白藜芦醇对大鼠脊髓损伤早期Bcl-2和Bax表达的影响

目的:探讨脊髓损伤后使用白藜芦醇对脊髓损伤早期Bcl-2和Bax表达的影响。方法:2004-06/09在武汉大学人民医院动物实验中心将62只SD健康成年雄性大鼠随机分成5组,据Allen's法制成中度脊髓损伤模型,术后立即腹腔注射白藜芦醇100mg/kg或甲基强的松龙(MPSS)100mg/kg;通过免疫组织化学染色观察脊髓损伤8,24及72h后白藜芦醇组脊髓Bcl-2和Bax表达的变化,并与MPSS组进行疗效对比。结果:与损伤组比较,Bcl-2表达在损伤后8h差异无显著性意义(P>0.05),显示白藜芦醇对损伤后的脊髓无干预作用,而24及72h后差异有显著性意义P<0.01),表明白藜芦醇能够增强Bcl-2表达,对(损伤后脊髓有明显作用;Bax表达在损伤后8及72h差异有显著性意义(P<0.05),其中24h时最为显著(P<0.01),表明白藜芦醇可抑制Bax表达,对损伤后的脊髓有干预作用;白藜芦醇与MPSS组间差异无显著性意义(P>0.05),即白藜芦醇对损伤后脊髓有相似作用。结论:白藜芦醇在脊髓损伤早期能够有效上调Bcl-2表达及下调Bax表达,对损伤后脊髓起保护作用。     

异氟醚对人单核细胞株THP-1细胞凋亡的影响

目的:检验异氟醚是否诱导入单核细胞株THP-1细胞凋亡。方法:培养THP-1细胞于RPMI1640培养基中,检测THP-1细胞与不同浓度(0.5、1.0、2.0MAC)异氟醚接触不同时间(0、2、4、6h)的细胞凋亡率,同时检测接触异氟醚6h后再继续培养至24h的细胞凋亡率。细胞用碘化丙啶染色后通过流式细胞仪检测细胞凋亡率。结果:THP-1细胞凋亡率呈剂量依赖方式增加,在接触异氟醚6h为12.62±4.56%[1.0MAC],16.02±4.31%[2.0MAC]),对照为2.50±0.66%;在接触异氟醚24h为35.49±5.89%[1.0MAC],37.50±5.36%[2.0MAC]),对照为7.71±1.36%。THP-1细胞凋亡率也呈时间依赖方式增加,在接触1.0MAC异氟醚为1.14±0.34%[0h],8.55±1.44%[4h],12.62±4.56%[6h],35.49±5.89%[24h],对照为1.11±0.35%[0h],1.27±0.18%[4h],2.50±0.66%[6h],7.71±1.36%[24h];在接触2.0MAC异氟醚为1.20±0.25%[0h],9.30±1.78%[4h],16.02±4.31%[6h],37.50±5.36%[24h],对照为1.11±0.35%[0h],1.27±0.18%[4h],2.50±0.66%[6h],7.71±1.36%[24h]。结论:吸入0.5MAC以下浓度异氟醚对THP-1细胞凋亡无明显影响,当吸入浓度大于1.0MAC时,异氟醚以剂量和时间依赖方式诱导THP-1细胞凋亡。     

Phosphodiesterase 4D gene polymorphism is associated with ischaemic and haemorrhagic stroke

It has been reported that the variants of the PDE4D (phosphodiesterase 4D) gene are associated with stroke, especially with the combination of cardio-embolic and carotid stroke in the Icelandic population, but it is still very controversial as to whether PDE4D is a susceptible gene for stroke in other populations. In the present study, we tested whether the PDE4D gene variation also confers stroke risk in a Chinese population. Our hypothesis was tested in a case-control study of a Chinese population comprising 639 stroke patients (including 253 with cerebral thrombosis, 171 with lacunar infarction and 215 with intracerebral haemorrhage) and 887 healthy controls. Three SNPs (single nucleotide polymorphisms) (rs966221, rs456009 and rs2910829) in PDE4D were chosen based on the significant association with stroke reported previously in a Western population, and these were genotyped using PCR/RFLP (restriction-fragment-length polymorphism) and confirmed by sequencing. We found that only SNP83 (rs966221) was associated with stroke. Allele C of rs966221 is a risk allele, conferring an increased risk for atherothrombotic strokes [OR (odds ratio), 1.51; 95% CI (confidence interval), 1.09-2.10] independent of conventional risk factors. Haplotype analysis confirmed that haplotype G-C-C was associated with increased risk for atherothrombotic stroke (OR, 1.80; 95% CI, 1.300-2.491). Our findings support that SNP83 of PDE4D is a genetic risk factor for atherothrombotic strokes in a Chinese population.     

