目的:从形态学、免疫学、分子生物学角度探讨不同灸量治疗溃疡性结肠炎(UC)效果的异同。方法:32只SD大鼠随机分为空白组6只、模型复制组26只。采用三硝基苯甲酸/葡聚糖硫酸钠制备UC大鼠模型。模型复制成功后的大鼠按随机数字表分为模型...目的:从形态学、免疫学、分子生物学角度探讨不同灸量治疗溃疡性结肠炎(UC)效果的异同。方法:32只SD大鼠随机分为空白组6只、模型复制组26只。采用三硝基苯甲酸/葡聚糖硫酸钠制备UC大鼠模型。模型复制成功后的大鼠按随机数字表分为模型组、3壮组、6壮组、9壮组,每组各6只。各治疗组所取穴位为"天枢""大横",艾炷直接灸法,每次分别施灸3壮(3min)、6壮(6min)、9壮(9min),共治疗14次。观察大鼠治疗前后疾病活动指数(DAI),电镜、光镜观察结肠组织形态学改变,酶联免疫法检测大鼠血清中白介素-8(IL-8)、白介素-10(IL-10)含量,Western blot法检测大鼠结肠中Toll样受体9(TLR-9)和核转录因子-κB(NF-κB)p 65表达。结果:灸法可明显降低大鼠DAI的评分(与模型组比较均P<0.05);光镜与电镜结果显示,灸量越大,结肠组织腺体排列越规则。模型组血清IL-8含量升高,IL-10含量降低;与模型组比较,各治疗组IL-8降低,IL-10增高,其中9壮组和6壮组的变化较3壮组更明显(均P<0.05)。模型组结肠组织中TLR-9、NF-κB p 65大量表达;与模型组比较,各治疗组TLR-9、NF-κB p 65表达均降低,且以9壮组的变化最为明显(均P<0.05)。结论:艾灸可修复UC大鼠受损黏膜上皮,抑制血清中IL-8含量,提高血清中IL-10含量,通过抑制结肠组织中NF-κB p 65转录而下调TLR-9表达。灸量越大治疗效果越明显。展开更多
目的:观察头穴针刺对局灶性脑缺血大鼠海马旁回核因子(NF)-κB p 65mRNA、IκB mRNA及白介素(IL)-1β、肿瘤坏死因子(TNF)-α表达的影响,探讨头穴针刺调控缺血性脑血管病炎性反应的机制。方法:SD大鼠随机分为正常组、模型组、药物组及...目的:观察头穴针刺对局灶性脑缺血大鼠海马旁回核因子(NF)-κB p 65mRNA、IκB mRNA及白介素(IL)-1β、肿瘤坏死因子(TNF)-α表达的影响,探讨头穴针刺调控缺血性脑血管病炎性反应的机制。方法:SD大鼠随机分为正常组、模型组、药物组及头针组,每组16只。采用线栓法建立大鼠急性局灶性脑缺血模型。药物组腹腔注射吡咯烷二硫代氨基甲酸铵盐(100mg·kg^(-1)·d^(-1)),1次/d,共7d。头针组取双侧顶颞前斜线和顶颞后斜线行快速捻转透刺治疗,每次30min,1次/d,共7d。干预前后进行神经功能缺损评分及神经行为学评分。RT-PCR法检测海马旁回NF-κB p 65mRNA、IκB mRNA的表达,免疫组织化学法检测海马旁回IL-1β、TNF-α的表达。结果:与正常组比较,模型组大鼠神经功能缺损评分和神经行为学评分明显增高(P<0.01),海马旁回NF-κB p 65 mRNA、IL-1β、TNF-α的表达均明显增高(P<0.01),IκB mRNA表达显著降低(P<0.01)。与模型组比较,头针组和药物组大鼠神经功能缺损评分和神经行为学评分明显降低(P<0.01),海马旁回NF-κB p 65 mRNA、IL-1β、TNF-α表达均明显降低(P<0.05),IκB mRNA表达明显增高(P<0.05)。结论:上调缺血后脑组织IκB的表达,抑制NF-κB的解离,进而降低炎性因子IL-1β、TNF-α的表达是头穴针刺控制缺血性脑血管病炎性反应的分子机制之一。展开更多
AIM: To determine the prognostic value of circulating indicators of cell death in acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B virus (HBV) infection as the single etiology. METHODS: Full len...AIM: To determine the prognostic value of circulating indicators of cell death in acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B virus (HBV) infection as the single etiology. METHODS: Full length and caspase cleaved cytokeratin 18 (detected as M65 and M30 antigens) represent circulating indicators of necrosis and apoptosis. M65 and M30 were identified by enzyme-linked immunosorbent assay in 169 subjects including healthy controls (n = 33), patients with chronic hepatitis B (CHB, n = 55) and patients with ACLF (n = 81). According to the 3-mo survival period, ACLF patients were defined as having spontaneous recovery (n = 33) and non-spontaneous recovery which included deceased patients and those who required liver transplantation (n = 48). RESULTS: Both biomarker levels significantly increased gradually as liver disease progressed (for M65: P < 0.001 for all; for M30: control vs CHB, P = 0.072; others: P < 0.001 for all). In contrast, the M30/M65 ratio was significantly higher in controls compared with CHB patients (P = 0.010) or ACLF patients (P < 0.001). In addition, the area under receiver operating characteristic curve (AUC) analysis demonstrated that both biomarkers had diagnostic value (AUC >= 0.80) in identifying ACLF from CHB patients. Interestingly, it is