格列奎酮的药动力学与动态血糖等多相关性研究

目的:探讨格列奎酮治疗2型糖尿病的药代动力学与动态血糖等多项目指标临床相关性.方法:近年诊断2型糖尿病患者22名,应用美国动态血糖监测系统(CGMS Mini Med Inc),测量药物治疗后不间断连续血糖监测曲线,与本药药代动力学水平作一动态分析.结果:1)口服本药2.5 h时血糖水平曲线最低平,与其它时段血糖水平曲线有统计学差异(P＜0.001).2)其中每日6Am口服本药2.5 h时血糖水平曲线为24h最低平,与其它时段血糖水平曲线有统计学差异(P＜0.001).3)口服本药7.5 h后血糖水平曲线渐次升高,至直再次口服本药后血糖水平曲线渐次降低至直口服本药2.5 h时血糖水平曲线最低平.4)每日服药一次24h血糖水平曲线较不服药者血糖水平曲线明显低平(P＜0.001).结论:每日6Am口服本药为最佳服药时间,口服本药2.5h时降糖作用最强,本药可在体内维持7.5.24h.     

血必净注射液联合静脉胰岛素泵入治疗糖尿病酮症酸中毒的效果及对氧化应激反应的影响

目的:探讨血必净注射液联合静脉胰岛素泵入治疗糖尿病酮症酸中毒的效果及对氧化应激反应的影响。方法:选择2016年8月至2018年8月我院收治的糖尿病酮症酸中毒患者80例,根据随机数表法分为观察组(n=41)和对照组(n=39)。对照组给予胰岛素泵治疗,观察组在对照组的基础上采用血必净注射液治疗。比较两组患者的临床疗效、治疗前后单核细胞趋化蛋白(MCP)、空腹血糖(FBG)、餐后血糖(PBG)、丙二醛(MDA)、超氧化物歧化酶(SOD)、总抗氧化能力(TAC)水平的变化及临床症状改善时间。结果:治疗后,两组单核细胞趋化蛋白水平均较治疗前显著下降,且观察组明显低于对照组(P0.05)。治疗后,观察组MDA低于对照组,SOD、TAC水平均显著高于对照组(P0.05);观察组血糖达标、尿酮体转阴、PH恢复时间及胰岛素用量均显著低于对照组(P0.05)。结论:血必净注射液联合胰岛素泵治疗糖尿病酮症酸中毒患者的效果显著明显优于单用血必净治疗,可能与其有效提高机体的抗氧化能力有关。     

罗格列酮联合胰岛素治疗老年2型糖尿病的临床研究

目的 观察罗格列酮联合胰岛素治疗老年2型糖尿病的疗效及安全性.方法 将60例老年2型糖尿病患者随机分为治疗组和对照组各30例,治疗组用罗格列酮4 mg/d,同时加用胰岛素;两组均随访12周,观测血糖、胰岛素用量指标变化及药物的不良反应;对照组单用胰岛素治疗并根据病情调整用量.结果 治疗组血糖水平从第2周开始明显下降,第8～12周血糖水平降幅最大,有21例达到空腹血糖＜6.5 mmol/L,餐后2 h血糖＜8.0 mmol/L的良好控制水平;从第2周开始,治疗组胰岛素用量也逐渐减少,至12周时,治疗组胰岛素用量较基础值减少(7.6±4.3)u;而对照组胰岛素用量却平均增加(9.1±5.1)u.治疗后两组血糖和胰岛素用量比较差异有统计学意义(P＜0.05).结论 罗格列酮联合胰岛素治疗老年2型糖尿病能有效控制患者的血糖水平,且安全,无不良反应.     

