帕金森病合并抑郁与脑血流灌注的关系及经颅磁刺激的影响

目的：应用CT灌注成像技术观察帕金森病合并抑郁患者局灶脑血流灌注的特点,进一步探讨抑郁症发生与脑血流的关系.方法：将41例帕金森患者根据是否合并抑郁症分为帕金森病组22例、帕金森病合并抑郁症者为抑郁组19例、其中抑郁组分为经颅磁刺激（rTMS）治疗前组、治疗后组,3组均进行CT局部脑血流灌注显像,半定量分析各脑区血流灌注情况.结果：帕金森合并抑郁症组患者双侧额叶、颞叶和基底节的脑血流量测定（CBF）较帕金森病组显著下降（P＜0.05）;抑郁组左、右侧脑血流低灌注存在不对称性,左侧额叶、顶叶的CBF较右侧显著下降（P＜0.01）;rTMS治疗后脑血流灌注较治疗前改善,HAMD评分改善（P＜0.05）.结论：帕金森患者存在局灶性脑血流灌注降低,合并抑郁症患者额、顶叶下降更明显,经颅磁刺激治疗后脑血流低灌注改善.     

慢性间断性低氧大鼠认知功能和脑胆碱能神经元的进行性变化

目的：探讨慢性间断性低氧（CIH）大鼠认知功能的进行性变化及其与脑胆碱能神经元变化的关系。方法：成年雄性SD大鼠40只,随机均分为对照组、慢性间断性低氧1,3,5周组。应用Morris水迷宫检测认知功能的变化;利用HE染色在光镜下计数前额叶皮层和海马坏死神经元数;利用免疫组化方法检测前额叶皮层和海马胆碱乙酰转移酶（ChAT）阳性表达。结果：CIH各组大鼠学习记忆能力呈进行性下降趋势;与对照组比较,CIH5w组出现明显学习记忆功能障碍（P〈0.05）。CIH各组前额叶皮层和海马变性坏死神经元数增多,且随低氧时间延长,上述改变呈慢性进行性加重趋势。CIH各组前额叶皮层和海马ChAT阳性表达逐渐下降;与对照组比较,CIH3w组和CIH5w组前额叶皮层和海马ChAT阳性表达明显减少,差异具有显著性（P〈0.05）。结论：慢性间断性低氧大鼠认知功能进行性下降与前额叶皮层和海马神经元病理性损伤、ChAT表达进行性减少有关。     

大鼠力竭运动中丘脑底核和皮层神经元电活动的变化

目的：探讨力竭过程中丘脑底核（SIN）对皮层兴奋性的调控作用。方法：采用皮层脑电（ECoG）及局部场电（LFPs）同步记录技术,对一次性力竭运动过程中大鼠SIN、皮层神经元电活动变化规律进行同步、动态观察。结果：运动开始阶段大鼠能够自主跟随跑台进行运动,运动持续约45min时（45±11．5min）,自我驱动下的运动能力明显降低;此时STN兴奋性显著增加（P〈0．01）,皮层兴奋性显著下降（P〈0．01）。如果给予大鼠一定的外部刺激后仍可继续运动一段时间直至力竭;力竭即刻皮层兴奋性降到最低值（P〈0．01）,而SIN兴奋性变化不显著（P〉0．05）。结论：大鼠在力竭运动过程中,皮层运动区神经元电活动随着运动疲劳的发生呈现广泛的抑制现象,而SIN神经元电活动在疲劳初期则明显增强,SIN通过负诱导作用参与了运动性中枢疲劳的调控,且STN神经元兴奋性增强可能是皮层实现保护性抑制机制的重要途径之一。     

