BACKGROUND Lung cancer bone metastasis(LCBM)is a disease with a poor prognosis,high risk and large patient population.Although considerable scientific output has accumulated on LCBM,problems have emerged,such as confu...BACKGROUND Lung cancer bone metastasis(LCBM)is a disease with a poor prognosis,high risk and large patient population.Although considerable scientific output has accumulated on LCBM,problems have emerged,such as confusing research structures.AIM To organize the research frontiers and body of knowledge of the studies on LCBM from the last 22 years according to their basic research and translation,clinical treatment,and clinical diagnosis to provide a reference for the development of new LCBM clinical and basic research.METHODS We used tools,including R,VOSviewer and CiteSpace software,to measure and visualize the keywords and other metrics of 1903 articles from the Web of Science Core Collection.We also performed enrichment and proteinprotein interaction analyses of gene expression datasets from LCBM cases worldwide.RESULTS Research on LCBM has received extensive attention from scholars worldwide over the last 20 years.Targeted therapies and immunotherapies have evolved into the mainstream basic and clinical research directions.The basic aspects of drug resistance mechanisms and parathyroid hormone-related protein may provide new ideas for mechanistic study and improvements in LCBM prognosis.The produced molecular map showed that ribosomes and focal adhesion are possible pathways that promote LCBM occurrence.CONCLUSION Novel therapies for LCBM face animal testing and drug resistance issues.Future focus should centre on advancing clinical therapies and researching drug resistance mechanisms and ribosome-related pathways.展开更多
目的探讨目标-活动-运动环境(goals-activity-motor enrichment,GAME)疗法与姿势控制对重度脑性瘫痪患儿运动功能发育的影响,为改善重度脑性瘫痪患儿的运动功能提供循证医学依据。方法采用前瞻性病例对照研究,纳入重度脑性瘫痪患儿92例...目的探讨目标-活动-运动环境(goals-activity-motor enrichment,GAME)疗法与姿势控制对重度脑性瘫痪患儿运动功能发育的影响,为改善重度脑性瘫痪患儿的运动功能提供循证医学依据。方法采用前瞻性病例对照研究,纳入重度脑性瘫痪患儿92例,按照随机数字表法分为研究组(n=46)和常规治疗组(n=46)。研究组采用GAME疗法与姿势控制训练,常规治疗组采用神经发育学疗法。比较2组患儿治疗前及治疗6个月、治疗12个月时粗大运动功能量表88项评估(gross motor function measure,GMFM-88)中的仰卧位与俯卧位(A区)和坐位(B区)、精细功能评估(fine motor function measure,FMFM)中视觉追踪(A区)和上肢关节活动(B区)、坐位能力(level of sitting scale,LSS)、疼痛(face-legs-activity-cry-consolability,FLACC)和日常生活活动能力量表(activitydaily livingscale,ADL)评分。结果2组GMFM-88(A区与B区)、FMFM(A区与B区)、LSS及ADL评分均呈逐渐升高趋势,FLACC评分呈逐渐降低趋势,研究组GMFM-88(A区与B区)、FMFM(A区与B区)、LSS及ADL评分高于常规治疗组,FLACC评分低于常规治疗组,组间、时点间、组间·时点间交互作用差异有统计学意义(P<0.05)。结论GAME疗法与姿势控制可以提高重度脑性瘫痪患儿粗大运动功能、坐位能力和精细运动功能,缓解疼痛,改善日常生活活动能力。展开更多
Pancreatic cancer(PanCa)presents a catastrophic disease with poor overall survival at advanced stages,with immediate requirement of new and effective treatment options.Besides genetic mutations,epigenetic dysregulatio...Pancreatic cancer(PanCa)presents a catastrophic disease with poor overall survival at advanced stages,with immediate requirement of new and effective treatment options.Besides genetic mutations,epigenetic dysregulation of signaling pathway-associated enriched genes are considered as novel therapeutic target.Mechanisms beneath the deoxyribonucleic acid methylation and its utility in developing of epi-drugs in PanCa are under trails.Combinations of epigenetic medicines with conventional cytotoxic treatments or targeted therapy are promising options to improving the dismal response and survival rate of PanCa patients.Recent studies have identified potentially valid pathways that support the prediction that future PanCa clinical trials will include vigorous testing of epigenomic therapies.Epigenetics thus promises to generate a significant amount of new knowledge of biological and medical importance.Our review could identify various components of epigenetic mechanisms known to be involved in the initiation and development of pancreatic ductal adenocarcinoma and related precancerous lesions,and novel pharmacological strategies that target these components could potentially lead to breakthroughs.We aim to highlight the possibilities that exist and the potential therapeutic interventions.展开更多