吡格列酮联合阿卡波糖对2型糖尿病患者血清RBP4、Leptin、Visfatin水平的影响

目的:探讨吡格列酮联合阿卡波糖治疗2型糖尿病的临床效果及对患者血清视黄醇结合蛋白4(RBP4)、瘦素(Leptin)、内脂素(Visfatin)表达的影响。方法:选择2015年10月至2017年10月我院接诊的90例2型糖尿病患者为本研究对象,通过随机数表法将其分为观察组(n=46)和对照组(n=44)。对照组在常规治疗基础上给予阿卡波糖治疗,观察组在对照组基础上联合吡格列酮治疗,两组均连续治疗12周。比较两组治疗前后血糖、动态血糖、胰岛细胞功能、血清RBP4、Leptin和Visfatin水平的变化和不良反应的发生情况。结果:治疗后,观察组空腹血糖(FBG)、餐后2 h血糖(2hPBG)、糖化血红蛋白(HbA1c)均明显低于对照组[(6.58±1.30)mmol/L vs.(7.47±1.44)mmol/L,(9.20±1.22)mmol/L vs.(10.36±1.31)mmol/L,(5.23±0.46)%vs.(5.88±0.62)%](P0.05);观察组最大血糖波动幅度(LAGS)、平均血糖波动幅度(MAGE)均明显低于对照组低,日平均达标率明显高于对照组[(7.43±1.26)mmol/L vs.(8.58±1.59)mmol/L,(3.39±0.42)mmol/L vs.(5.21±0.69)mmol/L,(90.34±2.40)%vs.(82.01±2.15)%](P0.05);观察组胰岛素β细胞(HOMA-β)明显高于对照组,胰岛素抵抗指数(HOMA-IR)明显低于对照组[(53.84±6.20) vs.(41.85±5.03),(2.84±0.40) vs.(3.72±0.72)](P0.05);观察组血清RBP4、Leptin、Visfatin水平均明显低于对照组[(8.30±1.20)mg/L vs.(10.57±1.65)mg/L,(8.23±1.42)μg/L vs.(10.84±1.79)μg/L,(17.40±2.42)μg/L vs.(24.03±3.06)μg/L](P0.05)。两组治疗期间均未发生头晕、低血糖等药物不良反应。结论:吡格列酮联合阿卡波糖治疗2型糖尿病患者的临床效果显著由于单用阿卡波糖的患者,其可显著患者降低血糖水平和改善IR,其内在机制可能和降低血清RBP4、Leptin、Visfatin的表达相关。     

中重度颅脑损伤患者早期血磷水平与近期预后的相关性分析

目的:探讨中重度颅脑损伤患者早期血磷水平与近期预后的相关性。方法:将97例中重度颅脑损伤患者按照入院后24 h内的血磷水平分为低磷血症组(n=23例,血磷0.80 mmol/L)和正常血磷组(n=74例,血磷≥0.80 mmol/L);记录患者入院后28 d的预后情况,按照是否死亡分为死亡组及存活组,比较两组相关指标的差异。用Logistic回归方程分析血磷水平与患者死亡的关系,应用ROC曲线评估血磷水平预测患者死亡的临床价值。结果:与血磷正常组比较,低磷血症组患者发病至入院时间较长、入院时血压及GCS评分较低、入院APACHEⅡ评分较高,死亡率偏高(P0.05);死亡组患者入院GCS评分低于存活组,而APACHEⅡ评分高于存活组(P0.05);血磷水平及低磷血症的发生率高于存活组(P0.05),多因素Logistic回归方程分析提示:血磷降低是中重度颅脑损伤患者入院28d后死亡的独立危险因素(P0.05)。血磷水平(≤0.68 mmol/L)预测患者死亡的曲线下面积(ROCAUC)分别为:0.889;灵敏度和特异度分别为:83.9%;77.6%。最佳诊断截点为0.68 mmol/L。结论:血磷水平降低可能是中重度颅脑损伤患者近期死亡的独立危险因素,早期检测血磷水平对评估患者近期预后具有一定的临床意义。     

