Chronic visceral pain is a persistent and debilitating condition arising from dysfunction or sensitization of the visceral organs and their associated nervous pathways.Increasing evidence suggests that imbalances in c...Chronic visceral pain is a persistent and debilitating condition arising from dysfunction or sensitization of the visceral organs and their associated nervous pathways.Increasing evidence suggests that imbalances in central nervous system function play an essential role in the progression of visceral pain,but the exact mechanisms underlying the neural circuitry and molecular targets remain largely unexplored.In the present study,the ventral tegmental area(VTA)was shown to mediate visceral pain in mice.Visceral pain stimulation increased c-Fos expression and Ca2+activity of glutamatergic VTA neurons,and optogenetic modulation of glutamatergic VTA neurons altered visceral pain.In particular,the upregulation of NMDA receptor 2A(NR2A)subunits within the VTA resulted in visceral pain in mice.Administration of a selective NR2A inhibitor decreased the number of visceral pain-induced c-Fos positive neurons and attenuated visceral pain.Pharmacology combined with chemogenetics further demonstrated that glutamatergic VTA neurons regulated visceral pain behaviors based on NR2A.In summary,our findings demonstrated that the upregulation of NR2A in glutamatergic VTA neurons plays a critical role in visceral pain.These insights provide a foundation for further comprehension of the neural circuits and molecular targets involved in chronic visceral pain and may pave the way for targeted therapies in chronic visceral pain.展开更多
Background:Post-operative recurrence rates are high for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).This study aimed to explore the factors associated with post-operative 1-year recurrence rate in pat...Background:Post-operative recurrence rates are high for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).This study aimed to explore the factors associated with post-operative 1-year recurrence rate in patients with HBV-related HCC who had a single small primary tumor(3 cmin diameter).Methods:This was a retrospective study of 203(training cohort)and 64(validation cohort)patients newly diagnosed with HBV-related HCC who had a single small primary tumor.The first year of post-operative follow-up was examined.Factors potentially associated with HCC recurrence were identified using Cox regression analyses.A model was constructed based on the factors identified and the prognostic value of the model was evaluated using receiver operating characteristic(ROC)curve analysis and calculation of the area under the ROC curve(AUC).Results:A history of alcoholismand serum levels of a-fetoprotein,total protein and c-glutamyl transpeptidase(GGT)were independently associated with 1-year recurrence rate after surgery.A predictive model based on these four factors had an AUC of 0.711(95%confidence interval,0.643–0.772)in the training cohort and 0.727(95%confidence interval,0.601–0.831)in the validation cohort.The 1-year recurrence rate was significantly lower in the low-risk group than in the high-risk group in both the training cohort(17.0%vs.49.5%,P<0.001)and the validation cohort(43.2%vs.74.1%,P=0.031).Conclusion:A history of alcoholism and serum levels of a-fetoprotein,total protein and c-glutamyl transpeptidase were independently associated with post-operative 1-year recurrence rate in patients with HBV-related HCC who had a single small primary tumor(3 cmin diameter).展开更多
Through several studies exploiting next-generation sequencing,we are obtaining a clearer picture of the complex genetic and molecular landscape of hepatocellular carcinoma(HCC).Consistent with the findings of other ca...Through several studies exploiting next-generation sequencing,we are obtaining a clearer picture of the complex genetic and molecular landscape of hepatocellular carcinoma(HCC).Consistent with the findings of other cancer types,telomerase reverse transcriptase(TERT)promoter mutations have been frequently reported in HCC.C228T and C250T are two major types of hot spot mutations in the TERT promoter region.Besides,in hepatitis B virus(HBV)-related HCC cases,the TERT promoter is recurrently interrupted by integration of HBV DNA.TERT promoter mutations are thought to be an early event in HCC carcinogenesis,and they are significantly associated with disease progression.In this review,we provide an updated overview of the somatic mutations in the TERT promoter region and discuss their possible roles in the development of HCC.展开更多
基金supported by grants from the National Natural Science Foundation of China(82401454 and 32230041)the Postdoctoral Fellowship Program of CPSF(GZC20231890)+1 种基金Zhangjiagang Technology Project for Youth(ZJGQNKJ202424)the Priority Academic Program Development of Jiangsu Higher Education Institutions of China.