基于NR2B基因探讨疏肝与补肾法对吗啡精神依赖的调节作用及机制

目的：探讨补肾法与舒肝法对大鼠吗啡精神依赖的调节作用及机制。方法：使用盐酸吗啡建立大鼠精神依赖模型（conditioned place preference,CPP）,采用Obersiver5．0行为学软件分析大鼠的CPP效应,并利用RealtimePCR方法测定伏核和前额叶皮质内NR2B亚基的mRNA含量。结果：与对照组相比,模型组大鼠在白侧累积停留时间极显著长于对照组（P〈0．01）,同时伏核与前额叶皮质中NR2B的mRNA水平也显著升高（P〈0．01和P〈0．05）;与模型组相比,补肾组和舒肝组大鼠在白侧的累积停留时间显著下调（P〈0．05）,疏肝组NR2B的mRNA也显著下降（P〈0．05）,而补肾组变化不显著。结论：①补肾法与舒肝法对吗啡引起的精神依赖均有调节作用。②舒肝法的作用机制可能在于通过影响伏核和前额叶皮质中NR2B亚基的mRNA表达进一步调节精神依赖的相关神经通路。③补肾法的作用机制与NR2B亚基的mRNA表达关系不密切,其调节的具体机制尚有待研究。     

经颅磁刺激对癫痫病灶脑电相关维数的影响

利用脑功能指标——大鼠病灶区脑电的相关维数,研究低频经颅磁刺激对慢性颞叶癫痫大鼠脑功能改善的作用。对一组颞叶癫痫大鼠施予频率为0．5Hz、强度为0．4T、20次／日、连续一周的低频重复性经颅磁刺激(rTMS)．在rTMS前后,分别测取颞叶癫痫大鼠责任病灶区皮层和海马区的脑电,重构时间延迟吸引子,用G-P算法估算反映对应脑区功能状态的相关维数。研究结果显示：施予适量的rTMS(0.4T、20次／日、连续一周),使颞叶癫痫大鼠海马和相应皮层脑电的相关维数比刺激前明显升高。研究表明适量的rTMS有抑制癫痫的作用。     

大鼠运动病敏感性性别差异与相关脑区AVP及其V1b受体表达的关系

目的：检测不同性别大鼠旋转刺激后脑内相关区域精氨酸加压素（AVP）含量及V1b受体表达的变化,探讨AVP及受体参与运动病的可能机制。方法：给予SD大鼠30 min绕水平轴的旋转刺激,然后采用放免法检测相关脑区AVP含量,并通过荧光免疫组化方法测定相应脑区V1b受体的表达情况。结果：①在雌性大鼠,旋转刺激组各脑区AVP含量无显著性改变;对于雄性大鼠,对照组各检测脑区AVP含量高于雌性,旋转刺激组小脑、延髓内AVP含量的变化无显著性意义,但前脑、间脑、脑桥内AVP含量较对照组明显降低（P〈0.05）。②雌性大鼠视上核AVP的V1b受体表达阳性神经元数量旋转刺激组显著低于对照组（P〈0.05）,而前庭核、最后区V1b受体表达阳性神经元数量明显多于对照组（P〈0.05）;在雄性大鼠,旋转刺激组视上核与前庭核V1b受体表达阳性神经元数量无显著性改变,而最后区V1b受体表达阳性神经元数量有所增加（P〈0.05）,但增加幅度没有雌性大鼠明显。结论：前脑、间脑、脑桥内AVP含量与前庭核和最后区V1b受体表达及对旋转刺激反应的差异可能与运动病敏感性性别差异有关,并且前庭核、最后区可能是AVP-V1受体拮抗剂抗运动病作用的靶点。     

