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
Insomnia is among the most common sleep disorders worldwide.Insomnia in older adults is a social and public health problem.Insomnia affects the physical and mental health of elderly hospitalized patients and can aggra...Insomnia is among the most common sleep disorders worldwide.Insomnia in older adults is a social and public health problem.Insomnia affects the physical and mental health of elderly hospitalized patients and can aggravate or induce physical illnesses.Understanding subjective feelings and providing reasonable and standardized care for elderly hospitalized patients with insomnia are urgent issues.AIM To explore the differences in self-reported outcomes associated with insomnia among elderly hospitalized patients.METHODS One hundred patients admitted to the geriatric unit of our hospital between June 2021 and December 2021 were included in this study.Self-reported symptoms were assessed using the Athens Insomnia Scale(AIS),Generalized Anxiety Disorder Scale-7(GAD-7),Geriatric Depression Scale-15(GDS-15),Memorial University of Newfoundland Scale of Happiness(MUNSH),Barthel Index Evaluation(BI),Morse Fall Scale(MFS),Mini-Mental State Examination,and the Short Form 36 Health Survey Questionnaire(SF-36).Correlation coefficients were used to analyze the correlation between sleep quality and self-reported symptoms.Effects of insomnia was analyzed using Logistic regression analysis.RESULTS Nineteen patients with AIS≥6 were included in the insomnia group,and the incidence of insomnia was 19%(19/100).The remaining 81 patients were assigned to the non-insomnia group.There were significant differences between the two groups in the GDA-7,GDS-15,MUNSH,BI,MFS,and SF-36 items(P<0.05).Patients in the insomnia group were more likely to experience anxiety,depression,and other mental illnesses,as well as difficulties with everyday tasks and a greater risk of falling(P<0.05).Subjective well-being and quality of life were poorer in the insomnia group than in the control group.The AIS scores positively correlated with the GAD-7,GDS-15,and MFS scores in elderly hospitalized patients with insomnia(P<0.05).Logistic regression analysis showed that GDS-15≥5 was an independent risk factor for insomnia in elderly hospitalized patients(P<0.05).CONCLUSION The number of self-reported symptoms was higher among elderly hospitalized patients with insomnia.Therefore,we should focus on the main complaints of patients to meet their care needs.展开更多
Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system.In the chronic inflammation microenvironment,the metabolic activity...Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system.In the chronic inflammation microenvironment,the metabolic activity of tissue cells undergoes extensive changes,which interfere with the normal function of immune cells.Dysregulation of cell metabolism and immune function has been identified as a key factor contributing to inflammation-mediated carcinogenesis within the major digestive organs,such as the stomach,liver,and colorectum.This metabolic-immune imbalance also corresponds to traditional Chinese medicine(TCM)theories of“yin-yang disharmony”and“disharmony between Ying-nutrients and Wei-defense.”The metabolic-immune imbalance has also been regarded as the key factor supporting“treatment of different diseases with the same method”,in which the same approach is adopted in the treatment of different conditions.In the TCM treatment process,it is necessary to first identify TCM patterns and then apply the corresponding TCM to correct the dysregulated metabolic and immune function,thereby blocking the progression from inflammation to malignancy.Our study findings deepen the TCM understanding of metabolic-immune dysregulation and the relationship between metabolic-immune dysregulation,pattern identification,and treatment method.They also provide new insights for the treatment of inflammation-mediated carcinogenesis in major digestive organs and help us further explore the scientific connotation of the TCM strategy of“treating different diseases with the same method”.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: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
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
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
Objective:Aging caused by a deficiency syndrome can be found in ancient and modern traditional Chinese medicine literature.Qi deficiency syndrome(QDS)is a vital factor in the aging process.This study aimed to establis...Objective:Aging caused by a deficiency syndrome can be found in ancient and modern traditional Chinese medicine literature.Qi deficiency syndrome(QDS)is a vital factor in the aging process.This study aimed to establish a full-scale trial to evaluate the prevalence,symptom severity,frequency,and distribution of QDS in different age groups and varying health status to elucidate the role of qi deficiency in the aging process and deterioration of health.Methods:This cross-sectional study was conducted in four hospitals in China,and data from 1220 participants were included.The participants,aged between 20 and 79 years,completed questionnaires that recorded prevalence of QDS and severity or frequency of relevant symptoms,then were interviewed by investigators.We used frequency analysis and chi-squared tests to perform comparative analysis of prevalence in different age and health groups;we used a ranksum tests for quantitative analysis of symptoms severity and frequency scores;we performed a regression analysis of correlation between syndrome occurrence and potential factors using nonconditional binary logistic stepwise regression of numerical variables.P<0.05 was considered statistically significant.Results:Prevalence,symptom severity and frequency scores of QDS showed a rising trend when physical condition worsened,rather than when age increased.Health status,fatigue,shortness of breath or no desire to talk,spontaneous sweating,swollen tongue with teeth marks on side,and deficient and weak pulse,rather than increasing age were contributing factors to this syndrome.Distribution of QDS in certain health and age stages showed remarkable irregularities.Conclusions:Qi deficiency may be a contributing factor for sub-health(sub-optimal health)and chronic diseases rather than aging.It may play a crucial role in chronic disease pathogenesis of young and middle-aged people,and in sub-health pathogenesis of older adults.Recognition of the warning signs and symptoms of QDS may lead to early intervention and prevention of subhealth,and chronic diseases.展开更多
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.
