【目的】系统评价益气养阴法联合西药治疗肾病综合征的有效性及安全性。【方法】检索中国知网(CNKI)、中国生物医学文献数据库(CBM)、万方(Wangfang)、维普(VIP)、PubMed、Web of Science、Cochrane Library、Embase等国内外主要文献数...【目的】系统评价益气养阴法联合西药治疗肾病综合征的有效性及安全性。【方法】检索中国知网(CNKI)、中国生物医学文献数据库(CBM)、万方(Wangfang)、维普(VIP)、PubMed、Web of Science、Cochrane Library、Embase等国内外主要文献数据库,筛选其中有关益气养阴法联合西药(试验组)对比单纯西药(对照组)治疗肾病综合征的临床随机对照试验(RCTs),采用Cochrane手册中的偏倚风险工具进行文献的质量评价,运用RevMan 5.3软件进行Meta分析。【结果】共纳入18个RCTs,包含1334例患者。Meta分析结果显示,益气养阴法联合西药在提高临床有效率(RR=1.24,95%CI[1.16,1.32],P<0.00001),改善24 h尿蛋白定量(24hUPRO)(MD=-0.92,95%CI[-1.09,-0.75],P<0.00001)、血清白蛋白(ALB)(MD=7.06,95%CI[4.73,9.39],P<0.00001)、尿素氮(BUN)(MD=-1.57,95%CI[-2.01,-1.13],P<0.00001)、血肌酐(SCr)(MD=-12.23,95%CI[-16.58,-7.88],P<0.00001)、总胆固醇(TC)(MD=-1.06,95%CI[-1.69,-0.43],P=0.0009)、甘油三酯(TG)(MD=-0.58,95%CI[-0.94,-0.21],P=0.002)水平,以及降低不良反应发生率(RR=0.50,95%CI[0.40,0.64],P<0.00001)方面优于单纯西药治疗。【结论】益气养阴法联合西药治疗肾病综合征在提高临床疗效及改善24hUPRO、ALB、BUN、SCr、TC、TG方面优于单纯西药治疗,且能降低激素产生的不良反应。因纳入文献较少,文献质量较低,潜在疗效需更多的高质量研究进行验证。展开更多
Objective Cholesterol 24-hydroxylase catalyzes the conversion of cholesterol to 24-hydroxycholesterol,which is a major pathway for cholesterol elimination from the brain,since 24-hydroxycholesterol can readily cross t...Objective Cholesterol 24-hydroxylase catalyzes the conversion of cholesterol to 24-hydroxycholesterol,which is a major pathway for cholesterol elimination from the brain,since 24-hydroxycholesterol can readily cross the blood brain barrier.The present study aimed to elucidate the distribution of cholesterol 24-hydroxylase in the monkey brain.Methods The distribution of cholesterol 24-hydroxylase in the monkey brain was examined using Western blot and immunohistochemistry methods,and was observed under light microscopy and electron microscopy.Results High levels of cholesterol 24-hydroxylase were observed in projection neurons and neuropil in structures derived from telencephalon,including the cerebral neocortex,hippocampus,amygdala,nucleus basalis of Meynert,and striatum.Electron microscopy revealed that the enzyme was localized in the axon terminals.One the other hand,cholesterol 24-hydroxylase was expressed at a lower level in the thalamus,globus pallidus and brainstem.Conclusion The high level of cholesterol 24-hydroxylase in the telencephalon possibly reflects a high rate of cholesterol turnover in this part of brain.展开更多
目的探讨正常老年大鼠空间学习记忆能力变化与海马背侧组织胆固醇代谢之间的关系。方法实验大鼠分老年实验组和青年对照组,利用Morris水迷宫方法评价空间学习记忆能力,然后测定海马背侧组织胆固醇含量及代谢相关酶羟甲基戊二酸单酰CoA...目的探讨正常老年大鼠空间学习记忆能力变化与海马背侧组织胆固醇代谢之间的关系。方法实验大鼠分老年实验组和青年对照组,利用Morris水迷宫方法评价空间学习记忆能力,然后测定海马背侧组织胆固醇含量及代谢相关酶羟甲基戊二酸单酰CoA还原酶(3-hydroxy-3-methylglutaryl coenzyme A reductase,HMG-CoAR)和胆固醇-24S-羟化酶(cholesterol24-hydroxylase,CYP46)mRNA表达的变化。结果与青年对照组相比,老年实验组逃避潜伏期明显延长(P<0.05),海马背侧组织总胆固醇的含量明显升高(P<0.05),HMG-CoAR mRNA相对表达量无明显变化,CYP46mRNA相对表达量明显降低(P<0.05)。结论正常老年大鼠空间学习记忆能力下降可能与海马背侧组织胆固醇含量增加有关。展开更多
Background:Colorectal cancer(CRC)is one of the most malignant tumorswith high incidence,yet its molecular mechanism is not fully understood,hindering the development of targeted therapy.Metabolic abnormalities are a h...Background:Colorectal cancer(CRC)is one of the most malignant tumorswith high incidence,yet its molecular mechanism is not fully understood,hindering the development of targeted therapy.Metabolic abnormalities are a hallmark of cancer.Targeting dysregulated metabolic features has become an important direction for modern anticancer therapy.In this study,we aimed to identify a new metabolic enzyme that promotes proliferation of CRC and to examine the related molecular mechanisms.Methods:We performed RNA sequencing and tissue microarray