Ras homolog enriched in brain(Rheb) is a small GTPase that activates mammalian target of rapamycin complex 1(mTORC1).Previous studies have shown that constitutively active Rheb can enhance the regeneration of sensory ...Ras homolog enriched in brain(Rheb) is a small GTPase that activates mammalian target of rapamycin complex 1(mTORC1).Previous studies have shown that constitutively active Rheb can enhance the regeneration of sensory axons after spinal cord injury by activating downstream effectors of mTOR.S6K1 and4E-BP1 are important downstream effectors of mTORC1.In this study,we investigated the role of Rheb/mTOR and its downstream effectors S6K1 and 4E-BP1in the protection of retinal ganglion cells.We transfected an optic nerve crush mouse model with adeno-associated viral 2-mediated constitutively active Rheb and observed the effects on retinal ganglion cell survival and axon regeneration.We found that overexpression of constitutively active Rheb promoted survival of retinal ganglion cells in the acute(14 days) and chronic(21 and 42 days) stages of injury.We also found that either co-expression of the dominant-negative S6K1mutant or the constitutively active 4E-BP1 mutant together with constitutively active Rheb markedly inhibited axon regeneration of retinal ganglion cells.This suggests that mTORC1-mediated S6K1 activation and 4E-BP1 inhibition were necessary components for constitutively active Rheb-induced axon regeneration.However,only S6K1 activation,but not 4E-BP1 knockdown,induced axon regeneration when applied alone.Furthermore,S6K1 activation promoted the survival of retinal ganglion cells at 14 days post-injury,whereas 4E-BP1 knockdown unexpectedly slightly decreased the survival of retinal ganglion cells at 14 days postinjury.Ove rexpression of constitutively active 4E-BP1 increased the survival of retinal ganglion cells at 14 days post-injury.Likewise,co-expressing constitutively active Rheb and constitutively active 4E-BP1 markedly increased the survival of retinal ganglion cells compared with overexpression of constitutively active Rheb alone at 14 days post-injury.These findings indicate that functional 4E-BP1 and S6K1 are neuroprotective and that 4E-BP1 may exert protective effects through a pathway at least partially independent of Rhe b/mTOR.Together,our results show that constitutively active Rheb promotes the survival of retinal ganglion cells and axon regeneration through modulating S6K1 and 4E-BP1 activity.Phosphorylated S6K1 and 4E-BP1 promote axon regeneration but play an antagonistic role in the survival of retinal ganglion cells.展开更多
Tinnitus is a heterogeneous hearing disorder with no cure at present,but some treatments,such as a combination of counselling and sound therapy,can alleviate the discomfort it causes.The sound therapy efficiency depen...Tinnitus is a heterogeneous hearing disorder with no cure at present,but some treatments,such as a combination of counselling and sound therapy,can alleviate the discomfort it causes.The sound therapy efficiency depends on both the type of sound stimulus and the time of exposure.This study describes the fundamentals of a personalized sound therapy that stimulates the auditory system with either continuous or sequential sounds whose spectra are adjusted to the hearing levels of the participants.This sound therapy is called Enriched Acoustic Environment and is assessed in a sample of 137 participants with tinnitus.Tinnitus-related distress relief was clinically relevant and statistically significant for 90%of these patients.This was quantified as a mean decrease of 24.3 points on the Tinnitus Handicap Inventory.31%of participants were treated with sequential stimuli and achieved greater relief of distress(29.4 points on their Tinnitus Handicap Inventory score)compared to those treated with continuous sound(69%).According to these results,sequential sound seems to be optimal compared to continuous sound.展开更多
