BACKGROUND microRNA-627-5p(miR-627-5p)dysregulation has been observed in several cancer types,such as hepatocellular carcinoma,oral squamous cell carcinoma,glioblastoma multiforme,and gastric cancer.The biological fun...BACKGROUND microRNA-627-5p(miR-627-5p)dysregulation has been observed in several cancer types,such as hepatocellular carcinoma,oral squamous cell carcinoma,glioblastoma multiforme,and gastric cancer.The biological function of miR-627-5p in colorectal cancer(CRC)growth and metastasis is yet unclear.AIM To investigate the effects of miR-627-5p on the malignant biological properties of colorectal malignant tumour cells by targeting Wnt2.METHODS The levels of miR-627-5p in colorectal tumour tissues were assessed in Gene Expression Omnibus datasets.In order to identify Wnt2 transcript expression in CRC tissues,quantitative real-time polymerase chain reaction(qRT-PCR)analysis was used.Luciferase reporter tests were used to explore whether miR-627-5p might potentially target Wnt2.Wnt2 transcript and protein levels were detected in CRC cells with high miR-627-5p expression.To learn more about how miR-627-5p affects CRC development,migration,apoptosis,and invasion,functional experiments were conducted.Cotransfection with the overexpression vector of Wnt2 and miR-627-5p mimics was utilized to verify whether overexpression of Wnt2 could cancel the impact of miR-627-5p in CRC.Western blot and qRT-PCR were conducted to investigate the effects of miR-627-5p on the Wnt/β-catenin signalling pathway.RESULTS miR-627-5p was notably decreased in colorectal tumour tissues,while the gene level of Wnt2 was notably upregulated.A dual luciferase reporter assay revealed that miR-627-5p specifically targets the 3’-untranslated regions of Wnt2 and miR-627-5p upregulation markedly reduced the protein and gene expression of Wnt2 in CRC cells.In vitro gain-of-function assays displayed that miR-627-5p overexpression decreased CRC cells’capabilities to invade,move,and remain viable while increasing apoptosis.Wnt2 overexpression could reverse the suppressive functions of miR-627-5p.Moreover,upregulation of miR-627-5p suppressed the transcript and protein levels of the downstream target factors in the canonical Wnt/β-catenin signalling,such as c-myc,CD44,β-catenin,and cyclinD1.CONCLUSION miR-627-5p acts as a critical inhibitory factor in CRC,possibly by directly targeting Wnt2 and negatively modulating the Wnt/β-catenin signalling,revealing that miR-627-5p could be a possible treatment target for CRC.展开更多
BACKGROUND Colorectal cancer(CRC)is the second leading cause of cancer-related death,with high morbidity worldwide.There is an urgent need to find reliable diagnostic biomarkers of CRC and explore the underlying molec...BACKGROUND Colorectal cancer(CRC)is the second leading cause of cancer-related death,with high morbidity worldwide.There is an urgent need to find reliable diagnostic biomarkers of CRC and explore the underlying molecular mechanisms.Exosomes are involved in intercellular communication and participate in multiple pathological processes,serving as an important part of the tumor microenvironment.AIM To investigate the proteomic characteristics of CRC tumor-derived exosomes and to identify candidate exosomal protein markers for CRC.METHODS In this study,10 patients over 50 years old who were diagnosed with moderately differentiated adenocarcinoma were recruited.We paired CRC tissues and adjacent normal intestinal tissues(>5 cm)to form the experimental and control groups.Purified exosomes were extracted separately from each tissue sample.Data-independent acquisition mass spectrometry was implemented in 8 matched samples of exosomes to explore the proteomic expression profiles,and differentially expressed proteins(DEPs)were screened by bioinformatics analysis.Promising exosomal proteins were verified using parallel reaction monitoring(PRM)analysis in 10 matched exosome samples.RESULTS A total of 1393 proteins were identified in the CRC tissue group,1304 proteins were identified in the adjacent tissue group,and 283 proteins were significantly differentially expressed between them.Enrichment analysis revealed that DEPs were involved in multiple biological processes related to cytoskeleton construction,cell movement and migration,immune response,tumor growth and telomere metabolism,as well as ECM-receptor interaction,focal adhesion and mTOR signaling pathways.Six differentially expressed exosomal proteins(NHP2,OLFM4,TOP1,SAMP,TAGL and TRIM28)were validated by PRM analysis and evaluated by receiver operating characteristic curve(ROC)analysis.The area under the ROC curve was 0.93,0.96,0.97,0.78,0.75,and 0.88(P<0.05)for NHP2,OLFM4,TOP1,SAMP,TAGL,and TRIM28,respectively,indicating their good ability to distinguish CRC tissues from adjacent intestinal tissues.CONCLUSION In our study,comprehensive proteomic profiles were obtained for CRC tissue exosomes.Six exosomal proteins,NHP2,OLFM4,TOP1,SAMP,TAGL and TRIM28,may be promising diagnostic markers and effective therapeutic targets for CRC,but further experimental investigation is needed.展开更多
In this paper,the superhydrophobic poly(vinylidene fuoride)/fuorinated ethylene propylene/SiO_(2)/CNTs-EDTA(PFSCEDTA)composite coating was successfully fabricated and applied for anti-scaling performance.The depositio...In this paper,the superhydrophobic poly(vinylidene fuoride)/fuorinated ethylene propylene/SiO_(2)/CNTs-EDTA(PFSCEDTA)composite coating was successfully fabricated and applied for anti-scaling performance.The deposition of CaCO_(3) on the surface of the superhydrophobic PFSC-EDTA composite coating reached 0.0444 mg/cm^(2) for 192-h immersion into the supersaturated CaCO_(3) solution,which was only 11.4%that of the superhydrophobic PFSC composite coating.At the interface between the CaCO_(3) solution and the PFSC-EDTA coating,the Ca^(2+)could be frstly chelated by EDTA that was beneft for improving the anti-scaling performance of the superhydrophobic PFSC-EDTA composite coating.In another hand,the addition of EDTA to the CNTs played an important role in fabricating the SiO_(2)-centric and CNTs-EDTA-surrounded multilevel micro-nanostructure in the superhydrophobic PFSC-EDTA composite coating,in favor of maintaining the air flm under the water and the stability of the superhydrophobic surface.The research supplies a new way of improving antiscaling performance of superhydrophobic coating by incorporating the organic chelating agent at the interface and changing the traditional way of scale prevention.展开更多
