Objective Magnetoencephalography(MEG),a non-invasive neuroimaging technique,meticulously captures the magnetic fields emanating from brain electrical activity.Compared with MEG based on superconducting quantum interfe...Objective Magnetoencephalography(MEG),a non-invasive neuroimaging technique,meticulously captures the magnetic fields emanating from brain electrical activity.Compared with MEG based on superconducting quantum interference devices(SQUID),MEG based on optically pump magnetometer(OPM)has the advantages of higher sensitivity,better spatial resolution and lower cost.However,most of the current studies are clinical studies,and there is a lack of animal studies on MEG based on OPM technology.Pain,a multifaceted sensory and emotional phenomenon,induces intricate alterations in brain activity,exhibiting notable sex differences.Despite clinical revelations of pain-related neuronal activity through MEG,specific properties remain elusive,and comprehensive laboratory studies on pain-associated brain activity alterations are lacking.The aim of this study was to investigate the effects of inflammatory pain(induced by Complete Freund’s Adjuvant(CFA))on brain activity in a rat model using the MEG technique,to analysis changes in brain activity during pain perception,and to explore sex differences in pain-related MEG signaling.Methods This study utilized adult male and female Sprague-Dawley rats.Inflammatory pain was induced via intraplantar injection of CFA(100μl,50%in saline)in the left hind paw,with control groups receiving saline.Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection.For MEG recording,anesthetized rats had an OPM positioned on their head within a magnetic shield,undergoing two 15-minute sessions:a 5-minute baseline followed by a 10-minute mechanical stimulation phase.Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms,generating spectrograms focused on the 4-30 Hz frequency range.Results MEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared,before and after saline/CFA injections.Mechanical stimulation elevated alpha activity in both male and female rats pre-and post-saline/CFA injections.Saline/CFA injections augmented average power in both sexes compared to pre-injection states.Remarkably,female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states.Furthermore,despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment,female rats displayed higher average power than males in the resting state after CFA injection.Conclusion These results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts.Our study exhibits sex differences in alpha activities following CFA injection,highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state.Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals.In addition,the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.展开更多
Potassium-calcium activates channel subfamily N member 3(KCNN3/SK3/KCa2.3)is involved in regulating cellular calcium signaling,muscle contraction and neurotransmitter release.Dysregulation of the KCNN3 channel is asso...Potassium-calcium activates channel subfamily N member 3(KCNN3/SK3/KCa2.3)is involved in regulating cellular calcium signaling,muscle contraction and neurotransmitter release.Dysregulation of the KCNN3 channel is associated with the development of various tumors.We use bioinformatics analysis to identify whether KCNN3 regulates the occurrence and development of stomach adenocarcinoma(STAD)as a prognostic target.By analyzing the Human Protein Atlas(HPA)database and The Cancer Genome Atlas(TCGA)database,we found that the protein and mRNA levels of KCNN3 were dramatically reduced in STAD,and TCGA database showed that KCNN3 significantly correlated with the prognosis and clinical features of STAD.In addition,we found that high expression of KCNN3 in STAD reduced the IC 50 of several drugs in STAD cells,suggesting that high expression of KCNN3 correlated with the drug sensitivity of STAD.To investigate the underlying biological mechanism,we identified a potential KCNN3 interaction factor,tumor necrosis factor receptor superfamily member 7(CD27/TNFRSF7),which is expressed at low levels in STAD.RT-qPCR and Western blotting confirmed that KCNN3 and CD27 positively correlated with each other at protein and mRNA levels,and co-immunoprecipitation and immunofluorescence experiments confirmed that the two proteins interact and colocalize in the cytoplasm.Moreover,we confirmed the inhibitory effect of KCNN3 on the proliferation,migration and invasion of human STAD cells in vitro and in vivo through subcutaneous tumorigenesis and cellular experiments.Furthermore,GO/KEGG enrichment analysis showed that KCNN3 was enriched in signaling pathways regulating the immune response and calcium or metal ion transport.Lastly,we verified through cell co-culture,RT-qPCR and CCK8 assays that high expression of KCNN3 can promote the increase of T cell activating factor and the killing effect of T cells on STAD cells.Therefore,our results suggest that KCNN3 is a potential inhibitory factor affecting the occurrence and progression of STAD.展开更多
