Functional gastrointestinal disorders(FGIDs),including irritable bowel syndrome(IBS),functional dyspepsia(FD),and gastroesophageal reflux disease(GERD),present persistent diagnostic and therapeutic challenges due to s...Functional gastrointestinal disorders(FGIDs),including irritable bowel syndrome(IBS),functional dyspepsia(FD),and gastroesophageal reflux disease(GERD),present persistent diagnostic and therapeutic challenges due to symptom heterogeneity and the absence of reliable biomarkers.Artificial intelligence(AI)enables the integration of multimodal data to enhance FGID management through precision diagnostics and preventive healthcare.This minireview summarizes recent advancements in AI applications for FGIDs,highlighting progress in diagnostic accuracy,subtype classification,personalized interventions,and preventive strategies inspired by the traditional Chinese medicine concept of“treating the undiseased”.Machine learning and deep learning algorithms have demonstrated value in improving IBS diagnosis,refining FD neuro-gastrointestinal subtyping,and screening for GERD-related complications.Moreover,AI supports dietary,psychological,and integrative medicine-based interventions to improve patient adherence and quality of life.Nonetheless,key challenges remain,including data heterogeneity,limited model interpretability,and the need for robust clinical validation.Future directions emphasize interdisciplinary collaboration,the development of multimodal and explainable AI models,and the creation of patientcentered platforms to facilitate a shift from reactive treatment to proactive prevention.This review provides a systematic framework to guide the clinical application and theoretical innovation of AI in FGIDs.展开更多
BACKGROUND Hepatic organoid-based modelling,through the elucidation of a range of in vivo biological processes and the recreation of the intricate liver microenvironment,is yielding groundbreaking insights into the pa...BACKGROUND Hepatic organoid-based modelling,through the elucidation of a range of in vivo biological processes and the recreation of the intricate liver microenvironment,is yielding groundbreaking insights into the pathophysiology and personalized medicine approaches for liver diseases.AIM This study was designed to analyse the global scientific output of hepatic organoid research and assess current achievements and future trends through bibliometric analysis.METHODS Articles were retrieved from the Web of Science Core Collection,and CiteSpace 6.3.R1 was employed to analyse the literature,including outputs,journals,and countries,among others.RESULTS Between 2010 and 2024,a total of 991 articles pertaining to hepatic organoid research were published.The journal Hepatology published the greatest number of papers,and journals with an impact factor greater than 10 constituted 60%of the top 10 journals.The United States and Utrecht University were identified as the most prolific country and institution,respectively.Clevers H emerged as the most prolific author,whereas Huch M had the highest number of cocitations,suggesting that both are ideal candidates for academic collaboration.Research on hepatic organoids has exhibited a progressive shift in focus,evolving from initial investigations into model building,differentiation research in stem cells,bile ducts,and progenitor cells,to a broader spectrum encompassing lipid metabolism,single-cell RNA sequencing,and therapeutic applications.The phrases exhibiting citation bursts from 2022 to 2024 include“drug resistance”,“disease model”,and“patient-derived tumor organoids”.CONCLUSION Research on hepatic organoids has increased over the past decade and is expected to continue to grow.Key research areas include applications for liver diseases and drug development.Future trends likely to gain focus include patient-derived tumour organoids,disease modelling,and personalized medicine.展开更多
BACKGROUND Precancerous lesions of gastric cancer(PLGC)represent a critical pathological stage in the development of intestinal gastric cancer.Early detection and diagnosis are key to reducing the incidence of gastric...BACKGROUND Precancerous lesions of gastric cancer(PLGC)represent a critical pathological stage in the development of intestinal gastric cancer.Early detection and diagnosis are key to reducing the incidence of gastric cancer.Substantial advancements have been made in PLGC research in recent years,making it necessary to provide updated reviews using bibliometric methods.We hypothesize that this review will identify emerging trends,key research areas,and gaps in PLGC research,providing insights that could guide future studies and enhance prevention strategies.AIM To comprehensively review the current state of research on PLGC,examining development trends and research hotspots.METHODS We conducted a bibliometric analysis of PLGC-related studies published between 2004 and 2023 using the Web of Science Core Collection database.We employed Software,including VOSviewer,CiteSpace,R software,and SCImago Graphica,to map scientific networks and visualize knowledge trends in terms of publication volume,countries/regions,institutions,journals,authors,and keywords.RESULTS A total of 4097 articles were included,and overall publication volume showed an increasing trend.Over the past two decades,China published the most articles,followed by the United States,Japan,South Korea,and Italy.Among