IL-10基因启动子区G-1082A及C-592A多态性与IgA肾病相关性研究

目的：探讨IL-10基因启动子区域G-1082A、C-592A多态性与汉族人群IgA肾病（IgAN）发病间关系。方法：用SSP-PCR方法对180例IgA肾病（IgAN）患者和163例健康对照组IL-10基因启动子区域-1082、-592位点单核苷酸多态性进行分析。结果：-1082位点IgA肾病患者AG/GG基因型频率显著高于正常对照组（为21.0% vs 11.7%,P〈0.05）;-1082位点G等位基因频率显著高于正常对照组（为11.0% vs 6.4%,P〈0.01）;携带有G等位基因者患IgA肾病危险性是携带有A等位基因者1.8倍,95%CI为1.12-3.20。-592位点IgA肾病患者AA、CA、CC基因型与正常对照组相比,无统计学差异（11.11% vs 16.56%;46.67% vs 51.53%;42.22% vs 31.90%,P〉0.05）;-592位点C等位基因频率与正常对照组相比,无统计学差异（32.21% vs 32.50%,P〉0.05）。结论：IL-10基因G-1082A是中国汉族人群IgA肾病患者的易感基因,携带G等位基因者患IgA肾病的危险性是携带A等位基因者的1.8倍。     

白细胞介素16基因多态性与大肠癌发病风险的关系

目的：探讨中国山东籍汉族大肠癌（CRC）患者人群中,IL-16基因多态性与大肠癌发病风险的关系。 方法：在164例CRC患者和121名健康对照个体中,采用放大阻碍突变PCR（ARMS-PCR）方法对IL-16基因序列中的2个单核苷酸多态性（SNP）位点rs11556218和rs4778889进行基因分型,分析该2个位点的等位基因频率和基因型分布与CRC发病风险的关系。 结果：在CRC患者中,rs11556218的T/G等位基因频率和基因型分布与对照组的差异有统计学意义（P=0.021?725,P=0.001?033）;rs4778889的T/C等位基因频率及基因型分布与正常对照组的差异无统计学意义（P=0.057?946,P=0.064?229）。 结论：IL-16的rs11556218基因多态性与可能与CRC的易感性增加有关。     

信号传导与转录激活因子-4基因rs7574865位点单核苷酸多态性与类风湿关节炎易感性荟萃分析

目的：综合评价信息传导与转录激活因子-4基因（STAT4基因）rs7574865位点单核苷酸多态性与类风湿关节炎易感性的相关性。方法：计算机检索Pubmed、Embase、中国生物医学文献数据库和万方数据库数据库等,并手工检索相关杂志,收集有关不同人群STAT4基因rs7574865位点单核苷酸多态性的等位基因频率、基因型频率与类风湿性关节炎易感性相关性的研究,采用Stata 12.0软件进行Meta分析;选择的遗传模型包括GT＋TT与GG比较,TT与GT＋GG比较,TT与GG比较以及等位基因T与G之间比较。结果：STAT4基因rs7574865位点T等位基因频率与类风湿性关节炎易感性可能具有相关性（OR=1.259,95%CI=1.202-1.319, P＜0.001）;T等位基因频率与类风湿性关节炎易感性的相关性在欧洲、亚洲、非洲、拉丁美洲人群中有统计学意义;在总体人口中STAT4基因rs7574865位点的基因型与类风湿性关节炎易感性可能具有相关性;在总体人口中STAT4基因rs7574865位点多态性与抗CCP抗体阳性或RF因子阳性类风湿性关节炎易感性仍可能具有相关性。结论：STAT4基因rs7574865位点单核苷酸多态性与类风湿性关节炎易感性可能具有相关性,而且这种相关性可能独立于患者RF因子以及抗CCP抗体水平。     