worth noting that the M30/M65 ratio was significantly different between spontaneous and non-spontaneous recovery in ACLF patients (P = 0.032). The prognostic value of the M30/M65 ratio was compared with the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores at the 3-mo survival period, the AUC of the M30/M65 ratio was 0.66 with a sensitivity of 52.9% and the highest specificity of 92.6% (MELD:AUC = 0.71; sensitivity, 79.4%; specificity, 63.0%; Child-Pugh: AUC = 0.77; sensitivity, 61.8%; specificity, 88.9%). CONCLUSION: M65 and M30 are strongly associated with liver disease severity. The M30/M65 ratio may be a potential prognostic marker for spontaneous recovery in patients with HBV-related ACLF. (C) 2014 Baishideng Pub展开更多
Ever since its first appearance among the multiple forms of diabetes,latent autoimmune diabetes in adults(LADA),has been the focus of endless discussions concerning mainly its existence as a special type of diabetes.I...Ever since its first appearance among the multiple forms of diabetes,latent autoimmune diabetes in adults(LADA),has been the focus of endless discussions concerning mainly its existence as a special type of diabetes.In this mini-review,through browsing important peer-reviewed publications,(original articles and reviews),we will attempt to refresh our knowledge regarding LADA hoping to enhance our understanding of this controversial diabetes entity.A unique combination of immunological,clinical and metabolic characteristics has been identified in this group of patients,namely persistent islet cell antibodies,high frequency of thyroid and gastric autoimmunity,DR3 and DR4 human leukocyte antigen haplotypes,progressive loss of beta cells,adult disease onset,normal weight,defective glycaemic control,and without tendency to ketoacidosis.Although anthropomorphic measurements are useful as a first line screening,the detection of C-peptide levels and the presence of glutamic acid decarboxylase(GAD)autoantibodies is undoubtedly the sine qua non condi-tion for a confirmatory LADA diagnosis.In point of fact,GAD autoantibodies are far from being solely a biomarker and the specific role of these autoantibodies in disease pathogenesis is still to be thoroughly studied.Nevertheless,the lack of diagnostic criteria and guidelines still puzzle the physicians,who struggle between early diagnosis and correct timing for insulin treatment.展开更多
目的分析乙型肝炎病毒相关慢加急性肝衰竭(hepatitis B virus related acute-on-chronic liver failure,HBV-ACLF)患者在人工肝治疗过程中的血清M30和M65水平变化趋势,并探讨其对肝衰竭短期预后的预测效用及临床价值。方法选择2016年5月...目的分析乙型肝炎病毒相关慢加急性肝衰竭(hepatitis B virus related acute-on-chronic liver failure,HBV-ACLF)患者在人工肝治疗过程中的血清M30和M65水平变化趋势,并探讨其对肝衰竭短期预后的预测效用及临床价值。方法选择2016年5月至2019年5月于嘉兴市第一医院感染科初次进行人工肝治疗的76例HBV-ACLF患者,根据3个月预后分为好转组38例,未愈组38例,并选取同期38名健康体检者作为对照。采用酶联免疫吸附法检测患者在2次人工肝治疗前后的血清M30和M65水平变化,通过受试者操作特征曲线评估M30和M65水平变化对患者人工肝治疗短期预后的预测价值。2次人工肝治疗前后M30、M65水平比较采用两因素重复测量的方差分析。结果在第1次人工肝治疗前,好转组、未愈组和健康对照组血清M30和M65水平比较差异均有统计学意义(F=109.36、90.42,均P<0.01),好转组与未愈组在治疗前M30和M65水平比较差异均无统计学意义(t=0.836、0.286,均P>0.05)。但经2次人工肝治疗后,未愈组的M30和M65水平高于好转组,差异均有统计学意义(t=30.699、64.777,均P<0.01),且第2次人工肝治疗后,好转组的M30和M65水平较第1次治疗后进一步下降,差异均有统计学意义(t=3.350、5.932,均P<0.01)。2次人工肝治疗后,M30、M65水平及两项联合检测判断预后的受试者操作特征曲线下面积分别为0.796、0.844和0.906,两项联合检测的曲线下面积均高于单独检测M30、M65水平的曲线下面积(Z=2.163、2.141,P=0.031、0.032)。M30水平、M65水平的临界值分别为591.91 U/L和924.50 U/L,联合检测的灵敏度为94.7%,特异度为82.5%。结论血清M30和M65水平变化能较好地预测HBV-ACLF患者经人工肝治疗后的短期预后情况,两项联合检测具有更高的预测价值。展开更多
