGROUND: The pathogenesis and progression of acute liver failure (ALF) are closely associated with intestinal endotoxemia because of the high permeability of the intestinal wall. Treatment with ethyl pyruvate (EP) has been shown to protect liver failure effectively. The current study aimed to explore the relationship between proinflammatory cytokines and intestinal permeability, and to investigate whether EP administration might prevent the release of multiple proinflammatory cytokines and decrease intestinal permeability and therefore, protect the liver from injury. METHODS: The ALF model was induced by D-galactosamine in rats. The rats were randomly divided into control (saline i.p.), model (D-galactosamine, 1.2 g/kg, i.p.), prevention [EP injection (40 mg/kg) 2 hours ahead of D-galactosamine] and treatment groups (EP injection 2 hours after D-galactosamine) Samples were obtained at 12 and 24 hours after ALF induction respectively. The histology of liver and intestinal tissue was accessed. Serum alanine aminotransferase, endotoxin, D(-) lactate, diamine oxidase (DAO), tumor necrosis factor-alpha (TNF-α), interferon-γ (IFN-γ) and high mobility group box-1 (HMGB1) were evaluated. The survival of rats was also recorded. RESULTS: The rats in model group showed severe damage to liver tissue and intestinal mucosa 12 and 24 hours after ALF induction. EP significantly improved liver or intestinal injury In addition, serum endotoxin, D(-)-lactate, DAO, TNF-α IFN-γ and HMGB1 levels were significantly increased in the model group compared with the control group. There was a positive correlation between intestinal permeability andproinflammatory cytokines. EP significantly reduced serum endotoxin, D(-)-lactate, DAO, TNF-α, IFN-γ and HMGB1 levels. The median survival time was significantly prolonged in both prevention and treatment groups (126 and 120 hours compared with 54 hours in the model group). CONCLUSIONS: EP has protective and therapeutic effects on intestinal mucosa. EP decreases intestinal permeability, and inhibits the release of multiple proinflammatory cytokines in rats with ALF.

Clinical significance of different periampullary diverticulum classifications for endoscopic retrograde cholangiopancreatography cannulation

BACKGROUND Different types of periampullary diverticulum(PAD) may differentially affect the success of endoscopic retrograde cholangiopancreatography(ERCP) cannulation,but the clinical significance of the two current PAD classifications for cannulation is limited.AIM To verify the clinical value of our newly proposed PAD classification.METHODS A new PAD classification(Li-Tanaka classification) was proposed at our center.All PAD patients with native papillae who underwent ERCP from January 2012 to December 2017 were classified according to three classification systems, and the effects of various types of PAD on ERCP cannulation were compared.RESULTS A total of 3564 patients with native papillae were enrolled, including 967(27.13%)PAD patients and 2597(72.87%) non-PAD patients. In the Li-Tanaka classification, type Ⅰ PAD patients exhibited the highest difficult cannulation rate(23.1%, P = 0.01), and type Ⅱ and Ⅳ patients had the highest cannulation success rates(99.4% in type Ⅱ and 99.3% in type Ⅳ, P < 0.001). In a multivariableadjusted logistic model, the overall successful cannulation rate in PAD patients was higher than that in non-PAD patients [odds ratio(OR) = 1.87, 95% confidence interval(CI): 1.04-3037, P = 0.037]. In addition, compared to the non-PAD group,the difficulty of cannulation in the type Ⅰ PAD group according to the Li-Tanaka classification was greater(OR = 2.04, 95%CI: 1.13-3.68, P = 0.004), and the successful cannulation rate was lower(OR = 0.27, 95%CI: 0.11-0.66, P < 0.001),while it was higher in the type Ⅱ PAD group(OR = 4.44, 95%CI: 1.61-12.29, P <0.01).CONCLUSION Among the three PAD classifications, the Li-Tanaka classification has an obvious clinical advantage for ERCP cannulation, and it is helpful for evaluating potentially difficult and successful cannulation cases among different types of PAD patients.

Expression and function of Delta-like ligand 4 in a rat model of retinopathy of prematurity

The Delta-like ligand 4/Notch signaling pathway was shown to participate in the process of retinal development and angiogenesis. However, the function of the Delta-like ligand 4/Notch signaling pathway in retinopathy of prematurity requires further study. Retinopathy of prematurity was induced in 5-day-old Sprague-Dawley rats exposed to hyperoxia for 7 days, and then returned to room air. Reverse transcription-PCR and western blot revealed that Delta-like ligand 4 levels decreased at postnatal day 12 and increased at postnatal day 17 in retinopathy of prematurity rats. Flat-mounted adenosine diphosphatase stained retina and hematoxylin-eosin stained retinal tissue slices showed that the clock hour scores and the nuclei counts in retinopathy of prematurity rats were significantly different compared to normal control rats. After retinopathy of prematurity rats were intravitreally injected with Delta-like ligand 4 monoclonal antibody to inhibit the Delta-like ligand 4/Notch signaling pathway, there was a significant increase in the severity of retinal neovascularization （clock hours） in the intravitreally injected eyes. The nuclei count was highly correlated with the clock hour score. These results suggest that Delta-like ligand 4/Notch signaling plays an essential role in the process of physiological and pathological angiogenesis in the retina.

