BACKGROUND Gastrointestinal tumor organoids serve as an effective model for simulating cancer in vitro and have been applied in basic biology and preclinical research.Despite over a decade of development and increasin...BACKGROUND Gastrointestinal tumor organoids serve as an effective model for simulating cancer in vitro and have been applied in basic biology and preclinical research.Despite over a decade of development and increasing research achievements in this field,a systematic and comprehensive analysis of the research hotspots and future trends is lacking.AIM To address this problem by employing bibliometric tools to explore the publication years,countries/regions,institutions,journals,authors,keywords,and references in this field.METHODS The literature was collected from Web of Science databases.CiteSpace-6.2R4,a widely used bibliometric analysis software package,was used for institutional analysis and reference burst analysis.VOSviewer 1.6.19 was used for journal cocitation analysis,author co-authorship and co-citation analysis.The‘online platform for bibliometric analysis(https://bibliometric.com/app)’was used to assess the total number of publications and the cooperation relationships between countries.Finally,we employed the bibliometric R software package(version R.4.3.1)in R-studio,for a comprehensive scientific analysis of the literature.RESULTS Our analysis included a total of 1466 publications,revealing a significant yearly increase in articles on the study of gastrointestinal tumor organoids.The United States(n=393)and Helmholtz Association(n=93)have emerged as the leading countries and institutions,respectively,in this field,with Hans Clevers and Toshiro Sato being the most contributing authors.The most influential journal in this field is Gastroenterology.The most impactful reference is"Long term expansion of epithelial organs from human colon,adenoma,adenocarcinoma,and Barrett's epithelium".Keywords analysis and citation burst analysis indicate that precision medicine,disease modeling,drug development and screening,and regenerative medicine are the most cutting-edge directions.These focal points were further detailed based on the literature.CONCLUSION This bibliometric study offers an objective and quantitative analysis of the research in this field,which can be considered as an important guide for next scientific research.展开更多
The high intraspecies heterogeneity of Baciillus coagulans leads to significant phenotypic differences among different strains.Thus,6 B.coagulans strains were tested in the present study using an irritable bowel syndr...The high intraspecies heterogeneity of Baciillus coagulans leads to significant phenotypic differences among different strains.Thus,6 B.coagulans strains were tested in the present study using an irritable bowel syndrome(IBS)animal model to determine whether the IBS-alleviating effects of B.coagulans strains are strain-specific.The results of this study showed that the ingestion of B.coagulans GBI-30,6086,and B.coagulans CCFM1041 significantly alleviated IBS symptoms in mice.In contrast,other B.coagulans strains showed no or limited alleviating effects on IBS symptoms.According to our experimental results,the two main common features of these strains were as follows:1)The resistance of vegetative cells to bile salts,and 2)ability to synthesize specific lipids and secondary metabolites.Screening strains based on these two indicators may greatly reduce costs and provide a basis for mining new functional B.coagulans strains.Our results also suggest that administration of B.coagulans could significantly regulate microbiota dysbiosis in animal models.Moreover,the close relationships between the gut microbiota,gut microbiota metabolites,and IBS were further confirmed in this study.展开更多
Inflammatory bowel disease(IBD)is a complex relapsing inflammatory disease in the gut and is driven by complicated host-gut microbiome interactions.Gut commensals have shown different functions in IBD prevention and t...Inflammatory bowel disease(IBD)is a complex relapsing inflammatory disease in the gut and is driven by complicated host-gut microbiome interactions.Gut commensals have shown different functions in IBD prevention and treatment.To gain a mechanistic understanding of how different commensals affect intestinal inflammation,we compared the protective effects of 6 probiotics(belonging to the genera Akkermansia,Bifidobacterium,Clostridium,and Enterococcus)on dextran sulfate sodium(DSS)-induced colitis in mice with or without gut microbiota.Anti-inflammatory properties(ratio of interleukin(IL)-10 and IL-12)of these strains were also evaluated in an in vitro mesenteric lymph nodes(MLN)co-culture system.Results showed that 4 probiotics(belonging to the species Bifidobacterium breve,Bifidobacterium bifidum,and Enterococcus faecalis)can alleviate colitis in normal mice.The probiotic strains differed in regulating the intestinal microbiota,cytokines(IL-10,IL-1βand interferon(IFN)-γ),and tight junction function(Zonulin-1 and Occludin).By constrast,Akkermansia muciniphila AH39 and Clostridium butyricum FHuNHHMY49T1 were not protective.Interestingly,B.breve JSNJJNM2 with high anti-inflammatory potential in the MLN model could relieve colitis symptoms in antibiotic cocktail(Abx)-treated mice.Meanwhile,E.faecalis FJSWX25M1induced low levels of cytokines in vitro and showed no beneficial effects.Therefore,we provided insight into the clinical application of probiotics in IBD treatment.展开更多
The following letter to the editor highlights the article“Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance”in Wor...The following letter to the editor highlights the article“Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance”in World J Diabetes 2023 Oct 15;14(10):1514-1523.It is necessary to explore the role of vitamin family members in insulin resistance and diabetes complications.展开更多
The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the princ...The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical b-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with b-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.展开更多
Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AF...Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.展开更多