补中益气汤联合低频脉冲电刺激促进产后盆底功能障碍的效果及血清松弛素、CTGF和MMP-1水平的影响

摘要 目的：探讨补中益气汤联合低频脉冲电刺激促进产后盆底功能障碍的效果及血清松弛素（RLX）、结缔组织生长因子（CTGF）和基质金属蛋白酶-1（MMP-1）水平的影响。方法：选取我院2022年4月到2023年4月收治的150例产后盆底功能障碍患者作为研究对象，分为观察组与对照组，各组均75例。对照组患者采取低频脉冲电刺激治疗，观察组患者采取补中益气汤联合低频脉冲电刺激治疗，对比两组患者的临床疗效，治疗前后盆底表面肌电变化情况，并分别在治疗前后应用盆腔脏器官脱垂-尿失禁性功能问卷（PISQ-12）、国际尿控协会盆腔脏器脱垂定量分析量表（POP-Q）、尿失禁问卷表简表（ICI-Q-SF）评估两组患者的性功能、盆腔脱垂程度及尿失禁情况，并对比治疗前后血清RLX、CTGF和MMP-1表达水平。结果：观察组总有效率93.33%明显高于对照组78.67%（P＜0.05）；两组患者治疗前耐力收缩（Ⅱ类肌）、持续收缩和快速收缩（Ⅰ类肌）、前静息电位、后静息电位肌电水平对比无差异（P＞0.05），治疗后观察组快速收缩（Ⅰ类肌）高于对照组（P＜0.05），静息电位与后静息电位低于对照组（P＜0.05）；两组患者治疗前PISQ-12、POP-Q和ICI-Q-SF评分对比无明显差异（P＞0.05），治疗后两组患者PISQ-12、ICI-Q-SF评分升高，观察组较对照组高，POP-Q评分均降低，观察组较对照组低（P＜0.05）；两组患者治疗前RLX、CTGF和MMP-1表达水平对比无差异（P＞0.05），治疗后两组患者RLX、CTGF和MMP-1表达水平均降低，且观察组低于对照组（P＜0.05）。结论：补中益气汤联合低频脉冲电刺激可提升产后盆底功能障碍的临床疗效，改善盆底肌表面肌电变化，改善患者性功能、盆腔脱垂程度及尿失禁情况，且能够降低血清松弛素、CTGF和MMP-1表达水平。     

利血平预处理抑制低频电刺激对大鼠脑组织Hsp-70和c-fos水平的上调

目的观察利血平对低频电刺激引起的应激的影响。方法给予Wistar大鼠利血平预处理再给予低频电刺激,即刻剥取脑组织,用酶联免疫吸附法(ELISA)和免疫组织化学(IHC)检测脑组织中c-fos和Hsp-70基因的表达。结果电刺激组大脑前额叶皮层(PFC)、中脑腹侧背盖区(VTA)、海马(Hipp)组织中Hsp-70和c-fos水平比对照组相应区域均显著升高,免疫反应阳性细胞数明显增多;利血平处理使电刺激产生的Hsp-70和c-fos水平的增加和免疫反应阳性细胞数的增加均明显减少。结论利血平预处理可减轻低频电刺激引起的应激损伤。     

自发性高血压大鼠心脏中ACE,AT1R,ACE2和MasR表达变化的研究

目的：通过观察血管紧张素转化酶（ACE）和血管紧张素转化酶2（ACE2）在Wistar-京都种大鼠（WKY）和自发性高血压（SHR）大鼠心脏组织中表达的差异,探讨ACE与ACE2在自发性高血压大鼠高血压形成中的作用。方法：自由饲喂14周龄WKY和SHR雄性大鼠一周后,用BSN-II多通道无创测压系统测定大鼠收缩压（SBP）、舒张压（DBP）、心率（HR）并称重;放免法测定血浆中血管血管紧张素Ⅱ（AngII）含量;Real-time PCR测定心脏组织中ACE,ATI受体（ATIR）,ACE2和Mas受体（MasR）mRNA的表达水平;Western blot法检测心脏组织中ACE2的蛋白表达。结果：SHR大鼠SBP和DBP均显著高于WKY大鼠（P〈0.01）;两组大鼠心率和体重无显著差异（P〉0.05）;SHR大鼠血浆中AngII含量显著升高（P〈0.05）;与WKY大鼠相比,SHR大鼠心脏中ACE mRNA表达均显著升高（P〈0.05）,ACE2的mRNA和蛋白表达水平均显著下降（P〈0.05）;心脏组织中AT1R和MasR的mRNA表达没有显著性变化（P〉0.05）。结论：ACE与ACE2表达失调是SHR大鼠高血压形成的主要原因之一,其机理可能与局部组织RAS系统ACE-AngII-AT1R通路过度活跃,ACE2-Ang（1-7）-MasR通路相对不足有关。     

