Mild traumatic brain injury(mTBI)-induced post-traumatic headache(PTH)is a pressing public health concern and leading cause of disability worldwide.Although PTH is often accompanied by neurological disorders,the exact...Mild traumatic brain injury(mTBI)-induced post-traumatic headache(PTH)is a pressing public health concern and leading cause of disability worldwide.Although PTH is often accompanied by neurological disorders,the exact underlying mechanism remains largely unknown.Identifying potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced PTH.In this study,a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term recovery.Results indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury stage.Metabolic kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum,temporal lobe/cortex,and hippocampal regions during the early stages of PTH.Additionally,variations in brain functional activities and connectivity were further detected in the early stage of PTH,particularly in the cerebellum and temporal cortex,suggesting that these regions play central roles in the mechanism underlying PTH.Moreover,our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for PTH.Future studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex,with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment.展开更多
It is estimated that there was 841 0 0 0 new cases of liver cancer and 782 0 0 0 associated deaths worldwide in 2018,ranking as the sixth most common cancer and the fourth leading cause of cancer-related deaths[1].Wit...It is estimated that there was 841 0 0 0 new cases of liver cancer and 782 0 0 0 associated deaths worldwide in 2018,ranking as the sixth most common cancer and the fourth leading cause of cancer-related deaths[1].With approximately 90%of total cases,hepatocellular carcinoma(HCC)is the most frequent type of primary liver cancer,and is a major public global health challenge at present[1].The majority of HCC patients are usually at advanced stages when diagnosed,which misses the optimal treatment and prognosis is poor.Alpha-fetoprotein(AFP)is the most widely applied diagnostic serum biomarker to detect HCC at present;however,the diagnostic accuracy of AFP is unsatisfactory,with sensitivity of 53%and specificity of 90%for early stage HCC[2].Recently,plenty of studies reported that microRNA-125b(miR-125b)might function as potential diagnostic biomarker in HCC[3–8].miR-125 family,consisting of miR-125a,miR-125b-1,and miR-125b-2,is closely associated with differentiation,proliferation,invasion,and metastasis of cancer cells.However,the diagnostic accuracy of miR-125b remains inconsistent.展开更多
Background： The radiochemotherapy regimen concomitantly employing temozolomide （TMZ） chemotherapy and radiotherapy （RT） 4 weeks after surgery, followed by 6 cycles of TMZ is a common treatment for glioblastoma （...Background： The radiochemotherapy regimen concomitantly employing temozolomide （TMZ） chemotherapy and radiotherapy （RT） 4 weeks after surgery, followed by 6 cycles of TMZ is a common treatment for glioblastoma （GBM）. However, its median overall survival （OS） is only 14.6 months. This study was to explore the effectiveness and safety of early TMZ chemotherapy between surgery and chemoradiotherapy plus the standard concomitant radiochemotherapy regimen. Methods： A randomized, parallel group, open-label study of 99 newly diagnosed GBM patients was conducted at 10 independent Chinese neurosurgical departments from June 2008 to June 2012. Patients were treated with concomitant radiochemotherapy regimen plus early postsurgical temozolomide （early TMZ group） or standard concomitant radiochemotherapy regimen （control group）. Overall response was assessed based on objective tumor assessments, administration ofcorticosteroid and neurological status test. Hematological, biochemical, laboratory, adverse event （AE）, and neurological condition were measured for 24 months of tbllow-up. The primary efficacy endpoint of this study was overall survival （OS）. The secondary endpoint was progression free survival （PFS）. Results： The median OS time in the early TMZ group was 17.6 months, compared with 13.2 months in the control group （log-rank test P 0.021 ）. In addition, the OS rate in the early TMZ group was higher at 6, 12, and 18 months than in the control group, respectively （P 〈 0.05）. The median PFS time was 8.7 months in the early TMZ group and 10.4 months in the control group （log-rank test P = 0.695）. AEs occurred in 29 （55.8%） and 31（73.8%） patients respectively in early and control groups, including nausea （15.4% vs. 33.3%）, vomiting （7.7% vs. 28.6%）, fever （7.7% vs. 11.9%）, and headache （3.8% vs. 23.8%）. Only 30.8% and 33.3% were drug-related, respectively. Conclusions： Addition of TMZ chemotherapy in the early break of the standard concomitant radiochemotherapy regimen was well tolerated and significantly improved the OS of the GBM patients, compared with standard concomitant radiochemotherapy regimen. However, a larger randomized trial is warranted to verify these results.展开更多