BACKGROUND The high morbidity and mortality of colorectal cancer(CRC)have posed great threats to human health.Circular RNA(CircRNA)and microRNA(miRNA),acting as competing endogenous RNAs(ceRNAs),have been found to pla...BACKGROUND The high morbidity and mortality of colorectal cancer(CRC)have posed great threats to human health.Circular RNA(CircRNA)and microRNA(miRNA),acting as competing endogenous RNAs(ceRNAs),have been found to play vital roles in carcinogenesis.However,the biological function of ceRNAs in CRC pathogenesis and prognosis remains largely unexplored.AIM To identify the CRC-specific circRNA-miRNA-mRNA regulatory network and uncover the subnetwork associated with its prognosis.METHODS CircRNAs,miRNAs and mRNAs differentially expressed(DE)in CRC tissues were selected by expression file analysis in the Gene Expression Omnibus(GEO)database,and the downstream target molecules of circRNAs and miRNAs were predicted.Then,the intersection of differentially expressed RNA molecules with the predicted targets was determined to obtain a ceRNA network.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to elucidate the possible mechanism of pathogenesis.A survival analysis using the gene profiles and clinical information in The Cancer Genome Atlas(TCGA)database was performed to identify the mRNAs associated with the clinical outcome of CRC patients and construct a prognostic subnetwork.RESULTS We downloaded three datasets(GSE126095,GSE41655 and GSE41657)of largescale CRC samples from the GEO database.There were 55 DEcircRNAs,114 DEmiRNAs and 267 DEmRNAs in CRC tissues compared with normal tissues.After intersecting these molecules with predicted targets,19 circRNAs,13 miRNAs and 28 mRNAs were chosen to develop a circRNA-miRNA-mRNA network.GO and KEGG functional enrichment analyses indicated that the retinol metabolic process,leukocyte chemotaxis,extracellular matrix remodeling,endoplasmic reticulum stress,alcohol dehydrogenase activity,gastric acid secretion,nitrogen metabolism and NOD-like receptor signaling pathway might participate in the tumorigenesis of CRC.After verifying the identified mRNA effect in the TCGA database,we finally recognized 3 mRNAs(CA2,ITLN1 and LRRC19)that were significantly associated with the overall survival of CRC patients and constructed a ceRNA subnetwork including 5 circRNAs(hsa_circ_0080210,hsa_circ_0007158,hsa_circ_0000375,hsa_circ_0018909 and hsa_circ_0011536)and 3 miRNAs(hsa-miR-601,hsa-miR-671-5p and hsa-miR-765),which could contain innovative and noninvasive indicators for the early screening and prognostic prediction of CRC.CONCLUSION We proposed a circRNA-miRNA-mRNA regulatory network closely associated with the progression and clinical outcome of CRC that might include promising biomarkers for carcinogenesis and therapeutic targets.展开更多
BACKGROUND Tumor mutational burden(TMB)is an important independent biomarker for the response to immunotherapy in multiple cancers.However,the clinical implications of TMB in gastric cancer(GC)have not been fully eluc...BACKGROUND Tumor mutational burden(TMB)is an important independent biomarker for the response to immunotherapy in multiple cancers.However,the clinical implications of TMB in gastric cancer(GC)have not been fully elucidated.AIM To explore the landscape of mutation profiles and determine the correlation between TMB and microRNA(miRNA)expression in GC.METHODS Genomic,transcriptomic,and clinical data from The Cancer Genome Atlas were used to obtain mutational profiles and investigate the statistical correlation between mutational burden and the overall survival of GC patients.The difference in immune infiltration between high-and low-TMB subgroups was evaluated by Wilcoxon rank-sum test.Furthermore,miRNAs differentially expressed between the high-and low-TMB subgroups were identified and the least absolute shrinkage and selection operator method was employed to construct a miRNA-based signature for TMB prediction.The biological functions of the predictive miRNAs were identified with DIANA-miRPath v3.0.RESULTS C>T single nucleotide mutations exhibited the highest mutation incidence,and the top three mutated genes were TTN,TP53,and MUC16 in GC.High TMB values(top 20%)were markedly correlated with better survival outcome,and multivariable regression analysis indicated that TMB remained prognostic independent of TNM stage,histological grade,age,and gender.Different TMB levels exhibited different immune infiltration patterns.Significant differences between the high-and low-TMB subgroups were observed in the infiltration of CD8+T cells,M1 macrophages,regulatory T cells,and CD4+T cells.In addition,we developed a miRNA-based signature using 23 differentially expressed miRNAs to predict TMB values of GC patients.The predictive performance of the signature was confirmed in the testing and the whole set.Receiver operating characteristic curve analysis demonstrated the optimal performance of the signature.Finally,enrichment analysis demonstrated that the set of miRNAs was significantly enriched in many key cancer and immune-related pathways.展开更多
BACKGROUND Colorectal cancer(CRC)imposes a tremendous burden on human health,with high morbidity and mortality.Circular ribonucleic acids(circRNAs),a new type of noncoding RNA,are considered to participate in cancer p...BACKGROUND Colorectal cancer(CRC)imposes a tremendous burden on human health,with high morbidity and mortality.Circular ribonucleic acids(circRNAs),a new type of noncoding RNA,are considered to participate in cancer pathogenesis as microRNA(miRNA)sponges.However,the dysregulation and biological functions of circRNAs in CRC remain to be explored.AIM To identify potential circRNA biomarkers of CRC and explore their functions in CRC carcinogenesis.METHODS CircRNAs and miRNAs differentially expressed in CRC tissues were identified by analyzing expression profiles from the Gene Expression Omnibus(GEO)database.Circ_0000375 and circ_0011536 were selected as CRC biomarker candidates.Quantitative real-time polymerase chain reaction was utilized to evaluate the expression of these 2 circRNAs in CRC tissues,serums and cell lines.Receiver operating characteristic curves were generated to assess the diagnostic performances of these 2 circRNAs.Then,functional experiments,including cell counting kit-8,wound healing and Transwell invasion assays,were performed after the overexpression of circ_0000375 and circ_0011536 in CRC cell lines.Furthermore,candidate target miRNAs of circ_0000375 and circ_0011536 were predicted via bioinformatics analysis.The expression levels of these miRNAs were explored in CRC cell lines and tissues from GEO datasets.A luciferase reporter assay was developed to examine the interactions between circRNAs and miRNAs.Based on the target miRNAs and downstream genes,functional enrichment analyses were applied to reveal the critical signaling pathways involved in CRC carcinogenesis.RESULTS Downregulated circ_0000375 and circ_0011536 expression was observed in CRC tissues in GSE126095,clinical CRC tissue and serum samples and CRC cell lines.The areas under the curve for circ_0000375 and circ_0011536 were 0.911 and 0.885 in CRC tissue and 0.976 and 0.982 in CRC serum,respectively.Moreover,the serum levels of these 2 circRNAs were higher in patients at 30 d postsurgery than in patients before surgery,suggesting that the serum expression of circ_0000375 and circ_0011536 is related to CRC tumorigenesis.Circ_0000375 and circ_0011536 overexpression inhibited the proliferation,migration and invasion of CRC cells.Furthermore,miR-1182 and miR-1246,which were overexpressed in CRC tissues in GSE41655,GSE49246 and GSE115513,were verified as target miRNAs of circ_0000375 and circ_0011536,respectively,by luciferase reporter assays.The downstream genes of miR-1182 and miR-1246 were enriched in some CRC-associated pathways,such as the Wnt signaling pathway.CONCLUSION Circ_0000375 and circ_0011536 may function as tumor suppressors in CRC progression,serving as novel biomarkers for CRC diagnosis and as promising candidates for therapeutic exploration.展开更多