analyses of human CRC samples to identify new genes involved in CRC.Squalene epoxidase(SQLE)was identified to be highly upregulated in CRC patients.The regulatory function of SQLE in CRC progression and the therapeutic effect of SQLE inhibitors were determined by measuring CRC cell viability,colony and organoid formation,intracellular cholesterol concentration and xenograft tumor growth.Themolecularmechanism of SQLE functionwas explored by combining transcriptome and untargeted metabolomics analysis.Western blotting and realtime PCR were used to assess MAPK signaling activation by SQLE.Results:SQLE-related control of cholesterol biosynthesis was highly upregulated in CRC patients and associated with poor prognosis.SQLE promoted CRC growth in vitro and in vivo.Inhibition of SQLE reduced the levels of calcitriol(active form of vitamin D3)and CYP24A1,followed by an increase in intracellular Ca2+concentration.Subsequently,MAPK signaling was suppressed,resulting in the inhibition of CRC cell growth.Consistently,terbinafine,an SQLE inhibitor,suppressed CRC cell proliferation and organoid and xenograft tumor growth.Conclusions:Our findings demonstrate that SQLE promotes CRC through the accumulation of calcitriol and stimulation of CYP24A1-mediated MAPK signaling,highlighting SQLE as a potential therapeutic target for CRC treatment.展开更多
目的:探讨电针督脉对癫痫后脑损伤的神经保护作用及其神经保护作用机制。方法:采用侧脑室立体定位注射海人酸(KA)建立大鼠癫痫持续状态(SE)模型后进行电针督脉百会和筋缩穴合刺干预。首先通过尼氏染色实验观察电针督脉对痫症继发脑损伤...目的:探讨电针督脉对癫痫后脑损伤的神经保护作用及其神经保护作用机制。方法:采用侧脑室立体定位注射海人酸(KA)建立大鼠癫痫持续状态(SE)模型后进行电针督脉百会和筋缩穴合刺干预。首先通过尼氏染色实验观察电针督脉对痫症继发脑损伤是否有神经保护作用。进一步利用Western Blotting和Real-time PCR分析胆固醇代谢相关酶胆固醇24S-羟化酶(CYP46)在蛋白和基因水平上的变化。结果:长时间电针督脉可以有效改善KA诱导的SE继发脑损伤,调节胆固醇代谢酶CYP46的表达,并抑制KA诱导的CYP46 m RNA升高。结论:电针督脉可以通过影响胆固醇代谢途径对癫痫后的脑损伤发挥神经保护作用。展开更多
目的:观察补肾健脾活血法治疗糖尿病肾病的临床疗效。方法:采取随机数字表将70例早期糖尿病肾病患者随机分为观察组(35例)和对照组(35例)。对照组给予常规治疗;观察组在对照组治疗基础上给予补肾健脾活血中药口服,疗程均为4周。分别测...目的:观察补肾健脾活血法治疗糖尿病肾病的临床疗效。方法:采取随机数字表将70例早期糖尿病肾病患者随机分为观察组(35例)和对照组(35例)。对照组给予常规治疗;观察组在对照组治疗基础上给予补肾健脾活血中药口服,疗程均为4周。分别测定观察组和对照组治疗前后24小时尿蛋白定量、尿白蛋白排泄率(urinary albumin excretion rate,UAER)、血肌酐(serum creatinine,Scr)、空腹血糖、血浆白蛋白、胆固醇。结果:对照组和观察组24小时尿蛋白定量、UAER、Scr、空腹血糖、血浆白蛋白、血胆固醇指标均有明显改善,观察组24小时尿蛋白定量、UAER、Scr、血浆白蛋白等指标改善与对照组比较,差异有统计学意义(P<0.05)。结论:补肾健脾活血法治疗早期糖尿病肾病疗效显著,优于常规单用西药治疗方法。展开更多
基金supported by the National Natural Science Foundation of China(No.30901940)the Scientific Research Foundation for the Returned Overseas Chinese Scholars,Education Ministry of China
文摘Objective Cholesterol 24-hydroxylase catalyzes the conversion of cholesterol to 24-hydroxycholesterol,which is a major pathway for cholesterol elimination from the brain,since 24-hydroxycholesterol can readily cross the blood brain barrier.The present study aimed to elucidate the distribution of cholesterol 24-hydroxylase in the monkey brain.Methods The distribution of cholesterol 24-hydroxylase in the monkey brain was examined using Western blot and immunohistochemistry methods,and was observed under light microscopy and electron microscopy.Results High levels of cholesterol 24-hydroxylase were observed in projection neurons and neuropil in structures derived from telencephalon,including the cerebral neocortex,hippocampus,amygdala,nucleus basalis of Meynert,and striatum.Electron microscopy revealed that the enzyme was localized in the axon terminals.One the other hand,cholesterol 24-hydroxylase was expressed at a lower level in the thalamus,globus pallidus and brainstem.Conclusion The high level of cholesterol 24-hydroxylase in the telencephalon possibly reflects a high rate of cholesterol turnover in this part of brain.