BACKGROUND Upper gastrointestinal(GI)bleeding is a life-threatening condition with high mortality rates.AIM To compare the performance of pre-endoscopic risk scores in predicting the following primary outcomes:In-hosp...BACKGROUND Upper gastrointestinal(GI)bleeding is a life-threatening condition with high mortality rates.AIM To compare the performance of pre-endoscopic risk scores in predicting the following primary outcomes:In-hospital mortality,intervention(endoscopic or surgical)and length of admission(≥7 d).METHODS We performed a retrospective analysis of 363 patients presenting with upper GI bleeding from December 2020 to January 2021.We calculated and compared the area under the receiver operating characteristics curves(AUROCs)of Glasgow-Blatchford score(GBS),pre-endoscopic Rockall score(PERS),albumin,international normalized ratio,altered mental status,systolic blood pressure,age older than 65(AIMS65)and age,blood tests and comorbidities(ABC),including their optimal cut-off in variceal and non-variceal upper GI bleeding cohorts.We subsequently analyzed through a logistic binary regression model,if addition of lactate increased the score performance.RESULTS All scores had discriminative ability in predicting in-hospital mortality irrespective of study group.AIMS65 score had the best performance in the variceal bleeding group(AUROC=0.772;P<0.001),and ABC score(AUROC=0.775;P<0.001)in the non-variceal bleeding group.However,ABC score,at a cut-off value of 5.5,was the best predictor(AUROC=0.770,P=0.001)of inhospital mortality in both populations.PERS score was a good predictor for endoscopic treatment(AUC=0.604;P=0.046)in the variceal population,while GBS score,(AUROC=0.722;P=0.024),outperformed the other scores in predicting surgical intervention.Addition of lactate to AIMS65 score,increases by 5-fold the probability of in-hospital mortality(P<0.05)and by 12-fold if added to GBS score(P<0.003).No score proved to be a good predictor for length of admission.CONCLUSION ABC score is the most accurate in predicting in-hospital mortality in both mixed and non-variceal bleeding population.PERS and GBS should be used to determine need for endoscopic and surgical intervention,respectively.Lactate can be used as an additional tool t展开更多
