文拉法辛联合认知行为疗法治疗帕金森病抑郁、认知功能障碍的临床疗效评价

目的:探讨文拉法辛联合认知行为疗法治疗帕金森病(PD)抑郁、认知功能障碍的临床疗效和安全性。方法:选择我院收治的60例PD合并抑郁、认知功能障碍患者并将其随机分为三组,分别为对照组(单用文拉法辛治疗),联合奥氮平组(文拉法辛联合奥氮平),联合认知行为疗法组(文拉法辛联合认知行为疗法),每组20例,于治疗前及治疗后4、8周末采用汉密尔顿抑郁量表(HAMD)进行抑郁程度评定,简易精神状态评价量表(MMSE)和事件相关电位(event-related potentials,ERPs)P300进行认知功能评定。结果:治疗4、8周时,三组的HAMD评分均较治疗前有不同程度下降,P300潜伏期较治疗前有不同程度缩短,P300波幅、MMSE评分有不同程度升高(P0.05),联合奥氮平组和联合认知行为疗法组HAMD评分较对照组明显下降,P300潜伏期较对照组明显缩短,P300波幅、MMSE评分明显升高(P0.05),联合认知行为疗法组HAMD评分较联合奥氮平组明显下降,P300潜伏期明显缩短,P300波幅、MMSE评分明显升高(P0.05)。三组均无特殊不良反应。结论:文拉法辛联合认知行为疗法治疗PD抑郁、认知功能障碍疗效确切,能显著改善患者抑郁症状,提高患者的认知功能,疗效较单用文拉法辛或文拉法辛联合奥氮平治疗更好,且安全性高。     

中药点舌疗法治疗急性脑梗死伴意识障碍的效果

目的观察中药点舌疗法治疗急性脑梗死伴意识障碍的疗效。方法选取2017年6月～2018年6月在我院诊断为急性脑梗死伴意识障碍患者80例为研究对象,按照随机数字表法分为实验组和对照组各40例。对照组采用常规治疗及护理干预,实验组在常规治疗和护理干预基础上采用中药点舌疗法针对性干预治疗。观察比较两组患者的治疗效果及治疗1个月后格拉斯哥昏迷评分(glasgow coma scale,GCS)情况。结果治疗前,两组患者的GCS评分比较差异无统计学意义(P0.05)。治疗1个月后,实验组的GCS评分明显高于对照组,差异具有统计学意义(P0.05);两组治疗效果比较,实验组的总有效率明显高于对照组,差异有统计学意义(P0.05)。结论中药点舌疗法治疗急性脑梗死伴意识障碍患者的疗效确切,安全可靠,值得临床进一步推广。     

产后与非产后抑郁症患者事件相关电位P300的对比研究

目的:探讨产后抑郁症与非产后抑郁症患者事件相关电位P300的差异,为产后抑郁症的预防提供参考指标。方法:选择2011年1月~2012年10月解放军第三医院精神科收治的35例产后抑郁症患者(产后组)和36例非产后抑郁症患者(非产后组)为研究对象,并检测其事件相关电位P300,并与36名健康志愿者(对照组)的结果进行比较。结果:(1)与对照组相比,产后组、非产后组P2、N2、P3潜伏期均显著延迟,P2、N2、P3波幅均明显降低,差异均有统计学意义(P0.05)。(2)与产后组相比,非产后组P2、N2、P3潜伏期差异均无统计学意义(P0.05)。P2、N2波幅均偏高,差异均有统计学意义(P2[(5.0±2.1)ms vs.(3.9±1.8)μV],N2[(3.2±1.7)μV vs.(2.1±1.0)μV],P0.05),P3波幅差异无统计学意义(P0.05)。结论:产后与非产后抑郁症患者认知功能均受损,非产后抑郁患者受损程度大于产后抑郁患者;产后抑郁的外界感知能力和早期注意受损程度大于非产后抑郁患者。     