BACKGROUND The carcinogenesis of colorectal cancer(CRC)involves many different molecules and multiple pathways,and the specific mechanism has not been elucidated until now.Existing studies on the proteomic signature p...BACKGROUND The carcinogenesis of colorectal cancer(CRC)involves many different molecules and multiple pathways,and the specific mechanism has not been elucidated until now.Existing studies on the proteomic signature profiles of CRC are relatively limited.Therefore,we herein aimed to provide a more comprehensive proteomic signature profile and discover new prognostic markers and therapeutic targets by performing proteomic analysis of CRC and paired normal tissues.AIM To investigate the proteomic signature and identify novel protein prognostic biomarkers of CRC.METHODS Cancer tissues and paired normal tissues were collected from 48 patients who underwent surgical removal at the China-Japan Friendship Hospital from January 2020 to June 2021.Data independent acquisition(DIA)quantitative proteomic analysis was performed using high-performance liquid chromatography–mass spectrometry/mass spectrometry(nano-UHPLC–MS/MS)to identify differen tially expressed proteins,among which those with a P adj value(t test,BH correction)<0.05 and an absolute fold change(|log2FC|)>2 were identified as potential markers.Differentially expressed proteins were selected by bioinformatics analysis and validated by immunohistochemical tissue microarrays,and their association with prognosis was further analyzed with the Gene Expression Profiling Interactive Analysis database to identify prognostic protein biomarkers of CRC.RESULTS Significantly differential protein expression was observed between cancer tissues and normal tissues.Compared with normal tissues,1115 proteins were upregulated and 705 proteins were downregulated in CRC based on P adj<0.05 and|log2FC|>2,and bioinformatics analysis revealed that the differentially expressed proteins were involved in multiple biological processes associated with tumorigenesis,including ribosome biogenesis in eukaryotes,focal adhesion,extracellular matrix-receptor interactions and other tumor metabolism processes.Moreover,cyclin-dependent kinase inhibitor 2A(CDKN2A)expression was markedly upregulated in CRC,as validated by immunohistochemistry(0.228 vs 0.364,P=0.0044),and was significantly enriched in tumor proliferation and signal transduction pathways such as the cell cycle and p53 signaling pathways.High CDKN2A expression was significantly correlated with poor prognosis(P=0.021).These results demonstrated that CDKN2A functions as a driver of CRC.CONCLUSION Our study provides a comprehensive proteomic signature of CRC and highlights CDKN2A as a potential powerful prognostic marker and precision therapeutic target.展开更多
BACKGROUND Gut tryptophan(Trp)metabolites are produced by microbiota and/or host metabolism.Some of them have been proven to promote or inhibit colorectal cancer(CRC)in vitro and animal models.We hypothesized that the...BACKGROUND Gut tryptophan(Trp)metabolites are produced by microbiota and/or host metabolism.Some of them have been proven to promote or inhibit colorectal cancer(CRC)in vitro and animal models.We hypothesized that there is an alteration of gut Trp metabolism mediated by microbiota and that it might be involved in the pathogenesis of cancer in patients with CRC.AIM To investigate the features of Trp metabolism in CRC and the correlation between fecal Trp metabolites and gut microbiota.METHODS Seventy-nine patients with colorectal neoplastic lesions(33 with colon adenoma and 46 with sporadic CRC)and 38 healthy controls(HCs)meeting the inclusion and exclusion criteria were included in the study.Their demographic and clinical features were collected.Fecal Trp,kynurenine(KYN),and indoles(metabolites of Trp metabolized by gut microbiota)were examined by ultraperformance liquid chromatography coupled to tandem mass spectrometry.Gut barrier marker and indoleamine 2,3-dioxygenase 1(IDO1)mRNA were analyzed by quantitative realtime polymerase chain reaction.Zonula occludens-1(ZO-1)protein expression was analyzed by immunohistochemistry.The gut microbiota was detected by 16S ribosomal RNA gene sequencing.Correlations between fecal metabolites and other parameters were examined in all patients.RESULTS The absolute concentration of KYN[1.51(0.70,3.46)nmol/g vs 0.81(0.64,1.57)nmol/g,P=0.036]and the ratio of KYN to Trp[7.39(4.12,11.72)×10^-3 vs 5.23(1.86,7.99)×10^-3,P=0.032]were increased in the feces of patients with CRC compared to HCs,while the indoles to Trp ratio was decreased[1.34(0.70,2.63)vs 2.46(1.25,4.10),P=0.029].The relative ZO-1 mRNA levels in patients with CRC(0.27±0.24)were significantly lower than those in HCs(1.00±0.31)(P<0.001),and the relative IDO1 mRNA levels in patients with CRC[1.65(0.47-2.46)]were increased(P=0.035).IDO1 mRNA levels were positively associated with the KYN/Trp ratio(r=0.327,P=0.003).ZO-1 mRNA and protein levels were positively correlated with the indoles/Trp ratio(P=0.035 and P=0.009,respectively).In addition,the genera Asaccharobacter(Actinobacteria)and Parabacteroides(Bacteroidetes),and members of the phylum Firmicutes(Clostridium XlVb,Fusicatenibacter,Anaerofilum,and Anaerostipes)decreased in CRC and exhibited a positive correlation with indoles in all subjects.CONCLUSION Alteration of fecal Trp metabolism mediated by microbiota is associated with intestinal barrier function and tissue Trp metabolism,and may be involved in the pathogenesis of CRC.展开更多
BACKGROUND Early detection of colorectal neoplasms,including colorectal cancers(CRCs)and advanced colorectal adenomas(AAs),is crucial to improve patient survival.Circulating microRNAs(miRNAs)in peripheral blood are em...BACKGROUND Early detection of colorectal neoplasms,including colorectal cancers(CRCs)and advanced colorectal adenomas(AAs),is crucial to improve patient survival.Circulating microRNAs(miRNAs)in peripheral blood are emerging as noninvasive diagnostic markers for multiple cancers,but their potential for screening colorectal neoplasms remains ambiguous.AIM To identify candidate circulating cell-free miRNAs as diagnostic biomarkers in patients with colorectal neoplasms.METHODS The study was divided into three phases:(1)Candidate miRNAs were selected from three public miRNA datasets using differential gene expression analysis methods;(2)an independent set of serum samples from 60 CRC patients,60 AA patients and 30 healthy controls(HCs)was included and analyzed by quantitative real-time polymerase chain reaction for miRNAs,and their diagnostic power was detected by receiver operating characteristic(ROC)analysis;and(3)the origin and function of miRNAs in cancer patients were investigated in cancer cell lines and tumor tissues.RESULTS Based on bioinformatics analysis,miR-627-5p and miR-199a-5p were differentially expressed in both the serum and tissues of patients with colorectal neoplasms and HCs and were selected for further study.Further validation in an independent cohort revealed that both circulating miR-627-5p and miR-199a-5p were sequentially increased from HCs and AAs to CRCs.The diagnostic power of miR-672-5p yielded an area under the curve(AUC)value of 0.90,and miR-199a-5p had an AUC of 0.83 in discriminating colorectal neoplasms from HCs.A logistic integrated model combining miR-199a-5p and miR-627-5p exhibited a higher diagnostic performance than either miRNA.Additionally,the levels of serum miR-627-5p and miR-199a-5p in CRC patients were significantly lower after surgery than before surgery and the expression of both miRNAs was increased with culture time in the culture media of several CRC cell lines,suggesting that the upregulated serum expression of both miRNAs in CRC might be tumor derived.Furthermore,in vitro experiments revealed that miR-627-5p and miR-199a-5p acted as tumor suppressors in CRC cells.CONCLUSION Serum levels of miR-199a-5p and miR-627-5p were markedly increased in patients with colorectal neoplasms and showed strong potential as minimally invasive biomarkers for the early screening of colorectal neoplasms.展开更多