Background:High-grade glioma(HGG)is a fatal human cancer.Bortezomib,a proteasome inhibitor,has been approved for the treatment of multiple myeloma but its use in glioma awaits further investigation.This study aimed to...Background:High-grade glioma(HGG)is a fatal human cancer.Bortezomib,a proteasome inhibitor,has been approved for the treatment of multiple myeloma but its use in glioma awaits further investigation.This study aimed to explore the chemotherapeutic effect and the underlying mechanism of bortezomib on gliomas.Methods:U251 and U87 cell viability and proliferation were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT)assay,tumor cell spheroid growth,and colony formation assay.Cell apoptosis and cell cycle were detected by flow cytometry.Temozolomide(TMZ)-insensitive cell lines were induced by long-term TMZ treatment,and cells with stem cell characteristics were enriched with stem cell culture medium.The mRNA levels of interested genes were measured via reverse transcription-quantitative polymerase chain reaction,and protein levels were determined via Western blotting/immunofluorescent staining in cell lines and immunohistochemical staining in paraffin-embedded sections.Via inoculating U87 cells subcutaneously,glioma xenograft models in nude mice were established for drug experiments.Patient survival data were analyzed using the Kaplan-Meier method.Results:Bortezomib inhibited the viability and proliferation of U251 and U87 cells in a dose-and time-dependent manner by inducing apoptosis and cell cycle arrest.Bortezomib also significantly inhibited the spheroid growth,colony formation,and stem-like cell proliferation of U251 and U87 cells.When administrated in combination,bortezomib showed synergistic effect with TMZ in vitro and sensitized glioma to TMZ treatment both in vitro and in vivo.Bortezomib reduced both the mRNA and protein levels of Forkhead Box M1(FOXM1)and its target gene Survivin.The FOXM1-Survivin axis was markedly up-regulated in established TMZ-insensitive glioma cell lines and HGG patients.Expression levels of FOXM1 and Survivin were positively correlated with each other and both related to poor progno-sis in glioma patients.Conclusions:Bortezomib was found to inhibit glioma growth and improved TMZ chemotherapy efficacy,probably via down-regulating the FOXM1-Survivin axis.Bortezomib might be a promising agent for treating malignant glioma,alone or in combination with TMZ.展开更多
基金supported by the Natural Science Foundation of Guangdong Province,China(2021A1515010897)Discipline Construction Fund of Central People’s Hospital of Zhanjiang(2020A01,2020A02)+1 种基金National Natural Science Foundation of China(31970973,21921004,32271148)Biosecurity Research Project(23SWAQ24)。
文摘Mild traumatic brain injury(mTBI)-induced post-traumatic headache(PTH)is a pressing public health concern and leading cause of disability worldwide.Although PTH is often accompanied by neurological disorders,the exact underlying mechanism remains largely unknown.Identifying potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced PTH.In this study,a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term recovery.Results indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury stage.Metabolic kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum,temporal lobe/cortex,and hippocampal regions during the early stages of PTH.Additionally,variations in brain functional activities and connectivity were further detected in the early stage of PTH,particularly in the cerebellum and temporal cortex,suggesting that these regions play central roles in the mechanism underlying PTH.Moreover,our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for PTH.Future studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex,with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment.
基金supported by grants from the National Natural Science Foundation of China(81872072 and 81572501)
文摘It is estimated that there was 841 0 0 0 new cases of liver cancer and 782 0 0 0 associated deaths worldwide in 2018,ranking as the sixth most common cancer and the fourth leading cause of cancer-related deaths[1].With approximately 90%of total cases,hepatocellular carcinoma(HCC)is the most frequent type of primary liver cancer,and is a major public global health challenge at present[1].The majority of HCC patients are usually at advanced stages when diagnosed,which misses the optimal treatment and prognosis is poor.Alpha-fetoprotein(AFP)is the most widely applied diagnostic serum biomarker to detect HCC at present;however,the diagnostic accuracy of AFP is unsatisfactory,with sensitivity of 53%and specificity of 90%for early stage HCC[2].Recently,plenty of studies reported that microRNA-125b(miR-125b)might function as potential diagnostic biomarker in HCC[3–8].miR-125 family,consisting of miR-125a,miR-125b-1,and miR-125b-2,is closely associated with differentiation,proliferation,invasion,and metastasis of cancer cells.However,the diagnostic accuracy of miR-125b remains inconsistent.