目的:评估富含IgM免疫球蛋白辅助治疗极低出生体重儿院内感染败血症的临床和实验室参数。方法:选取2015年2月至2016年2月入住本院共53例院内感染败血症的极低出生体重儿为研究对象,将所有患儿分为治疗组28例,对照组25例,治疗组患儿在传...目的:评估富含IgM免疫球蛋白辅助治疗极低出生体重儿院内感染败血症的临床和实验室参数。方法:选取2015年2月至2016年2月入住本院共53例院内感染败血症的极低出生体重儿为研究对象,将所有患儿分为治疗组28例,对照组25例,治疗组患儿在传统抗生素治疗方案的基础上,进行连续3 d,每日4 h内静注富含IgM免疫球蛋白5 m L/kg,对照组患儿则只进行传统抗生素治疗方案,观察对比两组治疗前后的临床及实验室参数。结果:两组患儿于治疗前在C-反应蛋白、体温、白细胞计数、未成熟白细胞占总白细胞比值等方面比较,差异无统计学意义,观察治疗后两组患儿上述参数相比治疗前明显改善且治疗组优于对照组,差异具有统计学意义(P<0.05);两组患儿治疗结束总有效率分别为82.1%、64.0%,治疗组明显优于对照组,差异具有统计学意义(P<0.05);治疗组与对照组治疗中均出现低血糖、消化道出血、贫血、呼吸暂停、休克等并发症,且并发症发病率分别为28.6%、44.0%,治疗组显著低于对照组,差异具有统计学意义(P<0.05)。结论:富含IgM免疫球蛋白可以用于极低出生体重儿院内感染败血症的辅助治疗。展开更多
文摘BACKGROUND Lung cancer bone metastasis(LCBM)is a disease with a poor prognosis,high risk and large patient population.Although considerable scientific output has accumulated on LCBM,problems have emerged,such as confusing research structures.AIM To organize the research frontiers and body of knowledge of the studies on LCBM from the last 22 years according to their basic research and translation,clinical treatment,and clinical diagnosis to provide a reference for the development of new LCBM clinical and basic research.METHODS We used tools,including R,VOSviewer and CiteSpace software,to measure and visualize the keywords and other metrics of 1903 articles from the Web of Science Core Collection.We also performed enrichment and proteinprotein interaction analyses of gene expression datasets from LCBM cases worldwide.RESULTS Research on LCBM has received extensive attention from scholars worldwide over the last 20 years.Targeted therapies and immunotherapies have evolved into the mainstream basic and clinical research directions.The basic aspects of drug resistance mechanisms and parathyroid hormone-related protein may provide new ideas for mechanistic study and improvements in LCBM prognosis.The produced molecular map showed that ribosomes and focal adhesion are possible pathways that promote LCBM occurrence.CONCLUSION Novel therapies for LCBM face animal testing and drug resistance issues.Future focus should centre on advancing clinical therapies and researching drug resistance mechanisms and ribosome-related pathways.
文摘目的探讨目标-活动-运动环境(goals-activity-motor enrichment,GAME)疗法与姿势控制对重度脑性瘫痪患儿运动功能发育的影响,为改善重度脑性瘫痪患儿的运动功能提供循证医学依据。方法采用前瞻性病例对照研究,纳入重度脑性瘫痪患儿92例,按照随机数字表法分为研究组(n=46)和常规治疗组(n=46)。研究组采用GAME疗法与姿势控制训练,常规治疗组采用神经发育学疗法。比较2组患儿治疗前及治疗6个月、治疗12个月时粗大运动功能量表88项评估(gross motor function measure,GMFM-88)中的仰卧位与俯卧位(A区)和坐位(B区)、精细功能评估(fine motor function measure,FMFM)中视觉追踪(A区)和上肢关节活动(B区)、坐位能力(level of sitting scale,LSS)、疼痛(face-legs-activity-cry-consolability,FLACC)和日常生活活动能力量表(activitydaily livingscale,ADL)评分。结果2组GMFM-88(A区与B区)、FMFM(A区与B区)、LSS及ADL评分均呈逐渐升高趋势,FLACC评分呈逐渐降低趋势,研究组GMFM-88(A区与B区)、FMFM(A区与B区)、LSS及ADL评分高于常规治疗组,FLACC评分低于常规治疗组,组间、时点间、组间·时点间交互作用差异有统计学意义(P<0.05)。结论GAME疗法与姿势控制可以提高重度脑性瘫痪患儿粗大运动功能、坐位能力和精细运动功能,缓解疼痛,改善日常生活活动能力。
文摘Pancreatic cancer(PanCa)presents a catastrophic disease with poor overall survival at advanced stages,with immediate requirement of new and effective treatment options.Besides genetic mutations,epigenetic dysregulation of signaling pathway-associated enriched genes are considered as novel therapeutic target.Mechanisms beneath the deoxyribonucleic acid methylation and its utility in developing of epi-drugs in PanCa are under trails.Combinations of epigenetic medicines with conventional cytotoxic treatments or targeted therapy are promising options to improving the dismal response and survival rate of PanCa patients.Recent studies have identified potentially valid pathways that support the prediction that future PanCa clinical trials will include vigorous testing of epigenomic therapies.Epigenetics thus promises to generate a significant amount of new knowledge of biological and medical importance.Our review could identify various components of epigenetic mechanisms known to be involved in the initiation and development of pancreatic ductal adenocarcinoma and related precancerous lesions,and novel pharmacological strategies that target these components could potentially lead to breakthroughs.We aim to highlight the possibilities that exist and the potential therapeutic interventions.