玻璃体腔联合注射赖氨酸－纤溶酶原和瑞替普酶诱导兔眼玻璃体后脱离的有效性

目的:探讨兔眼玻璃体腔联合注射赖氨酸-纤溶酶原和瑞替普酶诱导玻璃体后脱离(PVD)的有效性。方法:选取30只健康的新西兰白兔,以白兔右眼作为实验眼,左眼作为对照眼。随机分为A、B、C三组(每组10只),三组实验眼分别联合应用1万U瑞替普酶+125μg赖氨酸—纤溶酶原、2万U瑞替普酶+125μg赖氨酸—纤溶酶原、3万U瑞替普酶+125μg赖氨酸—纤溶酶原进行玻璃体腔内注射,对照眼均注射平衡盐溶液。应用视网膜电图、扫描电镜及光镜观察、比较各组诱导PVD的效果。结果:三组实验眼均形成不同程度PVD。A组实验眼注药前与注药后24 h、注药后2周的最大混合反应a波振幅、b波振幅比较均无明显差异(P0.05);B组实验眼注药后24 h的a波振幅、b波振幅均有轻度下降,2周后均恢复正常,注药前后的a波振幅、b波振幅比较均无明显差异(P0.05)。C组实验眼注药后24 h的a波振幅、b波振幅均明显低于注药前和对照眼,注药后2周的b波振幅均明显低于注药前和对照眼(P0.05)。光学组织切片观察显示:A组实验眼及所有对照眼、B组实验眼、C组实验眼的视网膜组织细胞形态正常,结构清晰,但B组神经节内核层、细胞层细胞略有减少,C组神经节内核层及细胞层细胞明显减少。结论:玻璃体腔内联合注射赖氨酸-纤溶酶原和瑞替普酶能有效诱导PVD,1万U瑞替普酶+125μg赖氨酸-纤溶酶原可诱导实现完全性PVD,不会对视功能、视网膜结构造成损害。     

氯喹对戊四氮致痫大鼠皮质和海马谷氨酸和NMDAR1表达的影响

目的观察氯喹对戊四氮致痫大鼠皮质和海马谷氨酸(glutamate,Glu)和N-甲基-D-天冬氨酸受体1(NMDAR1,NR1)表达的影响,探讨氯喹在癫痫发生发展过程中对神经递质传导的作用。方法48只健康雄性SD大鼠随机分为对照组(12只)、戊四氮致痫组(60mg/kg,i.p.,18只)和氯喹干预组(0.61mg/kg,i.c.v.,18只)。每组分6个时间点:1h、2h、4h、8h、12h和24h。观察大鼠行为表现和脑电图改变,用免疫组化检测大鼠皮质和海马Glu和NR1的变化。结果对照组无痫样发作,戊四氮致痫组有重型的痫样发作(Ⅲ-Ⅴ级),氯喹干预组有轻型的痫样发作(Ⅰ-Ⅲ级)(P<0.05);戊四氮致痫组脑电记录呈频发高幅的痫样波,氯喹干预组痫样波幅低且缓;Glu和NR1在戊四氮致痫组表达强,以海马为著,与对照组比较有显著性差异(P<0.05),氯喹干预组与对照组比较无显著性差异(P>0.05)。结论氯喹通过对戊四氮致痫大鼠皮质和海马神经递质Glu和NR1信号传导通路的抑制作用,影响致痫大鼠痫样发作的发生和发展。     

缺氧条件下建立SD大鼠牙周炎动物模型的研究

目的:在模拟高原缺氧条件下建立稳定的缺氧SD大鼠牙周炎动物模型。方法:40只SD大鼠,雌雄各半,采用随机数字表法分为4组:常氧对照组(A组),常氧牙周炎组(B组),缺氧对照组(C组),缺氧牙周炎组(D组),每组10只。B、D组大鼠结扎牙颈部、高糖饮食、口腔涂菌及注射激素,A、C组不作任何处理,正常饮食。C、D组喂养的同时进入模拟海拔5000 m的低压氧舱。8 w后检测牙龈指数GI、菌斑指数PLI、牙周袋深度PD、牙槽骨吸收度ABL及组织病理学观察,对模型进行评估。结果:GI、PD及ABL指数在B组与A组,D组与C组,C组与A组,D组与B组比较均有统计学差异(P0.05)。PLI指数在B组与A组,D组与C组比较有统计学差异(P0.05),在C组与A组,D组与B组比较无统计学差异(P0.05)。HE染色见A、C组无明显改变,B、D组牙龈糜烂,结合上皮向根方增殖迁移,牙周膜间隙增宽。结论:将采用结扎牙颈部、高糖饮食、口腔涂菌及注射激素综合方法作用的SD大鼠放入模拟海拔5000 m的低压氧舱,建立模拟高原缺氧大鼠牙周炎模型具有可行性,为高原牙周病的防治奠基了实验基础。     