the top 10 contributors,the United States ranked highest in institutions,authors,and citations and demonstrated the strongest international collaboration.Research keywords in this field were clustered into three main categories:Risk factors,pathogenesis,and diagnosis and treatment.Pathogenesis and molecular biomarkers remain key areas of focus.Future research should explore the mechanisms of gut microbiota,immune microenvironment,metabolic reprogramming,and epigenetics.Advanced technologies,including single-cell sequencing,spatially resolved analysis,multi-omics approaches,artificial intelligence,and machine learning,will likely accelerate in-depth investigations of PLGC.CONCLUSION PLGC research has rapidly developed in recent years,gaining considerable attention.This bibliometric analysis reveals research state and emerging trends over the past 20 years,providing insights for future studies.展开更多
Dear Editor, Chromosome movements during mitosis are orches- trated primarily by the interaction of spindle microtu- bules with the kinetochore [1], the site for attachment of spindle microtubules to the centromere. ...Dear Editor, Chromosome movements during mitosis are orches- trated primarily by the interaction of spindle microtu- bules with the kinetochore [1], the site for attachment of spindle microtubules to the centromere. The kinetochore has an active function in chromosomal segregation through microtubule-based motors located at or near it [1-2]. CENP-E is a microtubule-based kinesin motor [3],展开更多
Cytotoxic lymphocytes are key players in the orchestration of immune response and elimination of defective cells. We have previously reported that natural killer （NK） cells enter target tumor ceils, leading to eithe...Cytotoxic lymphocytes are key players in the orchestration of immune response and elimination of defective cells. We have previously reported that natural killer （NK） cells enter target tumor ceils, leading to either target cell death or self-destruction within tumor cells. However, it has remained elusive as to the fate of NK cells after internalization and whether the heterotypic cell-in-cell process is different from that of the homotypic cell-in-cell event recently named entosis. Here, we show that NK cells undergo a cell-in-cell process with the ultimate fate of apoptosis within tumor cells and reveal that the internalization process requires the actin cytoskeletal regulator, ezrin. To visualize how NK cells enter into tumor cells, we carried out real-time dual color imaging analyses of NK cell internalization into tumor cells. Surprisingly, most NK cells commit to programmed cell death after their entry into tumor cells, which is distinctively different from entosis observed in the homotypic cell-in-cell process. The apoptotic cell death of the internalized NK cells was evident by activation of caspase 3 and DNA fragmentation. Furthermore, NK cell death after internalization is attenuated by the caspase inhibitor, Z-VAD-FMK, confirming apoptosis as the mode of NK cell death within tumor cells. To determine protein factors essential for the entry of NK cells into tumor cells, we car- ried out siRNA-based knockdown analysis and discovered a critical role of ezrin in NK cell internalization. Impor- tantly, PKA-mediated phosphorylation of ezrin promotes the NK cell internalization process. Our findings suggest a novel regulatory mechanism by which ezrin governs NK cell internalization into tumor cells.展开更多
Chromosome segregation in mitosis is orchestrated by the interaction of the kinetochore with spindle microtubules. Our recent study shows that NEK2A interacts with MAD 1 at the kinetochore and possibly functions as a ...Chromosome segregation in mitosis is orchestrated by the interaction of the kinetochore with spindle microtubules. Our recent study shows that NEK2A interacts with MAD 1 at the kinetochore and possibly functions as a novel integrator of spindle checkpoint signaling. However, it is unclear how NEK2A regulates kinetochore-microtubule attachment in mitosis. Here we show that NEK2A phosphorylates human Sgo 1 and such phosphorylation is essential for faithful chromosome congression in mitosis. NEK2A binds directly to HsSgol in vitro and co-distributes with HsSgol to the kinetochore of mitotic cells. Our in vitro phosphorylation experiment demonstrated that HsSgo 1 is a substrate of NEK2A and the phosphorylation sites were mapped to Ser^14 and Ser^507 as judged by the incorporation of 32^P. Although such phosphorylation is not required for assembly of HsSgo 1 to the kinetochore, expression of non-phosphorylatable mutant HsSgo 1 perturbed chromosome congression and resulted in a dramatic increase in microtubule attachment errors, including syntelic and monotelic attachments. These findings reveal a key role for the NEK2A-mediated phosphorylation ofHsSgo 1 in orchestrating dynamic kinetochore-microtubule interaction. We propose that NEK2A-mediated phosphorylation of human Sgo 1 provides a link between centromeric cohesion and spindle microtubule attachment at the kinetochores.展开更多
