BACKGROUND Partial splenic embolization(PSE)has been suggested as an alternative to splenectomy in the treatment of hypersplenism.However,some patients may experience recurrence of hypersplenism after PSE and require ...BACKGROUND Partial splenic embolization(PSE)has been suggested as an alternative to splenectomy in the treatment of hypersplenism.However,some patients may experience recurrence of hypersplenism after PSE and require splenectomy.Currently,there is a lack of evidence-based medical support regarding whether preoperative PSE followed by splenectomy can reduce the incidence of complications.AIM To investigate the safety and therapeutic efficacy of preoperative PSE followed by splenectomy in patients with cirrhosis and hypersplenism.METHODS Between January 2010 and December 2021,321 consecutive patients with cirrhosis and hypersplenism underwent splenectomy at our department.Based on whether PSE was performed prior to splenectomy,the patients were divided into two groups:PSE group(n=40)and non-PSE group(n=281).Patient characteristics,postoperative complications,and follow-up data were compared between groups.Propensity score matching(PSM)was conducted,and univariable and multivariable analyses were used to establish a nomogram predictive model for intraoperative bleeding(IB).The receiver operating characteristic curve,Hosmer-Lemeshow goodness-of-fit test,and decision curve analysis(DCA)were employed to evaluate the differentiation,calibration,and clinical performance of the model.RESULTS After PSM,the non-PSE group showed significant reductions in hospital stay,intraoperative blood loss,and operation time(all P=0.00).Multivariate analysis revealed that spleen length,portal vein diameter,splenic vein diameter,and history of PSE were independent predictive factors for IB.A nomogram predictive model of IB was constructed,and DCA demonstrated the clinical utility of this model.Both groups exhibited similar results in terms of overall survival during the follow-up period.CONCLUSION Preoperative PSE followed by splenectomy may increase the incidence of IB and a nomogram-based prediction model can predict the occurrence of IB.展开更多
Ferroptosis is a type of programmed cell death dependent on iron.It is different from other forms of cell death such as apoptosis,classic necrosis and autophagy.Ferroptosis is involved in many neurodegenerative diseas...Ferroptosis is a type of programmed cell death dependent on iron.It is different from other forms of cell death such as apoptosis,classic necrosis and autophagy.Ferroptosis is involved in many neurodegenerative diseases.The role of ferroptosis in glutamate-induced neuronal toxicity is not fully understood.To test its toxicity,glutamate(1.25–20 mM)was applied to HT-22 cells for 12 to 48 hours.The optimal experimental conditions occurred at 12 hours after incubation with 5 mM glutamate.Cells were cultured with 3–12μM ferrostatin-1,an inhibitor of ferroptosis,for 12 hours before exposure to glutamate.The cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Autophagy was determined by monodansylcadaverine staining and apoptosis by caspase 3 activity.Damage to cell structures was observed under light and by transmission electron microscopy.The release of lactate dehydrogenase was detected by the commercial kit.Reactive oxygen species were measured by flow cytometry.Glutathione peroxidase activity,superoxide dismutase activity and malondialdehyde level were detected by the appropriate commercial kit.Prostaglandin peroxidase synthase 2 and glutathione peroxidase 4 gene expression was detected by real-time quantitative polymerase chain reaction.Glutathione peroxidase 4 and nuclear factor erythroid-derived-like 2 protein expression was detected by western blot analysis.Results showed that ferrostatin-1 can significantly counter the effects of glutamate on HT-22 cells,improving the survival rate,reducing the release of lactate dehydrogenase and reducing the damage to mitochondrial ultrastructure.However,it did not affect the caspase-3 expression and monodansylcadaverine-positive staining in glutamate-injured HT-22 cells.Ferrostatin-1 reduced the levels of reactive oxygen species and malondialdehyde and enhanced superoxide dismutase activity.It decreased gene expression of prostaglandin peroxidase synthase 2 and increased gene expression of glutathione peroxidase 4 and protein expressions of glutathione peroxidase 4 and nuclear factor(erythroid-derived)-like 2 in glutamate-injured HT-22 cells.Treatment of cultured cells with the apoptosis inhibitor Z-Val-Ala-Asp(OMe)-fluoromethyl ketone(2–8μM),autophagy inhibitor 3-methyladenine(100–400μM)or necrosis inhibitor necrostatin-1(10–40μM)had no effect on glutamate induced cell damage.However,the iron chelator deferoxamine mesylate salt inhibited glutamate induced cell death.Thus,the results suggested that ferroptosis is caused by glutamate-induced toxicity and that ferrostatin-1 protects HT-22 cells from glutamate-induced oxidative toxicity by inhibiting the oxidative stress.展开更多