Neuroplastin 65 (Np65) is an immunoglobulin superfamily cell adhesion molecule involved in synaptic formation and plasticity. Our recent study showed that Np65-knockout (KO) mice exhibit abnormal cognition and emo...Neuroplastin 65 (Np65) is an immunoglobulin superfamily cell adhesion molecule involved in synaptic formation and plasticity. Our recent study showed that Np65-knockout (KO) mice exhibit abnormal cognition and emotional disorders. However, the underlying mechanisms remain unclear. In this study, we found 588 differentially- expressed genes in Np65-KO mice by microarray analysis. RT-PCR analysis also revealed the altered expression of genes associated with development and synaptic structure, such as Cdhl, Htr3a, and Kcnj9. In addition, the expression of Wnt-3, a Wnt protein involved in development, was decreased in Np65-KO mice as evidenced by western blotting. Surprisingly, MRI and DAPI staining showed a significant reduction in the lateral ventricular volume of Np65-KO mice. Together, these findings suggest that ablation of Np65 influences gene expression, which may contribute to abnormal brain development. These results provide clues to the mechanisms underlying the altered brain functions of Np65-deficient mice.展开更多
文摘目的:从形态学、免疫学、分子生物学角度探讨不同灸量治疗溃疡性结肠炎(UC)效果的异同。方法:32只SD大鼠随机分为空白组6只、模型复制组26只。采用三硝基苯甲酸/葡聚糖硫酸钠制备UC大鼠模型。模型复制成功后的大鼠按随机数字表分为模型组、3壮组、6壮组、9壮组,每组各6只。各治疗组所取穴位为"天枢""大横",艾炷直接灸法,每次分别施灸3壮(3min)、6壮(6min)、9壮(9min),共治疗14次。观察大鼠治疗前后疾病活动指数(DAI),电镜、光镜观察结肠组织形态学改变,酶联免疫法检测大鼠血清中白介素-8(IL-8)、白介素-10(IL-10)含量,Western blot法检测大鼠结肠中Toll样受体9(TLR-9)和核转录因子-κB(NF-κB)p 65表达。结果:灸法可明显降低大鼠DAI的评分(与模型组比较均P<0.05);光镜与电镜结果显示,灸量越大,结肠组织腺体排列越规则。模型组血清IL-8含量升高,IL-10含量降低;与模型组比较,各治疗组IL-8降低,IL-10增高,其中9壮组和6壮组的变化较3壮组更明显(均P<0.05)。模型组结肠组织中TLR-9、NF-κB p 65大量表达;与模型组比较,各治疗组TLR-9、NF-κB p 65表达均降低,且以9壮组的变化最为明显(均P<0.05)。结论:艾灸可修复UC大鼠受损黏膜上皮,抑制血清中IL-8含量,提高血清中IL-10含量,通过抑制结肠组织中NF-κB p 65转录而下调TLR-9表达。灸量越大治疗效果越明显。
文摘目的:观察头穴针刺对局灶性脑缺血大鼠海马旁回核因子(NF)-κB p 65mRNA、IκB mRNA及白介素(IL)-1β、肿瘤坏死因子(TNF)-α表达的影响,探讨头穴针刺调控缺血性脑血管病炎性反应的机制。方法:SD大鼠随机分为正常组、模型组、药物组及头针组,每组16只。采用线栓法建立大鼠急性局灶性脑缺血模型。药物组腹腔注射吡咯烷二硫代氨基甲酸铵盐(100mg·kg^(-1)·d^(-1)),1次/d,共7d。头针组取双侧顶颞前斜线和顶颞后斜线行快速捻转透刺治疗,每次30min,1次/d,共7d。干预前后进行神经功能缺损评分及神经行为学评分。RT-PCR法检测海马旁回NF-κB p 65mRNA、IκB mRNA的表达,免疫组织化学法检测海马旁回IL-1β、TNF-α的表达。结果:与正常组比较,模型组大鼠神经功能缺损评分和神经行为学评分明显增高(P<0.01),海马旁回NF-κB p 65 mRNA、IL-1β、TNF-α的表达均明显增高(P<0.01),IκB mRNA表达显著降低(P<0.01)。与模型组比较,头针组和药物组大鼠神经功能缺损评分和神经行为学评分明显降低(P<0.01),海马旁回NF-κB p 65 mRNA、IL-1β、TNF-α表达均明显降低(P<0.05),IκB mRNA表达明显增高(P<0.05)。结论:上调缺血后脑组织IκB的表达,抑制NF-κB的解离,进而降低炎性因子IL-1β、TNF-α的表达是头穴针刺控制缺血性脑血管病炎性反应的分子机制之一。
基金Supported by National Science and Technology Key Project of China on"Major Infectious Diseases",No.2012ZX10002004-006,No.2012ZX10004904-003-001,No.2013ZX10002002-006-001Beijing Municipal Science and Technology Commission,No.Z131107002213019,No.Z131100004613030+2 种基金High Technical Personnel Training Program in Beijing Health System,No.2011-3-083,No.2013-3-071Special Scientific Research Fund for Beijing Health Development,No.2011-2018-04National Natural Science Foundation of China,No.30800979,No.30800517