Sodium butyrate protects against toxin-induced acute liver failure in rats

BACKGROUND: Acute liver failure(ALF) is a serious clinical syndrome with high mortality. Sodium butyrate has been shown to alleviate organ injury in a wide variety of preclinical models of critical diseases. The aim of this study was to investigate the protective effect of sodium butyrate on ALF in rats.METHODS: All rats were randomly divided into control,model and sodium butyrate treatment groups. Except the control group, the rats were induced ALF animal model by subcutaneous injection of human serum albumin+D- galactosamine+lipopolysaccharide. After induction of ALF,the rats in the treatment group received sodium butyrate(500mg/kg) at 12-hour or 24-hour time point. Fourty-eight hours after ALF induction, the animals were sacrificed and samples were harvested. Serum endotoxin, high mobility group box-1(HMGB1), liver function parameters, tumor necrosis factoralpha(TNF-α) and interferon-gamma(IFN-γ) were measured.The expression of HMGB1 and nuclear factor-kappa B(NF-κB)p65 protein in liver tissue was detected by Western blotting. The histological changes of liver and intestine were examined. The survival duration was also observed.RESULTS: Serum endotoxin, alanine aminotransferase, HMGB1,TNF-α and IFN-γ were significantly increased and the liver histology showed more severe histopathological injury in the model group compared with the control group(P<0.05).Compared to the model group, sodium butyrate treatment significantly improved the histopathological changes in the liver and intestine, reduced serum endotoxin and inflammatory cytokines, suppressed HMGB1 and NF-кB p65 proteins in liver tissue, and prolonged the survival duration regardless of treatment at 12 hours or 24 hours after induction of ALF(P<0.05).CONCLUSIONS: Sodium butyrate protected the liver from toxin-induced ALF in rats. The mechanisms may be due to direct hepatoprotection and decreased intestinal permeability.

Could saline irrigation clear all residual common bile duct stones after lithotripsy?A self-controlled prospective cohort study

BACKGROUND A previous study showed that irrigation with 100 mL saline reduced residual common bile duct(CBD)stones,which potentially cause recurrent stones after endoscopic retrograde cholangiopancreatography.AIM To determine whether saline irrigation can improve CBD clearance after lithotripsy.METHODS This prospective self-controlled study enrolled patients receiving mechanical lithotripsy for large(>1.2 cm)CBD stones.After occlusion cholangiography confirmed CBD stone clearance,peroral cholangioscopy(POC)was performed to determine clearance scores based on the number of residual stones.The amounts of residual stones spotted via POC were graded on a 5-point scale(score 1,worst;score 5,best).Scores were documented after only stone removal(control)and after irrigation with 50 mL and 100 mL saline,respectively.The stone composition was analyzed using infrared spectroscopy.RESULTS Between October 2018 and January 2020,47 patients had CBD clearance scores of 2.4±1.1 without saline irrigation,3.5±0.7 with 50 mL irrigation,and 4.6±0.6 with 100 mL irrigation(P<0.001).Multivariate analysis showed that CBD diameter>15 mm[odds ratio(OR)=0.08,95%confidence interval(CI):0.01-0.49;P=0.007]and periampullary diverticula(PAD)(OR=6.51,95%CI:1.08-39.21;P=0.041)were independent risk factors for residual stones.Bilirubin pigment stones constituted the main residual stones found in patients with PAD(P=0.004).CONCLUSION Irrigation with 100 mL of saline may not clear all residual CBD stones after lithotripsy,especially in patients with PAD and/or a dilated(>15 mm)CBD.Pigment residual stones are soft and commonly found in patients with PAD.Additional saline irrigation may be required to remove retained stones.