Objective INF2 is a member of the formins family.Abnormal expression and regulation of INF2 have been associated with the progression of various tumors,but the expression and role of INF2 in hepatocellular carcinoma(H...Objective INF2 is a member of the formins family.Abnormal expression and regulation of INF2 have been associated with the progression of various tumors,but the expression and role of INF2 in hepatocellular carcinoma(HCC)remain unclear.HCC is a highly lethal malignant tumor.Given the limitations of traditional treatments,this study explored the expression level,clinical value and potential mechanism of INF2 in HCC in order to seek new therapeutic targets.Methods In this study,we used public databases to analyze the expression of INF2 in pan-cancer and HCC,as well as the impact of INF2 expression levels on HCC prognosis.Quantitative real time polymerase chain reaction(RT-qPCR),Western blot,and immunohistochemistry were used to detect the expression level of INF2 in liver cancer cells and human HCC tissues.The correlation between INF2 expression and clinical pathological features was analyzed using public databases and clinical data of human HCC samples.Subsequently,the effects of INF2 expression on the biological function and Drp1 phosphorylation of liver cancer cells were elucidated through in vitro and in vivo experiments.Finally,the predictive value and potential mechanism of INF2 in HCC were further analyzed through database and immunohistochemical experiments.Results INF2 is aberrantly high expression in HCC samples and the high expression of INF2 is correlated with overall survival,liver cirrhosis and pathological differentiation of HCC patients.The expression level of INF2 has certain diagnostic value in predicting the prognosis and pathological differentiation of HCC.In vivo and in vitro HCC models,upregulated expression of INF2 triggers the proliferation and migration of the HCC cell,while knockdown of INF2 could counteract this effect.INF2 in liver cancer cells may affect mitochondrial division by inducing Drp1 phosphorylation and mediate immune escape by up-regulating PD-L1 expression,thus promoting tumor progression.Conclusion INF2 is highly expressed in HCC and is associated with poor prognosis.High expression of INF2 may promote HCC progression by inducing Drp1 phosphorylation and up-regulation of PD-L1 expression,and targeting INF2 may be beneficial for HCC patients with high expression of INF2.展开更多
目的:通过Meta分析评价单开门椎管扩大成形术(laminoplasty,LP)与全椎板切除减压融合术(laminectomy and fusion,LF)治疗多节段颈椎后纵韧带骨化症(ossification of posterior longitudinal ligament,OPLL)的临床疗效。方法:计算机检索...目的:通过Meta分析评价单开门椎管扩大成形术(laminoplasty,LP)与全椎板切除减压融合术(laminectomy and fusion,LF)治疗多节段颈椎后纵韧带骨化症(ossification of posterior longitudinal ligament,OPLL)的临床疗效。方法:计算机检索中国知网、万方数据库、Pubmed、Cochrane Library、EMBASE等数据库自建库起至2023年6月公开发表的对比LP与LF治疗多节段颈椎OPLL疗效的临床研究。运用Cochrane风险偏倚评估工具和纽卡斯尔-渥太华量表(Newcastle-Ottawa Scale,NOS)评价纳入研究的质量,提取相关数据,包括手术时间、术中出血量、末次随访时日本骨科协会(Japanese Orthopaedic Association,JOA)评分较术前的改善率、视觉模拟量表(visual analogue scale,VAS)评分及颈椎功能障碍指数(neck disability index,NDI)较术前的改变值、末次随访时颈椎曲度指数(cervical curvature index,CCI)、颈椎矢状面轴向距离(sagittal vertical axis,SVA)、颈椎矢状面活动度(cervical range of motion,CROM)较术前的改变值、术后并发症发生率及OPLL进展率。整理数据后应用RevMan 5.4及Stata SE 16.0软件完成Meta分析。结果:共纳入12篇文献,包括3篇随机对照研究,9篇队列研究,样本总量1496例,其中LP组患者839例,LF组患者657例。Meta分析结果显示,手术时间[WMD=-28.01,95%CI(-36.25,-19.77),P<0.00001]、术中出血量[WMD=-115.09,95%CI(-197.91,-32.27),P=0.006]、末次随访时较术前的CROM改变值[WMD=-7.83,95%CI(-8.10,-7.55),P<0.00001]、术后C5神经根麻痹发生率[OR=0.32,95%CI(0.21,0.50),P<0.00001]、术后轴性症状发生率[OR=0.44,95%CI(0.28,0.71),P=0.0006]两组间差异有统计学意义,LP组优于LF组。末次随访时较术前的CCI改变值[WMD=-0.75,95%CI(-0.92,-0.58),P<0.00001]、SVA改变值[WMD=5.49,95%CI(5.30,5.68),P<0.00001],术后OPLL进展率[OR=1.76,95%CI(1.26,2.46),P=0.0009],两组间差异亦有统计学意义,LF组优于LP组。末次随访时较术前的JOA评分改善率[WMD=-1.24,95%CI(-4.02,1.54),P=0.38]、VAS评分改变值[WMD=0.03,95%CI(-0.43,0.49),P=0.89]、NDI改变值[WMD=0.54,95%CI(-0.07,1.14),P=0.08]、术后脑脊液漏发生率[OR=0.58,95%CI(0.24,1.39),P=0.22]、术后切口感染发生率[OR=0.71,95%CI(0.32,1.57),P=0.39]、术后硬膜外血肿发生率[OR=0.37,95%CI(0.06,2.16),P=0.27],两组间差异无统计学意义。结论:LF和LP两种手术策略均能有效治疗多节段颈椎OPLL、改善患者神经功能。与LF相比,LP创伤小,术后能保留更多的颈椎活动度,且C5神经根麻痹和轴性症状发生率更低,而LF能更好地维持术后颈椎的曲度与稳定性,并延缓骨化物进展。展开更多