An overwhelming majority of the transcribed genome encodes for non-coding RNA(ncR NA) sequences. Deep sequencing of the transcriptome has uncovered tens of thousands of long ncR NA(lncR NA) sequences. However, little ...An overwhelming majority of the transcribed genome encodes for non-coding RNA(ncR NA) sequences. Deep sequencing of the transcriptome has uncovered tens of thousands of long ncR NA(lncR NA) sequences. However, little is known regarding the possible functions for a vast majority of these sequences. Among those lncR NAs whose function has been experimentally validated, most serve as regulators of gene expression. LncR NAs have been found to be critical to development and homeostasis and they have been implicated in several pathologies including cancer. Here, we examine the functions and underlying mechanisms of lnc RNAs in stem cells and in cancer biology, areas linked by the actions of lncR NAs.展开更多
BACKGROUND Due to the special clinical features and biologic characteristics of adolescent and young adult(AYA)cancers,AYA cancers are different from cancers in children and elderly individuals.However,there are few r...BACKGROUND Due to the special clinical features and biologic characteristics of adolescent and young adult(AYA)cancers,AYA cancers are different from cancers in children and elderly individuals.However,there are few reports on AYA hepatocellular carcinoma(HCC).AIM To investigate the overall survival(OS)of AYA(15-39 years)and elderly(40-74 years)patients with HCC.METHODS The data of all the HCC cases were extracted from the Surveillance,Epidemiology,and End Results database from 2004 to 2015 and were then divided into two groups based on age:AYA group(15-39 years)and older group(40-74 years).Kaplan-Meier curves and log-rank tests were used to compare the OS of the two groups.Propensity score matching(PSM)was employed to analyze the OS difference between the two groups.The Cox proportional hazards regression model was used to perform multivariate analysis to explore the risk factors for OS of HCC patients.RESULTS Compared to elderly cancer patients,AYA patients with HCC had a worse Surveillance,Epidemiology,and End Results stage,including the distant stage(22.1%vs 15.4%,P<0.001),and a more advanced American Joint Committee on Cancer(AJCC)stage,including AJCC III and IV(49.2%vs 38.3%,P<0.001),and were more likely to receive surgery(64.5%vs 47.5%,P<0.001).Before PSM,the AYA group had a longer survival in months(median:20.00,interquartile range[IQR]:5.00-62.50)than the older group(median:15.00,IQR:4.00-40.00)(P<0.001).After PSM,the AYA group still had a longer survival in months(median:21.00,IQR:5.00-64.50)than the older group(median:18.00,IQR:6.00-53.00)(P<0.001).The Cox proportional hazards regression model showed that advanced age(hazard ratio[HR]=1.405,95%CI:1.218-1.621,P<0.001)was a risk factor for OS of HCC patients.In the subgroup analysis,the Cox proportional hazards regression model showed that in AJCC I/II HCC patients,advanced age(HR=1.749,95%CI:1.352-2.263,P<0.001)was a risk factor for OS,while it was not a risk factor in AJCC III/IV HCC patients(HR=1.186,95%CI:0.997-1.410,P=0.054)before PSM.After PSM,advanced age(HR=1.891,95%CI:1.356-2.637,P<0.001)was still a risk factor for OS in AJCC I/II HCC patients,but was not a risk factor for OS in AJCC III/IV HCC patients(HR=1.192,95%CI:0.934-1.521,P=0.157)after PSM.CONCLUSION AYA patients with HCC have different clinical characteristics from older adults.In different AJCC stages,the two groups of patients have different OS:In AJCC I/II HCC patients,advanced age is a risk factor for OS,but it is not a risk factor for OS in the AJCC III/IV HCC patient group.展开更多