基金National Natural Science Foundation of China,Nos.82070967,81770930the Natural Science Foundation of Hunan Province,No.2020jj4788 (all to BJ)。
文摘Ras homolog enriched in brain(Rheb) is a small GTPase that activates mammalian target of rapamycin complex 1(mTORC1).Previous studies have shown that constitutively active Rheb can enhance the regeneration of sensory axons after spinal cord injury by activating downstream effectors of mTOR.S6K1 and4E-BP1 are important downstream effectors of mTORC1.In this study,we investigated the role of Rheb/mTOR and its downstream effectors S6K1 and 4E-BP1in the protection of retinal ganglion cells.We transfected an optic nerve crush mouse model with adeno-associated viral 2-mediated constitutively active Rheb and observed the effects on retinal ganglion cell survival and axon regeneration.We found that overexpression of constitutively active Rheb promoted survival of retinal ganglion cells in the acute(14 days) and chronic(21 and 42 days) stages of injury.We also found that either co-expression of the dominant-negative S6K1mutant or the constitutively active 4E-BP1 mutant together with constitutively active Rheb markedly inhibited axon regeneration of retinal ganglion cells.This suggests that mTORC1-mediated S6K1 activation and 4E-BP1 inhibition were necessary components for constitutively active Rheb-induced axon regeneration.However,only S6K1 activation,but not 4E-BP1 knockdown,induced axon regeneration when applied alone.Furthermore,S6K1 activation promoted the survival of retinal ganglion cells at 14 days post-injury,whereas 4E-BP1 knockdown unexpectedly slightly decreased the survival of retinal ganglion cells at 14 days postinjury.Ove rexpression of constitutively active 4E-BP1 increased the survival of retinal ganglion cells at 14 days post-injury.Likewise,co-expressing constitutively active Rheb and constitutively active 4E-BP1 markedly increased the survival of retinal ganglion cells compared with overexpression of constitutively active Rheb alone at 14 days post-injury.These findings indicate that functional 4E-BP1 and S6K1 are neuroprotective and that 4E-BP1 may exert protective effects through a pathway at least partially independent of Rhe b/mTOR.Together,our results show that constitutively active Rheb promotes the survival of retinal ganglion cells and axon regeneration through modulating S6K1 and 4E-BP1 activity.Phosphorylated S6K1 and 4E-BP1 promote axon regeneration but play an antagonistic role in the survival of retinal ganglion cells.
文摘Tinnitus is a heterogeneous hearing disorder with no cure at present,but some treatments,such as a combination of counselling and sound therapy,can alleviate the discomfort it causes.The sound therapy efficiency depends on both the type of sound stimulus and the time of exposure.This study describes the fundamentals of a personalized sound therapy that stimulates the auditory system with either continuous or sequential sounds whose spectra are adjusted to the hearing levels of the participants.This sound therapy is called Enriched Acoustic Environment and is assessed in a sample of 137 participants with tinnitus.Tinnitus-related distress relief was clinically relevant and statistically significant for 90%of these patients.This was quantified as a mean decrease of 24.3 points on the Tinnitus Handicap Inventory.31%of participants were treated with sequential stimuli and achieved greater relief of distress(29.4 points on their Tinnitus Handicap Inventory score)compared to those treated with continuous sound(69%).According to these results,sequential sound seems to be optimal compared to continuous sound.
文摘目的:评估富含IgM免疫球蛋白辅助治疗极低出生体重儿院内感染败血症的临床和实验室参数。方法:选取2015年2月至2016年2月入住本院共53例院内感染败血症的极低出生体重儿为研究对象,将所有患儿分为治疗组28例,对照组25例,治疗组患儿在传统抗生素治疗方案的基础上,进行连续3 d,每日4 h内静注富含IgM免疫球蛋白5 m L/kg,对照组患儿则只进行传统抗生素治疗方案,观察对比两组治疗前后的临床及实验室参数。结果:两组患儿于治疗前在C-反应蛋白、体温、白细胞计数、未成熟白细胞占总白细胞比值等方面比较,差异无统计学意义,观察治疗后两组患儿上述参数相比治疗前明显改善且治疗组优于对照组,差异具有统计学意义(P<0.05);两组患儿治疗结束总有效率分别为82.1%、64.0%,治疗组明显优于对照组,差异具有统计学意义(P<0.05);治疗组与对照组治疗中均出现低血糖、消化道出血、贫血、呼吸暂停、休克等并发症,且并发症发病率分别为28.6%、44.0%,治疗组显著低于对照组,差异具有统计学意义(P<0.05)。结论:富含IgM免疫球蛋白可以用于极低出生体重儿院内感染败血症的辅助治疗。