文摘Objective Magnetoencephalography(MEG),a non-invasive neuroimaging technique,meticulously captures the magnetic fields emanating from brain electrical activity.Compared with MEG based on superconducting quantum interference devices(SQUID),MEG based on optically pump magnetometer(OPM)has the advantages of higher sensitivity,better spatial resolution and lower cost.However,most of the current studies are clinical studies,and there is a lack of animal studies on MEG based on OPM technology.Pain,a multifaceted sensory and emotional phenomenon,induces intricate alterations in brain activity,exhibiting notable sex differences.Despite clinical revelations of pain-related neuronal activity through MEG,specific properties remain elusive,and comprehensive laboratory studies on pain-associated brain activity alterations are lacking.The aim of this study was to investigate the effects of inflammatory pain(induced by Complete Freund’s Adjuvant(CFA))on brain activity in a rat model using the MEG technique,to analysis changes in brain activity during pain perception,and to explore sex differences in pain-related MEG signaling.Methods This study utilized adult male and female Sprague-Dawley rats.Inflammatory pain was induced via intraplantar injection of CFA(100μl,50%in saline)in the left hind paw,with control groups receiving saline.Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection.For MEG recording,anesthetized rats had an OPM positioned on their head within a magnetic shield,undergoing two 15-minute sessions:a 5-minute baseline followed by a 10-minute mechanical stimulation phase.Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms,generating spectrograms focused on the 4-30 Hz frequency range.Results MEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared,before and after saline/CFA injections.Mechanical stimulation elevated alpha activity in both male and female rats pre-and post-saline/CFA injections.Saline/CFA injections augmented average power in both sexes compared to pre-injection states.Remarkably,female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states.Furthermore,despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment,female rats displayed higher average power than males in the resting state after CFA injection.Conclusion These results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts.Our study exhibits sex differences in alpha activities following CFA injection,highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state.Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals.In addition,the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.
文摘Potassium-calcium activates channel subfamily N member 3(KCNN3/SK3/KCa2.3)is involved in regulating cellular calcium signaling,muscle contraction and neurotransmitter release.Dysregulation of the KCNN3 channel is associated with the development of various tumors.We use bioinformatics analysis to identify whether KCNN3 regulates the occurrence and development of stomach adenocarcinoma(STAD)as a prognostic target.By analyzing the Human Protein Atlas(HPA)database and The Cancer Genome Atlas(TCGA)database,we found that the protein and mRNA levels of KCNN3 were dramatically reduced in STAD,and TCGA database showed that KCNN3 significantly correlated with the prognosis and clinical features of STAD.In addition,we found that high expression of KCNN3 in STAD reduced the IC 50 of several drugs in STAD cells,suggesting that high expression of KCNN3 correlated with the drug sensitivity of STAD.To investigate the underlying biological mechanism,we identified a potential KCNN3 interaction factor,tumor necrosis factor receptor superfamily member 7(CD27/TNFRSF7),which is expressed at low levels in STAD.RT-qPCR and Western blotting confirmed that KCNN3 and CD27 positively correlated with each other at protein and mRNA levels,and co-immunoprecipitation and immunofluorescence experiments confirmed that the two proteins interact and colocalize in the cytoplasm.Moreover,we confirmed the inhibitory effect of KCNN3 on the proliferation,migration and invasion of human STAD cells in vitro and in vivo through subcutaneous tumorigenesis and cellular experiments.Furthermore,GO/KEGG enrichment analysis showed that KCNN3 was enriched in signaling pathways regulating the immune response and calcium or metal ion transport.Lastly,we verified through cell co-culture,RT-qPCR and CCK8 assays that high expression of KCNN3 can promote the increase of T cell activating factor and the killing effect of T cells on STAD cells.Therefore,our results suggest that KCNN3 is a potential inhibitory factor affecting the occurrence and progression of STAD.