经颅直流电刺激对帕金森病伴快速眼动相睡眠行为障碍患者认知功能及神经功能的影响

摘要 目的：探讨经颅直流电刺激对帕金森病伴快速眼动相睡眠行为障碍患者认知功能及神经功能的影响。方法：选择2018年9月-2019年9月在我院接受治疗的69例帕金森病伴快速眼动相睡眠行为障碍患者,采用随机数表法分为电刺激组（n=35）和对照组（n=34）。对照组给予常规抗帕金森病治疗,观察组在对照组的基础上给予经颅直流电刺激治疗。比较两组临床疗效、蒙特利尔认知评估量表（MoCA）、自主神经症状量表（SCOPA-AUT）、睡眠情况、汉密尔顿抑郁量表(HAMD)、Epworth嗜睡量表（ESS）评分、匹兹堡睡眠指数（PSQI）、帕金森氏病综合评分量表（UPDRS）变化情况。结果：治疗后,电刺激组有效率91.43%（32/35）较对照组70.59%（24/34）显著升高,差异显著（P<0.05）;治疗前,电刺激组与对照组之间认知功能及神经功能结果无差异;治疗后,电刺激组与对照组MoCA均随着时间的推移均呈上升趋势,且电刺激组上升程度较较组更低,SCOPA-AUT均随着时间的推移均呈下降趋势,且电刺激组下降程度较对照组更低（P<0.05）;治疗前,电刺激组与对照组之间临床睡眠情况结果无差异;治疗后,电刺激组与对照组总睡眠时间、睡眠效率均随着时间的推移均呈上升趋势,且电刺激组上升程度较对照组更低,醒觉指数均随着时间的推移呈下降趋势,且电刺激组下降程度较对照组更低（P<0.05）;治疗前,电刺激组与对照组之间抑郁、嗜睡情况无差异;治疗后,电刺激组与对照组抑郁、嗜睡均随着时间的推移均呈下降趋势,且电刺激组下降程度较对照组更低（P<0.05）;治疗前,电刺激组与对照组之间PSQI、UPDRS评分无差异;治疗后,电刺激组与对照组PSQI、UPDRS评分均随着时间的推移均呈下降趋势,且电刺激组下降程度较对照组更低（P<0.05）。结论：在帕金森病伴快速眼动相睡眠行为障碍患者中应用经颅直流电刺激效果显著,可有效改善认知功能及神经功能水平。     

Cell Wall,Cytoskeleton, and Cell Expansion in Higher Plants

To accommodate two seemingly contradictory biological roles in plant physiology, providing both the rigid structural support of plant cells and the adjustable elasticity needed for cell expansion, the composition of the plant cell wall has evolved to become an intricate network of cellulosic, hemicellulosic, and pectic polysaccharides and protein. Due to its complexity, many aspects of the cell wall influence plant cell expansion, and many new and insightful observations and technologies are forthcoming. The biosynthesis of cell wall polymers and the roles of the variety of proteins involved in polysaccharide synthesis continue to be characterized. The interactions within the cell wall polymer network and the modification of these interactions provide insight into how the plant cell wall provides its dual function. The complex cell wall architecture is controlled and organized in part by the dynamic intracellular cytoskeleton and by diverse trafficking pathways of the cell wall polymers and cell wall-related machinery. Meanwhile, the cell wall is continually influenced by hormonal and integrity sensing stimuli that are perceived by the cell. These many processes cooperate to construct, maintain, and manipulate the intricate plant cell wall--an essential structure for the sustaining of the plant stature, growth, and life.     

Dissecting the Heat Stress Response in Chlamydomonas by Pharmaceutical and RNAi Approaches Reveals Conserved and Novel Aspects

To study how conserved fundamental concepts of the heat stress response （HSR） are in photosynthetic eukaryotes, we applied pharmaceutical and antisense/amiRNA approaches to the unicellular green alga Chlamydomonas reinhardtii. The Chlamydomonas HSR appears to be triggered by the accumulation of unfolded proteins, as it was induced at ambient temperatures by feeding cells with the arginine analog canavanine. The protein kinase inhibitor staurosporine strongly retarded the HSR, demonstrating the importance of phosphorylation during activation of the HSR also in Chlamydomonas. While the removal of extracellular calcium by the application of EGTA and BAPTA inhibited the HSR in moss and higher plants, only the addition of BAPTA, but not of EGTA, retarded the HSR and impaired thermotoler- ance in Chlamydomonas. The addition of cycloheximide, an inhibitor of cytosolic protein synthesis, abolished the attenu- ation of the HSR, indicating that protein synthesis is necessary to restore proteostasis. HSP90 inhibitors induced a stress response when added at ambient conditions and retarded attenuation of the HSR at elevated temperatures. In addition, we detected a direct physical interaction between cytosolic HSP90A/HSP70A and heat shock factor 1, but surprisingly this interaction persisted after the onset of stress. Finally, the expression of antisense constructs targeting chloroplast HSP70B resulted in a delay of the cell＇s entire HSR, thus suggesting the existence of a retrograde stress signaling cascade that is desensitized in HSP7OB-antisense strains.     