Background Sustained yet intractable immunosuppression is commonly observed in septic patients,resulting in aggravated clinical outcomes.However,due to the substantial heterogeneity within septic patients,precise indi...Background Sustained yet intractable immunosuppression is commonly observed in septic patients,resulting in aggravated clinical outcomes.However,due to the substantial heterogeneity within septic patients,precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking.Methods We adopted cross-species,single-cell RNA sequencing(scRNA-seq)analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis.Flow cytometry,laser scanning confocal microscopy(LSCM)imaging and Western blotting were applied to identify the presence of S100A9^(+)monocytes at protein level.To interrogate the immunosuppressive function of this subset,splenic monocytes isolated from septic wild-type or S100a9^(–/–)mice were co-cultured with naive CD4^(+)T cells,followed by proliferative assay.Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage.Results scRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis,for which distinct monocyte subsets were enriched in disparate subclusters of septic patients.We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR(HLA-DR),which were prominently enriched in septic patients and might exert immunosuppressive function.By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments,we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice,corresponding to HLA-DR^(low)S100A^(high)monocytes in human sepsis.Moreover,we found that S100A9^(+)monocytes exhibited profound immunosuppressive function on CD4^(+)T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression.Conclusions This study identifies HLA-DR^(low)S100A^(high)monocytes correlated with immunosuppressive state upon septic challenge,inhibition of which can markedly mitigate sepsis-induced immune depression,thereby providing a novel therapeutic strategy for the management of sepsis.展开更多
This meta-analysis of randomized controlled trials aimed to evaluate the effects of probiotic supplementation on glucose homeostasis in patients with polycystic ovary syndrome(PCOS).The meta-analysis was performed in ...This meta-analysis of randomized controlled trials aimed to evaluate the effects of probiotic supplementation on glucose homeostasis in patients with polycystic ovary syndrome(PCOS).The meta-analysis was performed in accordance with the Cochrane Handbook guidelines and relevant the preferred reporting items for systematic reviews and meta-analyses(PRISMA)statement criteria.Of 825 identified reports,11 randomized clinical trials were included in the meta-analysis.An analysis of pooled extracted data revealed that supplementation with probiotics significantly decreased fasting blood glucose(FBG,n=7;standardized mean difference(SMD)=−0.40;95%confidence interval(CI):−2.02,−0.02;P=0.04)and insulin levels(n=6;SMD=−0.57;95%CI:−0.89,−0.25;P=0.0004)and the homeostatic model assessment of insulin resistance(n=7;SMD=−0.64;95%CI:−0.96,−0.31;P=0.0001)while increasing the quantitative insulin sensitivity check index(QUICKI,n=5;SMD=0.58;95%CI:0.08,1.09;P=0.02)in patients with PCOS.The FBG-reducing effect decreased as the baseline body mass index(BMI)and mean age of the participants increased.Indeed,a greater number of bacterial species and a higher bacterial dose were shown to reduce QUICKI effectively.The systematic review indicated that probiotic supplementation may help to control glucose homeostasis in adults with polycystic ovarian syndrome.展开更多
An increasing number of studies demonstrated that alcohol vapor chamber is an effective way to model physical signs of alcohol use disorders. Although researchers are developing different vapor chambers to study chron...An increasing number of studies demonstrated that alcohol vapor chamber is an effective way to model physical signs of alcohol use disorders. Although researchers are developing different vapor chambers to study chronic alcohol exposure model worldwide, few studies build and modify their own vapor chambers in China.Here, we designed and established an alcohol vapor chamber system for small animals. We described a paradigm showing how to control and monitor alcohol concentration in whole system. The vapor chamber system with several advantages including accommodating up to ten standard mouse cages. Furthermore, the system was tested by evaluating the blood alcohol concentration and neuron injury in mice. Importantly, the alcohol withdrawal after vapor exposure caused motor coordination impairment, anxiolytic-and depression-like behavior. Finally, the Nmethyl-D-aspartate receptor(NMDAR)-mediated glutamatergic transmissions in the medial prefrontal cortex was changed after alcohol vapor exposure-induced behaviors. The frequency and amplitude of spontaneous excitatory postsynaptic currents between control and alcohol groups were not different, suggesting that alcohol exposureinduced behaviors are associated with the change in NMDAR response. Taken together, the new alcohol vapor chamber system was constructed, which would help to research the relationship between the stable alcohol exposure and withdrawal behaviors and to study chronic alcohol exposure-induced disorders in China.展开更多
Akkermansia muciniphila, one of the most promising next-generation probiotics, was reported to exhibit beneficial modulatory effects on the gut barrier. However, the strain-specific and underlying regulatory mechanism...Akkermansia muciniphila, one of the most promising next-generation probiotics, was reported to exhibit beneficial modulatory effects on the gut barrier. However, the strain-specific and underlying regulatory mechanisms of this species on gut barrier function were not well studied. Therefore, this study evaluated the protective effect of A. muciniphila strains on the intestinal barrier and investigated the mode of action and material basis of this modulatory effect. We first confirmed the strain-specific effects of A. muciniphila on intestinal barrier regulation and found that this phenomenon may be explained by the different abilities of strains to affect tight junction protein expression in enterocytes. Comparative genomic analysis proved that the ability of A. muciniphila to regulate the intestinal barrier was exerted in part by the functional genes(such as COG0438, COG0463, and COG2244)related to the synthesis of cellular surface proteins. The role of these surface proteins in intestinal barrier regulation was further verified by strain-comparative experiments in animal and cell models and surface protein removal trials. This study confirmed the different effects of A. muciniphila strains on gut barrier modulation and provided molecular and genetic targets for the screening of A. muciniphila strains with superior protection against gut barrier dysfunction.展开更多
Stachyose is a prebiotic that traditionally extracted from plants,such as vegetable.It has been demonstrated to alleviate intestinal inflammation by regulating gut microbiota,but the mechanism has been unclear.This re...Stachyose is a prebiotic that traditionally extracted from plants,such as vegetable.It has been demonstrated to alleviate intestinal inflammation by regulating gut microbiota,but the mechanism has been unclear.This research aims to detect the potential mechanism of stachyose in alleviating the severity of ulcerative colitis(UC).The results indicated that the administration of stachyose could recover the body weight,protect against the colonic tissue damage,reduce the pro-inflammatory cytokines levels,and reverse the histological abnormalities in UC mice.Oral stachyose could restore dextran sulfate sodium(DSS)-induced disturbance in intestinal bacteria.Besides,the metabolome result of serum samples showed that stachyose treatment significantly altered serum metabolites against inflammatory responses in colitis mice.Also,a significant correlation can be found between 23 metabolite biomarkers and 18 differential genera.Our results provided a strong foundation for the future study of the protective role of stachyose in maintaining intestinal homeostasis.展开更多