文摘Objective INF2 is a member of the formins family.Abnormal expression and regulation of INF2 have been associated with the progression of various tumors,but the expression and role of INF2 in hepatocellular carcinoma(HCC)remain unclear.HCC is a highly lethal malignant tumor.Given the limitations of traditional treatments,this study explored the expression level,clinical value and potential mechanism of INF2 in HCC in order to seek new therapeutic targets.Methods In this study,we used public databases to analyze the expression of INF2 in pan-cancer and HCC,as well as the impact of INF2 expression levels on HCC prognosis.Quantitative real time polymerase chain reaction(RT-qPCR),Western blot,and immunohistochemistry were used to detect the expression level of INF2 in liver cancer cells and human HCC tissues.The correlation between INF2 expression and clinical pathological features was analyzed using public databases and clinical data of human HCC samples.Subsequently,the effects of INF2 expression on the biological function and Drp1 phosphorylation of liver cancer cells were elucidated through in vitro and in vivo experiments.Finally,the predictive value and potential mechanism of INF2 in HCC were further analyzed through database and immunohistochemical experiments.Results INF2 is aberrantly high expression in HCC samples and the high expression of INF2 is correlated with overall survival,liver cirrhosis and pathological differentiation of HCC patients.The expression level of INF2 has certain diagnostic value in predicting the prognosis and pathological differentiation of HCC.In vivo and in vitro HCC models,upregulated expression of INF2 triggers the proliferation and migration of the HCC cell,while knockdown of INF2 could counteract this effect.INF2 in liver cancer cells may affect mitochondrial division by inducing Drp1 phosphorylation and mediate immune escape by up-regulating PD-L1 expression,thus promoting tumor progression.Conclusion INF2 is highly expressed in HCC and is associated with poor prognosis.High expression of INF2 may promote HCC progression by inducing Drp1 phosphorylation and up-regulation of PD-L1 expression,and targeting INF2 may be beneficial for HCC patients with high expression of INF2.
文摘目的:通过Meta分析评价单开门椎管扩大成形术(laminoplasty,LP)与全椎板切除减压融合术(laminectomy and fusion,LF)治疗多节段颈椎后纵韧带骨化症(ossification of posterior longitudinal ligament,OPLL)的临床疗效。方法:计算机检索中国知网、万方数据库、Pubmed、Cochrane Library、EMBASE等数据库自建库起至2023年6月公开发表的对比LP与LF治疗多节段颈椎OPLL疗效的临床研究。运用Cochrane风险偏倚评估工具和纽卡斯尔-渥太华量表(Newcastle-Ottawa Scale,NOS)评价纳入研究的质量,提取相关数据,包括手术时间、术中出血量、末次随访时日本骨科协会(Japanese Orthopaedic Association,JOA)评分较术前的改善率、视觉模拟量表(visual analogue scale,VAS)评分及颈椎功能障碍指数(neck disability index,NDI)较术前的改变值、末次随访时颈椎曲度指数(cervical curvature index,CCI)、颈椎矢状面轴向距离(sagittal vertical axis,SVA)、颈椎矢状面活动度(cervical range of motion,CROM)较术前的改变值、术后并发症发生率及OPLL进展率。整理数据后应用RevMan 5.4及Stata SE 16.0软件完成Meta分析。结果:共纳入12篇文献,包括3篇随机对照研究,9篇队列研究,样本总量1496例,其中LP组患者839例,LF组患者657例。Meta分析结果显示,手术时间[WMD=-28.01,95%CI(-36.25,-19.77),P<0.00001]、术中出血量[WMD=-115.09,95%CI(-197.91,-32.27),P=0.006]、末次随访时较术前的CROM改变值[WMD=-7.83,95%CI(-8.10,-7.55),P<0.00001]、术后C5神经根麻痹发生率[OR=0.32,95%CI(0.21,0.50),P<0.00001]、术后轴性症状发生率[OR=0.44,95%CI(0.28,0.71),P=0.0006]两组间差异有统计学意义,LP组优于LF组。末次随访时较术前的CCI改变值[WMD=-0.75,95%CI(-0.92,-0.58),P<0.00001]、SVA改变值[WMD=5.49,95%CI(5.30,5.68),P<0.00001],术后OPLL进展率[OR=1.76,95%CI(1.26,2.46),P=0.0009],两组间差异亦有统计学意义,LF组优于LP组。末次随访时较术前的JOA评分改善率[WMD=-1.24,95%CI(-4.02,1.54),P=0.38]、VAS评分改变值[WMD=0.03,95%CI(-0.43,0.49),P=0.89]、NDI改变值[WMD=0.54,95%CI(-0.07,1.14),P=0.08]、术后脑脊液漏发生率[OR=0.58,95%CI(0.24,1.39),P=0.22]、术后切口感染发生率[OR=0.71,95%CI(0.32,1.57),P=0.39]、术后硬膜外血肿发生率[OR=0.37,95%CI(0.06,2.16),P=0.27],两组间差异无统计学意义。结论:LF和LP两种手术策略均能有效治疗多节段颈椎OPLL、改善患者神经功能。与LF相比,LP创伤小,术后能保留更多的颈椎活动度,且C5神经根麻痹和轴性症状发生率更低,而LF能更好地维持术后颈椎的曲度与稳定性,并延缓骨化物进展。