吡格列酮治疗对2 型糖尿病合并代谢综合征患者血糖、胰岛素抵抗和炎症因子的影响

目的:探讨吡格列酮治疗对2型糖尿病合并代谢综合征患者血糖、胰岛素抵抗和炎症因子的影响。方法:回顾性分析我院2013年8月-2015年2月收治的96例2型糖尿病合并代谢综合征患者病例资料,根据治疗方法的不同分为观察组和对照组,每组48例,两组患者均给予糖尿病常规基础治疗,在此基础上,观察组患者给予吡格列酮治疗,治疗3个月。检测治疗前后血糖指标包括空腹血糖(FPG)、餐后2小时血糖(2h PG)以及糖化血糖蛋白(Hb A1c),胰岛素抵抗指标包括空腹胰岛素(FINS)和胰岛素抵抗指数(HOMA-IR)和炎症因子包括超敏C反应蛋白(hs-CRP)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)。结果:观察组治疗后FPG、2 h PG、Hb A1c分别为(6.19±2.24)mmol/L、(8.30±2.48)mmol/L和(6.01±1.23)%,均显著低于治疗前和对照组治疗后,差异有统计学意义(P0.05);观察组治疗后FINS和HOMA-IR分别为(6.60±1.92)m IU/L和2.08±1.00,均较治疗前和对照组治疗后显著降低,差异有统计学意义(P0.05);观察组治疗后hs-CRP、IL-6和TNF-α分别为(6.12±1.67)ng/L、(62.65±10.30)ng/L和(83.16±16.55)ng/L,均较治疗前和对照组治疗后显著降低,差异有统计学意义(P0.05)。结论:吡格列酮治疗可以显著降低2型糖尿病合并代谢综合征患者血糖水平,改善胰岛素抵抗,降低炎症反应,值得进一步研究。     

糖尿病患者外科手术麻醉的临床研究与探讨

目的:研究与探讨糖尿病患者外科手术麻醉的安全性和有效性。方法:糖尿病外科手术患者262例。其中急性胆囊炎64例,胃穿孔52例,化脓性阑尾炎71例,阑尾穿孔弥漫性腹膜炎各63例,外伤性脾破裂12例。采用硬膜外麻醉146例,全身麻醉116例。结果:所有患者均手术顺利,麻醉平稳,麻醉手术过程中血糖水平较术前均有不同程度升高,按升高的血糖量适当增加胰岛素用量,血糖控制在10-12mmol/L,尿酮体(-),无糖尿病酮症酸中毒、高渗性非酮症性高血糖昏迷及低糖症发生。术毕均及时清醒,拔管,血糖水平较平稳。结论:急诊糖尿病患者手术时采用硬膜外麻醉对血糖影响小于全麻。     

人脐带间充质干细胞对猕猴糖尿病治疗效果的研究

目的通过用人脐带间充质干细胞(huMSCs)治疗猕猴糖尿病模型观察其血糖的变化。方法猕猴9只,分为对照组3只和模型组6只,模型组通过高糖高脂饮食及静脉注射链尿佐菌素(STZ)诱导成糖尿病模型,两组间比较用t检验。12周时再分为模型对照组3只和治疗组3只,治疗组每只每周静脉回输huMSCs 1×10~6个/kg,连续3周,每周检测各组血糖变化,三组间比较用方差分析。结果两组猕猴高糖高脂饮食喂养第8周时模型组空腹血糖值[(22.00±3.00)mmol/L]与对照组[(4.75±0.20)mmol/L]相比差异有统计学意义(t=9.94,P0.01)。40周时1只猕猴因糖尿病死亡,病理切片证实心、肝、脾、肺、肾和胰腺均有病变,符合糖尿病特征。huMSCs治疗后,3周血糖连续下降,到第4周对照组、模型组、治疗组空腹血糖分别为(4.85±0.35)mmol/L、(18.20±1.00)mmol/L、(4.09±0.50)mmol/L,3组差异有统计学意义(F=388.10,P0.01)。两两比较结果表明对照组和模型组比较差异有统计学意义(t=24.173,P0.01),模型组与治疗组比较差异有统计学意义(t=25.549,P=0.014)。结论 STZ联合高糖高脂饲料能成功诱导出猕猴糖尿病模型,用huMSCs能有效降低血糖,使糖尿病猕猴恢复正常血糖,方法简便。     