The effect of different contents of Y, Zr and Er on microstructure and properties of Al-5 Cu-0.4 Mn alloy was investigated. T6 heat treatment, OM, SEM and EDS methods were applied to the alloy. The results showed that...The effect of different contents of Y, Zr and Er on microstructure and properties of Al-5 Cu-0.4 Mn alloy was investigated. T6 heat treatment, OM, SEM and EDS methods were applied to the alloy. The results showed that fluidity and elongation of alloy adding Y, Zr and Er were improved, while with the increase of addition amounts, θ phase increased and grains were trended to grow up gradually. The Al-5 Cu-0.4 Mn alloy presented the maxed style of ductile and brittle fracture. After T6 heat treatment, the precipitation amounts of θ phase decreased dramatically and tensile strength and hardness significantly increased. Especially when addition contents were among 0.1-0.3 wt.%, tensile strength and hardness of heat-treated alloy increased greatly, almost doubled as that of the as-cast state. The tensile strength reached its maximum of 378.43 MPa when the addition amount was 0.3 wt.%. With the further increase of addition amounts, the elongation deteriorated and the proportion of ductile fracture reduced due to the limited dispersion strengthening effect of θ phase and Al_8Cu_4 Er. It demonstrated that addition of 0.1-0.3 wt.% Y, Zr and Er would generate positive effects and influences on Al-5 Cu-0.4 Mn alloy, which is significant for optimizing components and improving properties of Al-5 Cu-0.4 Mn alloy.展开更多
According to the selection principle of grain refiners and calculation of planar disregistries, CeO2 and TiB2 particles were selected as the grain refiners of pure nickel. The change of grain size and refining effects...According to the selection principle of grain refiners and calculation of planar disregistries, CeO2 and TiB2 particles were selected as the grain refiners of pure nickel. The change of grain size and refining effects of different refiners under the same melting conditions were investigated. The results show that the grain size of pure nickel gradually reduces with increasing the amount of grain refiners. And with increasing the amount of CeO2 up to 0.7 wt%, the grain size of pure nickel decreases from 323.0 to 53.5 lm. In addition, when the amount of TiB2is0.7 wt%, the grain size is reduced to 41.3 lm.展开更多
Objective Osteoarthritis(OA) is a kind of degenerative arthritis, involving degradation of joints, including articular cartilage and subchondral bone. Bushen-Huoxue Herb Couple(BHHC) is a Chinese herb pair with in...Objective Osteoarthritis(OA) is a kind of degenerative arthritis, involving degradation of joints, including articular cartilage and subchondral bone. Bushen-Huoxue Herb Couple(BHHC) is a Chinese herb pair with invigorating the kidney and promoting blood circulation. In our study, a Gas Chromatography-Mass Spectrometer(GC-MS) based metabolomics was developed to achieve a systematic observation of the progression of OA and evaluate the efficacy of BHHC in OA rats. Methods Forty Sprague-Dawley rats(half males and half females) were randomly divided into five groups, including normal group, OA model group, sham-operated group, BHHC group, positive medicine(PM) group after anterior cruciate ligament reconstruction and meniscectomy on rats. Urine samples for analysis were collected on week 0, 2, 4, 6, 8, 10, 12, and 14 during the experiment. Results The histological results showed that BHHC had a strong action of repairment and reconstruction of joint damage. By combining with partial least squares discriminant analysis(PLS-DA), 14 biomarkers were identified in urine samples. The biomarkers were mainly involved 10 metabolism pathways, such as tricarboxylic acid cycle metabolism, acid amino metabolism, tryptophan metabolism, lipid metabolism and phenylalanine metabolism. Using these potential biomarkers as a screening index, it indicated that BHHC could reverse the pathological process of OA through regulating amino acid metabolism, lipid metabolism, nucleotide metabolism and energy metabolism. Conclusions This study demonstrates that a metabolomics is a useful tool for identifying potential OA biomarkers and investigating the underlying mechanisms of Traditional Chinese Medicine in OA treatment.展开更多
基金Supported by National Natural Science Foundations of China,No.82174160and Anhui Natural Science Foundation,No.2008085QH389。