The performance degradation of gate-recessed metal–oxide–semiconductor high electron mobility transistor(MOSHEMT)is compared with that of conventional high electron mobility transistor(HEMT)under direct current(DC)s...The performance degradation of gate-recessed metal–oxide–semiconductor high electron mobility transistor(MOSHEMT)is compared with that of conventional high electron mobility transistor(HEMT)under direct current(DC)stress,and the degradation mechanism is studied.Under the channel hot electron injection stress,the degradation of gate-recessed MOS-HEMT is more serious than that of conventional HEMT devices due to the combined effect of traps in the barrier layer,and that under the gate dielectric of the device.The threshold voltage of conventional HEMT shows a reduction under the gate electron injection stress,which is caused by the barrier layer traps trapping the injected electrons and releasing them into the channel.However,because of defects under gate dielectrics which can trap the electrons injected from gate and deplete part of the channel,the threshold voltage of gate-recessed MOS-HEMT first increases and then decreases as the conventional HEMT.The saturation phenomenon of threshold voltage degradation under high field stress verifies the existence of threshold voltage reduction effect caused by gate electron injection.展开更多
BACKGROUND The intestinal mucosal barrier is the first line of defense against numerous harmful substances,and it contributes to the maintenance of intestinal homeostasis.Recent studies reported that structural and fu...BACKGROUND The intestinal mucosal barrier is the first line of defense against numerous harmful substances,and it contributes to the maintenance of intestinal homeostasis.Recent studies reported that structural and functional changes in the intestinal mucosal barrier were involved in the pathogenesis of several intestinal diseases.However,no study thoroughly evaluated this barrier in patients with functional constipation(FC).AIM To investigate the intestinal mucosal barrier in FC,including the mucus barrier,intercellular junctions,mucosal immunity and gut permeability.METHODS Forty FC patients who fulfilled the Rome IV criteria and 24 healthy controls were recruited in the Department of Gastroenterology of China-Japan Friendship Hospital.The colonic mucus barrier,intercellular junctions in the colonic epithelium,mucosal immune state and gut permeability in FC patients were comprehensively examined.Goblet cells were stained with Alcian Blue/Periodic acid Schiff(AB/PAS)and counted.The ultrastructure of intercellular junctional complexes was observed under an electron microscope.Occludin and zonula occludens-1(ZO-1)in the colonic mucosa were located and quantified using immunohistochemistry and quantitative real-time polymerase chain reaction.Colonic CD3+intraepithelial lymphocytes(IELs)and CD3+lymphocytes in the lamina propria were identified and counted using immunofluorescence.The serum levels of D-lactic acid and zonulin were detected using enzyme-linked immunosorbent assay.RESULTS Compared to healthy controls,the staining of mucus secreted by goblet cells was darker in FC patients,and the number of goblet cells per upper crypt in the colonic mucosa was significantly increased in FC patients(control,18.67±2.99;FC,22.42±4.09;P=0.001).The intercellular junctional complexes in the colonic epithelium were integral in FC patients.The distribution of mucosal occludin and ZO-1 was not altered in FC patients.No significant differences were found in occludin(control,5.76E-2±1.62E-2;FC,5.17E-2±1.80E-2;P=0.240)and ZO-1(control,2.29E-2±0.93E-2;FC,2.68E-2±1.60E-2;P=0.333)protein expression between the two groups.The mRNA levels in occludin and ZO-1 were not modified in FC patients compared to healthy controls(P=0.145,P=0.451,respectively).No significant differences were observed in the number of CD3+IELs per 100 epithelial cells(control,5.62±2.06;FC,4.50±2.16;P=0.070)and CD3+lamina propria lymphocytes(control,19.69±6.04/mm^(2);FC,22.70±11.38/mm^(2);P=0.273).There were no significant differences in serum D-lactic acid[control,5.21(4.46,5.49)mmol/L;FC,4.63(4.31,5.42)mmol/L;P=0.112]or zonulin[control,1.36(0.53,2.15)ng/mL;FC,0.94(0.47,1.56)ng/mL;P=0.185]levels between FC patients and healthy controls.CONCLUSION The intestinal mucosal barrier in FC patients exhibits a compensatory increase in goblet cells and integral intercellular junctions without activation of mucosal immunity or increased gut permeability.展开更多
Objective:To evaluate the clinical efficacy and safety of berberine in the treatment of non-alcoholic fatty liver.Methods:Randomized controlled studies were searched in Chinese and English databases from March 30,2020...Objective:To evaluate the clinical efficacy and safety of berberine in the treatment of non-alcoholic fatty liver.Methods:Randomized controlled studies were searched in Chinese and English databases from March 30,2020.The quality was evaluated after literature screening and statistical analysis by RevMan5.3 software.Results:Nine studies were included,involving 780 patients.Meta analysis showed that berberine alone or in combination could reduce total cholesterol(MD=-0.50,95%CI),low density lipoprotein(MD=-0.34,95%CI)and glutamyltransferase(MD=-20.79,95CI%).Subgroup analysis showed that berberine combined with berberine could reduce glycosylated hemoglobin level[MD=-0.68,95%CI(-0.98 maxim 0.38)],while in patients with diabetes treated with berberine,alanine aminotransferase(MD=-9.38,95CI%)and aspartate oxaloacetic transaminase(MD=-9.03,95CI%)decreased significantly.The above differences were statistically significant(P<0.01).In addition,berberine has a tendency to decrease triglyceride,fasting blood glucose,body mass index and improve insulin resistance.There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:Berberine can regulate glucose and lipid metabolism in patients with non-alcoholic fatty liver and has a tendency to improve liver function and insulin resistance.展开更多
Background Acute kidney injury(AKI)after cardiopulmonary bypass(CPB)is a common complication especially in pedi-atric population.Plasma gelsolin(pGSN)is an anti-inflammatory factor through binding with actin and pro-i...Background Acute kidney injury(AKI)after cardiopulmonary bypass(CPB)is a common complication especially in pedi-atric population.Plasma gelsolin(pGSN)is an anti-inflammatory factor through binding with actin and pro-inflammatory cytokines in circulation.Decrease in pGSN has been reported in some pathologic conditions.The purpose of the study was to determine the alterations of pGSN level in infants and young children after CPB and the role of pGSN as a predictor for the morbidity and severity of post-CPB AKI.Methods Sixty-seven infants and young children at age≤3 years old undergoing CPB were prospectively enrolled.PGSN levels were measured during peri-operative period with enzyme-linked immuno-sorbent assay and normalized with plasma total protein concentration.Other clinical characteristics of the patients were also recorded.Results In patients developing AKI,the normalized pGSN(pGSN_(N))levels significantly decreased at 6 h post-operation and remained low for 24 h post-operation as compared to the patients with non-AKI.PGSNN at 6 h post-operation combining with CPB time presents an excellent predictive value for AKI.Conclusions Decreased pGSN_(N)identifies post-CPB AKI in the patients≤3 years old,and is associated with adverse clini-cal outcomes.The findings suggest that circulating GSN in post-CPB patients may have beneficial effects on diminishing inflammatory responses.展开更多
基金Supported by the National Key Development Plan for Precision Medicine Research,No.2017YFC0910002.