AIM: To conduct a systematic review and Meta-analysis of the published literature to evaluate the pooled prevalence rate of amblyopia in patients with congenital ptosis.METHODS: We searched the PubMed, Embase, the Coc...AIM: To conduct a systematic review and Meta-analysis of the published literature to evaluate the pooled prevalence rate of amblyopia in patients with congenital ptosis.METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Data, and Chongqing VIP databases for studies reporting the prevalence of amblyopia in patients with congenital ptosis. The reference lists of relevant studies were scanned. Heterogeneity of effect sizes across studies was tested. We calculated prevalence ratios to compare prevalence estimates for different causes of amblyopia in patients with congenital ptosis, as well as for different geographical regions, year of publication and sample size in subgroup analyses. A systematic review and Meta-analysis were performed.RESULTS: We identified 29 eligible surveys with a total population of 2436. Prevalence rates of amblyopia ranged from 13.8% to 69%. We noted substantial heterogeneity in prevalence estimates for amblyopia in congenital ptosis(Cochran’s χ2 significant at P<0.0001; I2=90%). The pooled prevalence using random-effects models of 29 studies was 32.8%(95%CI: 27.3%-38.4%) in the overall population. Compared to the overall pooled prevalence, amblyopia prevalence was higher in studies in which only subjects with blepharophimosis syndrome were included.CONCLUSION: We confirm that nearly one-third of congenital ptosis patients are suffering from or at risk for amblyopia. Patients with blepharophimosis syndrome are more likely to develop amblyopia. The identificationand management of amblyopia should be integral to the treatment of congenital ptosis.展开更多
Objective:To investigate the protective effect of Dahuang Fuzi Decoction(DHFZD),a traditional Chinese prescription,at alleviating sepsis-induced inflammation and gut barrier damage in rats.Methods:Forty clean-grade ma...Objective:To investigate the protective effect of Dahuang Fuzi Decoction(DHFZD),a traditional Chinese prescription,at alleviating sepsis-induced inflammation and gut barrier damage in rats.Methods:Forty clean-grade male Sprague-Dawley rats were divided randomly into three groups:normal control group(NCG,n?10),model control group(MCG,n?15)and DHFZD-treated group(DHFZDG,n?15).NCG rats were sham operated on and used as the controls,whereas MCG and DHFZDG rats were used to replicate the rat sepsis model using cecal ligation and puncture(CLP).The DHFZDG rats received DHFZD by gavage(4.5 mg/g of body weight)2 h prior to CLP and after its successful induction,while the NCG and MCG rats received equivalent amounts of sterilized water by gavage.All rat groups were starved and had free access to water.At 24 h post-experimental set up,the mortality of rats in each group was recorded,and peritoneal inflammation assessment and pathological changes related to the intestinal mucosal injury index(IMII)in the surviving rats were evaluated.D-lactic acid,tumor necrosis factor(TNF)-a,interleukin(IL)-6 and IL-10 peripheral blood concentrations,along with secretory immunoglobulin A(sIgA)in the intestinal mucosa were evaluated by enzyme-linked immunosorbent assays.Gut microbes were detected using 16S rRNA gene sequencing.Results:DHFZD reduced sepsis-related mortality in the rats.Moreover,it alleviated peritoneal inflammation and pathological changes according to the IMII.DHFZD reduced serum procalcitonin,TNF-a and IL-6 concentrations,but not the IL-10 concentration.It also reduced serum D-lactic acid and increased sIgA concentrations in intestinal mucosa.Notably,DHFZDG restored gut microbiota diversity and regulated the decrease in Bacteroidetes induced by sepsis,compared with the MCG rats.Conclusion:DHFZDG may play a protective role in sepsis by alleviating sepsis-induced inflammation and gut barrier damage in rats.展开更多
Objective:Traditional Chinese medicine(TCM)and modern medicine have both been used in arresting malignant transformation of chronic atrophic gastritis(CAG)in China with good therapeutic effect.However,no studies have ...Objective:Traditional Chinese medicine(TCM)and modern medicine have both been used in arresting malignant transformation of chronic atrophic gastritis(CAG)in China with good therapeutic effect.However,no studies have been undertaken to assess the risk of malignant transformation in CAG patients using both modern medicine and TCM features.Our study aimed to develop risk assessment models for malignant transformation of CAG combining indicators of both TCM and modern medicine.These models will facilitate early warning and control of malignant transformation of CAG from the perspective of evidence-based integrative medicine.Methods:In the proposed registry study,a total of 1000 eligible CAG patients will be recruited from four hospitals in China.A 10-year follow-up study will be conducted both on-site and off-site to track the events of malignant transformation.Frequency analysis and chi-squared tests will be used to perform the comparative analysis on the prevalence of malignant transformation events and indicators in TCM or modern medicine in different groups.A multivariate Cox proportional hazard model will be used to perform correlation analyses of malignant transformation events and factors of TCM or modern medicine.Conclusion:The proposed study has been designed with a large sample size and long follow-up period,in which wide-ranging modern medicine and TCM indicators can be gathered over the whole process of malignant transformation of CAG.Based on this study,risk assessment models for malignant transformation ofCAGmaybe constructed fromthe perspective of integrative medicine.This may provide clinicians and patients with an optimized early warning system as well as prevention strategies for malignant transformation of CAG.展开更多