Primary liver cancer is a severe and complex disease,leading to 800000 global deaths annually.Emerging evidence suggests that inflammation is one of the critical factors in the development of hepatocellular carcinoma(...Primary liver cancer is a severe and complex disease,leading to 800000 global deaths annually.Emerging evidence suggests that inflammation is one of the critical factors in the development of hepatocellular carcinoma(HCC).Patients with viral hepatitis,alcoholic hepatitis,and steatohepatitis symptoms are at higher risk of developing HCC.However,not all inflammatory factors have a pathogenic function in HCC development.The current study describes the process and mechanism of hepatitis development and its progression to HCC,particularly focusing on viral hepatitis,alcoholic hepatitis,and steatohepatitis.Furthermore,the roles of some essential inflammatory cytokines in HCC progression are described in addition to a summary of future research directions.展开更多
Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis.To provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing ...Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis.To provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed.Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed,Web of Science,and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire.Then,the Delphi method was used to form consensus opinions,and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions.This consensus achieved satisfactory results through two rounds of questionnaire survey,with 2 statements rated as perfect consistency,13 as very good consistency,and 9 as good consistency.After summarizing the results,a total of 14 strong recommended opinions,8 weak recommended opinions and 2 non-recommended opinions were produced.Finally,a face-to-face discussion of the consensus opinions was performed through an online meeting,and all judges unanimously agreed on the content of this consensus.In summary,this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.展开更多
Brain-derived neurotrophic factor(BDNF) regulates many neurological functions and plays a vital role during the recovery from central nervous system injuries. However, the changes in BDNF expression and associated fac...Brain-derived neurotrophic factor(BDNF) regulates many neurological functions and plays a vital role during the recovery from central nervous system injuries. However, the changes in BDNF expression and associated factors following hypoxia-ischemia induced neonatal brain damage, and the significance of these changes are not fully understood. In the present study, a rat model of hypoxic-ischemic brain damage was established through the occlusion of the right common carotid artery, followed by 2 hours in a hypoxic-ischemic environment. Rats with hypoxic-ischemic brain damage presented deficits in both sensory and motor functions, and obvious pathological changes could be detected in brain tissues. The m RNA expression levels of BDNF and its processing enzymes and receptors(Furin, matrix metallopeptidase 9, tissuetype plasminogen activator, tyrosine Kinase receptor B, plasminogen activator inhibitor-1, and Sortilin) were upregulated in the ipsilateral hippocampus and cerebral cortex 6 hours after injury;however, the expression levels of these m RNAs were found to be downregulated in the contralateral hippocampus and cerebral cortex. These findings suggest that BDNF and its processing enzymes and receptors may play important roles in the pathogenesis and recovery from neonatal hypoxic-ischemic brain damage. This study was approved by the Animal Ethics Committee of the University of South Australia(approval No. U12-18) on July 30, 2018.展开更多
Introduction:Most hepatocellular carcinomas(HCC) develop in a background of underlying liver disease including chronic hepatitis B.However,the effect of antiviral therapy on the long-term outcome of patients with hepa...Introduction:Most hepatocellular carcinomas(HCC) develop in a background of underlying liver disease including chronic hepatitis B.However,the effect of antiviral therapy on the long-term outcome of patients with hepatitis B virus(HBV)-related HCC treated with chemoembolization is unclear.This study aimed to evaluate the survival benefits of anti-HBV therapy after chemoembolization for patients with HBV-related HCC.Methods:A total of 224 HCC patients who successfully underwent chemoembolization were identified,and their survival and other relevant clinical data were reviewed.Kaplan-Meier and Cox regression analyses were performed to validate possible effects of antiviral treatment on overall survival(OS).Results:The median survival time(MST) was 15.9(95%confidence interval[CI],9.5-27.7) months in the antiviral group and 9.6(95%CI,7.8-13.7) months in the non-antiviral group(log-rank test,P = 0.044).Cox multivariate analysis revealed that antiviral treatment was a prognostic factor for OS(P = 0.008).Additionally,a further analysis was based on the stratification of the TNM tumor stages.In the subgroup of early stages,MST was significantly longer in the antiviral-treatment group than in the non-antiviral group(61.8 months[95%CI,34.8 months to beyond the follow-up period]versus 26.2[95%CI,14.5-37.7]months,P= 0.012).Multivariate analysis identified antiviral treatment as a prognostic factor for OS in the early-stage subgroup(P = 0.006).However,in the subgroup of advanced stages,MST of the antiviral-treated group was comparable to that of the non-antiviral group(8.4[95%CI,5.2-13.5]months versus 7.4[95%CI,5.9-9.3]months,P = 0.219).Multivariate analysis did not indicate that antiviral treatment was a significant prognostic factor in this subgroup.Conclusion:Antiviral treatment is associated with prolonged OS time after chemoembolization for HCC,especially in patients with early-stage tumors.展开更多
AIM: To investigate multiple polyps in a Chinese PeutzJeghers syndrome(PJS) infant. METHODS: A nine-month-old PJS infant was admitted to our hospital for recurrent prolapsed rectal polyps for one month. The clinical c...AIM: To investigate multiple polyps in a Chinese PeutzJeghers syndrome(PJS) infant. METHODS: A nine-month-old PJS infant was admitted to our hospital for recurrent prolapsed rectal polyps for one month. The clinical characteristics, a colonoscopic image, the pathological characteristics of the polyps and X-ray images of the intestinal perforation were obtained. Serine threonine-protein kinase 11(STK11) gene analysis was also performed using a DNA sample from this infant.RESULTS: Here we describe the youngest known Chinese infant with PJS. Five polyps, including a giant polyp of approximately 4 cm × 2 cm in size, were removed from the infant's intestine. Laparotomy was performed to repair a perforation caused by pneumoperitoneum. The pathological results showed that this child had PJS. Molecular analysis of the STK11 gene further revealed a novel frameshift mutation(c.64_65het_del AT) in exon 1 in this PJS infant.CONCLUSION: The appropriate treatment method for multiple polyps in an infant must be carefully considered. Our results also show that the STK11 gene mutation is the primary cause of PJS.展开更多