脐带间充质干细胞移植对糖尿病肾病的临床观察

目的探讨脐带间充质干细胞(UCMSC)移植治疗糖尿病肾病的临床效果及安全性。方法选择福州总医院干细胞治疗科收治的15例经胰背动脉、双肾动脉介入及外周静脉移植UCMSC治疗糖尿病肾病的患者为实验组,肾内科收治的15例单纯采用口服缬沙坦,皮下注射胰岛素治疗糖尿病肾病的患者为对照组。通过监测两组患者治疗前及治疗后3个月的血压、血糖、C肽值以及肾功能指标的变化情况来分析比较两组患者的治疗效果。采用配对样本t检验分别对实验组治疗前、后及对照组治疗前、后各项指标的差异进行统计分析比较,采用两独立样本t检验对实验组、对照组治疗前、后各项指标的差值进行统计分析比较。结果两组患者各项监测指标治疗后均较治疗前有所下降,差异均有统计学意义(P0.05)。对两组患者治疗前及治疗后3个月各项指标差值进行比较,实验组、对照组患者舒张压、尿素氮、血清肌酐、24 h尿白蛋白定量治疗前后差值分别为[(14.6±3.68)mm Hg,(12.1±2.49)mm Hg,t=2.208,P=0.037],[(1.97±0.77)mmol/L,(1.04±0.32)mmol/L,t=4.261,P=0.000],[(57.6±14.08)μmol/L,(39.5±14.61)μmol/L,t=3.448,P=0.002],[(1.48±0.45)g/d,(0.74±0.35)g/d,t=5.017,P=0.000],差异有统计学意义(P0.05)。结论经胰背动脉、双肾动脉介入及外周静脉移植UCMSC治疗糖尿病肾病安全有效,在改善舒张压、肾功能方面的临床疗效优于单纯控制血压、血糖等常规方法治疗糖尿病肾病。     

前列腺增生伴Ⅱ型糖尿病患者的尿流动力学分析

目的:探讨前列腺增生伴Ⅱ型糖尿病患者的尿流动力学改变,并对该类患者提出合理的治疗和处理。方法:选取从2010年9月~2013年9月在本院泌尿外科一病房行经尿道前列腺电切,术后病理诊断为前列腺增生术前行尿流动力学检查的患者349例,分为单纯前列腺增生组158例(对照组)及前列腺增生合并Ⅱ型糖尿病组191例(研究组),前列腺增生合并Ⅱ型糖尿病组又分为两个亚组,即空腹血糖≤6.1 mmol/L组(亚1组)96例及空腹血糖6.1 mmol/L组95例(亚2组)。比较各组患者尿流动力学各项检查结果。结果:1)、比较亚2组和对照组患者残余尿量、最大尿流率、最大尿流率时逼尿肌压、最大逼尿肌压及顺应性,P值均0.05。2)、亚1组和对照组患者残余尿量、最大尿流率、最大尿流率时逼尿肌压、最大逼尿肌压及顺应性,除亚1组病程5年的残余尿量、顺应性P值0.05外,其他均0.05。3)、亚1组和亚2组患者残余尿量、最大尿流率、最大尿流率时逼尿肌压、最大逼尿肌压及顺应性,P值均0.05。4)、亚1组和亚2组不稳定膀胱率明显高于对照组。结论:Ⅱ型糖尿病能加重前列腺增生患者膀胱功能障碍,及早控制血糖能减轻、延缓膀胱功能障碍。     

Anthropology and genetics of the caucasus peoples and the problem of the origin of the caucasoids

The electrophoretical polymorphisms of some blood proteins were studied in the Talysh population of Pirasora situated in South-East Azerbaidjan. We calculated the gene frequencies of these polymorphisms and determined the genetic distances between the Talyshes and some Iranian populations of North, Central and South Iran, Afghans, and three populations of Azerbaijan. The Talyshes are very close to Iranians of Shiraz, whereas they are distant from the Azerbaijanians. Anthropological investigations showed that the Caucasoids and Mongoloids lived in the Aragvi Basin since the Eneolithic period. This was stated by Alexeev (1974), who emphasized the mixture of the Caucasus populations from ancient times on. We calculated the genetic distances between the Caucasus populations and numerous populations of other geographic regions, considering 28 alleles of 12 loci of blood group, serum protein and red cell enzyme polymorphisms and constructed the dendrogram of these populations. The position of the Caucasus populations in the dendrogram corresponds on principle to the earlier anthropological observations. The clustering of the Caucasoid populations corresponds completely with anthropological and historical data, and supports our earlier hypothesis (Nazarova 1999) concerning the differentiation of Caucasoids, Northern Mongoloids and Amerinds from the populations, which inhabitated Asia in palaeolithic times.     