BACKGROUND Drug-induced liver injury(DILI)is one of the most common adverse events of medication use,and its incidence is increasing.However,early detection of DILI is a crucial challenge due to a lack of biomarkers a...BACKGROUND Drug-induced liver injury(DILI)is one of the most common adverse events of medication use,and its incidence is increasing.However,early detection of DILI is a crucial challenge due to a lack of biomarkers and noninvasive tests.AIM To identify salivary metabolic biomarkers of DILI for the future development of noninvasive diagnostic tools.METHODS Saliva samples from 31 DILI patients and 35 healthy controls(HCs)were subjected to untargeted metabolomics using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry.Subsequent analyses,including partial least squares-discriminant analysis modeling,t tests and weighted metabolite coexpression network analysis(WMCNA),were conducted to identify key differentially expressed metabolites(DEMs)and metabolite sets.Furthermore we utilized least absolute shrinkage and selection operato and random fores analyses for biomarker prediction.The use of each metabolite and metabolite set to detect DILI was evaluated with area under the receiver operating characteristic curves.RESULTS We found 247 differentially expressed salivary metabolites between the DILI group and the HC group.Using WMCNA,we identified a set of 8 DEMs closely related to liver injury for further prediction testing.Interestingly,the distinct separation of DILI patients and HCs was achieved with five metabolites,namely,12-hydroxydodecanoic acid,3-hydroxydecanoic acid,tetradecanedioic acid,hypoxanthine,and inosine(area under the curve:0.733-1).CONCLUSION Salivary metabolomics revealed previously unreported metabolic alterations and diagnostic biomarkers in the saliva of DILI patients.Our study may provide a potentially feasible and noninvasive diagnostic method for DILI,but further validation is needed.展开更多
Previous studies have shown that 5-hydroxymethylfurfural, a compound extracted from wine- processed Fructus corni, has a protective effect on hippocampal neurons. The present study was designed to explore the related ...Previous studies have shown that 5-hydroxymethylfurfural, a compound extracted from wine- processed Fructus corni, has a protective effect on hippocampal neurons. The present study was designed to explore the related mechanisms. Our study revealed that high and medium doses （10, 1 μmol/L） of 5-hydroxymethylfurfural could improve the morphology of H2O2-treated rat hippocampal neurons as revealed by inverted phase-contrast microscopy and transmission electron microscopy. MTT results showed that incubation with high and medium doses of 5-hydroxymethylfurfural caused a significant increase in the viability of neuronal cells injured by H2O2. Flow cytometry assays con- firmed that H2O2 could induce cell apoptosis, while high and medium doses of 5-hydroxymethylfurfural had a visible protective effect on apoptotic rat hippocampal neurons. Real-time PCR and western blot analysis showed that high and medium doses of 5-hydroxymethylfurfural prevented H2O2-induced up-regulation of p53, Bax and caspase-3 and an- tagonized the down-regulation of Bcl-2 induced by H2O2 treatment. These results suggested that 5-hydroxymethylfurfural could inhibit apoptosis of cultured rat hippocampal neurons injured by H2O2 via increase in Bcl-2 levels and decrease in p53, Bax and caspase-3 protein expression levels.展开更多
基金Supported by The Natural Science Foundation of China,No.82374292the Plans for Major Provincial Science and Technology Projects of Anhui Province,No.202303a07020003the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine,No.ZYYCXTD-C-202401.
文摘Functional gastrointestinal disorders(FGIDs),including irritable bowel syndrome(IBS),functional dyspepsia(FD),and gastroesophageal reflux disease(GERD),present persistent diagnostic and therapeutic challenges due to symptom heterogeneity and the absence of reliable biomarkers.Artificial intelligence(AI)enables the integration of multimodal data to enhance FGID management through precision diagnostics and preventive healthcare.This minireview summarizes recent advancements in AI applications for FGIDs,highlighting progress in diagnostic accuracy,subtype classification,personalized interventions,and preventive strategies inspired by the traditional Chinese medicine concept of“treating the undiseased”.Machine learning and deep learning algorithms have demonstrated value in improving IBS diagnosis,refining FD neuro-gastrointestinal subtyping,and screening for GERD-related complications.Moreover,AI supports dietary,psychological,and integrative medicine-based interventions to improve patient adherence and quality of life.Nonetheless,key challenges remain,including data heterogeneity,limited model interpretability,and the need for robust clinical validation.Future directions emphasize interdisciplinary collaboration,the development of multimodal and explainable AI models,and the creation of patientcentered platforms to facilitate a shift from reactive treatment to proactive prevention.This review provides a systematic framework to guide the clinical application and theoretical innovation of AI in FGIDs.