BACKGROUND: Inevitable warm ischemia time before organ procurement aggravates posttransplantation ischemia- reperfusion injury. Endoplasmic reticulum (ER) stress is involved in ischemia-reperfusion injury, but its ...BACKGROUND: Inevitable warm ischemia time before organ procurement aggravates posttransplantation ischemia- reperfusion injury. Endoplasmic reticulum (ER) stress is involved in ischemia-reperfusion injury, but its role in donation after cardiac death (DCD) liver transplantation is not clear and the effect of ER stress inhibitors, tauroursodeoxycholic acid (TUDCA) and 4-phenyl butyric acid (PBA), on the prognosis of recipient of DCD liver transplantation remains unclear. METHODS: Male Sprague-Dawley rats (8-10 weeks) were randomly divided into control group: liver grafts without warm ischemia were implanted; DCD group: warm ischemia time of the liver grafts was 60 minutes; TUDCA and PBA groups: based on the DCD group, donors were intraperitoneally injected with TUDCA or PBA 30 minutes before the organ procurements. Serum aminotransferase levels, oxidative stress activation and expression of ER stress signal molecules were evaluated. Pathological examinations were performed. The survivals of the recipients in each group were compared for 14 days.RESULTS: Compared with the control group, DCD rats had significantly higher levels of serum aminotransferase at 6 hours, 1 day and 3 days after operation (P〈0.01, 0.01 and 0.05, respectively) and oxidative indices (P〈0.01 for both malondialdehyde and 8-hydroxy deoxyguanosine), more severe liver damage (P〈0.01) and up-regulated ER stress signal expressions (P〈0.01 for GRP78, phos-eIF2al, CHOP, ATF-4, ATF-6, PERK, XBP-1 and pro-caspase-12). All recipients died within 3 days after liver transplantation. Administration of TUDCA or PBA significantly decreased aminotransferase levels (P〈0.05), increased superoxide dismutase activities (P〈0.01), alleviated liver damage (P〈0.01), down-regulated ER stress signal expressions (P〈0.01) and improved postoperative survivals (P〈0.01). CONCLUSIONS: ER stress was involved with DCD liver trans- plantation in rats. Preoperative intraperitoneally injection of TUDCA or PBA protected ER stress and improved prognosis.展开更多
Hepatitis C virus(HCV) is a major human pathogen of chronic hepatitis and related liver diseases. Innate immunity is the first line of defense against invading foreign pathogens, and its activation is dependent on the...Hepatitis C virus(HCV) is a major human pathogen of chronic hepatitis and related liver diseases. Innate immunity is the first line of defense against invading foreign pathogens, and its activation is dependent on the recognition of these pathogens by several key sensors. The interferon(IFN) system plays an essential role in the restriction of HCV infection via the induction of hundreds of IFN-stimulated genes(ISGs) that inhibit viral replication and spread. However, numerous factors that trigger immune dysregulation, including viral factors and host genetic factors, can help HCV to escape host immune response, facilitating viral persistence. In this review, we aim to summarize recent advances in understanding the innate immune response to HCV infection and the mechanisms of ISGs to suppress viral survival, as well as the immune evasion strategies for chronic HCV infection.展开更多
A case control study including 45 acute pancreatitis and 44 healthy volunteers was performed to investigate the association between intestinal microbial community and acute pancreatitis. High-throughput 16S r RNA gene...A case control study including 45 acute pancreatitis and 44 healthy volunteers was performed to investigate the association between intestinal microbial community and acute pancreatitis. High-throughput 16S r RNA gene amplicon sequencing was used to profile the microbiological composition of the samples. In total, 27 microbial phyla were detected and the samples of pancreatitis patients contained fewer phyla. Samples from acute pancreatitis patients contained more Bacteroidetes and Proteobacteria and fewer Firmicutes and Actinobacteria than those from healthy volunteers. PCo A analyses distinguished the fecal microbial communities of acute pancreatitis patients from those of healthy volunteers. The intestinal microbes of acute pancreatitis patients are different from those of healthy volunteers. Modulation of the intestinal microbiome may serve as an alternative strategy for treating acute pancreatitis.展开更多
基金Supported by The Science and Technology Program of Gansu Province,No.23JRRA1015.
文摘BACKGROUND Gastrointestinal tumor organoids serve as an effective model for simulating cancer in vitro and have been applied in basic biology and preclinical research.Despite over a decade of development and increasing research achievements in this field,a systematic and comprehensive analysis of the research hotspots and future trends is lacking.AIM To address this problem by employing bibliometric tools to explore the publication years,countries/regions,institutions,journals,authors,keywords,and references in this field.METHODS The literature was collected from Web of Science databases.CiteSpace-6.2R4,a widely used bibliometric analysis software package,was used for institutional analysis and reference burst analysis.VOSviewer 1.6.19 was used for journal cocitation analysis,author co-authorship and co-citation analysis.The‘online platform for bibliometric analysis(https://bibliometric.com/app)’was used to assess the total number of publications and the cooperation relationships between countries.Finally,we employed the bibliometric R software package(version R.4.3.1)in R-studio,for a comprehensive scientific analysis of the literature.RESULTS Our analysis included a total of 1466 publications,revealing a significant yearly increase in articles on the study of gastrointestinal tumor organoids.The United States(n=393)and Helmholtz Association(n=93)have emerged as the leading countries and institutions,respectively,in this field,with Hans Clevers and Toshiro Sato being the most contributing authors.The most influential journal in this field is Gastroenterology.The most impactful reference is"Long term expansion of epithelial organs from human colon,adenoma,adenocarcinoma,and Barrett's epithelium".Keywords analysis and citation burst analysis indicate that precision medicine,disease modeling,drug development and screening,and regenerative medicine are the most cutting-edge directions.These focal points were further detailed based on the literature.CONCLUSION This bibliometric study offers an objective and quantitative analysis of the research in this field,which can be considered as an important guide for next scientific research.