γ-氨基丁酸对隔离皮层电活动的影响

局部施加γ-氮基丁酸(GABA)后,猫、兔的隔离皮层的电活动频率降低,振幅加大。隔离区施加五甲烯四氮唑后,癎样峰波发放仅在该区出现,且不为GABA所阻抑。有时五甲烯四氮唑可引起峰波和慢波的复合波,施加GABA可使其峰波消失,慢波加大。实验结果提示,在慢性实验中施加GABA于完整皮层表面时,皮层电活动所呈现的高幅慢波有可能起源于皮层。     

复方辣木颗粒剂影响雄性小鼠性功能的实验研究

目的观察复方辣木颗粒剂对雄性小鼠性功能的影响。方法建立醋酸铅致雄性小鼠生精障碍模型。将60只实验小鼠分为正常组、模型组、阳性对照组和复方辣木颗粒剂高、中、低剂量组,每组10只。给药后,观察小鼠体重、脏器指数、附睾精子活力、精子活率及睾丸的病理形态等。结果复方辣木颗粒剂对醋酸铅致少弱精子症小鼠体重无明显影响,各给药组小鼠附睾系数、睾丸系数、精子活力、精子活率均有所上升,生精细胞和间质细胞数量增多、排列更紧密。各剂量间比较,高剂量效果更显著(均P0.05)。结论复方辣木颗粒剂可显著改善小鼠性功能,为临床合理应用提供有利参考。     

体外反搏治疗急性重症病毒性脑炎的临床疗效观察

目的:探讨以体外反搏为主的康复手段治疗急性重症病毒性脑炎的临床疗效。方法:选择2015年6月～2016年6月在我院康复科就诊的42例急性重症病毒性脑炎患儿,按照家长治疗意愿分成治疗组和对照组,每组21例。治疗一个月和三个月后,分析和比较两组的治疗前后粗大运动功能评定量表(GMFM)、平衡功能测量(Berg量表)和修订的Glasgow意识障碍评分量表评分的变化。结果:两组患儿平衡能力总有效率(显效率与有效率之和)分别为85.7%和57.1%,以及95.2%和66.7%,治疗组疗效明显优于对照组(P0.05)。两组治疗后1、3个月,GMFM、Glasgow意识障碍评分均较治疗前明显提高(P0.01),且治疗组治疗1、3个月后GMFM显著高于对照组(P0.01)。结论:以体外反搏为主的早期康复治疗有助于急性重症病毒性脑炎患者促醒及运动功能恢复。     

帕罗西汀联合微生态制剂 治疗伴有功能性消化不良症状的焦虑障碍患者疗效

目的观察帕罗西汀联合微生态制剂对伴有功能性消化不良症状的焦虑障碍患者临床疗效。方法选取伴有功能性消化不良症状的焦虑障碍患者128例,随机分成两组,每组64例:单用组给予帕罗西汀治疗;联用组除帕罗西汀治疗外,加用微生态制剂(双歧杆菌三联活菌肠溶胶囊)早晚各210mg(本品为复方制剂,每克含长型双歧杆菌≥1.0×106 CFU、嗜酸乳杆菌≥1.0×106 CFU、粪肠球菌≥1.0×106 CFU),最多早晚各840mg,共10周。治疗前后应用HAMA量表和水负荷试验进行疗效评定,应用需处理的不良反应症状的量表(treatment emergent symptoms scale,TESS)进行安全性评定。结果在10周末,两组患者治疗后HAMA评分均低于治疗前,联用组的显效率高于单用组(P0.05);水负荷试验水负荷量高于治疗前,联用组水负荷量高于单用组。在治疗后第10周末单用组常见胃肠道不良反应有便秘、恶心等,联用组不良反应少,联用组TESS评分显著降低(P0.05)。结论联合微生态制剂对伴有功能性消化不良的焦虑症患者有显著疗效,胃肠道不良反应小。     

Studies on the energy coupling sites of photophosphorylation IV. The relation of proton fluxes to the electron transport and ATP formation associated with Photosystem II

1. By using dibromothymoquinone as the electron acceptor, it is possible to isolate functionally that segment of the chloroplast electron transport chain which includes only Photosystem II and only one of the two energy conservation sites coupled to the complete chain (Coupling Site II, observed P/e₂ = 0.3–0.4). A light-dependent, reversible proton translocation reaction is associated with the electron transport pathway: H₂O → Photosystem II → dibromothymoquinone. We have studied the characteristics of this proton uptake reaction and its relationship to the electron transport and ATP formation associated with Coupling Site II.