文摘BACKGROUND Partial splenic embolization(PSE)has been suggested as an alternative to splenectomy in the treatment of hypersplenism.However,some patients may experience recurrence of hypersplenism after PSE and require splenectomy.Currently,there is a lack of evidence-based medical support regarding whether preoperative PSE followed by splenectomy can reduce the incidence of complications.AIM To investigate the safety and therapeutic efficacy of preoperative PSE followed by splenectomy in patients with cirrhosis and hypersplenism.METHODS Between January 2010 and December 2021,321 consecutive patients with cirrhosis and hypersplenism underwent splenectomy at our department.Based on whether PSE was performed prior to splenectomy,the patients were divided into two groups:PSE group(n=40)and non-PSE group(n=281).Patient characteristics,postoperative complications,and follow-up data were compared between groups.Propensity score matching(PSM)was conducted,and univariable and multivariable analyses were used to establish a nomogram predictive model for intraoperative bleeding(IB).The receiver operating characteristic curve,Hosmer-Lemeshow goodness-of-fit test,and decision curve analysis(DCA)were employed to evaluate the differentiation,calibration,and clinical performance of the model.RESULTS After PSM,the non-PSE group showed significant reductions in hospital stay,intraoperative blood loss,and operation time(all P=0.00).Multivariate analysis revealed that spleen length,portal vein diameter,splenic vein diameter,and history of PSE were independent predictive factors for IB.A nomogram predictive model of IB was constructed,and DCA demonstrated the clinical utility of this model.Both groups exhibited similar results in terms of overall survival during the follow-up period.CONCLUSION Preoperative PSE followed by splenectomy may increase the incidence of IB and a nomogram-based prediction model can predict the occurrence of IB.
基金Acknowledgments We thank Dr Boja Emily S (NHLBI, NIH, USA) for expert technical assistance in mass spectrometry analyses, and our colleagues Drs Bin Lu, Zhao-Qiu Wu for helpful comments. This work was supported by a National Basic Research Program grant from the Ministry of Science and Technology of China (G2003CB515401), National Science Fund for Distinguished Young Scholar from the National Natural Science Foundation of China (30425002) and a fund supported by the "100 Talents Project" of Chinese Academy of Sciences (J-G Liu).
文摘Ferroptosis is a type of programmed cell death dependent on iron.It is different from other forms of cell death such as apoptosis,classic necrosis and autophagy.Ferroptosis is involved in many neurodegenerative diseases.The role of ferroptosis in glutamate-induced neuronal toxicity is not fully understood.To test its toxicity,glutamate(1.25–20 mM)was applied to HT-22 cells for 12 to 48 hours.The optimal experimental conditions occurred at 12 hours after incubation with 5 mM glutamate.Cells were cultured with 3–12μM ferrostatin-1,an inhibitor of ferroptosis,for 12 hours before exposure to glutamate.The cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Autophagy was determined by monodansylcadaverine staining and apoptosis by caspase 3 activity.Damage to cell structures was observed under light and by transmission electron microscopy.The release of lactate dehydrogenase was detected by the commercial kit.Reactive oxygen species were measured by flow cytometry.Glutathione peroxidase activity,superoxide dismutase activity and malondialdehyde level were detected by the appropriate commercial kit.Prostaglandin peroxidase synthase 2 and glutathione peroxidase 4 gene expression was detected by real-time quantitative polymerase chain reaction.Glutathione peroxidase 4 and nuclear factor erythroid-derived-like 2 protein expression was detected by western blot analysis.Results showed that ferrostatin-1 can significantly counter the effects of glutamate on HT-22 cells,improving the survival rate,reducing the release of lactate dehydrogenase and reducing the damage to mitochondrial ultrastructure.However,it did not affect the caspase-3 expression and monodansylcadaverine-positive staining in glutamate-injured HT-22 cells.Ferrostatin-1 reduced the levels of reactive oxygen species and malondialdehyde and enhanced superoxide dismutase activity.It decreased gene expression of prostaglandin peroxidase synthase 2 and increased gene expression of glutathione peroxidase 4 and protein expressions of glutathione peroxidase 4 and nuclear factor(erythroid-derived)-like 2 in glutamate-injured HT-22 cells.Treatment of cultured cells with the apoptosis inhibitor Z-Val-Ala-Asp(OMe)-fluoromethyl ketone(2–8μM),autophagy inhibitor 3-methyladenine(100–400μM)or necrosis inhibitor necrostatin-1(10–40μM)had no effect on glutamate induced cell damage.However,the iron chelator deferoxamine mesylate salt inhibited glutamate induced cell death.Thus,the results suggested that ferroptosis is caused by glutamate-induced toxicity and that ferrostatin-1 protects HT-22 cells from glutamate-induced oxidative toxicity by inhibiting the oxidative stress.
