BACKGROUND Perihilar cholangiocarcinoma(pCCA)has a poor prognosis and urgently needs a better predictive method.The predictive value of the age-adjusted Charlson comorbidity index(ACCI)for the long-term prognosis of p...BACKGROUND Perihilar cholangiocarcinoma(pCCA)has a poor prognosis and urgently needs a better predictive method.The predictive value of the age-adjusted Charlson comorbidity index(ACCI)for the long-term prognosis of patients with multiple malignancies was recently reported.However,pCCA is one of the most surgically difficult gastrointestinal tumors with the poorest prognosis,and the value of the ACCI for the prognosis of pCCA patients after curative resection is unclear.AIM To evaluate the prognostic value of the ACCI and to design an online clinical model for pCCA patients.METHODS Consecutive pCCA patients after curative resection between 2010 and 2019 were enrolled from a multicenter database.The patients were randomly assigned 3:1 to training and validation cohorts.In the training and validation cohorts,all patients were divided into low-,moderate-,and high-ACCI groups.Kaplan-Meier curves were used to determine the impact of the ACCI on overall survival(OS)for pCCA patients,and multivariate Cox regression analysis was used to determine the independent risk factors affecting OS.An online clinical model based on the ACCI was developed and validated.The concordance index(C-index),calibration curve,and receiver operating characteristic(ROC)curve were used to evaluate the predictive performance and fit of this model.RESULTS A total of 325 patients were included.There were 244 patients in the training cohort and 81 patients in the validation cohort.In the training cohort,116,91 and 37 patients were classified into the low-,moderate-and high-ACCI groups.The Kaplan-Meier curves showed that patients in the moderate-and high-ACCI groups had worse survival rates than those in the low-ACCI group.Multivariable analysis revealed that moderate and high ACCI scores were independently associated with OS in pCCA patients after curative resection.In addition,an online clinical model was developed that had ideal C-indexes of 0.725 and 0.675 for predicting OS in the training and validation cohorts.The calibration curve and ROC curve indicated that the model had a good fit and prediction performance.CONCLUSION A high ACCI score may predict poor long-term survival in pCCA patients after curative resection.High-risk patients screened by the ACCI-based model should be given more clinical attention in terms of the management of comorbidities and postoperative follow-up.展开更多
Objective:To observe the effect of nuclear transcription factor- κB(NF- κB) on cerebral edema in rats with traumatic brain injury(TBI).Methods:Male SD rau with fluid percussion injury(FPI) were selected.After separa...Objective:To observe the effect of nuclear transcription factor- κB(NF- κB) on cerebral edema in rats with traumatic brain injury(TBI).Methods:Male SD rau with fluid percussion injury(FPI) were selected.After separation and culture,rats' astrocytes all suffered FPL The expression of NF-κB and the water content were detected at the animal and cellular levels,while the activity of NOX was evaluated at the cellular level.Results:According to the results,the positive expression of NF-κB and expression of mRNA were significantly increased and the water content was increased for rats after TBI.while NF-κB inhibitor BAY 11-7082 could significantly reduce the effect of TBI.1 and 3h after FPI of astrocytes,the activation of NFkB was incrcased and BAY 11-7082 could significantly improve the injury-induced swelling of astrocytes.After the injury of astrocytes,the activity of NOX was also increased,while BAY11-7082 could reduce the activity of NOX.Conclusions:The results show that the activation of NF- κB in astrocytes is a key factor in the process of cerebral edema after TBI of rats.展开更多
In insects,the juvenile hormone(JH)and 20-hydroxyecdysone(20E)pathways jointly regulate fecundity,but only methyl farnesoate(MF)and ponasterone A exist in mites.Comparative transcriptomic analysis in Panonychus citri ...In insects,the juvenile hormone(JH)and 20-hydroxyecdysone(20E)pathways jointly regulate fecundity,but only methyl farnesoate(MF)and ponasterone A exist in mites.Comparative transcriptomic analysis in Panonychus citri showed that E75B was significantly downregulated when exposed to lufenuron.Knockdown of E75B significantly affects the expression of vitellogenin(Vg),Fushi tarazu factor 1(Ftz-f1)and juvenile hormone acid O-methyltransferase(JHAMT),reducing fecundity in mites.The knockdown of Ftz-f1 produced a more significant effect than the knockdown of E75B,indicating that the ponasterone A pathway positively regulates fecundity in P.citri.After the knockdown of JHAMT,the expression levels of both Vg and Ftz-f1 and fecundity were significantly increased,along with the inhibition of Kr-h1,suggesting that JHAMT was negatively correlated with fecundity in the regulatory network.Knockdown of Kr-h1 inhibited the expression of Vg and Ftz-f1 and fecundity,and whether the drop in fecundity is caused by Kr-h1 or Ftz-f1 is unclear.Subsequent feeding with MF induced Kr-h1 and Vg expression,whereas no significant effects were observed for JHAMT and Ftz-f1.Therefore,the MF pathway stimulates fecundity independently.RNA interference(RNAi)showed that JHAMT and Ftz-f1 inhibited each other,resulting in opposite effects of MF and ponasterone A pathways on steady-state fecundity when either factor changed.Meanwhile,JHAMT knockdown led to increased fecundity,indicating that the stimulating effect of the ponasterone A pathway was greater than the inhibiting effect of the MF pathway,and demonstrating the dominant role of the ponasterone A pathway.Therefore,the interaction between JHAMT and Ftz-f1 may be closely associated with the maintenance of MF-ponasterone A regulatory network homeostasis and is involved in the reduction of fecundity in P.citri induced by exposure to lufenuron.展开更多
