Objective To observe changes of plain MR T1WI signal intensity of dentate nucleus in nasopharyngeal carcinoma patients after radiotherapy and multiple times of intravenous injection of gadolinium-based contrast agent(...Objective To observe changes of plain MR T1WI signal intensity of dentate nucleus in nasopharyngeal carcinoma patients after radiotherapy and multiple times of intravenous injection of gadolinium-based contrast agent(GBCA).Methods Fifty patients with pathologically confirmed nasopharyngeal carcinoma and received intensity-modulated radiotherapy were retrospectively enrolled as the nasopharyngeal carcinoma group,and 50 patients with other malignant tumors and without history of brain radiotherapy were retrospectively enrolled as the control group.All patients received yearly GBCA enhanced MR examinations for the nasopharynx or the head.T1WI signal intensities of the dentate nucleus and the pons on same plane were measured based on images in the year of confirmed diagnosis(recorded as the first year)and in the second to the fifth years.T1WI signal intensity ratio of year i(ranging from 1 to 5)was calculated with values of dentate nucleus divided by values of the pons(ΔSI i),while the percentage of relative changes of year j(ranging from 2 to 5)was calculated withΔSI j compared toΔSI 1(Rchange j).The values of these two parameters were compared,and the correlation ofΔSI and GBCA injection year-time was evaluated within each group.Results No significant difference of gender,age norΔSI 1 was found between groups(all P>0.05).The second to the fifth yearΔSI and Rchange in nasopharyngeal carcinoma group were all higher than those in control group(all P<0.05).Within both groups,ΔSI was positively correlated with GBCA injection year-time(both P<0.05).Conclusion Patients with nasopharyngeal carcinoma who underwent radiotherapy and multiple times of intravenous injection of GBCA tended to be found with gradually worsening GBCA deposition in dentate nucleus,for which radiotherapy might be a risk factor.展开更多
Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor therapy.This study aimed to evaluate the efficacy and...Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor therapy.This study aimed to evaluate the efficacy and safety of Renshenguben(RSGB)oral solution,a ginseng-based traditional Chinese medicine,in alleviating CRF in patients with advanced hepatocellular carcinoma(HCC)receiving antitumor treatment.Methods:In this prospective,open-label,controlled,multicenter study,patients with advanced HCC at BCLC stage C and a brief fatigue inventory(BFI)score of≥4 were enrolled.Participants were assigned to the RSGB group(RSGB,10 mL twice daily)or the control group(with supportive care).Primary and secondary endpoints were the change in multidimensional fatigue inventory(MFI)score,and BFI and functional assessment of cancer therapy-hepatobiliary(FACT-Hep)scores at weeks 4 and 8 after enrollment.Adverse events(AEs)and toxicities were assessed.Results:A total of 409 participants were enrolled,with 206 assigned to the RSGB group.At week 4,there was a trend towards improvement,but the differences were not statistically significant.At week 8,the RSGB group exhibited a significantly lower MFI score(P<0.05)compared to the control group,indicating improved fatigue levels.Additionally,the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8(P<0.05).Subgroup analyses among patients receiving various antitumor treatments showed similar results.Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI,BFI,and FACT-Hep scores at week 8.No serious drug-related AEs or toxicities were observed.Conclusions:RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period,with no discernible toxicities.These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.展开更多
The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous syst...The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.展开更多
General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells.Oligodendrocytes perform essential roles in the central nervous system,including myelin sheath for...General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells.Oligodendrocytes perform essential roles in the central nervous system,including myelin sheath formation,axonal metabolism,and neuroplasticity regulation.They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation,differentiation,and apoptosis.Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes.These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways,but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function.In this review,we summarize the effects of general anesthetic agents on oligodendrocytes.We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.展开更多
Medical journals play a vital role in reporting the latest discoveries,applications,and trends within the health science research community.With the recent launch of new journal hLife,we look back at the history of me...Medical journals play a vital role in reporting the latest discoveries,applications,and trends within the health science research community.With the recent launch of new journal hLife,we look back at the history of medical journals,learn they have changed over time,and most importantly,how they can integrate new ideas and adapt to the dynamic world of medicine.展开更多