Knights in Action： Lectin Receptor-Like Kinases in Plant Development and Stress Responses

The Receptor-Like Kinase （RLK） is a vast protein family with over 600 genes in Arabidopsis and 1100 in rice. The Lectin RLK （LecRLK） family is believed to play crucial roles in saccharide signaling as well as stress perception. All the LecRLKs possess three domains： an N-terminal lectin domain, an intermediate transmembrane domain, and a C-terminal kinase domain. On the basis of lectin domain variability, LecRLKs have been subgrouped into three subclasses： L-, G-, and C-type LecRLKs. While the previous studies on LecRLKs were dedicated to classification, comparative structural analysis and expression analysis by promoter-based studies, most of the recent studies on LecRLKs have laid special emphasis on the potential of this gene family in regulating biotic/abiotic stress and developmental pathways in plants, thus mak- ing the prospects of studying the LecRLK-mediated regulatory mechanism exceptionally promising. In this review, we have described in detail the LecRLK gene family with respect to a historical, evolutionary, and structural point of view. Furthermore, we have laid emphasis on the LecRLKs roles in development, stress conditions, and hormonal response. We have also discussed the exciting research prospects offered by the current knowledge on the LecRLK gene family. The multitude of the LecRLK gene family members and their functional diversity mark these genes as both interesting and worthy candidates for further analysis, especially in the field of crop improvement.     

Perturbation of Auxin Homeostasis Caused by Mitochondrial FtSH4 Gene-Mediated Peroxidase Accumulation Regulates Arabiclopsis Architecture

Reactive oxygen species and auxin play important roles in the networks that regulate plant development and morphogenetic changes, However, the molecular mechanisms underlying the interactions between them are poorly understood. This study isolated a mas （More Axillary Shoots） mutant, which was identified as an allele of the mitochondrial AAA-protease AtFtSH4, and characterized the function of the FtSH4 gene in regulating plant development by medi- ating the peroxidase-dependent interplay between hydrogen peroxide （H2Oz） and auxin homeostasis. The phenotypes of dwarfism and increased axillary branches observed in the mas （renamed as ftsh4-4） mutant result from a decrease in the IAA concentration. The expression levels of several auxin signaling genes, including IAA1, IAA2, and IAA3, as well as several auxin binding and transport genes, decreased significantly in ftsh4-4 plants. However, the H202 and peroxidases levels, which also have IAA oxidase activity, were significantly elevated in ftsh4-4 plants. The ftsh4-4 phenotypes could be reversed by expressing the iaaM gene or by knocking down the peroxidase genes PRX34 and PRX33. Both approaches can increase auxin levels in the ftsh4-4 mutant. Taken together, these results provided direct molecular and genetic evidence for the interaction between mitochondrial ATP-dependent protease, H2O2, and auxin homeostasis to regulate plant growth and development.     

Regulation of Cytokinesis by Exocyst Subunit SEC6 and KEULE in Arabidopsis thaliana

Proper vesicle tethering and membrane fusion at the cell plate are essential for cytokinesis. Both the vesicle tethering complex exocyst and membrane fusion regulator KEULE were shown to function in cell plate formation, but the exact mechanisms still remain to be explored. In this study, using yeast two-hybrid （Y-2-H） assay, we found that SEC6 interacted with KEULE, and that a small portion of C-terminal region of KEULE was required for the interaction. The direct SEC6-KEULE interaction was supported by further studies using in vitro pull-down assay, immunoprecipitation, and in vivo bimolecular florescence complementation （BIFC） microscopy, sec6 mutants were male gametophytic lethal as reported; however, pollen-rescued sec6 mutants （PRsec6） displayed cytokinesis defects in the embryonic cells and later in the leaf pavement cells and the guard cells. SEC6 and KEULE proteins were co-localized to the cell plate during cytokine- sis in transgenic Arabidopsis. Furthermore, only SEC6 but not other exocyst subunits located in the cell plate interacted with KEULE in vitro. These results demonstrated that, like KEULE, SEC6 plays a physiological role in cytokinesis, and the SEC6-KEULE interaction may serve as a novel molecular linkage between arriving vesicles and membrane fusion machin- ery or directly regulate membrane fusion during cell plate formation in plants.     