Associations between serum uric acid and hepatobiliary-pancreatic cancer:A cohort study

BACKGROUND Uric acid is the end product of purine metabolism.Previous studies have found that serum uric acid(SUA)levels are associated with the total cancer risk.However,due to the dual effect of uric acid on cancer,the relationship between the SUA levels and most specific-site cancer remains unclear.AIM To investigate the associations between the SUA levels and incidence of hepatobiliary-pancreatic cancer.METHODS In this prospective cohort study,444462 participants free of cancer from the UK Biobank were included.The SUA levels were measured at baseline,and the incidence of hepatobiliary-pancreatic cancer was determined by contacting the cancer registry.The hazard ratios(HRs)and 95%confidence intervals(CIs)between the SUA levels and hepatobiliary-pancreatic cancer were investigated using multiple adjusted Cox regression models adjusted for potential confounders.RESULTS In total,920 participants developed liver,gallbladder,biliary tract or pancreatic cancer during a median of 6.6 yrs of follow-up.We found that the HR of pancreatic cancer in the highest SUA group was 1.77(95%CI:1.29-2.42)compared with that in the lowest group.After stratifying by gender,we further found that SUA was associated with an increased risk of pancreatic cancer only among the females(highest quartile vs lowest quartile HR 2.04,95%CI:1.35-3.08).Among the males,the SUA levels were positively associated with the gallbladder cancer risk(highest quartile vs lowest quartile HR 3.09,95%CI:1.28-7.46),but a U-shaped association with the liver cancer risk was observed(P-nonlinear=0.03).CONCLUSION SUA is likely to have gender-specific effects on hepatobiliary-pancreatic cancer.High SUA levels are a risk factor for pancreatic cancer in females and gallbladder cancer in males.A U-shaped association with the liver cancer risk was identified.

Granulocyte-macrophage colony-stimulating factor protects mice against hepatocellular carcinoma by ameliorating intestinal dysbiosis and attenuating inflammation

BACKGROUND Hepatocellular carcinoma(HCC)is the third leading cause of cancer mortality worldwide.The gut microbiota can help maintain healthy metabolism and immunity.Granulocyte-macrophage colony-stimulating factor(GM-CSF)is a critical factor in promoting health and homeostasis;it promotes intestinal immunity,stimulates bone marrow precursors to generate macrophage colonies,and enhances the antibacterial and antitumor activity of circulating monocytes.As such,GM-CSF may protect against HCC development by regulating immunity as well as intestinal microecology.AIM To investigate the impact of GM-CSF on the gut microbiome and metabolic characteristics of HCC.METHODS Thirty-six male BALB/c nude mice were divided into three groups:Control(n=10),HCC(n=13),and HCC+GM-CSF(GM-CSF overexpression,n=13).We utilized HCC cells to establish orthotopic transplantation tumor models of HCC with normal and over-expressing GM-CSF.Liver injury,immune inflammatory function and intestinal barrier function were evaluated.The fecal microbiome and metabolome were studied using 16S rRNA absolute quantification sequencing and gas chromatography-mass spectrometry.RESULTS GM-CSF overexpression significantly affected the gut microbiome of mice with HCC and resulted in a high abundance of organisms of the genera Roseburia,Blautia and Butyricimonass,along with a significant reduction in Prevotella,Parabacteroides,Anaerotruncus,Streptococcus,Clostridium,and Mucispirillum.Likewise,GM-CSF overexpression resulted in a substantial increase in fecal biotin and oleic acid levels,along with a prominent decrease in the fecal succinic acid,adenosine,fumaric acid,lipoic acid,and maleic acid levels.Correlation analysis revealed that the intestinal microbiota and fecal metabolites induced by GM-CSF were primarily involved in pathways related to reducing the inflammatory response,biotin metabolism,and intestinal barrier dysfunction.CONCLUSION GM-CSF can protect against HCC development by regulating immunity and modulating the abundance of specific intestinal microorganisms and their metabolites.This study provides new insights into the therapeutic approaches for HCC.

Contribution of soil fauna to the degradation of recalcitrant components in Cinnamomum camphora foliar litter in different-sized gaps in Pinus massoniana plantations

Forest gaps are important in forest dynamics and management, but little is known about how soil fauna influence the degradation of recalcitrant litter components in different-sized forest gaps. This investigation uses litterbags with two different mesh sizes (0.04 and 3 mm) to control the meso- and microfauna entering the bags to quantify the contribution of soil fauna to the degradation of recalcitrant components (including condensed tannins, total phenol, lignin and cellulose) during litter decomposition. The experiment was conducted in seven different forest gap sizes in Pinus massoniana plantations over 1 year. One closed-canopy site (CC) and forest gap sizes of 100, 225, 400, 625, 900, 1225 and 1600 m^2 were created in a P. massoniana plantation in the Sichuan basin of China;the CC was treated as the control. Cinnamomum camphora foliage from local native trees was used in all forest gap experiments. We found the following:(1) Gap size had significant effects on the degradation rates (E) of condensed tannins and lignin and on the contributions of soil fauna;medium-sized gaps also presented high degradation rates. Soil fauna obviously contributed to the degradation of recalcitrant foliar litter components in medium-sized gaps.(2) The highest contribution to degradation (40.98%) was recorded for lignin, and the lowest contribution (0.29%) was recorded for condensed tannins. The results indicate that medium-sized gaps (900 m^2) were conducive to the degradation of recalcitrant litter components by soil fauna.