Medical journals and scientific journals in general,have been our community’s way of reporting scientific findings for the past three-hundred years.During this time,they have been in continuous evolution,undergoing m...Medical journals and scientific journals in general,have been our community’s way of reporting scientific findings for the past three-hundred years.During this time,they have been in continuous evolution,undergoing many changes,with the aim to better and more efficiently communicate research to other specialists and thewider public.Here,the hLife’s co-Editor-in-Chief Dr.Chen Dong speaks with Dr.Eric Rubin and Dr.Rui-Ping Xiao from The New England Journal of Medicine(NJEM)on the history and development of medical journals,a dialogue which took place immediately following the launch ceremony of hLife.They reflect on how reporting of medical discoveries has changed over time,the future medical challenges that society faces and how journals can address these issues,and they also give their views on how new technologies,including the use of artificial intelligence(AI),will be incorporated into the medical research and publishing.展开更多
The development of distinct dendritic cell(DC)subsets,namely,plasmacytoid DCs(pDCs)and conventional DC subsets(cDC1s and cDC2s),is controlled by specific transcription factors.IRF8 is essential for the fate specificat...The development of distinct dendritic cell(DC)subsets,namely,plasmacytoid DCs(pDCs)and conventional DC subsets(cDC1s and cDC2s),is controlled by specific transcription factors.IRF8 is essential for the fate specification of cDC1s.However,how the expression of Irf8 is regulated is not fully understood.In this study,we identified TRIM33 as a critical regulator of DC differentiation and maintenance.TRIM33 deletion in Trim33fl/fl Cre-ERT2 mice significantly impaired DC differentiation from hematopoietic progenitors at different developmental stages.TRIM33 deficiency downregulated the expression of multiple genes associated with DC differentiation in these progenitors.TRIM33 promoted the transcription of Irf8 to facilitate the differentiation of cDC1s by maintaining adequate CDK9 and Ser2 phosphorylated RNA polymerase II(S2 Pol II)levels at Irf8 gene sites.Moreover,TRIM33 prevented the apoptosis of DCs and progenitors by directly suppressing the PU.1-mediated transcription of Bcl2l11,thereby maintaining DC homeostasis.Taken together,our findings identified TRIM33 as a novel and crucial regulator of DC differentiation and maintenance through the modulation of Irf8 and Bcl2l11 expression.The finding that TRIM33 functions as a critical regulator of both DC differentiation and survival provides potential benefits for devising DC-based immune interventions and therapies.展开更多
文摘Objective To observe changes of plain MR T1WI signal intensity of dentate nucleus in nasopharyngeal carcinoma patients after radiotherapy and multiple times of intravenous injection of gadolinium-based contrast agent(GBCA).Methods Fifty patients with pathologically confirmed nasopharyngeal carcinoma and received intensity-modulated radiotherapy were retrospectively enrolled as the nasopharyngeal carcinoma group,and 50 patients with other malignant tumors and without history of brain radiotherapy were retrospectively enrolled as the control group.All patients received yearly GBCA enhanced MR examinations for the nasopharynx or the head.T1WI signal intensities of the dentate nucleus and the pons on same plane were measured based on images in the year of confirmed diagnosis(recorded as the first year)and in the second to the fifth years.T1WI signal intensity ratio of year i(ranging from 1 to 5)was calculated with values of dentate nucleus divided by values of the pons(ΔSI i),while the percentage of relative changes of year j(ranging from 2 to 5)was calculated withΔSI j compared toΔSI 1(Rchange j).The values of these two parameters were compared,and the correlation ofΔSI and GBCA injection year-time was evaluated within each group.Results No significant difference of gender,age norΔSI 1 was found between groups(all P>0.05).The second to the fifth yearΔSI and Rchange in nasopharyngeal carcinoma group were all higher than those in control group(all P<0.05).Within both groups,ΔSI was positively correlated with GBCA injection year-time(both P<0.05).Conclusion Patients with nasopharyngeal carcinoma who underwent radiotherapy and multiple times of intravenous injection of GBCA tended to be found with gradually worsening GBCA deposition in dentate nucleus,for which radiotherapy might be a risk factor.
基金This study was supported by grants from the National Natural Science Foundation of China(81972726,82273074 and 82372813)Dawn Project Foundation of Shanghai(21SG36)+2 种基金Shanghai Health Academic Leader Program(2022XD001)the Natural Science Foundation of Shanghai(22ZR1477900)Adjunct Talent Fund of Zhejiang Provincial People’s Hospital(2021-YT).