易感基因CELSR2与汉族青少年特发性脊柱侧凸的相关性研究

目的 :在中国汉族人群中验证易感基因CELSR2与青少年特发性脊柱侧凸(adolescent idiopathic scoliosis,AIS)发病的相关性。方法:利用等位基因特异性多重连接酶检测反应在1794例AIS患者和1040例正常对照人群中对既往报道的CELSR2基因的易感位点rs141489111、rs6698843和rs2281894进行基因分型。同时在本中心全基因组数据库中分析CELSR2基因其他单核苷酸多态性位点(SNP)的基因分型信息。术中收集45例AIS患者(AIS组)和10例年龄匹配的脊柱外伤患者(对照组)的椎旁肌,比较两组椎旁肌中基因表达水平的差异。利用卡方检验分析组间SNP位点最小等位基因频率差异,采用T检验对组间的基因表达水平进行统计分析。结果:1794例AIS患者和1040例正常对照人群中,rs141489111位点未检测到突变,所有研究对象基因型均为GG。SNP位点rs6698843和rs2281894的基因型及等位基因频率在AIS和正常对照人群间未见显著性差异(P0.05)。GWAS数据库显示其他7个位于CELSR2基因上的SNP位点与AIS亦无显著相关性(P0.05)。CELSR2基因在AIS组和对照组椎旁肌的表达水平无显著性差异(P0.05)。结论:既往报道的易感基因CELSR2上的突变位点和多态性位点均未在中国汉族人群中得到验证,AIS患者椎旁肌组织中CELSR2表达未见明显异常。CELSR2可能与汉族AIS的发生无关。     

耐酒石酸酸性磷酸酶5基因多态性与青少年特发性脊柱侧凸患者相关性研究

目的 探讨耐酒石酸酸性磷酸酶5 (ACP5)基因多态性与青少年特发性脊柱侧凸(AIS)易感性和严重程度的相关性.方法 选择2006年1月至2008年12月372例AIS患者(AIS组)和2005年3月至2006年8月239名健康青少年(正常对照组),所有AIS患者Cobb角均≥10°.结合汉族人单倍体型资料,选取rs2229531、rs2071484两个单核苷酸多态性位点,采用PCR-限制性片段长度多态性的方法对这两个位点进行基因分型.比较不同基因型在AIS组与正常对照组之间的分布差异,并分析基因多态性与Cobb角的相关性.结果 AIS组与正常对照组的rs2229531位点均未见多态性.AIS组ACP5基因rs2071484位点的基因型及等位基因分布与正常对照组比较差异无统计学意义(x2=3.336和1.438,P＞0.05).rs2071484多态性位点AA、AG、GG基因型所对应的平均最大Cobb角分别为38°±19°、34°±14°、38°±21°,三者相比差异无统计学意义(P =0.157).结论 ACP5基因多态性可能与AIS的发生发展没有明显关系.     

pre-miR-146a基因rs2910164位点单核苷酸多态性与胆管癌的关系

目的：探讨pre-miR-146a基因表达及其rs2910164位点多态性与胆管癌的关系。 方法：分别用基因直接测序与定量PCR方法检测70例胆管癌患者的胆管癌组织（胆管癌组）及 39例胆管非肿瘤性疾病患者的胆管组织（对照组）中pre-miR-146a基因rs2910164位点单核苷酸多态性与pre-miR-146a表达,分析不同基因型与pre-miR-146a表达量、胆管癌临床病理及其预后的关系。 结果：胆管癌组的pre-miR-146a基因型分布与对照组有明显差异,前者表现为GG和GC基因型比例明显高于CC基因型,且G等位基因频率明显高于C等位基因（均P<0.05）;对照组GG和GC基因型人群的pre-miR-146a表达量较CC基因型低,但差异无统计学意义（P>0.05）,胆管癌组织pre-miR-146a表达量明显低于对照组胆管组织（P<0.05）;Logistic多元回归分析显示GG和GC基因型可能是胆管癌的危险因素（P=0.052）,分层分析显示GG和GC基因型与胆管癌患者的临床分期和淋巴结转移有关（均P<0.05）;生存分析显示GG和GC基因型胆管癌患者的生存率低于CC基因型胆管癌患者,但差异无统计学意义（P=0.178）。 结论：pre-miR-146a基因rs2910164位点G等位基因频率升高可能是导致pre-miR-146a基因表达降低以及胆管癌发生发展的危险因素。

     

褪黑素受体1A基因多态性与青少年特发性脊柱侧凸相关性研究

目的研究褪黑素受体1A基因（MTNR1A）多态性与青少年特发性脊柱侧凸（AIS）发生发展的关系。方法共纳入226例AIS患者及277例正常对照者。记录AIS患者组最大Cobb角。采用PCR-RFLP的方法对MTNR1A基因启动子区域多态性位点rs2119882进行基因分型。结果AIS患者组MTNR1A基因多态性位点rs2119882的基因型及等位基因分布与正常对照组比较没有明显差异。在AIS组内,多态性位点rs2119882不同基因型所对应的最大Cobb角没有明显差异。结论MTNR1A基因rs2119882位点多态性与AIS的发生发展都没有关系。     