Treatment of gastric hepatoid adenocarcinoma with pembrolizumab and bevacizumab combination chemotherapy:A case report

BACKGROUND Gastric hepatoid adenocarcinoma(GHA)is a rare and aggressive cancer that is characterized by foci with features of both hepatocellular differentiation and adenomatous differentiation.However,there is currently no standard treatment for this disease,which has a poor prognosis.CASE SUMMARY A 72-year-old male with a body mass index of 20.9 was diagnosed with GHA with perigastric lymph node and liver metastasis.He underwent first-line chemotherapy but that failed.Pembrolizumab and bevacizumab with chemotherapy were used in the second-line treatment.The progression-free survival and overall survival were 14 mo and 16 mo,respectively,after treatment.In addition,the main adverse reaction was tolerable.The patient did not die of tumor progression.CONCLUSION The combination of pembrolizumab and bevacizumab with chemotherapy is an effective and safe regimen for GHA and may be recommended as a new choice for GHA treatment.Further studies should evaluate this treatment in a larger cohort or a randomized controlled trial.

Choledocholithiasis characteristics with periampullary diverticulum and endoscopic retrograde cholangiopancreatography procedures:Comparison between two centers from Lanzhou and Kyoto

BACKGROUND Most of study regarding periampullary diverticulum(PAD)impact on endoscopic retrograde cholangiopancreatography(ERCP)therapy for choledocholithiasis based on data from one endoscopy center and lacked to compare the clinical characteristic of choledocholithiasis with PAD from different geographical patients.AIM To compare the choledocholithiasis clinical characteristics between two regional endoscopy centers and analyze impacts of clinical characteristics on ERCP methods for choledocholithiasis patients with PAD.METHODS Patients seen in two endoscopy centers(The First Hospital of Lanzhou University,Lanzhou,Gansu Province,China,and Kyoto Second Red Cross Hospital,Kyoto,Japan)underwent ERCP treatment for the first time between January 2012 and December 2017.The characteristics of choledocholithiasis with PAD were compared between the two centers,and their ERCP procedures and therapeutic outcomes were analyzed.RESULTS A total of 829 out of 3608 patients in the Lanzhou center and 241 out of 1198 in the Kyoto center had choledocholithiasis with PAD.Lots of clinical characteristics were significantly different between the two centers.The common bile duct(CBD)diameter was wider,choledocholithiasis size was lager and multiple CBD stones were more in the Lanzhou center patients than those in the Kyoto center patients(14.8±5.2 mm vs 11.6±4.2 mm,12.2±6.5 mm vs 8.2±5.3 mm,45.3%vs 20.3%,P<0.001 for all).In addition,concomitant diseases,such as acute cholangitis,gallbladder stones,obstructive jaundice,cholecystectomy,and acute pancreatitis,were significantly different between the two centers(P=0.03 to<0.001).In the Lanzhou center,CBD diameter and choledocholithiasis size were lower,and multiple CBD stones and acute cholangitis were less in non-PAD patients than those in PAD patients(13.4±5.1 mm vs 14.8±5.2 mm,10.3±5.4 mm vs 12.2±6.5,39%vs 45.3%,13.9%vs 18.5%,P=0.002 to<0.001).But all these characteristics were not significantly different in the Kyoto center.The proportions of endoscopic sphincterotomy(EST),endoscopic balloon dilatation(EPBD),and EST+EPBD were 50.5%,1.7%,and 42.5%in the Lanzhou center and 90.0%,0.0%,and 0.4%in the Kyoto center,respectively.However,the overall post-ERCP complication rate was not significantly different between the two centers(8.9%in the Lanzhou and 5.8%in the Kyoto.P=0.12).In the Lanzhou center,the difficulty rate in removing CBD stones in PAD was higher than in non-PAD group(35.3%vs 26.0%,P<0.001).But the rate was no significant difference between the two groups in Kyoto center.The residual rates of choledocholithiasis were not significantly different between the two groups in both centers.Post-ERCP complications occurred in 8.9%of the PAD patients and 8.1%of the non-PAD patients in the Lanzhou Center,and it occurred in 5.8%in PAD patients and 10.0%in non-PAD patients in the Kyoto center,all P>0.05.CONCLUSION Many clinical characteristics of choledocholithiasis patients with PAD were significantly different between the Lanzhou and Kyoto centers.The patients had larger and multiple stones,wider CBD diameter,and more possibility of acute cholangitis and obstructive jaundice in the Lanzhou center than those in the Kyoto center.The ERCP procedures to manage native duodenal papilla were different depending on the different clinical characteristics while the overall post-ERCP complications were not significantly different between the two centers.The stone residual rate and post-ERCP complications were not significantly different between choledocholithiasis patients with PAD and without PAD in each center.