文摘An overwhelming majority of the transcribed genome encodes for non-coding RNA(ncR NA) sequences. Deep sequencing of the transcriptome has uncovered tens of thousands of long ncR NA(lncR NA) sequences. However, little is known regarding the possible functions for a vast majority of these sequences. Among those lncR NAs whose function has been experimentally validated, most serve as regulators of gene expression. LncR NAs have been found to be critical to development and homeostasis and they have been implicated in several pathologies including cancer. Here, we examine the functions and underlying mechanisms of lnc RNAs in stem cells and in cancer biology, areas linked by the actions of lncR NAs.
文摘BACKGROUND Due to the special clinical features and biologic characteristics of adolescent and young adult(AYA)cancers,AYA cancers are different from cancers in children and elderly individuals.However,there are few reports on AYA hepatocellular carcinoma(HCC).AIM To investigate the overall survival(OS)of AYA(15-39 years)and elderly(40-74 years)patients with HCC.METHODS The data of all the HCC cases were extracted from the Surveillance,Epidemiology,and End Results database from 2004 to 2015 and were then divided into two groups based on age:AYA group(15-39 years)and older group(40-74 years).Kaplan-Meier curves and log-rank tests were used to compare the OS of the two groups.Propensity score matching(PSM)was employed to analyze the OS difference between the two groups.The Cox proportional hazards regression model was used to perform multivariate analysis to explore the risk factors for OS of HCC patients.RESULTS Compared to elderly cancer patients,AYA patients with HCC had a worse Surveillance,Epidemiology,and End Results stage,including the distant stage(22.1%vs 15.4%,P<0.001),and a more advanced American Joint Committee on Cancer(AJCC)stage,including AJCC III and IV(49.2%vs 38.3%,P<0.001),and were more likely to receive surgery(64.5%vs 47.5%,P<0.001).Before PSM,the AYA group had a longer survival in months(median:20.00,interquartile range[IQR]:5.00-62.50)than the older group(median:15.00,IQR:4.00-40.00)(P<0.001).After PSM,the AYA group still had a longer survival in months(median:21.00,IQR:5.00-64.50)than the older group(median:18.00,IQR:6.00-53.00)(P<0.001).The Cox proportional hazards regression model showed that advanced age(hazard ratio[HR]=1.405,95%CI:1.218-1.621,P<0.001)was a risk factor for OS of HCC patients.In the subgroup analysis,the Cox proportional hazards regression model showed that in AJCC I/II HCC patients,advanced age(HR=1.749,95%CI:1.352-2.263,P<0.001)was a risk factor for OS,while it was not a risk factor in AJCC III/IV HCC patients(HR=1.186,95%CI:0.997-1.410,P=0.054)before PSM.After PSM,advanced age(HR=1.891,95%CI:1.356-2.637,P<0.001)was still a risk factor for OS in AJCC I/II HCC patients,but was not a risk factor for OS in AJCC III/IV HCC patients(HR=1.192,95%CI:0.934-1.521,P=0.157)after PSM.CONCLUSION AYA patients with HCC have different clinical characteristics from older adults.In different AJCC stages,the two groups of patients have different OS:In AJCC I/II HCC patients,advanced age is a risk factor for OS,but it is not a risk factor for OS in the AJCC III/IV HCC patient group.