文摘Background： The radiochemotherapy regimen concomitantly employing temozolomide （TMZ） chemotherapy and radiotherapy （RT） 4 weeks after surgery, followed by 6 cycles of TMZ is a common treatment for glioblastoma （GBM）. However, its median overall survival （OS） is only 14.6 months. This study was to explore the effectiveness and safety of early TMZ chemotherapy between surgery and chemoradiotherapy plus the standard concomitant radiochemotherapy regimen. Methods： A randomized, parallel group, open-label study of 99 newly diagnosed GBM patients was conducted at 10 independent Chinese neurosurgical departments from June 2008 to June 2012. Patients were treated with concomitant radiochemotherapy regimen plus early postsurgical temozolomide （early TMZ group） or standard concomitant radiochemotherapy regimen （control group）. Overall response was assessed based on objective tumor assessments, administration ofcorticosteroid and neurological status test. Hematological, biochemical, laboratory, adverse event （AE）, and neurological condition were measured for 24 months of tbllow-up. The primary efficacy endpoint of this study was overall survival （OS）. The secondary endpoint was progression free survival （PFS）. Results： The median OS time in the early TMZ group was 17.6 months, compared with 13.2 months in the control group （log-rank test P 0.021 ）. In addition, the OS rate in the early TMZ group was higher at 6, 12, and 18 months than in the control group, respectively （P 〈 0.05）. The median PFS time was 8.7 months in the early TMZ group and 10.4 months in the control group （log-rank test P = 0.695）. AEs occurred in 29 （55.8%） and 31（73.8%） patients respectively in early and control groups, including nausea （15.4% vs. 33.3%）, vomiting （7.7% vs. 28.6%）, fever （7.7% vs. 11.9%）, and headache （3.8% vs. 23.8%）. Only 30.8% and 33.3% were drug-related, respectively. Conclusions： Addition of TMZ chemotherapy in the early break of the standard concomitant radiochemotherapy regimen was well tolerated and significantly improved the OS of the GBM patients, compared with standard concomitant radiochemotherapy regimen. However, a larger randomized trial is warranted to verify these results.
基金This work was primarily supported by Grants from the National Natural Science Foundation of China(NSFC-81972360)
文摘Background:High-grade glioma(HGG)is a fatal human cancer.Bortezomib,a proteasome inhibitor,has been approved for the treatment of multiple myeloma but its use in glioma awaits further investigation.This study aimed to explore the chemotherapeutic effect and the underlying mechanism of bortezomib on gliomas.Methods:U251 and U87 cell viability and proliferation were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT)assay,tumor cell spheroid growth,and colony formation assay.Cell apoptosis and cell cycle were detected by flow cytometry.Temozolomide(TMZ)-insensitive cell lines were induced by long-term TMZ treatment,and cells with stem cell characteristics were enriched with stem cell culture medium.The mRNA levels of interested genes were measured via reverse transcription-quantitative polymerase chain reaction,and protein levels were determined via Western blotting/immunofluorescent staining in cell lines and immunohistochemical staining in paraffin-embedded sections.Via inoculating U87 cells subcutaneously,glioma xenograft models in nude mice were established for drug experiments.Patient survival data were analyzed using the Kaplan-Meier method.Results:Bortezomib inhibited the viability and proliferation of U251 and U87 cells in a dose-and time-dependent manner by inducing apoptosis and cell cycle arrest.Bortezomib also significantly inhibited the spheroid growth,colony formation,and stem-like cell proliferation of U251 and U87 cells.When administrated in combination,bortezomib showed synergistic effect with TMZ in vitro and sensitized glioma to TMZ treatment both in vitro and in vivo.Bortezomib reduced both the mRNA and protein levels of Forkhead Box M1(FOXM1)and its target gene Survivin.The FOXM1-Survivin axis was markedly up-regulated in established TMZ-insensitive glioma cell lines and HGG patients.Expression levels of FOXM1 and Survivin were positively correlated with each other and both related to poor progno-sis in glioma patients.Conclusions:Bortezomib was found to inhibit glioma growth and improved TMZ chemotherapy efficacy,probably via down-regulating the FOXM1-Survivin axis.Bortezomib might be a promising agent for treating malignant glioma,alone or in combination with TMZ.