Serology and systematics of the Ebenales and the Theales

The systematic position ofthe Ebenaceae, Sapotaceae, Styracaceae, Ochnaceae, Stachyuraceae, Dipterocarpaceae, Clusiaceae and Hypericaceae has been investigated using serological comparisons of sets of antigenic determinants. The results show that the Sytracaceae and Sapotaceae are undoubtedly more closely associated with the Actinidiaeceae and Theaceae, respectively, than with each other. We found no corresponding determinants betnween antigen systems from the Ebenaceae and systems from any other family whose relations to this family have been proposed. As discovered previously, investigations of antigen systems from the Ochnaceae, Dipterocarpaceae, Stachyuraceae, Clusiaceae and Hypericaceae are against the idea of a natural order “Theales” in which these families, or at least some of them, are combined with the Theaceae and Actinidiaceae. This paper completes our previous investigations which largely support a superorder Ericanae sensu Ehrendorfer and Takhtajan. We propose to include the Actinidiaceae and Theaceae in this superorder, assigning them a central position laong with the Sapotaceae and Sytracaeae on one side and the Primulales and Ericales on the other. Another most interesting finding is that there are corresponding determinants between antigen systems from the members of the Ericanae and representatives of the Polemoniaceae and Loasaceae.     

人类基因组及后基因组研究进展及其应用与开发研究现状

人类对自身基因组的研究,随着人类基因组工作草图的绘制完成和对基因功能研究的深入已加快进入了实质性、关键性的开发利用阶段。本文概述了人类基因组及后基因组的研究进展及依此开展基因治疗及基因（组）药物研制等应用开发研究的现状。     

On the structure and dynamics of the complex of the nucleosome and the linker histone

Several different models of the linker histone (LH)–nucleosome complex have been proposed, but none of them has unambiguously revealed the position and binding sites of the LH on the nucleosome. Using Brownian dynamics-based docking together with normal mode analysis of the nucleosome to account for the flexibility of two flanking 10 bp long linker DNAs (L-DNA), we identified binding modes of the H5-LH globular domain (GH5) to the nucleosome. For a wide range of nucleosomal conformations with the L-DNA ends less than 65 Å apart, one dominant binding mode was identified for GH5 and found to be consistent with fluorescence recovery after photobleaching (FRAP) experiments. GH5 binds asymmetrically with respect to the nucleosomal dyad axis, fitting between the nucleosomal DNA and one of the L-DNAs. For greater distances between L-DNA ends, docking of GH5 to the L-DNA that is more restrained and less open becomes favored. These results suggest a selection mechanism by which GH5 preferentially binds one of the L-DNAs and thereby affects DNA dynamics and accessibility and contributes to formation of a particular chromatin fiber structure. The two binding modes identified would, respectively, favor a tight zigzag chromatin structure or a loose solenoid chromatin fiber.     

Kinematics and dynamics of the temporomandibular joint and of the movements of the mandible