文摘BACKGROUND microRNA-627-5p(miR-627-5p)dysregulation has been observed in several cancer types,such as hepatocellular carcinoma,oral squamous cell carcinoma,glioblastoma multiforme,and gastric cancer.The biological function of miR-627-5p in colorectal cancer(CRC)growth and metastasis is yet unclear.AIM To investigate the effects of miR-627-5p on the malignant biological properties of colorectal malignant tumour cells by targeting Wnt2.METHODS The levels of miR-627-5p in colorectal tumour tissues were assessed in Gene Expression Omnibus datasets.In order to identify Wnt2 transcript expression in CRC tissues,quantitative real-time polymerase chain reaction(qRT-PCR)analysis was used.Luciferase reporter tests were used to explore whether miR-627-5p might potentially target Wnt2.Wnt2 transcript and protein levels were detected in CRC cells with high miR-627-5p expression.To learn more about how miR-627-5p affects CRC development,migration,apoptosis,and invasion,functional experiments were conducted.Cotransfection with the overexpression vector of Wnt2 and miR-627-5p mimics was utilized to verify whether overexpression of Wnt2 could cancel the impact of miR-627-5p in CRC.Western blot and qRT-PCR were conducted to investigate the effects of miR-627-5p on the Wnt/β-catenin signalling pathway.RESULTS miR-627-5p was notably decreased in colorectal tumour tissues,while the gene level of Wnt2 was notably upregulated.A dual luciferase reporter assay revealed that miR-627-5p specifically targets the 3’-untranslated regions of Wnt2 and miR-627-5p upregulation markedly reduced the protein and gene expression of Wnt2 in CRC cells.In vitro gain-of-function assays displayed that miR-627-5p overexpression decreased CRC cells’capabilities to invade,move,and remain viable while increasing apoptosis.Wnt2 overexpression could reverse the suppressive functions of miR-627-5p.Moreover,upregulation of miR-627-5p suppressed the transcript and protein levels of the downstream target factors in the canonical Wnt/β-catenin signalling,such as c-myc,CD44,β-catenin,and cyclinD1.CONCLUSION miR-627-5p acts as a critical inhibitory factor in CRC,possibly by directly targeting Wnt2 and negatively modulating the Wnt/β-catenin signalling,revealing that miR-627-5p could be a possible treatment target for CRC.
基金Supported by National Key Development Plan for Precision Medicine Research,No.2017YFC0910002。
文摘BACKGROUND Colorectal cancer(CRC)is the second leading cause of cancer-related death,with high morbidity worldwide.There is an urgent need to find reliable diagnostic biomarkers of CRC and explore the underlying molecular mechanisms.Exosomes are involved in intercellular communication and participate in multiple pathological processes,serving as an important part of the tumor microenvironment.AIM To investigate the proteomic characteristics of CRC tumor-derived exosomes and to identify candidate exosomal protein markers for CRC.METHODS In this study,10 patients over 50 years old who were diagnosed with moderately differentiated adenocarcinoma were recruited.We paired CRC tissues and adjacent normal intestinal tissues(>5 cm)to form the experimental and control groups.Purified exosomes were extracted separately from each tissue sample.Data-independent acquisition mass spectrometry was implemented in 8 matched samples of exosomes to explore the proteomic expression profiles,and differentially expressed proteins(DEPs)were screened by bioinformatics analysis.Promising exosomal proteins were verified using parallel reaction monitoring(PRM)analysis in 10 matched exosome samples.RESULTS A total of 1393 proteins were identified in the CRC tissue group,1304 proteins were identified in the adjacent tissue group,and 283 proteins were significantly differentially expressed between them.Enrichment analysis revealed that DEPs were involved in multiple biological processes related to cytoskeleton construction,cell movement and migration,immune response,tumor growth and telomere metabolism,as well as ECM-receptor interaction,focal adhesion and mTOR signaling pathways.Six differentially expressed exosomal proteins(NHP2,OLFM4,TOP1,SAMP,TAGL and TRIM28)were validated by PRM analysis and evaluated by receiver operating characteristic curve(ROC)analysis.The area under the ROC curve was 0.93,0.96,0.97,0.78,0.75,and 0.88(P<0.05)for NHP2,OLFM4,TOP1,SAMP,TAGL,and TRIM28,respectively,indicating their good ability to distinguish CRC tissues from adjacent intestinal tissues.CONCLUSION In our study,comprehensive proteomic profiles were obtained for CRC tissue exosomes.Six exosomal proteins,NHP2,OLFM4,TOP1,SAMP,TAGL and TRIM28,may be promising diagnostic markers and effective therapeutic targets for CRC,but further experimental investigation is needed.
基金The research was fnancially supported by the National Science Foundation for Distinguished Young Scholars of China(Grant No.51925403)the Major Research Plan of National Natural Science Foundation of China(Grant No.91934302)the National Science Foundation of China(21676052,21606042).
文摘In this paper,the superhydrophobic poly(vinylidene fuoride)/fuorinated ethylene propylene/SiO_(2)/CNTs-EDTA(PFSCEDTA)composite coating was successfully fabricated and applied for anti-scaling performance.The deposition of CaCO_(3) on the surface of the superhydrophobic PFSC-EDTA composite coating reached 0.0444 mg/cm^(2) for 192-h immersion into the supersaturated CaCO_(3) solution,which was only 11.4%that of the superhydrophobic PFSC composite coating.At the interface between the CaCO_(3) solution and the PFSC-EDTA coating,the Ca^(2+)could be frstly chelated by EDTA that was beneft for improving the anti-scaling performance of the superhydrophobic PFSC-EDTA composite coating.In another hand,the addition of EDTA to the CNTs played an important role in fabricating the SiO_(2)-centric and CNTs-EDTA-surrounded multilevel micro-nanostructure in the superhydrophobic PFSC-EDTA composite coating,in favor of maintaining the air flm under the water and the stability of the superhydrophobic surface.The research supplies a new way of improving antiscaling performance of superhydrophobic coating by incorporating the organic chelating agent at the interface and changing the traditional way of scale prevention.
基金Supported by National Key Development Plan for Precision Medicine Research,No.2017YFC0910002.