基金Supported by National Natural Science Foundation of China,No.81630080,No.82305179,and No.82374181The China Postdoctoral Science Foundation Grant,No.2019M650600+1 种基金The Beijing University of Chinese Medicine“Decoding Traditional Chinese Medicine”Project,No.2023-JYB-JBZD-036The Hefei National Research Center for Physical Sciences at the Microscale,No.KF2021104.
文摘BACKGROUND Hepatic organoid-based modelling,through the elucidation of a range of in vivo biological processes and the recreation of the intricate liver microenvironment,is yielding groundbreaking insights into the pathophysiology and personalized medicine approaches for liver diseases.AIM This study was designed to analyse the global scientific output of hepatic organoid research and assess current achievements and future trends through bibliometric analysis.METHODS Articles were retrieved from the Web of Science Core Collection,and CiteSpace 6.3.R1 was employed to analyse the literature,including outputs,journals,and countries,among others.RESULTS Between 2010 and 2024,a total of 991 articles pertaining to hepatic organoid research were published.The journal Hepatology published the greatest number of papers,and journals with an impact factor greater than 10 constituted 60%of the top 10 journals.The United States and Utrecht University were identified as the most prolific country and institution,respectively.Clevers H emerged as the most prolific author,whereas Huch M had the highest number of cocitations,suggesting that both are ideal candidates for academic collaboration.Research on hepatic organoids has exhibited a progressive shift in focus,evolving from initial investigations into model building,differentiation research in stem cells,bile ducts,and progenitor cells,to a broader spectrum encompassing lipid metabolism,single-cell RNA sequencing,and therapeutic applications.The phrases exhibiting citation bursts from 2022 to 2024 include“drug resistance”,“disease model”,and“patient-derived tumor organoids”.CONCLUSION Research on hepatic organoids has increased over the past decade and is expected to continue to grow.Key research areas include applications for liver diseases and drug development.Future trends likely to gain focus include patient-derived tumour organoids,disease modelling,and personalized medicine.
基金the National Natural Science Foundation of China,No.82374292,82205095,and 82305179the Horizontal Development Foundation of Beijing University of Chinese Medicine,No.BUCM-2021-JS-KF-065the China Postdoctoral Science Foundation Grant,No.2022M720520.
文摘BACKGROUND Precancerous lesions of gastric cancer(PLGC)represent a critical pathological stage in the development of intestinal gastric cancer.Early detection and diagnosis are key to reducing the incidence of gastric cancer.Substantial advancements have been made in PLGC research in recent years,making it necessary to provide updated reviews using bibliometric methods.We hypothesize that this review will identify emerging trends,key research areas,and gaps in PLGC research,providing insights that could guide future studies and enhance prevention strategies.AIM To comprehensively review the current state of research on PLGC,examining development trends and research hotspots.METHODS We conducted a bibliometric analysis of PLGC-related studies published between 2004 and 2023 using the Web of Science Core Collection database.We employed Software,including VOSviewer,CiteSpace,R software,and SCImago Graphica,to map scientific networks and visualize knowledge trends in terms of publication volume,countries/regions,institutions,journals,authors,and keywords.RESULTS A total of 4097 articles were included,and overall publication volume showed an increasing trend.Over the past two decades,China published the most articles,followed by the United States,Japan,South Korea,and Italy.Among the top 10 contributors,the United States ranked highest in institutions,authors,and citations and demonstrated the strongest international collaboration.Research keywords in this field were clustered into three main categories:Risk factors,pathogenesis,and diagnosis and treatment.Pathogenesis and molecular biomarkers remain key areas of focus.Future research should explore the mechanisms of gut microbiota,immune microenvironment,metabolic reprogramming,and epigenetics.Advanced technologies,including single-cell sequencing,spatially resolved analysis,multi-omics approaches,artificial intelligence,and machine learning,will likely accelerate in-depth investigations of PLGC.CONCLUSION PLGC research has rapidly developed in recent years,gaining considerable attention.This bibliometric analysis reveals research state and emerging trends over the past 20 years,providing insights for future studies.
