尿酸及NLRP3炎症小体与妊娠期高血压的相关性分析

目的:观察妊娠期高血压孕产妇尿酸与Nod样受体蛋白3(nucleotide-binding oligomerization domain-leucine-rich repeats containing pyrin domain 3,NLRP3)炎症小体表达,分析二者与疾病的相关性,为妊娠期高血压的诊断提供参考。方法:选择我院产科2016年3月至2019年3月常规产检并诊断为妊娠期高血压孕产妇200例为研究组,参照《妊娠期高血压诊治指南(2015)》中各妊娠期高血压分级标准将研究组200例孕产妇分为妊娠期高血压组(86例)、轻度子痫前期组(57例)、重度子痫前期组(57例),另选择同期在我院接受常规产检的200例健康孕产妇作为对照组。检测并比较4组孕产妇血清尿酸、NLRP3炎症小体m RNA及NLRP3蛋白表达,经双变量Spearman相关性分析检验各指标与疾病的相关性。结果:4组孕产妇年龄、孕周、孕次、产次等一般资料比较差异无统计学意义(P>0.05);重度子痫前期组血清尿酸水平、NLRP3 mRNA及NLRP3蛋白表达最高,后由高至低依次为轻度子痫前期组、妊娠期高血压组、对照组,组间两两比较差异均有统计学意义(P<0.05);经双变量Spearman相关性分析检验证实,血清尿酸、NLRP3 mRNA表达和蛋白表达与妊娠期高血压发生发展均呈正相关(r=0.709、0.833、0.693,P均<0.001)。结论:妊娠期高血压孕产妇血清尿酸与NLRP3炎症小体水平上调,且随着孕产妇病情的加重升高,可考虑将其作为妊娠期高血压疾病早期诊断及预后评估的血清学参考指标。     

孕早期血清雌激素水平与妊娠期高血压疾病发病风险的关系研究

摘要 目的：探讨孕早期血清雌二醇（E₂）水平与妊娠期高血压疾病（HDCP）发病风险的关系。方法：选取2021年12月至2022年12月我院收治的100例HDCP患者（HDCP组）,另取同期产前检查健康孕妇80例为对照组,根据HDCP分类分为妊娠期高血压组（26例）、子痫前期-子痫组（35例）、妊娠合并慢性高血压组（21例）、慢性高血压伴发子痫前期组（18例）。检测血清E₂水平,比较对比不同妊娠期高血压疾病分类血清E₂水平差异。采用Logistic回归方法分析影响HDCP发病的危险因素。受试者工作特征（ROC）曲线分析血清E2水平预测HDCP的价值。结果：HDCP组血清E₂水平低于对照组（P＜0.05）,子痫前期-子痫组血清E2水平低于慢性高血压伴发子痫前期组、妊娠合并慢性高血压组、妊娠期高血压组（P＜0.05）,慢性高血压伴发子痫前期组血清E₂水平低于妊娠合并慢性高血压组、妊娠期高血压组（P＜0.05）。年龄≥35岁、高孕前BMI、产次≥2次、高血压家族史、母亲HDCP病史是HDCP发病的危险因素（P＜0.05）,E₂是保护因素（P＜0.05）。E₂预测HDCP的临界值为162.35 ng/L,曲线下面积为0.744,灵敏度为79.00%,特异度为76.25%。结论：HDCP患者孕早期血清E₂水平显著降低,且与HDCP病情加重有关,检测E₂水平可预测HDCP风险。     

二甲双胍联合门冬胰岛素对妊娠期糖尿病患者血清胆固醇、总胆红素、尿酸和尿微量蛋白水平及母婴结局的影响

目的:探讨二甲双胍联合门冬胰岛素对妊娠期糖尿病患者血清胆固醇(TC)、总胆红素(TBil)、尿酸(UA)、尿微量蛋白(mAlb)水平及母婴结局的影响。方法:选择2014年6月至2016年6月我院接诊的84例妊娠期糖尿病患者,通过随机数表法分为观察组(n=42)和对照组(n=42)。在常规治疗基础上,对照组使用门冬胰岛素治疗,观察组再联合盐酸二甲双胍。比较两组治疗前后血糖指标、TC、TBil、UA、m Alb的变化以及母婴结局。结果:治疗后,观察组空腹血糖(FBG)、餐后2h血糖(2hPG)、糖化血红蛋白(HbA1c)、TC、UA、m Alb水平均显著低于对照组(P0.05),TBil水平明显高于对照组(P0.05),妊娠期高血压、羊水过多、早产、剖宫产、巨大儿、新生儿黄疸的发生率均显著低于对照组(P0.05)。结论:二甲双胍联合门冬胰岛素对妊娠期糖尿病患者的疗效显著,可有效改善患者血糖指标以及TC、TBil、UA、m Alb水平,改善母婴结局。     