文摘BACKGROUND The high morbidity and mortality of colorectal cancer(CRC)have posed great threats to human health.Circular RNA(CircRNA)and microRNA(miRNA),acting as competing endogenous RNAs(ceRNAs),have been found to play vital roles in carcinogenesis.However,the biological function of ceRNAs in CRC pathogenesis and prognosis remains largely unexplored.AIM To identify the CRC-specific circRNA-miRNA-mRNA regulatory network and uncover the subnetwork associated with its prognosis.METHODS CircRNAs,miRNAs and mRNAs differentially expressed(DE)in CRC tissues were selected by expression file analysis in the Gene Expression Omnibus(GEO)database,and the downstream target molecules of circRNAs and miRNAs were predicted.Then,the intersection of differentially expressed RNA molecules with the predicted targets was determined to obtain a ceRNA network.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to elucidate the possible mechanism of pathogenesis.A survival analysis using the gene profiles and clinical information in The Cancer Genome Atlas(TCGA)database was performed to identify the mRNAs associated with the clinical outcome of CRC patients and construct a prognostic subnetwork.RESULTS We downloaded three datasets(GSE126095,GSE41655 and GSE41657)of largescale CRC samples from the GEO database.There were 55 DEcircRNAs,114 DEmiRNAs and 267 DEmRNAs in CRC tissues compared with normal tissues.After intersecting these molecules with predicted targets,19 circRNAs,13 miRNAs and 28 mRNAs were chosen to develop a circRNA-miRNA-mRNA network.GO and KEGG functional enrichment analyses indicated that the retinol metabolic process,leukocyte chemotaxis,extracellular matrix remodeling,endoplasmic reticulum stress,alcohol dehydrogenase activity,gastric acid secretion,nitrogen metabolism and NOD-like receptor signaling pathway might participate in the tumorigenesis of CRC.After verifying the identified mRNA effect in the TCGA database,we finally recognized 3 mRNAs(CA2,ITLN1 and LRRC19)that were significantly associated with the overall survival of CRC patients and constructed a ceRNA subnetwork including 5 circRNAs(hsa_circ_0080210,hsa_circ_0007158,hsa_circ_0000375,hsa_circ_0018909 and hsa_circ_0011536)and 3 miRNAs(hsa-miR-601,hsa-miR-671-5p and hsa-miR-765),which could contain innovative and noninvasive indicators for the early screening and prognostic prediction of CRC.CONCLUSION We proposed a circRNA-miRNA-mRNA regulatory network closely associated with the progression and clinical outcome of CRC that might include promising biomarkers for carcinogenesis and therapeutic targets.
基金Supported by National Key Development Plan for Precision Medicine Research,No.2017YFC0910002.
文摘BACKGROUND Tumor mutational burden(TMB)is an important independent biomarker for the response to immunotherapy in multiple cancers.However,the clinical implications of TMB in gastric cancer(GC)have not been fully elucidated.AIM To explore the landscape of mutation profiles and determine the correlation between TMB and microRNA(miRNA)expression in GC.METHODS Genomic,transcriptomic,and clinical data from The Cancer Genome Atlas were used to obtain mutational profiles and investigate the statistical correlation between mutational burden and the overall survival of GC patients.The difference in immune infiltration between high-and low-TMB subgroups was evaluated by Wilcoxon rank-sum test.Furthermore,miRNAs differentially expressed between the high-and low-TMB subgroups were identified and the least absolute shrinkage and selection operator method was employed to construct a miRNA-based signature for TMB prediction.The biological functions of the predictive miRNAs were identified with DIANA-miRPath v3.0.RESULTS C>T single nucleotide mutations exhibited the highest mutation incidence,and the top three mutated genes were TTN,TP53,and MUC16 in GC.High TMB values(top 20%)were markedly correlated with better survival outcome,and multivariable regression analysis indicated that TMB remained prognostic independent of TNM stage,histological grade,age,and gender.Different TMB levels exhibited different immune infiltration patterns.Significant differences between the high-and low-TMB subgroups were observed in the infiltration of CD8+T cells,M1 macrophages,regulatory T cells,and CD4+T cells.In addition,we developed a miRNA-based signature using 23 differentially expressed miRNAs to predict TMB values of GC patients.The predictive performance of the signature was confirmed in the testing and the whole set.Receiver operating characteristic curve analysis demonstrated the optimal performance of the signature.Finally,enrichment analysis demonstrated that the set of miRNAs was significantly enriched in many key cancer and immune-related pathways.
基金Supported by the National Key Development Plan for Precision Medicine Research,No. 2017YFC0910002
文摘BACKGROUND Colorectal cancer(CRC)imposes a tremendous burden on human health,with high morbidity and mortality.Circular ribonucleic acids(circRNAs),a new type of noncoding RNA,are considered to participate in cancer pathogenesis as microRNA(miRNA)sponges.However,the dysregulation and biological functions of circRNAs in CRC remain to be explored.AIM To identify potential circRNA biomarkers of CRC and explore their functions in CRC carcinogenesis.METHODS CircRNAs and miRNAs differentially expressed in CRC tissues were identified by analyzing expression profiles from the Gene Expression Omnibus(GEO)database.Circ_0000375 and circ_0011536 were selected as CRC biomarker candidates.Quantitative real-time polymerase chain reaction was utilized to evaluate the expression of these 2 circRNAs in CRC tissues,serums and cell lines.Receiver operating characteristic curves were generated to assess the diagnostic performances of these 2 circRNAs.Then,functional experiments,including cell counting kit-8,wound healing and Transwell invasion assays,were performed after the overexpression of circ_0000375 and circ_0011536 in CRC cell lines.Furthermore,candidate target miRNAs of circ_0000375 and circ_0011536 were predicted via bioinformatics analysis.The expression levels of these miRNAs were explored in CRC cell lines and tissues from GEO datasets.A luciferase reporter assay was developed to examine the interactions between circRNAs and miRNAs.Based on the target miRNAs and downstream genes,functional enrichment analyses were applied to reveal the critical signaling pathways involved in CRC carcinogenesis.RESULTS Downregulated circ_0000375 and circ_0011536 expression was observed in CRC tissues in GSE126095,clinical CRC tissue and serum samples and CRC cell lines.The areas under the curve for circ_0000375 and circ_0011536 were 0.911 and 0.885 in CRC tissue and 0.976 and 0.982 in CRC serum,respectively.Moreover,the serum levels of these 2 circRNAs were higher in patients at 30 d postsurgery than in patients before surgery,suggesting that the serum expression of circ_0000375 and circ_0011536 is related to CRC tumorigenesis.Circ_0000375 and circ_0011536 overexpression inhibited the proliferation,migration and invasion of CRC cells.Furthermore,miR-1182 and miR-1246,which were overexpressed in CRC tissues in GSE41655,GSE49246 and GSE115513,were verified as target miRNAs of circ_0000375 and circ_0011536,respectively,by luciferase reporter assays.The downstream genes of miR-1182 and miR-1246 were enriched in some CRC-associated pathways,such as the Wnt signaling pathway.CONCLUSION Circ_0000375 and circ_0011536 may function as tumor suppressors in CRC progression,serving as novel biomarkers for CRC diagnosis and as promising candidates for therapeutic exploration.