基金Acknowledgments We thank members of our groups for insightful discussion during the course of this study. This work was initiated by the chemical biology grant PGX-t from the Proteomics Research Laboratory, and supported in part by Chinese Academy of Sciences Grants （KSCX2-YW-H-10 and KSCX2-YW-R195）, 973 projects （2002CB713700 2010CB912103）, National Natural Science Foundation of China （90913016）, and Georgia Cancer Coalition Eminent Scholar Award.
文摘Dear Editor, Chromosome movements during mitosis are orches- trated primarily by the interaction of spindle microtu- bules with the kinetochore [1], the site for attachment of spindle microtubules to the centromere. The kinetochore has an active function in chromosomal segregation through microtubule-based motors located at or near it [1-2]. CENP-E is a microtubule-based kinesin motor [3],
基金We thank members of our group for insightful discussion dur- ing the course of this study and Drs Haiming Wei and Zhigang Tian for NK92 cells. This work was supported by grants from National Natural Science Foundation of China （30972681 to XW 90508002 to XY+1 种基金 30872286 to LS）, Guangdong-NSFC Joint Key Program （to XW）, Chinese Academy of Sciences （KSCX1- YW-R65, KSCX2-YWH-10）, National Basic Research Program of China （973 Program） （2007CB512402 to XW 2007CB914503 and 2010CB912103 to XY）, Ministry of Science ＆ Technology of China International Collaboration Program （2009DFA31010 to XD）, China National Key Projects for Infectious Disease （2008ZX 10002-021 to XY）, 2007 National Undergraduate Innova- tive Research Program of China （PX） and KC Wong Education Foundation （ZG）.
文摘Cytotoxic lymphocytes are key players in the orchestration of immune response and elimination of defective cells. We have previously reported that natural killer （NK） cells enter target tumor ceils, leading to either target cell death or self-destruction within tumor cells. However, it has remained elusive as to the fate of NK cells after internalization and whether the heterotypic cell-in-cell process is different from that of the homotypic cell-in-cell event recently named entosis. Here, we show that NK cells undergo a cell-in-cell process with the ultimate fate of apoptosis within tumor cells and reveal that the internalization process requires the actin cytoskeletal regulator, ezrin. To visualize how NK cells enter into tumor cells, we carried out real-time dual color imaging analyses of NK cell internalization into tumor cells. Surprisingly, most NK cells commit to programmed cell death after their entry into tumor cells, which is distinctively different from entosis observed in the homotypic cell-in-cell process. The apoptotic cell death of the internalized NK cells was evident by activation of caspase 3 and DNA fragmentation. Furthermore, NK cell death after internalization is attenuated by the caspase inhibitor, Z-VAD-FMK, confirming apoptosis as the mode of NK cell death within tumor cells. To determine protein factors essential for the entry of NK cells into tumor cells, we car- ried out siRNA-based knockdown analysis and discovered a critical role of ezrin in NK cell internalization. Impor- tantly, PKA-mediated phosphorylation of ezrin promotes the NK cell internalization process. Our findings suggest a novel regulatory mechanism by which ezrin governs NK cell internalization into tumor cells.
基金We thank members of our group for insightful discussion during the course of this study.This work was supported by grants from Chinese Academy of Science(KSCX1-YW-R65,KSCX2-YW-H10)National Basic Research Program of China(2002CB713700)+4 种基金Hi-Tech Research and Development Program of China(2001AA215331)Chinese Minister of Education(20020358051 to XY,PCSIRT0413 to XD)National Natural Science Foundation of China(39925018,30270293 to XY,30500183 to XD,30600222 to JY)National Institutes of Health(USA)(DK56292,CA92080)to XY(a Georgia Cancer Coalition Eminent Scholar)JY was supported by China Postdoctor(2005037560).
文摘Chromosome segregation in mitosis is orchestrated by the interaction of the kinetochore with spindle microtubules. Our recent study shows that NEK2A interacts with MAD 1 at the kinetochore and possibly functions as a novel integrator of spindle checkpoint signaling. However, it is unclear how NEK2A regulates kinetochore-microtubule attachment in mitosis. Here we show that NEK2A phosphorylates human Sgo 1 and such phosphorylation is essential for faithful chromosome congression in mitosis. NEK2A binds directly to HsSgol in vitro and co-distributes with HsSgol to the kinetochore of mitotic cells. Our in vitro phosphorylation experiment demonstrated that HsSgo 1 is a substrate of NEK2A and the phosphorylation sites were mapped to Ser^14 and Ser^507 as judged by the incorporation of 32^P. Although such phosphorylation is not required for assembly of HsSgo 1 to the kinetochore, expression of non-phosphorylatable mutant HsSgo 1 perturbed chromosome congression and resulted in a dramatic increase in microtubule attachment errors, including syntelic and monotelic attachments. These findings reveal a key role for the NEK2A-mediated phosphorylation ofHsSgo 1 in orchestrating dynamic kinetochore-microtubule interaction. We propose that NEK2A-mediated phosphorylation of human Sgo 1 provides a link between centromeric cohesion and spindle microtubule attachment at the kinetochores.