基金supported by the Natural Science Foundation of Jiangsu Province(BK20200084)the National Natural Science Foundation of China(31871773 and 31820103010)+1 种基金the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province and Key Talents Project of“Strengthening Health through Science and Education”of Wuxi Health and Family Planning Commission(ZDRC039)Top Talents Project of“Six-one Project”for High-level Health Talents in Jiangsu Province(LGY2018016)。
文摘The high intraspecies heterogeneity of Baciillus coagulans leads to significant phenotypic differences among different strains.Thus,6 B.coagulans strains were tested in the present study using an irritable bowel syndrome(IBS)animal model to determine whether the IBS-alleviating effects of B.coagulans strains are strain-specific.The results of this study showed that the ingestion of B.coagulans GBI-30,6086,and B.coagulans CCFM1041 significantly alleviated IBS symptoms in mice.In contrast,other B.coagulans strains showed no or limited alleviating effects on IBS symptoms.According to our experimental results,the two main common features of these strains were as follows:1)The resistance of vegetative cells to bile salts,and 2)ability to synthesize specific lipids and secondary metabolites.Screening strains based on these two indicators may greatly reduce costs and provide a basis for mining new functional B.coagulans strains.Our results also suggest that administration of B.coagulans could significantly regulate microbiota dysbiosis in animal models.Moreover,the close relationships between the gut microbiota,gut microbiota metabolites,and IBS were further confirmed in this study.
基金supported by the Natural Science Foundation of Jiangsu Province (BK20200084)The National Natural Science Foundation of China (U1903205 and 31972971)Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘Inflammatory bowel disease(IBD)is a complex relapsing inflammatory disease in the gut and is driven by complicated host-gut microbiome interactions.Gut commensals have shown different functions in IBD prevention and treatment.To gain a mechanistic understanding of how different commensals affect intestinal inflammation,we compared the protective effects of 6 probiotics(belonging to the genera Akkermansia,Bifidobacterium,Clostridium,and Enterococcus)on dextran sulfate sodium(DSS)-induced colitis in mice with or without gut microbiota.Anti-inflammatory properties(ratio of interleukin(IL)-10 and IL-12)of these strains were also evaluated in an in vitro mesenteric lymph nodes(MLN)co-culture system.Results showed that 4 probiotics(belonging to the species Bifidobacterium breve,Bifidobacterium bifidum,and Enterococcus faecalis)can alleviate colitis in normal mice.The probiotic strains differed in regulating the intestinal microbiota,cytokines(IL-10,IL-1βand interferon(IFN)-γ),and tight junction function(Zonulin-1 and Occludin).By constrast,Akkermansia muciniphila AH39 and Clostridium butyricum FHuNHHMY49T1 were not protective.Interestingly,B.breve JSNJJNM2 with high anti-inflammatory potential in the MLN model could relieve colitis symptoms in antibiotic cocktail(Abx)-treated mice.Meanwhile,E.faecalis FJSWX25M1induced low levels of cytokines in vitro and showed no beneficial effects.Therefore,we provided insight into the clinical application of probiotics in IBD treatment.
基金Supported by the National Natural Science Foundation of China,No.82170286Basic Research Program of Guizhou Province(Natural Sciences),No.ZK[2023]321+1 种基金Start-up Fund of Guizhou Medical University,No.J2021032Postdoctoral Research Fund of Affiliated Hospital of Guizhou Medical University,No.BSH-Q-2021-10.
文摘The following letter to the editor highlights the article“Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance”in World J Diabetes 2023 Oct 15;14(10):1514-1523.It is necessary to explore the role of vitamin family members in insulin resistance and diabetes complications.
基金supported by“Jiaotong University Star”Program,China(Grant No.:YG2022QN082)the National Natural Science Foundation of China(Grant No.:82204887)+1 种基金the Science Foundation for Shanghai Committee of Science Project,China(Grant Nos.:21S21901400,23S21901200)the Natural Science Research Foundation of Jiading District,China(Grant No.:JDKW-2021-0023).
文摘The density and composition of lymphocytes infiltrating colon tumors serve as predictive factors for the clinical outcome of colon cancer.Our previous studies highlighted the potent anti-cancer properties of the principal compounds found in Garcinia yunnanensis(YTE-17),attributing these effects to the regu-lation of multiple signaling pathways.However,knowledge regarding the mechanism and effect of YTE-17 in the prevention of colorectal cancer is limited.In this study,we conducted isobaric tags for relative and absolute quantification(iTRAQ)analysis on intestinal epithelial cells(IECs)exposed YTE-17,both in vitro and in vivo,revealing a significant inhibition of the Wnt family member 5a(Wnt5a)/c-Jun N-terminal kinase(JNK)signaling pathway.Subsequently,we elucidated the influence and mechanism of YTE-17 on the tumor microenvironment(TME),specifically focusing on macrophage-mediated T helper 17(Th17)cell induction in a colitis-associated cancer(CAC)model with Wnt5a deletion.Additionally,we performed the single-cell RNA sequencing(scRNA-seq)on the colonic tissue from the Wnt5a-deleted CAC model to characterize the composition,lineage,and functional status of immune mesenchymal cells during different stages of colorectal cancer(CRC)progression.Remarkably,our findings demon-strate a significant reduction in M2 macrophage polarization and Th17 cell phenotype upon treatment with YTE-17,leading to the restoration of regulatory T(Treg)/Th17 cell balance in azoxymethane(AOM)/dextran sodium sulfate(DSS)model.Furthermore,we also confirmed that YTE-17 effectively inhibited the glycolysis of Th17 cells in both direct and indirect co-culture systems with M2 macrophages.Notably,our study shed light on potential mechanisms linking the non-canonical Wnt5a/JNK signaling pathway and well-established canonical b-catenin oncogenic pathway in vivo.Specifically,we proposed that Wnt5a/JNK signaling activity in IECs promotes the development of cancer stem cells with b-catenin activity within the TME,involving macrophages and T cells.In summary,our study undergoes the po-tential of YTE-17 as a preventive strategy against CRC development by addressing the imbalance with the immune microenvironment,thereby mitigating the risk of malignancies.