饮食运动干预联合格列本脲对妊娠期糖尿病患者血糖控制及新生儿结局的影响

摘要 目的：探讨饮食运动干预联合格列本脲对妊娠期糖尿病患者血糖控制及新生儿结局的影响。方法：选取2019年1月至2019年12月于我院诊治并分娩的的妊娠期糖尿病患者100例,将其随机分为研究组和对照组,每组各50例。研究组患者接受饮食运动干预联合格列本脲治疗,对照组患者仅接受格列本脲治疗。另选取于2019年1月至2019年12月于我院进行常规健康检查并分娩的孕妇50例作为健康组,观察并对比三组患者血糖控制情况,血清CysC和Irisin水平,胰岛素抵抗相关指标,产妇和新生儿结局,分娩方式。结果：干预后,研究组空腹血糖、餐后1 h血糖、餐后2 h血糖、HbA1c、血清CysC均低于干预前,且研究组以上指标均明显低于对照组(P＜0.05)。研究组干预后血清Irisin水平高于干预前,且高于对照组(P＜0.05)。干预后,研究组HOMA-IR显著低于对照组,HOMA-?茁均显著高于对照组(P＜0.05)。研究组产后出血比例、新生儿出生体质量、新生儿低血糖和早产儿比例均低于对照组(P＜0.05)。研究组剖宫产比例少于对照组,研究组的临床总有效率显著优于对照(P＜0.05)。治疗期间,研究组和对照组均未发生不良反应。结论：饮食运动干预联合格列本脲可显著改善妊娠期糖尿病产妇和新生儿结局。     

二甲双胍联合津力达颗粒治疗妊娠期糖尿病的临床效果及对患者血清VEGF、APN、Hcy水平的影响

目的:探讨二甲双胍联合津力达颗粒治疗妊娠期糖尿病的临床效果及对患者血清血管内皮生长因子(VEGF)、脂联素(APN)、同型半胱氨酸(Hcy)水平的影响。方法:选择2014年7月至2016年7月我院接诊的94例妊娠期糖尿病患者并通过随机数表法分为观察组(n=47)和对照组(n=47)。对照组使用二甲双胍治疗,观察组在对照组的基础上联合津力达颗粒治疗,均治疗至胎儿娩出。比较两组治疗前后血糖、血脂及血清VEGF、APN和Hcy水平的变化及产妇并发症和新生儿不良结局的发生情况。结果:与治疗前比较,两组治疗后血糖、血脂指标均显著改善(P0.05),观察组空腹血糖(FBG)、餐后2 h血糖(2h PG)、糖化血红蛋白(Hb A1c)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平均明显低于对照组,血清高密度脂蛋白胆固醇(HDL-C)水平明显高于对照组(P0.05)。两组治疗后血清VEGF、APN、Hcy水平较治疗前均显著改善(P0.05),且观察组血清VEGF、Hcy均明显低于对照组,血清APN水平明显高于对照组(P0.05)。观察组妊娠期高血压、羊水过多、剖宫产、早产、巨大儿、新生儿黄疸、新生儿呼吸窘迫的发生率均明显低于对照组(P0.05)。结论:二甲双胍联合津力达颗粒治疗妊娠期糖尿病的临床效果显著,可有效控制血糖、血脂水平,降低不良母婴结局的发生率,可能与其有效调节血清VEGF、APN、Hcy水平有关。     

同型半胱氨酸、超敏C反应蛋白与妊娠期高血压疾病的关系

目的：探讨血浆同型半胱氨酸（Hcy）及超敏C反应蛋白（hs—cRP）与妊娠期高血压疾病（HDP）的关系。方法：选择妊娠期高血压疾病患者104例作为实验组,包括妊娠期高血压53例、子痫前期轻度24例,子痫前期重度27例;并随机选取同期正常孕晚期孕妇60例做为对照组。测定血浆Hcy及hs-CRP水平。结果：实验组血浆Hcy、hs-CRP水平显著高于对照组,随着实验组病情加重．血浆Hcy、hs-CRP水平逐渐升高,与对照组相比差异有显著性（P〈0．05）。结论：妊娠期高血压病患者血浆Hcy和Hs-CRP水平随着病情发展不断升高,密切监测其变化,对妊娠期高血压疾病的预防、诊疗及动态监测有着重要的临床价值。     

Cyclin B1和p21在妊娠期高血压产妇胎盘组织中的表达及其临床意义

目的:观察CyclinB1和p21在妊娠期高血压产妇胎盘组织中的表达并探讨其临床意义.方法:采用免疫组化MaxVision法检测正常胎盘组织(20例)、妊娠期高血压胎盘组织(30例)、轻度子痫前期胎盘组织(30例)和重度子痫前期(30例)产妇胎盘组织中的cyclin B1和p21蛋白表达,并分析其与妊娠期高血压病情严重程度的相关性.结果:妊娠期高血压、轻度子痈前期、重度子痈前期胎盘组织中cyclinB1蛋白的表达均显著低于正常胎盘组织,差异均有统计学意义(P＜0.05),妊娠期高血压、轻度子痈前期、重度子痈前期胎盘组织中p21蛋白表达均显著高于正常胎盘组织,差异有统计学意义(P＜0.05).妊娠期高血压患者病情的严重程度与其胎盘组织中cyclinB1的蛋白表达呈显著负相关(r=0.641,P=0.000);而与其胎盘组织中p21蛋白的表达呈显著正相关(r=0.635,P=0.000).结论:Cyclin B1蛋白的表达下调和p21蛋白的表达上调可能参与了妊娠期高血压的发生发展,且二者在胎盘组织中的表达水平与妊娠期高血压病情的严重程度显著相关.     