Genotoxicity biomarkers in aquatic bioindicators

Pollution of the aquatic environment is an ever-growing problem, as waters are the ultimate sink for the large number of xenobiotics from multiple sources. DNA damaging agents have a significant ecological relevance since they are implicated in many pathological processes and exert effects beyond that of individual being active through following generations. A large number of methods have been applied to evaluate genotoxic damage in different aquatic species. Comet assay, as method for de- tecting DNA alterations, and micronucleus test, as an index of chromosomal damage are the most widely applied and validated methods in field studies. These methods were applied in different vertebrate and invertebrate aquatic species, but only mollusk and fish species have been employed in routine biomonitoring programs. Mussels, due to their widely geographical distribution and the suitability for caging represent the bioindicator of choice in field studies. Mytilus species is the most used marine mussel. The use of fish is limited to specific geographic areas. The present review mainly focuses on the application of comet assay and micronucleus test in mussels. A number of biomonitoring studies in mussels, using comet assay or micronucleus test, revealed exposure to different classes of genotoxic compounds with a good discrimination power. The different evidence from the two as- says, reflects different biological mechanisms for the two genetic endpoints, DNA damage and chromosomal damage, suggesting their combined application in the field. Different endogenous and exogenous factors have been shown to modulate the genotoxic responses in mussels, acting as confounding factors in environmental monitoring. The use of standardized protocol for caging, sampling and genotoxity evaluation is critical in biomonitoring studies. The use of a multimarker approach coupling genotoxicity biomarkers with physiological and biochemical factors allows to have a complete picture of the environmental pollution [Current Zoology 60 （2）： 273-284, 2014].     

Open and Closed： The Roles of Linker Histones in Plants and Animals

Histones package DNA in all eukaryotes and play key roles in regulating gene expression. Approximately 150 base pairs of DNA wraps around an octamer of core histones to form the nucleosome, the basic unit of chromatin. Linker histones compact chromatin further by binding to and neutralizing the charge of the DNA between nucleosomes. It is well established that chromatin packing is regulated by a complex pattern of posttranslational modifications （PTMs） to core histones, but linker histone function is less well understood. In this review, we describe the current understand- ing of the many roles that linker histones play in cellular processes, including gene regulation, cell division, and devel- opment, while putting the linker histone in the context of other nuclear proteins. Although intriguing roles for plant linker histones are beginning to emerge, much of our current understanding comes from work in animal systems. Many unanswered questions remain and additional work is required to fully elucidate the complex processes mediated by linker histones in plants.     

Arabidopsis tic62 trol Mutant Lacking Thylakoid- Bound Ferredoxin-NADP＋ Oxidoreductase Shows Distinct Metabolic Phenotype

Ferredoxin-NADP＋ oxidoreductase （FNR）, functioning in the last step of the photosynthetic electron transfer chain, exists both as a soluble protein in the chloroplast stroma and tightly attached to chloroplast membranes. Surface plasmon resonance assays showed that the two FNR isoforms, LFNR1 and LFNR2, are bound to the thylakoid membrane via the C-terminal domains of Tic62 and TROL proteins in a pH-dependent manner. The tic62 trol double mutants contained a reduced level of FNR, exclusively found in the soluble stroma. Although the mutant plants showed no visual phenotype or defects in the function of photosystems under any conditions studied, a low ratio of NADPH/NADP~ was detected. Since the CO2 fixation capacity did not differ between the tic62 trol plants and wild-type, it seems that the plants are able to funnel reducing power to most crucial reactions to ensure survival and fitness of the plants. However, the activity of malate dehydrogenase was down-regulated in the mutant plants. Apparently, the plastid metabolism is able to cope with substantial changes in directing the electrons from the light reactions to stromal metabolism and thus only few differences are visible in steady-state metabolite pool sizes of the tic62 trol plants.