先天性巨结肠的SEMA3A基因单核苷酸多态性分析

目的探讨SEMA3A基因单核苷酸多态性（SNP）与先天性巨结肠发生的关系。方法应用PCR扩增后直接测序的方法．分析119例先天性巨结肠患者和93例正常人群中SEMA3Ars7804122、rs7978212个SNP位点基因型。结果SEMA3A基因rs797821位点的等位基因频率和基因型频率在先天性巨结肠组和正常对照组的分布差异无统计学意义（P〉0．05）。rs7804122位点的G等位基因（26．9％）和GG（5．0％）,AG（43．7％）基因型在先天性巨结肠组中的频率明显高于正常对照组（12．9％、1．1％、23．7％,P〈0．05）。结论SEMA3A基因是先天性巨结肠重要的易感基因．其rs7804122位点G等位基因是先天性巨结肠发病的危险因素。     

中国汉族人群TGFBR2基因rs6785358、rs764522多态性与风湿性心脏病的关联研究

目的探讨中国汉族人群转化生长因子Ⅱ型受体(transforming growth factor-βreceptor typeⅡ,TGFBR2)基因rs6785358、rs764522位点多态性与风湿性心脏病(rheumatic heart disease,RHD)的关系。方法采用病例对照设计,选择2008年10月至2011年1月在南京医科大学附属南京第一医院住院的风湿性心脏病患者207例作为风湿性心脏病组(风心病组)及性别年龄匹配的健康成人225例作为对照组。采用聚合酶链反应-限制性片段多态性(PCR-RFLP)方法检测两组TGFBR2基因rs6785358、rs764522位点的多态性。结果风心病组和对照组TGFBR2基因rs6785358位点AA、AG、GG基因型频率分别为72.0%、25.1%、2.9%和68.9%、28.0%、3.1%,两组比较差异无统计学意义(χ2=0.50,P=0.78);A和G等位基因频率分别为84.5%、15.5%和82.9%、17.1%,两组比较差异无统计学意义(χ2=0.43,P=0.51)。风心病组和对照组rs764522位点CC、CG、GG基因型频率分别为77.3%、21.3%、1.4%和75.6%、21.3%、3.1%,两组比较差异无统计学意义(χ2=1.33,P=0.51);C和G等位基因频率分别为87.9%、12.1%和86.2%、13.8%,两组比较差异无统计学意义(χ2=0.55,P=0.46)。经性别分层后,rs6785358和rs764522的基因型和等位基因频率在风心病组和对照组中的分布差异仍无统计学意义(P0.05)。结论中国汉族人群TGFBR2基因rs6785358、rs764522位点多态性与风湿性心脏病无明显关联。     

CALM2基因多态性与青少年特发性脊柱侧凸遗传易感性的关联性研究

目的探讨钙调蛋白2基因（CALM2基因）与青少年特发性脊柱侧凸遗传易感性的相关性。方法采集北京协和医院骨科确诊的汉族青少年特发性脊柱侧凸患者107例,对照组107例,病例组按照PUMC分型进行分组。采外周血试剂盒提取DNA。根据国际人类基因组单倍体型图计划提供的基因型数据,选取CALM2基因的SNPs位点,应用VeraCode GoldenGate Genotyping Assay基因芯片进行SNPs基因型鉴定。用关联分析法探索CALM2基因与患者发病及临床表型之间的关系。结果 CALM2的rs10153674等位基因在病例组和对照组中的分布频率统计学上存在显著差异（P=0.003）,rs10153674位点等位基因G与AIS的易感性升高有关。结合PUMC分型,rs10153674和rs1027478基因型在PUMCI型和对照组中的分布频率统计学上存在显著差异（P值分别为0.038,0.006）,rs10153674基因型G/G、rs1027478基因型A/G与PUMCI型的发生有关。结论 CALM2基因遗传变异可能与青少年特发性脊柱侧凸发生相关,有可能是影响AIS易感性的重要因素。PUMCI型AIS的发生可能与rs10153674和rs1027478基因型多态性有关。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Immunomodulation in Transplantation with Photopheresis

Abstract: Photopheresis is a technique in which peripheral blood mononuclear cells, in the presence of a photoacti-vatable compound, are exposed extracorporeally to ultraviolet A light and reinfused, inducing a host autoregula-tory immune response. Experimental work and ongoing clinical studies are helping to define the role of this novel, safe, and non-toxic immunomodulating technology in the field of transplantation.