文摘AIM: To determine the prognostic value of circulating indicators of cell death in acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B virus (HBV) infection as the single etiology. METHODS: Full length and caspase cleaved cytokeratin 18 (detected as M65 and M30 antigens) represent circulating indicators of necrosis and apoptosis. M65 and M30 were identified by enzyme-linked immunosorbent assay in 169 subjects including healthy controls (n = 33), patients with chronic hepatitis B (CHB, n = 55) and patients with ACLF (n = 81). According to the 3-mo survival period, ACLF patients were defined as having spontaneous recovery (n = 33) and non-spontaneous recovery which included deceased patients and those who required liver transplantation (n = 48). RESULTS: Both biomarker levels significantly increased gradually as liver disease progressed (for M65: P < 0.001 for all; for M30: control vs CHB, P = 0.072; others: P < 0.001 for all). In contrast, the M30/M65 ratio was significantly higher in controls compared with CHB patients (P = 0.010) or ACLF patients (P < 0.001). In addition, the area under receiver operating characteristic curve (AUC) analysis demonstrated that both biomarkers had diagnostic value (AUC >= 0.80) in identifying ACLF from CHB patients. Interestingly, it is worth noting that the M30/M65 ratio was significantly different between spontaneous and non-spontaneous recovery in ACLF patients (P = 0.032). The prognostic value of the M30/M65 ratio was compared with the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores at the 3-mo survival period, the AUC of the M30/M65 ratio was 0.66 with a sensitivity of 52.9% and the highest specificity of 92.6% (MELD:AUC = 0.71; sensitivity, 79.4%; specificity, 63.0%; Child-Pugh: AUC = 0.77; sensitivity, 61.8%; specificity, 88.9%). CONCLUSION: M65 and M30 are strongly associated with liver disease severity. The M30/M65 ratio may be a potential prognostic marker for spontaneous recovery in patients with HBV-related ACLF. (C) 2014 Baishideng Pub
文摘Ever since its first appearance among the multiple forms of diabetes,latent autoimmune diabetes in adults(LADA),has been the focus of endless discussions concerning mainly its existence as a special type of diabetes.In this mini-review,through browsing important peer-reviewed publications,(original articles and reviews),we will attempt to refresh our knowledge regarding LADA hoping to enhance our understanding of this controversial diabetes entity.A unique combination of immunological,clinical and metabolic characteristics has been identified in this group of patients,namely persistent islet cell antibodies,high frequency of thyroid and gastric autoimmunity,DR3 and DR4 human leukocyte antigen haplotypes,progressive loss of beta cells,adult disease onset,normal weight,defective glycaemic control,and without tendency to ketoacidosis.Although anthropomorphic measurements are useful as a first line screening,the detection of C-peptide levels and the presence of glutamic acid decarboxylase(GAD)autoantibodies is undoubtedly the sine qua non condi-tion for a confirmatory LADA diagnosis.In point of fact,GAD autoantibodies are far from being solely a biomarker and the specific role of these autoantibodies in disease pathogenesis is still to be thoroughly studied.Nevertheless,the lack of diagnostic criteria and guidelines still puzzle the physicians,who struggle between early diagnosis and correct timing for insulin treatment.