基金Supported by National Key Development Plan for Precision Medicine Research,No. 2017YFC0910002
文摘BACKGROUND The carcinogenesis of colorectal cancer(CRC)involves many different molecules and multiple pathways,and the specific mechanism has not been elucidated until now.Existing studies on the proteomic signature profiles of CRC are relatively limited.Therefore,we herein aimed to provide a more comprehensive proteomic signature profile and discover new prognostic markers and therapeutic targets by performing proteomic analysis of CRC and paired normal tissues.AIM To investigate the proteomic signature and identify novel protein prognostic biomarkers of CRC.METHODS Cancer tissues and paired normal tissues were collected from 48 patients who underwent surgical removal at the China-Japan Friendship Hospital from January 2020 to June 2021.Data independent acquisition(DIA)quantitative proteomic analysis was performed using high-performance liquid chromatography–mass spectrometry/mass spectrometry(nano-UHPLC–MS/MS)to identify differen tially expressed proteins,among which those with a P adj value(t test,BH correction)<0.05 and an absolute fold change(|log2FC|)>2 were identified as potential markers.Differentially expressed proteins were selected by bioinformatics analysis and validated by immunohistochemical tissue microarrays,and their association with prognosis was further analyzed with the Gene Expression Profiling Interactive Analysis database to identify prognostic protein biomarkers of CRC.RESULTS Significantly differential protein expression was observed between cancer tissues and normal tissues.Compared with normal tissues,1115 proteins were upregulated and 705 proteins were downregulated in CRC based on P adj<0.05 and|log2FC|>2,and bioinformatics analysis revealed that the differentially expressed proteins were involved in multiple biological processes associated with tumorigenesis,including ribosome biogenesis in eukaryotes,focal adhesion,extracellular matrix-receptor interactions and other tumor metabolism processes.Moreover,cyclin-dependent kinase inhibitor 2A(CDKN2A)expression was markedly upregulated in CRC,as validated by immunohistochemistry(0.228 vs 0.364,P=0.0044),and was significantly enriched in tumor proliferation and signal transduction pathways such as the cell cycle and p53 signaling pathways.High CDKN2A expression was significantly correlated with poor prognosis(P=0.021).These results demonstrated that CDKN2A functions as a driver of CRC.CONCLUSION Our study provides a comprehensive proteomic signature of CRC and highlights CDKN2A as a potential powerful prognostic marker and precision therapeutic target.
基金Supported by National Key Research and Development Plan for Precision Medicine Research,No.2017YFC0910002.
文摘BACKGROUND Gut tryptophan(Trp)metabolites are produced by microbiota and/or host metabolism.Some of them have been proven to promote or inhibit colorectal cancer(CRC)in vitro and animal models.We hypothesized that there is an alteration of gut Trp metabolism mediated by microbiota and that it might be involved in the pathogenesis of cancer in patients with CRC.AIM To investigate the features of Trp metabolism in CRC and the correlation between fecal Trp metabolites and gut microbiota.METHODS Seventy-nine patients with colorectal neoplastic lesions(33 with colon adenoma and 46 with sporadic CRC)and 38 healthy controls(HCs)meeting the inclusion and exclusion criteria were included in the study.Their demographic and clinical features were collected.Fecal Trp,kynurenine(KYN),and indoles(metabolites of Trp metabolized by gut microbiota)were examined by ultraperformance liquid chromatography coupled to tandem mass spectrometry.Gut barrier marker and indoleamine 2,3-dioxygenase 1(IDO1)mRNA were analyzed by quantitative realtime polymerase chain reaction.Zonula occludens-1(ZO-1)protein expression was analyzed by immunohistochemistry.The gut microbiota was detected by 16S ribosomal RNA gene sequencing.Correlations between fecal metabolites and other parameters were examined in all patients.RESULTS The absolute concentration of KYN[1.51(0.70,3.46)nmol/g vs 0.81(0.64,1.57)nmol/g,P=0.036]and the ratio of KYN to Trp[7.39(4.12,11.72)×10^-3 vs 5.23(1.86,7.99)×10^-3,P=0.032]were increased in the feces of patients with CRC compared to HCs,while the indoles to Trp ratio was decreased[1.34(0.70,2.63)vs 2.46(1.25,4.10),P=0.029].The relative ZO-1 mRNA levels in patients with CRC(0.27±0.24)were significantly lower than those in HCs(1.00±0.31)(P<0.001),and the relative IDO1 mRNA levels in patients with CRC[1.65(0.47-2.46)]were increased(P=0.035).IDO1 mRNA levels were positively associated with the KYN/Trp ratio(r=0.327,P=0.003).ZO-1 mRNA and protein levels were positively correlated with the indoles/Trp ratio(P=0.035 and P=0.009,respectively).In addition,the genera Asaccharobacter(Actinobacteria)and Parabacteroides(Bacteroidetes),and members of the phylum Firmicutes(Clostridium XlVb,Fusicatenibacter,Anaerofilum,and Anaerostipes)decreased in CRC and exhibited a positive correlation with indoles in all subjects.CONCLUSION Alteration of fecal Trp metabolism mediated by microbiota is associated with intestinal barrier function and tissue Trp metabolism,and may be involved in the pathogenesis of CRC.
基金Supported by National Key Development Plan for Precision Medicine Research,No.2017YFC0910002.
文摘BACKGROUND Early detection of colorectal neoplasms,including colorectal cancers(CRCs)and advanced colorectal adenomas(AAs),is crucial to improve patient survival.Circulating microRNAs(miRNAs)in peripheral blood are emerging as noninvasive diagnostic markers for multiple cancers,but their potential for screening colorectal neoplasms remains ambiguous.AIM To identify candidate circulating cell-free miRNAs as diagnostic biomarkers in patients with colorectal neoplasms.METHODS The study was divided into three phases:(1)Candidate miRNAs were selected from three public miRNA datasets using differential gene expression analysis methods;(2)an independent set of serum samples from 60 CRC patients,60 AA patients and 30 healthy controls(HCs)was included and analyzed by quantitative real-time polymerase chain reaction for miRNAs,and their diagnostic power was detected by receiver operating characteristic(ROC)analysis;and(3)the origin and function of miRNAs in cancer patients were investigated in cancer cell lines and tumor tissues.RESULTS Based on bioinformatics analysis,miR-627-5p and miR-199a-5p were differentially expressed in both the serum and tissues of patients with colorectal neoplasms and HCs and were selected for further study.Further validation in an independent cohort revealed that both circulating miR-627-5p and miR-199a-5p were sequentially increased from HCs and AAs to CRCs.The diagnostic power of miR-672-5p yielded an area under the curve(AUC)value of 0.90,and miR-199a-5p had an AUC of 0.83 in discriminating colorectal neoplasms from HCs.A logistic integrated model combining miR-199a-5p and miR-627-5p exhibited a higher diagnostic performance than either miRNA.Additionally,the levels of serum miR-627-5p and miR-199a-5p in CRC patients were significantly lower after surgery than before surgery and the expression of both miRNAs was increased with culture time in the culture media of several CRC cell lines,suggesting that the upregulated serum expression of both miRNAs in CRC might be tumor derived.Furthermore,in vitro experiments revealed that miR-627-5p and miR-199a-5p acted as tumor suppressors in CRC cells.CONCLUSION Serum levels of miR-199a-5p and miR-627-5p were markedly increased in patients with colorectal neoplasms and showed strong potential as minimally invasive biomarkers for the early screening of colorectal neoplasms.