妊娠期糖耐量标准与妊娠结局的关系

目的:探讨不同的诊断标准的妊娠期糖尿病的妊娠结局。方法:回顾性分析我院2001-2004年产前检查并分娩,无显性糖尿病及其他内分泌疾病的单胎孕妇共337例,按糖尿痛不同的诊断标准分成三组进行比较:干预组78例(OGTT(oral glucose toler- ante test)血糖值达到妊娠期糖尿病诊断标准,予饮食调整、运动指导,和或胰岛素治疗);未干预组91例(OGTT值小于妊娠期糖尿病诊断标准,但第2小时血糖≥7.8mmol/L,一般产科检查,无相应血糖的检测与治疗);对照组168例(OGTT正常,且第2小时血糖<7.8mmol/L一般产科检查)。结果:未干预组在巨大胎与干预组及对照组间有显著差异。干预组在妊娠周数与对照组及未干预组之间有差异。三组在年龄、分娩前体重指数、分娩方式等方面无显著差异。结论:未干预糖尿病组与巨大胎有关。建议诊断妊娠期糖尿病标准采用空腹血糖≥5.8mmol/L和或75克糖耐量试验2小时血糖≥7.8mmol/L。     

妊娠期糖尿病血清和脂肪组织内脂素的表达

目的:探讨妊娠期糖尿病孕妇内脂素水平与糖代谢的关系.方法:检测血清中内脂素、FIN、FIG水平,计算HOMA-IR,用RT-PCR法检测脂肪组织中内脂素mRNA的表达.结果:(1)妊娠期糖尿病组孕妇血清内脂素、FPG、HOMA-IR、FIN明显高于对照组.(2)妊娠期糖尿病组孕妇内脏脂肪组织中的内脂素的表达明显高于对照组,且妊娠期糖尿病组孕妇内脏组织中内脂素的表达明显高于表皮脂肪组织.(3)血清中内脂素的水平与内脏脂肪组织及HOMA-IR呈正相关.结论:妊娠期糖尿病孕妇脂肪组织中内脂素表达上调,导致血液循环中内脂素水平升高,参与GDM孕妇血糖调节.     

血清VEGF、sFlt-1、IL-4水平与妊娠期高血压疾病患者预后的关系研究

摘要 目的：探讨血清血管内皮生长因子（VEGF）、可溶性Fms样酪氨酸激酶-1（sFlt-1）、白细胞介素-4（IL-4）水平与妊娠期高血压疾病（HDP）患者分类及妊娠结局的关系。方法：选取2019年7月～2021年1月我院收治的204例HDP患者（HDP组）,根据指南分类原则分为妊娠期高血压组（n=88）、子痫前期组（n=66）、子痫组（n=50）,根据妊娠结局分为结局不良组和结局良好组,另选取同期100名于我院产检健康孕产妇为对照组。采用单因素及多因素Logistic回归和受试者工作特征（ROC）曲线分析HDP患者妊娠结局不良的影响因素及血清VEGF、sFlt-1、IL-4水平对妊娠结局不良的预测价值。结果： 与对照组比较,HDP组血清VEGF、IL-4水平降低,sFlt-1水平升高（P＜0.05）。妊娠期高血压组、子痫前期组、子痫组血清VEGF、IL-4水平依次降低,sFlt-1水平依次升高（P＜0.05）。204例HDP患者妊娠结局不良发生率为29.90%（61/204）。单因素分析显示,妊娠结局不良与年龄、不同疾病分类、SBP、DBP、尿蛋白、VEGF、sFlt-1、IL-4有关（P＜0.05）。多因素Logistic回归分析显示,HDP患者妊娠结局不良的独立危险因素与独立保护因素分别为子痫、sFlt-1升高与VEGF、IL-4升高（P＜0.05）。血清VEGF、sFlt-1、IL-4水平单独与联合预测HDP患者妊娠结局不良的曲线下面积（AUC）分别为0.766、0.774、0.770、0.905,VEGF、sFlt-1、IL-4联合预测HDP患者妊娠结局不良的AUC最大。结论：HDP患者血清VEGF、IL-4水平降低,sFlt-1水平升高,与HDP分类和妊娠结局不良有关,VEGF、sFlt-1、IL-4联合对HDP患者妊娠结局不良的预测价值较高。     

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%。