基金Supported by the National Natural Science Foundation of China(No.81870688)Shanghai Science and Technology Commission Natural Science Foundation(No.16ZR1419600)the Science and Technology Commission of Shanghai(No.17DZ2260100)
文摘AIM: To conduct a systematic review and Meta-analysis of the published literature to evaluate the pooled prevalence rate of amblyopia in patients with congenital ptosis.METHODS: We searched the PubMed, Embase, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Data, and Chongqing VIP databases for studies reporting the prevalence of amblyopia in patients with congenital ptosis. The reference lists of relevant studies were scanned. Heterogeneity of effect sizes across studies was tested. We calculated prevalence ratios to compare prevalence estimates for different causes of amblyopia in patients with congenital ptosis, as well as for different geographical regions, year of publication and sample size in subgroup analyses. A systematic review and Meta-analysis were performed.RESULTS: We identified 29 eligible surveys with a total population of 2436. Prevalence rates of amblyopia ranged from 13.8% to 69%. We noted substantial heterogeneity in prevalence estimates for amblyopia in congenital ptosis(Cochran’s χ2 significant at P<0.0001; I2=90%). The pooled prevalence using random-effects models of 29 studies was 32.8%(95%CI: 27.3%-38.4%) in the overall population. Compared to the overall pooled prevalence, amblyopia prevalence was higher in studies in which only subjects with blepharophimosis syndrome were included.CONCLUSION: We confirm that nearly one-third of congenital ptosis patients are suffering from or at risk for amblyopia. Patients with blepharophimosis syndrome are more likely to develop amblyopia. The identificationand management of amblyopia should be integral to the treatment of congenital ptosis.
基金This work was supported by Chinese Natural Science Foundation Grants(81630080)the Fundamental Research Funds for the Central Universities of China(NO:2017-JYB-JS-101,2018-JYBZZ-JS075,2019-JYB-JSPYGD-011).
文摘Objective:To investigate the protective effect of Dahuang Fuzi Decoction(DHFZD),a traditional Chinese prescription,at alleviating sepsis-induced inflammation and gut barrier damage in rats.Methods:Forty clean-grade male Sprague-Dawley rats were divided randomly into three groups:normal control group(NCG,n?10),model control group(MCG,n?15)and DHFZD-treated group(DHFZDG,n?15).NCG rats were sham operated on and used as the controls,whereas MCG and DHFZDG rats were used to replicate the rat sepsis model using cecal ligation and puncture(CLP).The DHFZDG rats received DHFZD by gavage(4.5 mg/g of body weight)2 h prior to CLP and after its successful induction,while the NCG and MCG rats received equivalent amounts of sterilized water by gavage.All rat groups were starved and had free access to water.At 24 h post-experimental set up,the mortality of rats in each group was recorded,and peritoneal inflammation assessment and pathological changes related to the intestinal mucosal injury index(IMII)in the surviving rats were evaluated.D-lactic acid,tumor necrosis factor(TNF)-a,interleukin(IL)-6 and IL-10 peripheral blood concentrations,along with secretory immunoglobulin A(sIgA)in the intestinal mucosa were evaluated by enzyme-linked immunosorbent assays.Gut microbes were detected using 16S rRNA gene sequencing.Results:DHFZD reduced sepsis-related mortality in the rats.Moreover,it alleviated peritoneal inflammation and pathological changes according to the IMII.DHFZD reduced serum procalcitonin,TNF-a and IL-6 concentrations,but not the IL-10 concentration.It also reduced serum D-lactic acid and increased sIgA concentrations in intestinal mucosa.Notably,DHFZDG restored gut microbiota diversity and regulated the decrease in Bacteroidetes induced by sepsis,compared with the MCG rats.Conclusion:DHFZDG may play a protective role in sepsis by alleviating sepsis-induced inflammation and gut barrier damage in rats.
基金This study will be supported by grants from the National Natural Science Foundation of China(No.81630080,91129714,81270466,81173424 and 81373796)the Science Research Foundation of BUCM(No.2014-JYBZZ-XS-134)+1 种基金the Research Foundation of the Doctoral Program of Higher Education of China(No.20120013110014)the National Undergraduates Innovating Experimentation Project of the Ministry of Education of China(No.081002609).