基金the Laboratory Open Fund of Beijing Smart-chip Microelectronics Technology Co.Ltd and the National Natural Science Foundation of China(Grant No.11690042)+1 种基金the Science Challenge Project,China(Grant Nos.TZ2018004 and 12035019)the National Major Scientific Research Instrument Projects,China(Grant No.61727804)。
文摘The performance degradation of gate-recessed metal–oxide–semiconductor high electron mobility transistor(MOSHEMT)is compared with that of conventional high electron mobility transistor(HEMT)under direct current(DC)stress,and the degradation mechanism is studied.Under the channel hot electron injection stress,the degradation of gate-recessed MOS-HEMT is more serious than that of conventional HEMT devices due to the combined effect of traps in the barrier layer,and that under the gate dielectric of the device.The threshold voltage of conventional HEMT shows a reduction under the gate electron injection stress,which is caused by the barrier layer traps trapping the injected electrons and releasing them into the channel.However,because of defects under gate dielectrics which can trap the electrons injected from gate and deplete part of the channel,the threshold voltage of gate-recessed MOS-HEMT first increases and then decreases as the conventional HEMT.The saturation phenomenon of threshold voltage degradation under high field stress verifies the existence of threshold voltage reduction effect caused by gate electron injection.
基金the National Key Technology Support Program during“12th Five-Year Plan”Period of China,No.2014BAI08B00the Project“The role of the gut microbiota and metabolites in the pathogenesis of diarrheapredominant irritable bowel syndrome”of China-Japan Friendship Hospital,No.2019-64-K44.
文摘BACKGROUND The intestinal mucosal barrier is the first line of defense against numerous harmful substances,and it contributes to the maintenance of intestinal homeostasis.Recent studies reported that structural and functional changes in the intestinal mucosal barrier were involved in the pathogenesis of several intestinal diseases.However,no study thoroughly evaluated this barrier in patients with functional constipation(FC).AIM To investigate the intestinal mucosal barrier in FC,including the mucus barrier,intercellular junctions,mucosal immunity and gut permeability.METHODS Forty FC patients who fulfilled the Rome IV criteria and 24 healthy controls were recruited in the Department of Gastroenterology of China-Japan Friendship Hospital.The colonic mucus barrier,intercellular junctions in the colonic epithelium,mucosal immune state and gut permeability in FC patients were comprehensively examined.Goblet cells were stained with Alcian Blue/Periodic acid Schiff(AB/PAS)and counted.The ultrastructure of intercellular junctional complexes was observed under an electron microscope.Occludin and zonula occludens-1(ZO-1)in the colonic mucosa were located and quantified using immunohistochemistry and quantitative real-time polymerase chain reaction.Colonic CD3+intraepithelial lymphocytes(IELs)and CD3+lymphocytes in the lamina propria were identified and counted using immunofluorescence.The serum levels of D-lactic acid and zonulin were detected using enzyme-linked immunosorbent assay.RESULTS Compared to healthy controls,the staining of mucus secreted by goblet cells was darker in FC patients,and the number of goblet cells per upper crypt in the colonic mucosa was significantly increased in FC patients(control,18.67±2.99;FC,22.42±4.09;P=0.001).The intercellular junctional complexes in the colonic epithelium were integral in FC patients.The distribution of mucosal occludin and ZO-1 was not altered in FC patients.No significant differences were found in occludin(control,5.76E-2±1.62E-2;FC,5.17E-2±1.80E-2;P=0.240)and ZO-1(control,2.29E-2±0.93E-2;FC,2.68E-2±1.60E-2;P=0.333)protein expression between the two groups.The mRNA levels in occludin and ZO-1 were not modified in FC patients compared to healthy controls(P=0.145,P=0.451,respectively).No significant differences were observed in the number of CD3+IELs per 100 epithelial cells(control,5.62±2.06;FC,4.50±2.16;P=0.070)and CD3+lamina propria lymphocytes(control,19.69±6.04/mm^(2);FC,22.70±11.38/mm^(2);P=0.273).There were no significant differences in serum D-lactic acid[control,5.21(4.46,5.49)mmol/L;FC,4.63(4.31,5.42)mmol/L;P=0.112]or zonulin[control,1.36(0.53,2.15)ng/mL;FC,0.94(0.47,1.56)ng/mL;P=0.185]levels between FC patients and healthy controls.CONCLUSION The intestinal mucosal barrier in FC patients exhibits a compensatory increase in goblet cells and integral intercellular junctions without activation of mucosal immunity or increased gut permeability.
基金National key R&D Program Precision Medical Research key Project(No.2017YFC0910002)Beijing Science and Technology Commission G20 Engineering Innovation Research Ten Diseases and Ten drugs Research and Development Project(No.Z1711000017008)
文摘Objective:To evaluate the clinical efficacy and safety of berberine in the treatment of non-alcoholic fatty liver.Methods:Randomized controlled studies were searched in Chinese and English databases from March 30,2020.The quality was evaluated after literature screening and statistical analysis by RevMan5.3 software.Results:Nine studies were included,involving 780 patients.Meta analysis showed that berberine alone or in combination could reduce total cholesterol(MD=-0.50,95%CI),low density lipoprotein(MD=-0.34,95%CI)and glutamyltransferase(MD=-20.79,95CI%).Subgroup analysis showed that berberine combined with berberine could reduce glycosylated hemoglobin level[MD=-0.68,95%CI(-0.98 maxim 0.38)],while in patients with diabetes treated with berberine,alanine aminotransferase(MD=-9.38,95CI%)and aspartate oxaloacetic transaminase(MD=-9.03,95CI%)decreased significantly.The above differences were statistically significant(P<0.01).In addition,berberine has a tendency to decrease triglyceride,fasting blood glucose,body mass index and improve insulin resistance.There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:Berberine can regulate glucose and lipid metabolism in patients with non-alcoholic fatty liver and has a tendency to improve liver function and insulin resistance.
基金supported by grants from National Natural Science Foundation of China(81100050 to Shan-Shan Shi,81301612 to Xi-Wang Liu)Science and Technology Bureau of Zhejiang Province(2011C23011 to Qiang Shu)+1 种基金Ministry of Education Doctoral Station Foundation(20120101110049 to Qiang Shu)National Key Technology Support Program(2012BAI04B05 to Qiang Shu).
文摘Background Acute kidney injury(AKI)after cardiopulmonary bypass(CPB)is a common complication especially in pedi-atric population.Plasma gelsolin(pGSN)is an anti-inflammatory factor through binding with actin and pro-inflammatory cytokines in circulation.Decrease in pGSN has been reported in some pathologic conditions.The purpose of the study was to determine the alterations of pGSN level in infants and young children after CPB and the role of pGSN as a predictor for the morbidity and severity of post-CPB AKI.Methods Sixty-seven infants and young children at age≤3 years old undergoing CPB were prospectively enrolled.PGSN levels were measured during peri-operative period with enzyme-linked immuno-sorbent assay and normalized with plasma total protein concentration.Other clinical characteristics of the patients were also recorded.Results In patients developing AKI,the normalized pGSN(pGSN_(N))levels significantly decreased at 6 h post-operation and remained low for 24 h post-operation as compared to the patients with non-AKI.PGSNN at 6 h post-operation combining with CPB time presents an excellent predictive value for AKI.Conclusions Decreased pGSN_(N)identifies post-CPB AKI in the patients≤3 years old,and is associated with adverse clini-cal outcomes.The findings suggest that circulating GSN in post-CPB patients may have beneficial effects on diminishing inflammatory responses.