文摘Insomnia is among the most common sleep disorders worldwide.Insomnia in older adults is a social and public health problem.Insomnia affects the physical and mental health of elderly hospitalized patients and can aggravate or induce physical illnesses.Understanding subjective feelings and providing reasonable and standardized care for elderly hospitalized patients with insomnia are urgent issues.AIM To explore the differences in self-reported outcomes associated with insomnia among elderly hospitalized patients.METHODS One hundred patients admitted to the geriatric unit of our hospital between June 2021 and December 2021 were included in this study.Self-reported symptoms were assessed using the Athens Insomnia Scale(AIS),Generalized Anxiety Disorder Scale-7(GAD-7),Geriatric Depression Scale-15(GDS-15),Memorial University of Newfoundland Scale of Happiness(MUNSH),Barthel Index Evaluation(BI),Morse Fall Scale(MFS),Mini-Mental State Examination,and the Short Form 36 Health Survey Questionnaire(SF-36).Correlation coefficients were used to analyze the correlation between sleep quality and self-reported symptoms.Effects of insomnia was analyzed using Logistic regression analysis.RESULTS Nineteen patients with AIS≥6 were included in the insomnia group,and the incidence of insomnia was 19%(19/100).The remaining 81 patients were assigned to the non-insomnia group.There were significant differences between the two groups in the GDA-7,GDS-15,MUNSH,BI,MFS,and SF-36 items(P<0.05).Patients in the insomnia group were more likely to experience anxiety,depression,and other mental illnesses,as well as difficulties with everyday tasks and a greater risk of falling(P<0.05).Subjective well-being and quality of life were poorer in the insomnia group than in the control group.The AIS scores positively correlated with the GAD-7,GDS-15,and MFS scores in elderly hospitalized patients with insomnia(P<0.05).Logistic regression analysis showed that GDS-15≥5 was an independent risk factor for insomnia in elderly hospitalized patients(P<0.05).CONCLUSION The number of self-reported symptoms was higher among elderly hospitalized patients with insomnia.Therefore,we should focus on the main complaints of patients to meet their care needs.
基金supported by National Natural Science Foundation of China(92059102 and 81630080)the National Key Research and Development Plan of China(2018YFC1704106).
文摘Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system.In the chronic inflammation microenvironment,the metabolic activity of tissue cells undergoes extensive changes,which interfere with the normal function of immune cells.Dysregulation of cell metabolism and immune function has been identified as a key factor contributing to inflammation-mediated carcinogenesis within the major digestive organs,such as the stomach,liver,and colorectum.This metabolic-immune imbalance also corresponds to traditional Chinese medicine(TCM)theories of“yin-yang disharmony”and“disharmony between Ying-nutrients and Wei-defense.”The metabolic-immune imbalance has also been regarded as the key factor supporting“treatment of different diseases with the same method”,in which the same approach is adopted in the treatment of different conditions.In the TCM treatment process,it is necessary to first identify TCM patterns and then apply the corresponding TCM to correct the dysregulated metabolic and immune function,thereby blocking the progression from inflammation to malignancy.Our study findings deepen the TCM understanding of metabolic-immune dysregulation and the relationship between metabolic-immune dysregulation,pattern identification,and treatment method.They also provide new insights for the treatment of inflammation-mediated carcinogenesis in major digestive organs and help us further explore the scientific connotation of the TCM strategy of“treating different diseases with the same method”.
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 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.
文摘Objective:Aging caused by a deficiency syndrome can be found in ancient and modern traditional Chinese medicine literature.Qi deficiency syndrome(QDS)is a vital factor in the aging process.This study aimed to establish a full-scale trial to evaluate the prevalence,symptom severity,frequency,and distribution of QDS in different age groups and varying health status to elucidate the role of qi deficiency in the aging process and deterioration of health.Methods:This cross-sectional study was conducted in four hospitals in China,and data from 1220 participants were included.The participants,aged between 20 and 79 years,completed questionnaires that recorded prevalence of QDS and severity or frequency of relevant symptoms,then were interviewed by investigators.We used frequency analysis and chi-squared tests to perform comparative analysis of prevalence in different age and health groups;we used a ranksum tests for quantitative analysis of symptoms severity and frequency scores;we performed a regression analysis of correlation between syndrome occurrence and potential factors using nonconditional binary logistic stepwise regression of numerical variables.P<0.05 was considered statistically significant.Results:Prevalence,symptom severity and frequency scores of QDS showed a rising trend when physical condition worsened,rather than when age increased.Health status,fatigue,shortness of breath or no desire to talk,spontaneous sweating,swollen tongue with teeth marks on side,and deficient and weak pulse,rather than increasing age were contributing factors to this syndrome.Distribution of QDS in certain health and age stages showed remarkable irregularities.Conclusions:Qi deficiency may be a contributing factor for sub-health(sub-optimal health)and chronic diseases rather than aging.It may play a crucial role in chronic disease pathogenesis of young and middle-aged people,and in sub-health pathogenesis of older adults.Recognition of the warning signs and symptoms of QDS may lead to early intervention and prevention of subhealth,and chronic diseases.