基金Supported by National Natural Science Foundation of China,No. 81874211Chongqing Technology Innovation and Application Development Special Key Project,No. CSTC2021jscx-gksb-N0009
文摘BACKGROUND Perihilar cholangiocarcinoma(pCCA)has a poor prognosis and urgently needs a better predictive method.The predictive value of the age-adjusted Charlson comorbidity index(ACCI)for the long-term prognosis of patients with multiple malignancies was recently reported.However,pCCA is one of the most surgically difficult gastrointestinal tumors with the poorest prognosis,and the value of the ACCI for the prognosis of pCCA patients after curative resection is unclear.AIM To evaluate the prognostic value of the ACCI and to design an online clinical model for pCCA patients.METHODS Consecutive pCCA patients after curative resection between 2010 and 2019 were enrolled from a multicenter database.The patients were randomly assigned 3:1 to training and validation cohorts.In the training and validation cohorts,all patients were divided into low-,moderate-,and high-ACCI groups.Kaplan-Meier curves were used to determine the impact of the ACCI on overall survival(OS)for pCCA patients,and multivariate Cox regression analysis was used to determine the independent risk factors affecting OS.An online clinical model based on the ACCI was developed and validated.The concordance index(C-index),calibration curve,and receiver operating characteristic(ROC)curve were used to evaluate the predictive performance and fit of this model.RESULTS A total of 325 patients were included.There were 244 patients in the training cohort and 81 patients in the validation cohort.In the training cohort,116,91 and 37 patients were classified into the low-,moderate-and high-ACCI groups.The Kaplan-Meier curves showed that patients in the moderate-and high-ACCI groups had worse survival rates than those in the low-ACCI group.Multivariable analysis revealed that moderate and high ACCI scores were independently associated with OS in pCCA patients after curative resection.In addition,an online clinical model was developed that had ideal C-indexes of 0.725 and 0.675 for predicting OS in the training and validation cohorts.The calibration curve and ROC curve indicated that the model had a good fit and prediction performance.CONCLUSION A high ACCI score may predict poor long-term survival in pCCA patients after curative resection.High-risk patients screened by the ACCI-based model should be given more clinical attention in terms of the management of comorbidities and postoperative follow-up.
基金supported by Technology Program for Development of Pharmacy of Shandong 2013(No.2013WS0351)
文摘Objective:To observe the effect of nuclear transcription factor- κB(NF- κB) on cerebral edema in rats with traumatic brain injury(TBI).Methods:Male SD rau with fluid percussion injury(FPI) were selected.After separation and culture,rats' astrocytes all suffered FPL The expression of NF-κB and the water content were detected at the animal and cellular levels,while the activity of NOX was evaluated at the cellular level.Results:According to the results,the positive expression of NF-κB and expression of mRNA were significantly increased and the water content was increased for rats after TBI.while NF-κB inhibitor BAY 11-7082 could significantly reduce the effect of TBI.1 and 3h after FPI of astrocytes,the activation of NFkB was incrcased and BAY 11-7082 could significantly improve the injury-induced swelling of astrocytes.After the injury of astrocytes,the activity of NOX was also increased,while BAY11-7082 could reduce the activity of NOX.Conclusions:The results show that the activation of NF- κB in astrocytes is a key factor in the process of cerebral edema after TBI of rats.
基金supported financially by the Fundamental Research Funds for the Central Universities(SWU-XDPY22001)of China“Pioneer"and“Leading Goose"R&D Program of Zhejiang Province(2023C04014)the China Agriculture Research System of MOF and MARA.
文摘In insects,the juvenile hormone(JH)and 20-hydroxyecdysone(20E)pathways jointly regulate fecundity,but only methyl farnesoate(MF)and ponasterone A exist in mites.Comparative transcriptomic analysis in Panonychus citri showed that E75B was significantly downregulated when exposed to lufenuron.Knockdown of E75B significantly affects the expression of vitellogenin(Vg),Fushi tarazu factor 1(Ftz-f1)and juvenile hormone acid O-methyltransferase(JHAMT),reducing fecundity in mites.The knockdown of Ftz-f1 produced a more significant effect than the knockdown of E75B,indicating that the ponasterone A pathway positively regulates fecundity in P.citri.After the knockdown of JHAMT,the expression levels of both Vg and Ftz-f1 and fecundity were significantly increased,along with the inhibition of Kr-h1,suggesting that JHAMT was negatively correlated with fecundity in the regulatory network.Knockdown of Kr-h1 inhibited the expression of Vg and Ftz-f1 and fecundity,and whether the drop in fecundity is caused by Kr-h1 or Ftz-f1 is unclear.Subsequent feeding with MF induced Kr-h1 and Vg expression,whereas no significant effects were observed for JHAMT and Ftz-f1.Therefore,the MF pathway stimulates fecundity independently.RNA interference(RNAi)showed that JHAMT and Ftz-f1 inhibited each other,resulting in opposite effects of MF and ponasterone A pathways on steady-state fecundity when either factor changed.Meanwhile,JHAMT knockdown led to increased fecundity,indicating that the stimulating effect of the ponasterone A pathway was greater than the inhibiting effect of the MF pathway,and demonstrating the dominant role of the ponasterone A pathway.Therefore,the interaction between JHAMT and Ftz-f1 may be closely associated with the maintenance of MF-ponasterone A regulatory network homeostasis and is involved in the reduction of fecundity in P.citri induced by exposure to lufenuron.