基金funded by Suzhou Science and Technology Council(SNG201907)Universities Natural Science Foundation of Jiangsu Province(20KJB330002)+6 种基金General Program of China Postdoctoral Science Foundation(2022M711369)the Startup Funding of Soochow University,Jiangsu Province-Suzhou Science and Technology Planning Project(SL T201917)National Natural Science Foundation of China(32172922,31972741)Natural Science Foundation of Jiangsu Province of China(BK20211216,BK20221091)the Startup Funding of Hefei University of Technology(1302003712022058)China-CEEC Joint University Education Project(202010)the Excellence Project PrF UHK(2217/2022-2023)。
文摘Aflatoxin B_(1)(AFB_(1))is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB_(1)-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.
基金supported by the Key Project of National Natural Science Foundation of China(82130062,82241062 and 81930057)the National Key Research and Development Program of China(2022YFA1104604)+1 种基金the Key Project of Military Medical Innovation Program of Chinese PLA(18CXZ026 and BLJ18J006)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-076)。
文摘Background Sustained yet intractable immunosuppression is commonly observed in septic patients,resulting in aggravated clinical outcomes.However,due to the substantial heterogeneity within septic patients,precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking.Methods We adopted cross-species,single-cell RNA sequencing(scRNA-seq)analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis.Flow cytometry,laser scanning confocal microscopy(LSCM)imaging and Western blotting were applied to identify the presence of S100A9^(+)monocytes at protein level.To interrogate the immunosuppressive function of this subset,splenic monocytes isolated from septic wild-type or S100a9^(–/–)mice were co-cultured with naive CD4^(+)T cells,followed by proliferative assay.Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage.Results scRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis,for which distinct monocyte subsets were enriched in disparate subclusters of septic patients.We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR(HLA-DR),which were prominently enriched in septic patients and might exert immunosuppressive function.By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments,we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice,corresponding to HLA-DR^(low)S100A^(high)monocytes in human sepsis.Moreover,we found that S100A9^(+)monocytes exhibited profound immunosuppressive function on CD4^(+)T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression.Conclusions This study identifies HLA-DR^(low)S100A^(high)monocytes correlated with immunosuppressive state upon septic challenge,inhibition of which can markedly mitigate sepsis-induced immune depression,thereby providing a novel therapeutic strategy for the management of sepsis.
基金supported by the National Natural Science Foundation of China Program(31871773 and 32001665)the Natural Science Foundation of Jiangsu Province(BK20200084)+3 种基金National First-Class Discipline Program of Food Science and Technology(JUFSTR20180102)Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Provincethe Wuxi Health and Family Planning Commission(ZDRC039)High-level Health Talents in Jiangsu Province(LGY2018016).
文摘This meta-analysis of randomized controlled trials aimed to evaluate the effects of probiotic supplementation on glucose homeostasis in patients with polycystic ovary syndrome(PCOS).The meta-analysis was performed in accordance with the Cochrane Handbook guidelines and relevant the preferred reporting items for systematic reviews and meta-analyses(PRISMA)statement criteria.Of 825 identified reports,11 randomized clinical trials were included in the meta-analysis.An analysis of pooled extracted data revealed that supplementation with probiotics significantly decreased fasting blood glucose(FBG,n=7;standardized mean difference(SMD)=−0.40;95%confidence interval(CI):−2.02,−0.02;P=0.04)and insulin levels(n=6;SMD=−0.57;95%CI:−0.89,−0.25;P=0.0004)and the homeostatic model assessment of insulin resistance(n=7;SMD=−0.64;95%CI:−0.96,−0.31;P=0.0001)while increasing the quantitative insulin sensitivity check index(QUICKI,n=5;SMD=0.58;95%CI:0.08,1.09;P=0.02)in patients with PCOS.The FBG-reducing effect decreased as the baseline body mass index(BMI)and mean age of the participants increased.Indeed,a greater number of bacterial species and a higher bacterial dose were shown to reduce QUICKI effectively.The systematic review indicated that probiotic supplementation may help to control glucose homeostasis in adults with polycystic ovarian syndrome.
基金supported by the National Natural Science Foundation of China(Grant No.81971246)College Students’innovation and entrepreneurship training program in Jiangsu Province(Grant No.202010312042Y)。
文摘An increasing number of studies demonstrated that alcohol vapor chamber is an effective way to model physical signs of alcohol use disorders. Although researchers are developing different vapor chambers to study chronic alcohol exposure model worldwide, few studies build and modify their own vapor chambers in China.Here, we designed and established an alcohol vapor chamber system for small animals. We described a paradigm showing how to control and monitor alcohol concentration in whole system. The vapor chamber system with several advantages including accommodating up to ten standard mouse cages. Furthermore, the system was tested by evaluating the blood alcohol concentration and neuron injury in mice. Importantly, the alcohol withdrawal after vapor exposure caused motor coordination impairment, anxiolytic-and depression-like behavior. Finally, the Nmethyl-D-aspartate receptor(NMDAR)-mediated glutamatergic transmissions in the medial prefrontal cortex was changed after alcohol vapor exposure-induced behaviors. The frequency and amplitude of spontaneous excitatory postsynaptic currents between control and alcohol groups were not different, suggesting that alcohol exposureinduced behaviors are associated with the change in NMDAR response. Taken together, the new alcohol vapor chamber system was constructed, which would help to research the relationship between the stable alcohol exposure and withdrawal behaviors and to study chronic alcohol exposure-induced disorders in China.