文摘Objective:Traditional Chinese medicine(TCM)and modern medicine have both been used in arresting malignant transformation of chronic atrophic gastritis(CAG)in China with good therapeutic effect.However,no studies have been undertaken to assess the risk of malignant transformation in CAG patients using both modern medicine and TCM features.Our study aimed to develop risk assessment models for malignant transformation of CAG combining indicators of both TCM and modern medicine.These models will facilitate early warning and control of malignant transformation of CAG from the perspective of evidence-based integrative medicine.Methods:In the proposed registry study,a total of 1000 eligible CAG patients will be recruited from four hospitals in China.A 10-year follow-up study will be conducted both on-site and off-site to track the events of malignant transformation.Frequency analysis and chi-squared tests will be used to perform the comparative analysis on the prevalence of malignant transformation events and indicators in TCM or modern medicine in different groups.A multivariate Cox proportional hazard model will be used to perform correlation analyses of malignant transformation events and factors of TCM or modern medicine.Conclusion:The proposed study has been designed with a large sample size and long follow-up period,in which wide-ranging modern medicine and TCM indicators can be gathered over the whole process of malignant transformation of CAG.Based on this study,risk assessment models for malignant transformation ofCAGmaybe constructed fromthe perspective of integrative medicine.This may provide clinicians and patients with an optimized early warning system as well as prevention strategies for malignant transformation of CAG.
基金Supported by Medical Education Association Foundation of China,No.2020KTY001National Natural Science Foundation of China,No.81673806National Natural Science Foundation Youth Fund,No.82104702.
文摘BACKGROUND Drug-induced liver injury(DILI)is one of the most common adverse events of medication use,and its incidence is increasing.However,early detection of DILI is a crucial challenge due to a lack of biomarkers and noninvasive tests.AIM To identify salivary metabolic biomarkers of DILI for the future development of noninvasive diagnostic tools.METHODS Saliva samples from 31 DILI patients and 35 healthy controls(HCs)were subjected to untargeted metabolomics using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry.Subsequent analyses,including partial least squares-discriminant analysis modeling,t tests and weighted metabolite coexpression network analysis(WMCNA),were conducted to identify key differentially expressed metabolites(DEMs)and metabolite sets.Furthermore we utilized least absolute shrinkage and selection operato and random fores analyses for biomarker prediction.The use of each metabolite and metabolite set to detect DILI was evaluated with area under the receiver operating characteristic curves.RESULTS We found 247 differentially expressed salivary metabolites between the DILI group and the HC group.Using WMCNA,we identified a set of 8 DEMs closely related to liver injury for further prediction testing.Interestingly,the distinct separation of DILI patients and HCs was achieved with five metabolites,namely,12-hydroxydodecanoic acid,3-hydroxydecanoic acid,tetradecanedioic acid,hypoxanthine,and inosine(area under the curve:0.733-1).CONCLUSION Salivary metabolomics revealed previously unreported metabolic alterations and diagnostic biomarkers in the saliva of DILI patients.Our study may provide a potentially feasible and noninvasive diagnostic method for DILI,but further validation is needed.
基金financially supported by the National Natural Science Foundation of China,No.30772851a grant from the Six Talents Peaks Program of Jiangsu Province,Chinaa grant from the Priority Academic Program Development of Jiangsu Higher Education Institutions,PAPD(Traditional Chinese medicine combined with Western Medicine
文摘Previous studies have shown that 5-hydroxymethylfurfural, a compound extracted from wine- processed Fructus corni, has a protective effect on hippocampal neurons. The present study was designed to explore the related mechanisms. Our study revealed that high and medium doses （10, 1 μmol/L） of 5-hydroxymethylfurfural could improve the morphology of H2O2-treated rat hippocampal neurons as revealed by inverted phase-contrast microscopy and transmission electron microscopy. MTT results showed that incubation with high and medium doses of 5-hydroxymethylfurfural caused a significant increase in the viability of neuronal cells injured by H2O2. Flow cytometry assays con- firmed that H2O2 could induce cell apoptosis, while high and medium doses of 5-hydroxymethylfurfural had a visible protective effect on apoptotic rat hippocampal neurons. Real-time PCR and western blot analysis showed that high and medium doses of 5-hydroxymethylfurfural prevented H2O2-induced up-regulation of p53, Bax and caspase-3 and an- tagonized the down-regulation of Bcl-2 induced by H2O2 treatment. These results suggested that 5-hydroxymethylfurfural could inhibit apoptosis of cultured rat hippocampal neurons injured by H2O2 via increase in Bcl-2 levels and decrease in p53, Bax and caspase-3 protein expression levels.