2. The initial phase of H⁺ uptake, analyzed by a flash-yield technique, exhibits linear kinetics (0–3 s) with no sign of transient phenomena such as the very rapid initial uptake (“pH gush”) encountered in the overall Hill reaction with methylviologen. Thus the initial rate of H⁺ uptake obtained by the flash-yield method is in good agreement with the initial rate estimated from a pH change tracing obtained under continuous illumination.

3. Dibromothymoquinone reduction, observed as O₂ evolution by a similar flash-yield technique, is also linear for at least the first 5 s, the rate of O₂ evolution agreeing well with the steady-state rate observed under continuous illumination.

4. Such measurements of the initial rates of O₂ evolution and H⁺ uptake yield an H⁺/e⁻ ratio close to 0.5 for the Photosystem II partial reaction regardless of pH from 6 to 8. (Parallel experiments for the methylviologen Hill reaction yield an H⁺/e⁻ ratio of 1.7 at pH 7.6.)

5. When dibromothymoquinone is being reduced, concurrent phosphorylation (or arsenylation) markedly lowers the extent of H⁺ uptake (by 40–60%). These data, unlike earlier data obtained using the overall Hill reaction, lend themselves to an unequivocal interpretation since phosphorylation does not alter the rate of electron transport in the Photosystem II partial reaction. ADP, P_i and hexokinase, when added individually, have no effect on proton uptake in this system.

6. The involvement of a proton uptake reaction with an H⁺/e⁻ ratio of 0.5 in the Photosystem II partial reaction H₂O → Photosystem II → dibromothymoquinone strongly suggests that at least 50% of the protons produced by the oxidation of water are released to the inside of the thylakoid, thereby leading to an internal acidification. It is pointed out that the observed efficiencies for ATP formation (P/e₂) and proton uptake (H⁺/e⁻) associated with Coupling Site II can be most easily explained by the chemiosmotic hypothesis of energy coupling.     

Evidence that the C-terminus of OprM is involved in the assembly of the VceAB-OprM efflux pump

Although the architecture of tripartite multiple drug resistance (MDR) efflux pumps of Gram-negative bacteria has been well characterized, the means by which the components recognize each other and assemble into a functional pump remains obscure. In this study we present evidence that the C-terminal domain of the Pseudomonas aeruginosa OprM and the α-helical hairpin domain of Vibrio cholerae VceA play an important role in the recognition/specificity/recruitment step in the assembly of a functional, VceAB-OprM chimeric efflux pump. To our knowledge, this is the first evidence directly linking the C-terminal domain of an outer membrane efflux protein to its recruitment during the assembly of a tripartite efflux pump.     

心脑血管疾病大额住院消费统计分析

通过对医院2004-2006年心脑血管疾病大额住院消费(消费大于50000元,以下简称大额消费)病例发病率高的前五种疾病的构成情况、药费、材料费消耗情况进行分析,认为加强大额病例中发病率高的病种的重点管理,是降低医疗费用的有效途径。建议制定常见病大额病种预定额付费方案和审查报销制度;采用适宜技术;控制药费,防止过度医疗,有效地遏制医疗费用的过快增长。     

Partial purification and properties of Galleria mellonella larvae proteolytic inhibitors acting on Metarhizium anisopliae toxic protease

Gel permeation, preparative isoelectric focusing, and affinity chromatography were used to purify three inhibitors of proteolytic activity from perchloric acid extracts of last instar Galleria mellonella larvae. Electrofocusing experiments revealed three isoinhibitors with different isoelectric points: inhibitor I-1 with p1 of pH 5.6, inhibitor I-2, pH 7.7, and inhibitor I-3 (of small inhibitory activity), pH 8.6. By affinity chromatography on trypsin-Sepharose 4B the I-1 was purified 9.7 ×, but 71.1% of inhibitory activity was lost. Molecular mass of the inhibitory complex was 12,600 Da. I-1 and I-2 are relatively stable to heat at several pHs with minor stability at pH 10. I-1 and I-2 inhibit serine proteases about 2.5 times as much as sulfhydryl proteases. In the same ratio protease P-1 and protease P-2 from Metarhizium anisopliae are inhibited.     