基金supported by the Natural Science Foundation of Jiangsu Province (BK20200084)The National Natural Science Foundation of China (32021005 and 31871773)Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘Akkermansia muciniphila, one of the most promising next-generation probiotics, was reported to exhibit beneficial modulatory effects on the gut barrier. However, the strain-specific and underlying regulatory mechanisms of this species on gut barrier function were not well studied. Therefore, this study evaluated the protective effect of A. muciniphila strains on the intestinal barrier and investigated the mode of action and material basis of this modulatory effect. We first confirmed the strain-specific effects of A. muciniphila on intestinal barrier regulation and found that this phenomenon may be explained by the different abilities of strains to affect tight junction protein expression in enterocytes. Comparative genomic analysis proved that the ability of A. muciniphila to regulate the intestinal barrier was exerted in part by the functional genes(such as COG0438, COG0463, and COG2244)related to the synthesis of cellular surface proteins. The role of these surface proteins in intestinal barrier regulation was further verified by strain-comparative experiments in animal and cell models and surface protein removal trials. This study confirmed the different effects of A. muciniphila strains on gut barrier modulation and provided molecular and genetic targets for the screening of A. muciniphila strains with superior protection against gut barrier dysfunction.
文摘Stachyose is a prebiotic that traditionally extracted from plants,such as vegetable.It has been demonstrated to alleviate intestinal inflammation by regulating gut microbiota,but the mechanism has been unclear.This research aims to detect the potential mechanism of stachyose in alleviating the severity of ulcerative colitis(UC).The results indicated that the administration of stachyose could recover the body weight,protect against the colonic tissue damage,reduce the pro-inflammatory cytokines levels,and reverse the histological abnormalities in UC mice.Oral stachyose could restore dextran sulfate sodium(DSS)-induced disturbance in intestinal bacteria.Besides,the metabolome result of serum samples showed that stachyose treatment significantly altered serum metabolites against inflammatory responses in colitis mice.Also,a significant correlation can be found between 23 metabolite biomarkers and 18 differential genera.Our results provided a strong foundation for the future study of the protective role of stachyose in maintaining intestinal homeostasis.
基金Supported by the National Natural Science Foundation of China,No.82260567Science and Technology Fund of Guizhou Provincial Health Commission,No.gzwkj2022-082+2 种基金Excellent Young Talents Plan of Guizhou Medical University,No.2023(112)Taizhou Social Development Science and Technology Plan Project,No.23ywb146and Start-up Fund of Guizhou Medical University,No.J2021032.
文摘Primary liver cancer is a severe and complex disease,leading to 800000 global deaths annually.Emerging evidence suggests that inflammation is one of the critical factors in the development of hepatocellular carcinoma(HCC).Patients with viral hepatitis,alcoholic hepatitis,and steatohepatitis symptoms are at higher risk of developing HCC.However,not all inflammatory factors have a pathogenic function in HCC development.The current study describes the process and mechanism of hepatitis development and its progression to HCC,particularly focusing on viral hepatitis,alcoholic hepatitis,and steatohepatitis.Furthermore,the roles of some essential inflammatory cytokines in HCC progression are described in addition to a summary of future research directions.
基金supported by grants from the National Natural Science Foundation of China(81730057,82130062)the Key Project of Military Medical Innovation Program of Chinese PLA(18CXZ026)+1 种基金the Guangdong Clinical Research Center for Critical Care Medicine(2020B1111170005)the Sun Yat?sen University Clinical Research Program 5010(2019002)。
文摘Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis.To provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed.Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed,Web of Science,and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire.Then,the Delphi method was used to form consensus opinions,and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions.This consensus achieved satisfactory results through two rounds of questionnaire survey,with 2 statements rated as perfect consistency,13 as very good consistency,and 9 as good consistency.After summarizing the results,a total of 14 strong recommended opinions,8 weak recommended opinions and 2 non-recommended opinions were produced.Finally,a face-to-face discussion of the consensus opinions was performed through an online meeting,and all judges unanimously agreed on the content of this consensus.In summary,this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.
基金supported by the National Natural Science Foundation of China,No. 82001604 (to LLX)the Joint Subject of Southwest Medical University and Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University of China,No. 2018XYLH-004 (to LLX)+1 种基金the National Construction Project of Regional Chinese Medicine Treatment Centre of China,No. 2018205 (to XB)the National Construction Project of the Second Clinical Research Base of Chinese Medicine of China,No. 2018131 (to XB)。
文摘Brain-derived neurotrophic factor(BDNF) regulates many neurological functions and plays a vital role during the recovery from central nervous system injuries. However, the changes in BDNF expression and associated factors following hypoxia-ischemia induced neonatal brain damage, and the significance of these changes are not fully understood. In the present study, a rat model of hypoxic-ischemic brain damage was established through the occlusion of the right common carotid artery, followed by 2 hours in a hypoxic-ischemic environment. Rats with hypoxic-ischemic brain damage presented deficits in both sensory and motor functions, and obvious pathological changes could be detected in brain tissues. The m RNA expression levels of BDNF and its processing enzymes and receptors(Furin, matrix metallopeptidase 9, tissuetype plasminogen activator, tyrosine Kinase receptor B, plasminogen activator inhibitor-1, and Sortilin) were upregulated in the ipsilateral hippocampus and cerebral cortex 6 hours after injury;however, the expression levels of these m RNAs were found to be downregulated in the contralateral hippocampus and cerebral cortex. These findings suggest that BDNF and its processing enzymes and receptors may play important roles in the pathogenesis and recovery from neonatal hypoxic-ischemic brain damage. This study was approved by the Animal Ethics Committee of the University of South Australia(approval No. U12-18) on July 30, 2018.