文摘Background:Cancer-related fatigue(CRF)is a common and debilitating symptom experienced by patients with advanced-stage cancer,especially those undergoing antitumor therapy.This study aimed to evaluate the efficacy and safety of Renshenguben(RSGB)oral solution,a ginseng-based traditional Chinese medicine,in alleviating CRF in patients with advanced hepatocellular carcinoma(HCC)receiving antitumor treatment.Methods:In this prospective,open-label,controlled,multicenter study,patients with advanced HCC at BCLC stage C and a brief fatigue inventory(BFI)score of≥4 were enrolled.Participants were assigned to the RSGB group(RSGB,10 mL twice daily)or the control group(with supportive care).Primary and secondary endpoints were the change in multidimensional fatigue inventory(MFI)score,and BFI and functional assessment of cancer therapy-hepatobiliary(FACT-Hep)scores at weeks 4 and 8 after enrollment.Adverse events(AEs)and toxicities were assessed.Results:A total of 409 participants were enrolled,with 206 assigned to the RSGB group.At week 4,there was a trend towards improvement,but the differences were not statistically significant.At week 8,the RSGB group exhibited a significantly lower MFI score(P<0.05)compared to the control group,indicating improved fatigue levels.Additionally,the RSGB group showed significantly greater decrease in BFI and FACT-Hep scores at week 8(P<0.05).Subgroup analyses among patients receiving various antitumor treatments showed similar results.Multivariate linear regression analyses revealed that the RSGB group experienced a significantly substantial decrease in MFI,BFI,and FACT-Hep scores at week 8.No serious drug-related AEs or toxicities were observed.Conclusions:RSGB oral solution effectively reduced CRF in patients with advanced HCC undergoing antitumor therapy over an eight-week period,with no discernible toxicities.These findings support the potential of RSGB oral solution as an adjunctive treatment for managing CRF in this patient population.
文摘The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.
基金supported by the Natural Science Foundation of Zhejiang Province(LZ22H090002,2014C33170)National Natural Science Foundation of China(82171260,81641042,81471240)。
文摘General anesthetic agents can impact brain function through interactions with neurons and their effects on glial cells.Oligodendrocytes perform essential roles in the central nervous system,including myelin sheath formation,axonal metabolism,and neuroplasticity regulation.They are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation,differentiation,and apoptosis.Neurologists are increasingly interested in the effects of general anesthetic agents on oligodendrocytes.These agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways,but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and function.In this review,we summarize the effects of general anesthetic agents on oligodendrocytes.We anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.
文摘Medical journals play a vital role in reporting the latest discoveries,applications,and trends within the health science research community.With the recent launch of new journal hLife,we look back at the history of medical journals,learn they have changed over time,and most importantly,how they can integrate new ideas and adapt to the dynamic world of medicine.
文摘Medical journals and scientific journals in general,have been our community’s way of reporting scientific findings for the past three-hundred years.During this time,they have been in continuous evolution,undergoing many changes,with the aim to better and more efficiently communicate research to other specialists and thewider public.Here,the hLife’s co-Editor-in-Chief Dr.Chen Dong speaks with Dr.Eric Rubin and Dr.Rui-Ping Xiao from The New England Journal of Medicine(NJEM)on the history and development of medical journals,a dialogue which took place immediately following the launch ceremony of hLife.They reflect on how reporting of medical discoveries has changed over time,the future medical challenges that society faces and how journals can address these issues,and they also give their views on how new technologies,including the use of artificial intelligence(AI),will be incorporated into the medical research and publishing.
基金The Ministry of Science and Technology of China National Key Research Projects provided grants 2019YFA0508502 and 2022YFC2505001 to LWThe National Natural Science Foundation of China funded grant 31991174 to LW+4 种基金The National Natural Science Foundation of China provided Basic Research Center grant 82388101 to LWThe National Natural Science Foundation of China provided grant 81801641 to JLThe National Natural Science Foundation of China provided grant 31800769 to ZHThe Ministry of Science and Technology of China National Key Research Projects provided grants 2022YFC2505002 to TWFunding from the Tsinghua-Peking Center for Life Sciences to LW is acknowledged.
文摘The development of distinct dendritic cell(DC)subsets,namely,plasmacytoid DCs(pDCs)and conventional DC subsets(cDC1s and cDC2s),is controlled by specific transcription factors.IRF8 is essential for the fate specification of cDC1s.However,how the expression of Irf8 is regulated is not fully understood.In this study,we identified TRIM33 as a critical regulator of DC differentiation and maintenance.TRIM33 deletion in Trim33fl/fl Cre-ERT2 mice significantly impaired DC differentiation from hematopoietic progenitors at different developmental stages.TRIM33 deficiency downregulated the expression of multiple genes associated with DC differentiation in these progenitors.TRIM33 promoted the transcription of Irf8 to facilitate the differentiation of cDC1s by maintaining adequate CDK9 and Ser2 phosphorylated RNA polymerase II(S2 Pol II)levels at Irf8 gene sites.Moreover,TRIM33 prevented the apoptosis of DCs and progenitors by directly suppressing the PU.1-mediated transcription of Bcl2l11,thereby maintaining DC homeostasis.Taken together,our findings identified TRIM33 as a novel and crucial regulator of DC differentiation and maintenance through the modulation of Irf8 and Bcl2l11 expression.The finding that TRIM33 functions as a critical regulator of both DC differentiation and survival provides potential benefits for devising DC-based immune interventions and therapies.