文摘Chronic visceral pain is a persistent and debilitating condition arising from dysfunction or sensitization of the visceral organs and their associated nervous pathways.Increasing evidence suggests that imbalances in central nervous system function play an essential role in the progression of visceral pain,but the exact mechanisms underlying the neural circuitry and molecular targets remain largely unexplored.In the present study,the ventral tegmental area(VTA)was shown to mediate visceral pain in mice.Visceral pain stimulation increased c-Fos expression and Ca2+activity of glutamatergic VTA neurons,and optogenetic modulation of glutamatergic VTA neurons altered visceral pain.In particular,the upregulation of NMDA receptor 2A(NR2A)subunits within the VTA resulted in visceral pain in mice.Administration of a selective NR2A inhibitor decreased the number of visceral pain-induced c-Fos positive neurons and attenuated visceral pain.Pharmacology combined with chemogenetics further demonstrated that glutamatergic VTA neurons regulated visceral pain behaviors based on NR2A.In summary,our findings demonstrated that the upregulation of NR2A in glutamatergic VTA neurons plays a critical role in visceral pain.These insights provide a foundation for further comprehension of the neural circuits and molecular targets involved in chronic visceral pain and may pave the way for targeted therapies in chronic visceral pain.
基金This study was supported by the Beijing Municipal Science and Technology Commission[No.Z171100001017082]the Special Fund of Capital Health Research and Development[No.2016–2-2171]+1 种基金the Fund for Beijing Science&Technology Development of TCM[No.JJ2016-14]the Science and Technology Project of Beijing Municipal Education Commission[No.SQKM201610025026].
文摘Background:Post-operative recurrence rates are high for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).This study aimed to explore the factors associated with post-operative 1-year recurrence rate in patients with HBV-related HCC who had a single small primary tumor(3 cmin diameter).Methods:This was a retrospective study of 203(training cohort)and 64(validation cohort)patients newly diagnosed with HBV-related HCC who had a single small primary tumor.The first year of post-operative follow-up was examined.Factors potentially associated with HCC recurrence were identified using Cox regression analyses.A model was constructed based on the factors identified and the prognostic value of the model was evaluated using receiver operating characteristic(ROC)curve analysis and calculation of the area under the ROC curve(AUC).Results:A history of alcoholismand serum levels of a-fetoprotein,total protein and c-glutamyl transpeptidase(GGT)were independently associated with 1-year recurrence rate after surgery.A predictive model based on these four factors had an AUC of 0.711(95%confidence interval,0.643–0.772)in the training cohort and 0.727(95%confidence interval,0.601–0.831)in the validation cohort.The 1-year recurrence rate was significantly lower in the low-risk group than in the high-risk group in both the training cohort(17.0%vs.49.5%,P<0.001)and the validation cohort(43.2%vs.74.1%,P=0.031).Conclusion:A history of alcoholism and serum levels of a-fetoprotein,total protein and c-glutamyl transpeptidase were independently associated with post-operative 1-year recurrence rate in patients with HBV-related HCC who had a single small primary tumor(3 cmin diameter).
基金This work was supported by grants from the National Natural Science Foundation of China(81572312)Chinese National Key Project Specialized for Infectious Diseases(2017ZX10201201-008-003)+1 种基金National Key Research and Development Program of China(2017YFC0908103)Chinese State Key Laboratory of Oncogenes and Related Genes(91-14-16,91-15-06).
文摘Through several studies exploiting next-generation sequencing,we are obtaining a clearer picture of the complex genetic and molecular landscape of hepatocellular carcinoma(HCC).Consistent with the findings of other cancer types,telomerase reverse transcriptase(TERT)promoter mutations have been frequently reported in HCC.C228T and C250T are two major types of hot spot mutations in the TERT promoter region.Besides,in hepatitis B virus(HBV)-related HCC cases,the TERT promoter is recurrently interrupted by integration of HBV DNA.TERT promoter mutations are thought to be an early event in HCC carcinogenesis,and they are significantly associated with disease progression.In this review,we provide an updated overview of the somatic mutations in the TERT promoter region and discuss their possible roles in the development of HCC.