基金partly supported by the Foundation for the Outstanding Young Scholar Award(Dr.Xiang-Ming Lao) from Sun Yat-sen University Cancer Center
文摘Introduction:Most hepatocellular carcinomas(HCC) develop in a background of underlying liver disease including chronic hepatitis B.However,the effect of antiviral therapy on the long-term outcome of patients with hepatitis B virus(HBV)-related HCC treated with chemoembolization is unclear.This study aimed to evaluate the survival benefits of anti-HBV therapy after chemoembolization for patients with HBV-related HCC.Methods:A total of 224 HCC patients who successfully underwent chemoembolization were identified,and their survival and other relevant clinical data were reviewed.Kaplan-Meier and Cox regression analyses were performed to validate possible effects of antiviral treatment on overall survival(OS).Results:The median survival time(MST) was 15.9(95%confidence interval[CI],9.5-27.7) months in the antiviral group and 9.6(95%CI,7.8-13.7) months in the non-antiviral group(log-rank test,P = 0.044).Cox multivariate analysis revealed that antiviral treatment was a prognostic factor for OS(P = 0.008).Additionally,a further analysis was based on the stratification of the TNM tumor stages.In the subgroup of early stages,MST was significantly longer in the antiviral-treatment group than in the non-antiviral group(61.8 months[95%CI,34.8 months to beyond the follow-up period]versus 26.2[95%CI,14.5-37.7]months,P= 0.012).Multivariate analysis identified antiviral treatment as a prognostic factor for OS in the early-stage subgroup(P = 0.006).However,in the subgroup of advanced stages,MST of the antiviral-treated group was comparable to that of the non-antiviral group(8.4[95%CI,5.2-13.5]months versus 7.4[95%CI,5.9-9.3]months,P = 0.219).Multivariate analysis did not indicate that antiviral treatment was a significant prognostic factor in this subgroup.Conclusion:Antiviral treatment is associated with prolonged OS time after chemoembolization for HCC,especially in patients with early-stage tumors.
文摘AIM: To investigate multiple polyps in a Chinese PeutzJeghers syndrome(PJS) infant. METHODS: A nine-month-old PJS infant was admitted to our hospital for recurrent prolapsed rectal polyps for one month. The clinical characteristics, a colonoscopic image, the pathological characteristics of the polyps and X-ray images of the intestinal perforation were obtained. Serine threonine-protein kinase 11(STK11) gene analysis was also performed using a DNA sample from this infant.RESULTS: Here we describe the youngest known Chinese infant with PJS. Five polyps, including a giant polyp of approximately 4 cm × 2 cm in size, were removed from the infant's intestine. Laparotomy was performed to repair a perforation caused by pneumoperitoneum. The pathological results showed that this child had PJS. Molecular analysis of the STK11 gene further revealed a novel frameshift mutation(c.64_65het_del AT) in exon 1 in this PJS infant.CONCLUSION: The appropriate treatment method for multiple polyps in an infant must be carefully considered. Our results also show that the STK11 gene mutation is the primary cause of PJS.
基金supported by a grant from the National Natural Science Foundation of China (81273262)
文摘BACKGROUND: Inevitable warm ischemia time before organ procurement aggravates posttransplantation ischemia- reperfusion injury. Endoplasmic reticulum (ER) stress is involved in ischemia-reperfusion injury, but its role in donation after cardiac death (DCD) liver transplantation is not clear and the effect of ER stress inhibitors, tauroursodeoxycholic acid (TUDCA) and 4-phenyl butyric acid (PBA), on the prognosis of recipient of DCD liver transplantation remains unclear. METHODS: Male Sprague-Dawley rats (8-10 weeks) were randomly divided into control group: liver grafts without warm ischemia were implanted; DCD group: warm ischemia time of the liver grafts was 60 minutes; TUDCA and PBA groups: based on the DCD group, donors were intraperitoneally injected with TUDCA or PBA 30 minutes before the organ procurements. Serum aminotransferase levels, oxidative stress activation and expression of ER stress signal molecules were evaluated. Pathological examinations were performed. The survivals of the recipients in each group were compared for 14 days.RESULTS: Compared with the control group, DCD rats had significantly higher levels of serum aminotransferase at 6 hours, 1 day and 3 days after operation (P〈0.01, 0.01 and 0.05, respectively) and oxidative indices (P〈0.01 for both malondialdehyde and 8-hydroxy deoxyguanosine), more severe liver damage (P〈0.01) and up-regulated ER stress signal expressions (P〈0.01 for GRP78, phos-eIF2al, CHOP, ATF-4, ATF-6, PERK, XBP-1 and pro-caspase-12). All recipients died within 3 days after liver transplantation. Administration of TUDCA or PBA significantly decreased aminotransferase levels (P〈0.05), increased superoxide dismutase activities (P〈0.01), alleviated liver damage (P〈0.01), down-regulated ER stress signal expressions (P〈0.01) and improved postoperative survivals (P〈0.01). CONCLUSIONS: ER stress was involved with DCD liver trans- plantation in rats. Preoperative intraperitoneally injection of TUDCA or PBA protected ER stress and improved prognosis.
文摘Hepatitis C virus(HCV) is a major human pathogen of chronic hepatitis and related liver diseases. Innate immunity is the first line of defense against invading foreign pathogens, and its activation is dependent on the recognition of these pathogens by several key sensors. The interferon(IFN) system plays an essential role in the restriction of HCV infection via the induction of hundreds of IFN-stimulated genes(ISGs) that inhibit viral replication and spread. However, numerous factors that trigger immune dysregulation, including viral factors and host genetic factors, can help HCV to escape host immune response, facilitating viral persistence. In this review, we aim to summarize recent advances in understanding the innate immune response to HCV infection and the mechanisms of ISGs to suppress viral survival, as well as the immune evasion strategies for chronic HCV infection.
基金supported by Nanjing Medical Technology and Development General Subject[YKK14092]
文摘A case control study including 45 acute pancreatitis and 44 healthy volunteers was performed to investigate the association between intestinal microbial community and acute pancreatitis. High-throughput 16S r RNA gene amplicon sequencing was used to profile the microbiological composition of the samples. In total, 27 microbial phyla were detected and the samples of pancreatitis patients contained fewer phyla. Samples from acute pancreatitis patients contained more Bacteroidetes and Proteobacteria and fewer Firmicutes and Actinobacteria than those from healthy volunteers. PCo A analyses distinguished the fecal microbial communities of acute pancreatitis patients from those of healthy volunteers. The intestinal microbes of acute pancreatitis patients are different from those of healthy volunteers. Modulation of the intestinal microbiome may serve as an alternative strategy for treating acute pancreatitis.
基金This work was supported by grants from The National Natural Science Foundation of China (81201730), China Postdoctoral Science Foundation Grant (2012M521565), National Basic Research Program of China (2012CB517902), National Natural Science Foundation of China (81330027).