基金financially supported by the Gansu Province Science and Technology Major Special Program Foundation of China(Grant No.1302GKDA015)
文摘The effect of different contents of Y, Zr and Er on microstructure and properties of Al-5 Cu-0.4 Mn alloy was investigated. T6 heat treatment, OM, SEM and EDS methods were applied to the alloy. The results showed that fluidity and elongation of alloy adding Y, Zr and Er were improved, while with the increase of addition amounts, θ phase increased and grains were trended to grow up gradually. The Al-5 Cu-0.4 Mn alloy presented the maxed style of ductile and brittle fracture. After T6 heat treatment, the precipitation amounts of θ phase decreased dramatically and tensile strength and hardness significantly increased. Especially when addition contents were among 0.1-0.3 wt.%, tensile strength and hardness of heat-treated alloy increased greatly, almost doubled as that of the as-cast state. The tensile strength reached its maximum of 378.43 MPa when the addition amount was 0.3 wt.%. With the further increase of addition amounts, the elongation deteriorated and the proportion of ductile fracture reduced due to the limited dispersion strengthening effect of θ phase and Al_8Cu_4 Er. It demonstrated that addition of 0.1-0.3 wt.% Y, Zr and Er would generate positive effects and influences on Al-5 Cu-0.4 Mn alloy, which is significant for optimizing components and improving properties of Al-5 Cu-0.4 Mn alloy.
基金financially supported by the National Natural Science Foundation of China (No. E051004)
文摘According to the selection principle of grain refiners and calculation of planar disregistries, CeO2 and TiB2 particles were selected as the grain refiners of pure nickel. The change of grain size and refining effects of different refiners under the same melting conditions were investigated. The results show that the grain size of pure nickel gradually reduces with increasing the amount of grain refiners. And with increasing the amount of CeO2 up to 0.7 wt%, the grain size of pure nickel decreases from 323.0 to 53.5 lm. In addition, when the amount of TiB2is0.7 wt%, the grain size is reduced to 41.3 lm.
基金National Natural Science Foundation of China(No.81273772)the Natural Science Foundation of Zhejiang Province(No.Y2101229)+3 种基金the Project of Science and Technology for Chinese Medicine of Zhejiang province(No.2010ZA026)Public Welfare Technology Application Research Plan Project of Zhejiang Province in China(No.2014C33216)the New-Shoot Talented Man Plan Project of Zhejiang Provence(No.2014R410059)the Project of Zhejiang Chinese Medical University(No.2015ZG16)
文摘Objective Osteoarthritis(OA) is a kind of degenerative arthritis, involving degradation of joints, including articular cartilage and subchondral bone. Bushen-Huoxue Herb Couple(BHHC) is a Chinese herb pair with invigorating the kidney and promoting blood circulation. In our study, a Gas Chromatography-Mass Spectrometer(GC-MS) based metabolomics was developed to achieve a systematic observation of the progression of OA and evaluate the efficacy of BHHC in OA rats. Methods Forty Sprague-Dawley rats(half males and half females) were randomly divided into five groups, including normal group, OA model group, sham-operated group, BHHC group, positive medicine(PM) group after anterior cruciate ligament reconstruction and meniscectomy on rats. Urine samples for analysis were collected on week 0, 2, 4, 6, 8, 10, 12, and 14 during the experiment. Results The histological results showed that BHHC had a strong action of repairment and reconstruction of joint damage. By combining with partial least squares discriminant analysis(PLS-DA), 14 biomarkers were identified in urine samples. The biomarkers were mainly involved 10 metabolism pathways, such as tricarboxylic acid cycle metabolism, acid amino metabolism, tryptophan metabolism, lipid metabolism and phenylalanine metabolism. Using these potential biomarkers as a screening index, it indicated that BHHC could reverse the pathological process of OA through regulating amino acid metabolism, lipid metabolism, nucleotide metabolism and energy metabolism. Conclusions This study demonstrates that a metabolomics is a useful tool for identifying potential OA biomarkers and investigating the underlying mechanisms of Traditional Chinese Medicine in OA treatment.