文摘目的分析乙型肝炎病毒相关慢加急性肝衰竭(hepatitis B virus related acute-on-chronic liver failure,HBV-ACLF)患者在人工肝治疗过程中的血清M30和M65水平变化趋势,并探讨其对肝衰竭短期预后的预测效用及临床价值。方法选择2016年5月至2019年5月于嘉兴市第一医院感染科初次进行人工肝治疗的76例HBV-ACLF患者,根据3个月预后分为好转组38例,未愈组38例,并选取同期38名健康体检者作为对照。采用酶联免疫吸附法检测患者在2次人工肝治疗前后的血清M30和M65水平变化,通过受试者操作特征曲线评估M30和M65水平变化对患者人工肝治疗短期预后的预测价值。2次人工肝治疗前后M30、M65水平比较采用两因素重复测量的方差分析。结果在第1次人工肝治疗前,好转组、未愈组和健康对照组血清M30和M65水平比较差异均有统计学意义(F=109.36、90.42,均P<0.01),好转组与未愈组在治疗前M30和M65水平比较差异均无统计学意义(t=0.836、0.286,均P>0.05)。但经2次人工肝治疗后,未愈组的M30和M65水平高于好转组,差异均有统计学意义(t=30.699、64.777,均P<0.01),且第2次人工肝治疗后,好转组的M30和M65水平较第1次治疗后进一步下降,差异均有统计学意义(t=3.350、5.932,均P<0.01)。2次人工肝治疗后,M30、M65水平及两项联合检测判断预后的受试者操作特征曲线下面积分别为0.796、0.844和0.906,两项联合检测的曲线下面积均高于单独检测M30、M65水平的曲线下面积(Z=2.163、2.141,P=0.031、0.032)。M30水平、M65水平的临界值分别为591.91 U/L和924.50 U/L,联合检测的灵敏度为94.7%,特异度为82.5%。结论血清M30和M65水平变化能较好地预测HBV-ACLF患者经人工肝治疗后的短期预后情况,两项联合检测具有更高的预测价值。
文摘BACKGROUND Upper gastrointestinal(GI)bleeding is a life-threatening condition with high mortality rates.AIM To compare the performance of pre-endoscopic risk scores in predicting the following primary outcomes:In-hospital mortality,intervention(endoscopic or surgical)and length of admission(≥7 d).METHODS We performed a retrospective analysis of 363 patients presenting with upper GI bleeding from December 2020 to January 2021.We calculated and compared the area under the receiver operating characteristics curves(AUROCs)of Glasgow-Blatchford score(GBS),pre-endoscopic Rockall score(PERS),albumin,international normalized ratio,altered mental status,systolic blood pressure,age older than 65(AIMS65)and age,blood tests and comorbidities(ABC),including their optimal cut-off in variceal and non-variceal upper GI bleeding cohorts.We subsequently analyzed through a logistic binary regression model,if addition of lactate increased the score performance.RESULTS All scores had discriminative ability in predicting in-hospital mortality irrespective of study group.AIMS65 score had the best performance in the variceal bleeding group(AUROC=0.772;P<0.001),and ABC score(AUROC=0.775;P<0.001)in the non-variceal bleeding group.However,ABC score,at a cut-off value of 5.5,was the best predictor(AUROC=0.770,P=0.001)of inhospital mortality in both populations.PERS score was a good predictor for endoscopic treatment(AUC=0.604;P=0.046)in the variceal population,while GBS score,(AUROC=0.722;P=0.024),outperformed the other scores in predicting surgical intervention.Addition of lactate to AIMS65 score,increases by 5-fold the probability of in-hospital mortality(P<0.05)and by 12-fold if added to GBS score(P<0.003).No score proved to be a good predictor for length of admission.CONCLUSION ABC score is the most accurate in predicting in-hospital mortality in both mixed and non-variceal bleeding population.PERS and GBS should be used to determine need for endoscopic and surgical intervention,respectively.Lactate can be used as an additional tool t
基金supported by the National Natural Science Foundation of China(81371213,81070987,and30971531)the grants from the Ministry of Science and Technology of China(2010CB945600 and 2010CB945601)
文摘Neuroplastin 65 (Np65) is an immunoglobulin superfamily cell adhesion molecule involved in synaptic formation and plasticity. Our recent study showed that Np65-knockout (KO) mice exhibit abnormal cognition and emotional disorders. However, the underlying mechanisms remain unclear. In this study, we found 588 differentially- expressed genes in Np65-KO mice by microarray analysis. RT-PCR analysis also revealed the altered expression of genes associated with development and synaptic structure, such as Cdhl, Htr3a, and Kcnj9. In addition, the expression of Wnt-3, a Wnt protein involved in development, was decreased in Np65-KO mice as evidenced by western blotting. Surprisingly, MRI and DAPI staining showed a significant reduction in the lateral ventricular volume of Np65-KO mice. Together, these findings suggest that ablation of Np65 influences gene expression, which may contribute to abnormal brain development. These results provide clues to the mechanisms underlying the altered brain functions of Np65-deficient mice.