In order to analyze the complicated movements of the mandible as the open-closing movement and the protrusio are, it is useful to evaluate the basic kinematic principles and reduce them to simple technical constructions. Both the open-closing movement and the protrusio could be reduced to 4-bar links, which were used to simulate the movements with help of a computer. Besides, the polodes and the curves of points in the muscular attachments could be constructed. The 2 entirely different 4-bar links have 3 things in common: The resting system - cranium, the moving system - mandibula, and 1 of the 2 arms connecting these 2 systems - the ligamentum laterale. As this ligament is taut during movements it can be considered a "guiding ligament" representing 1 of the 3 determining components of the mandibular movements. The other of the 2 arms has no anatomical equivalent; this arm, however, is "replaced" by the 2 other determining components of the mandibular movements: the joint and the muscles. The curves, which the Caput mandibulae describes, are practically identical for the open-closing movement and the protrusio despite of the different 4-bar links and these curves exactly correspond to the Discus articularis, taut by the upper part of the M. pterygoideus lateralis. The muscles do not only just move the mandibula, but they are also the component, which can choose between the different mandibular movements. By means of the curves, which points in the muscular attachments describe, the function of the masticatory muscles could be analyzed exactly.     

Biophysics and Structure of the Patch and the Gigaseal

Interpreting channel behavior in patches requires an understanding of patch structure and dynamics, especially in studies of mechanosensitive channels. High resolution optical studies show that patch formation occurs via blebbing that disrupts normal membrane structure and redistributes in situ components including ion channels. There is a 1-2 μm region of the seal below the patch where proteins are excluded and this may consist of extracted lipids that form the gigaseal. Patch domes often have complex geometries with inhomogeneous stresses due to the membrane-glass adhesion energy (E_a), cytoskeletal forces, and possible lipid subdomains. The resting tension in the patch dome ranges from 1-4 mN/m, a significant fraction of the lytic tension of a bilayer (∼10 mN/m). Thus, all patch experiments are conducted under substantial, and uneven, resting tension that may alter the kinetics of many channels. E_a seems dominated by van der Waals attraction overlaid with a normally repulsive Coulombic force. High ionic strength pipette saline increased E_a and, surprisingly, increased cytoskeletal rigidity in cell-attached patches. Low pH pipette saline also increased E_a and reduced the seal selectivity for cations, presumably by neutralizing the membrane surface charge. The seal is a negatively charged, cation selective, space with a resistance of ∼7 gigohm/μm in 100 mM KCl, and the high resistivity of the space may result from the presence of high viscosity glycoproteins. Patches creep up the pipette over time with voltage independent and voltage dependent components. Voltage-independent creep is expected from the capillary attraction of E_a and the flow of fresh lipids from the cell. Voltage-dependent creep seems to arise from electroosmosis in the seal. Neutralization of negative charges on the seal membrane with low pH decreased the creep rate and reversed the direction of creep at positive pipette potentials.     

The efficacy of ropivacaine and bupivacaine in the caesarean section and the effect on the vital signs and the hemodynamics of the lying-in women

ObjectiveTo investigate the efficacy of ropivacaine and bupivacaine in caesarean section and vital signs and the hemodynamics of the lying-in women.MethodsA total of 480 lying-in women who were admitted to this hospital for treatment between December 2017 and June 2018 were enrolled into this study as the subjects, which were divided into the experiment group and the control group, with 240 subjects in each group. In the experiment group, subjects received the local anesthesia by infusion of 1.5 mL ropivacaine (0.75%), while those in the control group also took the local anesthesia by infusion of 1.5 mL bupivacaine (0.75%). Thereafter, we observed the differences in the anesthetic efficiency, vital signs and hemodynamics of the lying-in women between two groups.ResultsThe excellent and good rates of the anesthesia in two groups were 92.1% and 87.9%, showing no obvious difference; in the experiment group, the average arterial pressures and systolic pressures at 5 min and 10 min after combined spinal and epidural analgesia (CSEA) were all elevated when comparing to the control group (all P < 0.05); in the experiment group, the onset time was obviously extended, while duration of sensory and motor block and the duration of motor block were all shorter than those in the control group (all P < 0.05). During anesthesia, the incidence rate of the adverse reactions in the control group was 2.50%, significantly higher than 0.83% in the experiment group (P < 0.05).ConclusionDespite that ropivacaine and bupivacaine are efficient in anesthesia in the CSEA in the caesarean section, ropivacaine is more recommended for little influence on the hemodynamics, shorter duration of sensory block and motor block and low incidence rate of adverse reactions, which are conducive to the recovery and also safe to the patients.