文摘目的探讨正常老年大鼠空间学习记忆能力变化与海马背侧组织胆固醇代谢之间的关系。方法实验大鼠分老年实验组和青年对照组,利用Morris水迷宫方法评价空间学习记忆能力,然后测定海马背侧组织胆固醇含量及代谢相关酶羟甲基戊二酸单酰CoA还原酶(3-hydroxy-3-methylglutaryl coenzyme A reductase,HMG-CoAR)和胆固醇-24S-羟化酶(cholesterol24-hydroxylase,CYP46)mRNA表达的变化。结果与青年对照组相比,老年实验组逃避潜伏期明显延长(P<0.05),海马背侧组织总胆固醇的含量明显升高(P<0.05),HMG-CoAR mRNA相对表达量无明显变化,CYP46mRNA相对表达量明显降低(P<0.05)。结论正常老年大鼠空间学习记忆能力下降可能与海马背侧组织胆固醇含量增加有关。
基金National Natural Science Foundation of China,Grant/Award Numbers:31630047,81874201,81725014Natural Science Foundation of Shanghai,Grant/AwardNumber:20ZR1452300+1 种基金Shanghai Municipal Health Bureau,Grant/Award Number:201840359The National Key Research and Development Program of China,Grant/Award Numbers:2020YFA0509000,2017YFA0503600。
文摘Background:Colorectal cancer(CRC)is one of the most malignant tumorswith high incidence,yet its molecular mechanism is not fully understood,hindering the development of targeted therapy.Metabolic abnormalities are a hallmark of cancer.Targeting dysregulated metabolic features has become an important direction for modern anticancer therapy.In this study,we aimed to identify a new metabolic enzyme that promotes proliferation of CRC and to examine the related molecular mechanisms.Methods:We performed RNA sequencing and tissue microarray analyses of human CRC samples to identify new genes involved in CRC.Squalene epoxidase(SQLE)was identified to be highly upregulated in CRC patients.The regulatory function of SQLE in CRC progression and the therapeutic effect of SQLE inhibitors were determined by measuring CRC cell viability,colony and organoid formation,intracellular cholesterol concentration and xenograft tumor growth.Themolecularmechanism of SQLE functionwas explored by combining transcriptome and untargeted metabolomics analysis.Western blotting and realtime PCR were used to assess MAPK signaling activation by SQLE.Results:SQLE-related control of cholesterol biosynthesis was highly upregulated in CRC patients and associated with poor prognosis.SQLE promoted CRC growth in vitro and in vivo.Inhibition of SQLE reduced the levels of calcitriol(active form of vitamin D3)and CYP24A1,followed by an increase in intracellular Ca2+concentration.Subsequently,MAPK signaling was suppressed,resulting in the inhibition of CRC cell growth.Consistently,terbinafine,an SQLE inhibitor,suppressed CRC cell proliferation and organoid and xenograft tumor growth.Conclusions:Our findings demonstrate that SQLE promotes CRC through the accumulation of calcitriol and stimulation of CYP24A1-mediated MAPK signaling,highlighting SQLE as a potential therapeutic target for CRC treatment.
文摘目的:探讨电针督脉对癫痫后脑损伤的神经保护作用及其神经保护作用机制。方法:采用侧脑室立体定位注射海人酸(KA)建立大鼠癫痫持续状态(SE)模型后进行电针督脉百会和筋缩穴合刺干预。首先通过尼氏染色实验观察电针督脉对痫症继发脑损伤是否有神经保护作用。进一步利用Western Blotting和Real-time PCR分析胆固醇代谢相关酶胆固醇24S-羟化酶(CYP46)在蛋白和基因水平上的变化。结果:长时间电针督脉可以有效改善KA诱导的SE继发脑损伤,调节胆固醇代谢酶CYP46的表达,并抑制KA诱导的CYP46 m RNA升高。结论:电针督脉可以通过影响胆固醇代谢途径对癫痫后的脑损伤发挥神经保护作用。
文摘目的:观察补肾健脾活血法治疗糖尿病肾病的临床疗效。方法:采取随机数字表将70例早期糖尿病肾病患者随机分为观察组(35例)和对照组(35例)。对照组给予常规治疗;观察组在对照组治疗基础上给予补肾健脾活血中药口服,疗程均为4周。分别测定观察组和对照组治疗前后24小时尿蛋白定量、尿白蛋白排泄率(urinary albumin excretion rate,UAER)、血肌酐(serum creatinine,Scr)、空腹血糖、血浆白蛋白、胆固醇。结果:对照组和观察组24小时尿蛋白定量、UAER、Scr、空腹血糖、血浆白蛋白、血胆固醇指标均有明显改善,观察组24小时尿蛋白定量、UAER、Scr、血浆白蛋白等指标改善与对照组比较,差异有统计学意义(P<0.05)。结论:补肾健脾活血法治疗早期糖尿病肾病疗效显著,优于常规单用西药治疗方法。