THE DEATH OF BIOETHICS (AS WE ONCE KNEW IT)

Fast forward 50 years into the future. A look back at what occurred in the field of bioethics since 2010 reveals that a conference in 2050 commemorated the death of bioethics. In a steady progression over the years, the field became increasingly fragmented and bureaucratized. Disagreement and dissension were rife, and this once flourishing, multidisciplinary field began to splinter in multiple ways. Prominent journals folded, one by one, and were replaced with specialized publications dealing with genethics, reproethics, nanoethics, and necroethics. Mainstream bioethics organizations also collapsed, giving way to new associations along disciplinary and sub‐disciplinary lines. Physicians established their own journals, and specialty groups broke away from more general associations of medical ethics. Lawyers also split into three separate factions, and philosophers rejected all but the most rigorous, analytic articles into their newly established journal. Matters finally came to a head with global warming, the world‐wide spread of malaria and dengue, and the cost of medical treatments out of reach for almost everyone. The result was the need to develop plans for strict rationing of medical care. At the same time, recognition emerged of the importance of the right to health and the need for global justice in health. By 2060, a spark of hope was ignited, opening the door to the resuscitation of bioethics and involvement of the global community.     

Survival and metabolism of the harpacticoid copepod Thompsonula hyaenae (Thompson) fed on different diatoms

Survival times and oxygen consumption rates have been determined for a benthic harpacticoid copepod, Thompsonula hyaenae (Thompson), when fed different algal diets. Nauplii and adults lived slightly longer on a diet of Navicula sp. than did those fed N. pelliculosa or a mixture of both naviculoid species. Mean numbers of harpacticoids hatched were significantly higher in cultures of N. pelliculosa. Metabolic rates of non-gravid females fed for one week on N. sp. were significantly lower than those fed N. pelliculosa or the mixture. There was no significant difference in oxygen uptake between animals fed N. pelliculosa and those fed the mixed culture. The smaller size and lower food energy content of N. pelliculosa are reflected in the higher respiratory rates of animals led this diatom species.Based on a thesis submitted in partial fulfillment of the M.S. degree in Marine Science at the University of South Carolina. Belle W. Baruch Institute for Marine Biology and Coastal Research Contribution No. 114. Research supported by the Oceanography Section, National Science Foundation, NSF Grant DES72-01573 A01.     

Strategy for Stabilizing Enzymes Part Two: Increasing Enzyme Stability by Selective Chemical Modification

The molecular mechanisms of change in the thermal stability of proteins modified with low molecular weight reagents are discussed. The choice of stabilization mechanisms to be used as a general strategy for increasing enzyme stability by chemical modification is addressed. Hydrophilization of nonpolar surface areas is the most simple and reliable approach to artificial stabilization of enzymes for use in applied biochemistry and biotechnology.     

Primeval cells: Possible energy-generating and cell-division mechanisms

Summary It is proposed that the first entity capable of adaptive Darwinian evolution consisted of a liposome vesicle formed of (1) abiotically produced phospholipidlike molecules; (2) a very few informational macromolecules; and (3) some abiogenic, lipid-soluble, organic molecule serving as a symporter for phosphate and protons and as a means of high-energy-bond generation. The genetic material had functions that led to the production of phospholipidlike materials (leading to growth and division of the primitive cells) and of the carrier needed for energy transduction. It is suggested that the most primitive exploitable energy source was the donation of 2H⁺+2e^– at the external face of the primitive cell. The electrons were transferred (by metal impurities) to internal sinks of organic material, thus creating, via a deficit, a protonmotive force that could drive both the active transport of phosphate and high-energy-bond formation.This model implies that proton translocation in a closed-membrane system preceded photochemical or electron transport mechanisms and that chemically transferable metabolic energy was needed at a much earlier stage in the development of life than has usually been assumed. It provides a plausible mechanism whereby cell division of the earliest protocells could have been a spontaneous process powered by the internal development of phospholipids. The stimulus for developing this evolutionary sequence was the realization that cellular life was essential if Darwinian survival of the fittest was to direct evolution toward adaptation to the external environment.     

用离散量的方法识别蛋白质的超二级结构

用离散量的方法,对2208个分辨率在2.5I以上的高精度的蛋白质结构中四类超二级结构进行了识别。从蛋白质一级序列出发,以氨基酸(20种氨基酸加一个空位)和其紧邻关联共同为参数,当序列模式固定长取8个氨基酸残基时,对“822”序列模式3交叉检验的平均预测精度达到78.1%,jack-knife检验的平均预测精度达到76.7%;当序列模式固定长取10个氨基酸残基时,对“1041”序列模式3交叉检验的平均预测精度达到83.1%,jack-knife检验的平均预测精度达到79.8%。