氯胺酮在吗啡急性耐受大鼠的外周镇痛作用

我们产证明氯胺酮引起的外周镇痛作用与阿片受体的激活有关。本实验旨在建立吗啡外周镇痛耐受的大鼠模型，进一步观察氯胺酮的外周镇痛作用与阿片受体的关系。外周感受野局部皮下注射５μｌ吗啡（１０μｇ／μｌ）明显的抑制伤害性肌电反应。随吗啡注射次数的增加，伤害性反应的抑制逐渐减弱，一般于第五次注射，吗啡不再产生抑制，出现外周镇痛的急性耐受。但是，在耐受动物的同一部位注射０μｌ氯胺酮（５０μｇ／μｌ），仍产生很     

131碘治疗分化型甲状腺癌患者的健康教育

总结分化型甲状腺癌患者行131I治疗的健康教育内容及方式。为了缩短住院时间和有利于患者掌握健康教育内容,采用入院前、入院后、131I治疗前和出院前4个阶段进行健康教育,使每个患者知晓核素治疗的特点和要求,自觉遵守国家的放射防护法规,保护环境和家人,又达到治疗的目的。     

原发性胸腺癌15例外科治疗分析

目的：分析原发性胸腺癌临床特征和外科治疗。方法：对15例手术治疗并经病理证实的原发性胸腺癌患者的临床资料进行回顾性分析，讨论该病的诊断及治疗。结果：患者年龄19～70岁，平均52．8岁。大多具有临床症状，6例有咳嗽咳痰，4例有胸闷或胸部隐痛。X线和CT显示前纵隔内肿块影，术前能确诊仅8例(53．3％)。行手术切除11例，术后平均生存时间23．6个月，1年生存率为40．0％，3年生存率为13．3％，5年生存率为0，有2例复发，8例转移。结论：原发性胸腺癌是一种高度恶性肿瘤，术前确诊率较低，应早期采用外科手术治疗，预后不良。     

DURATION-1: Exenatide Once Weekly Produces Sustained Glycemic Control and Weight Loss Over 52 Weeks

OBJECTIVE

In the Diabetes Therapy Utilization: Researching Changes in A1C, Weight and Other Factors Through Intervention with Exenatide Once Weekly (DURATION-1) study, the safety and efficacy of 30 weeks of treatment with the glucagon-like peptide-1 receptor agonist exenatide once weekly (exenatide QW; 2 mg) was compared with exenatide BID in 295 patients with type 2 diabetes. We now report the safety and efficacy of exenatide QW in 1) patients who continued treatment for an additional 22 weeks (52 weeks total) and 2) patients who switched from exenatide BID to exenatide QW after 30 weeks.

RESEARCH DESIGN AND METHODS

In this randomized, multicenter, comparator-controlled, open-label trial, 258 patients entered the 22-week open-ended assessment phase (n = 128 QW-only; n = 130 BID→QW). A1C, fasting plasma glucose (FPG), body weight, blood pressure, fasting lipids, safety, and tolerability were assessed.

RESULTS

Patients continuing exenatide QW maintained A1C improvements through 52 weeks (least squares mean −2.0% [95% CI −2.1 to −1.8%]). Patients switching from exenatide BID to exenatide QW achieved further A1C improvements; both groups exhibited the same A1C reduction and mean A1C (6.6%) at week 52. At week 52, 71 and 54% of all patients achieved A1C <7.0% and ≤6.5%, respectively. In both treatment arms, FPG was reduced by >40 mg/dl, and body weight was reduced by >4 kg after 52 weeks. Nausea occurred less frequently in this assessment period and was predominantly mild. No major hypoglycemia was observed.

CONCLUSION

Exenatide QW elicited sustained improvements in glycemic control and body weight through 52 weeks of treatment. Patients switching to exenatide QW experienced further improvements in A1C and FPG, with sustained weight loss.Type 2 diabetes is a complex and increasingly prevalent disease associated with interrelated comorbidities, including obesity, dyslipidemia, and hypertension. The importance of treating not only hyperglycemia, but also the associated comorbidities, is recognized as necessary to reduce the risk of complications, particularly cardiovascular disease (1). Lifestyle modification can improve glycemic control as well as body weight, blood pressure, and lipid profiles; however, behavioral modifications are inherently difficult, and most patients eventually require multiple medications (2–6). Although several classes of antihyperglycemic medications are currently indicated for the treatment of type 2 diabetes, most of them do not improve the comorbidities and several are associated with weight gain.Exenatide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, improves glycemic control in patients with type 2 diabetes through multiple mechanisms of action: increased glucose-dependent insulin secretion, attenuated postprandial glucagon secretion, slowed gastric emptying, and increased satiety (7,8). The twice-daily formulation of exenatide (exenatide BID) improves both fasting and postprandial glucose control, resulting in A1C reductions of roughly 0.8–1.0% in placebo-controlled trials (9–12) and 1.0–1.4% in open-label trials (13–15). These improvements in glucose control were maintained in patients completing 3 years of treatment (−1.0%) (16). Exenatide therapy is also associated with weight loss and improvement in cardiovascular risk factors, including blood pressure and serum lipid profiles (16). Furthermore, the glucose-dependent mechanisms of action of exenatide minimize the risk of hypoglycemia. GLP-1R agonists have recently been added to the American Diabetes Association and European Association for the Study of Diabetes consensus algorithm for the treatment of type 2 diabetes as an option after the addition of metformin in patients in whom body weight and hypoglycemia risk are concerns (1).Exenatide BID is administered within the 60-min period before the morning and evening meals and primarily exerts its pharmacodynamic effects on glucose concentrations during the postprandial period. A long-acting once-weekly formulation of exenatide (exenatide QW) has been developed. Weekly administration of 2 mg exenatide QW results in therapeutic plasma exenatide concentrations within 2 weeks and steady-state plasma exenatide concentrations within the therapeutic target range 6–7 weeks after initiation of therapy (17,18).The Diabetes Therapy Utilization: Researching Changes in A1C, Weight and Other Factors Through Intervention with Exenatide Once Weekly (DURATION-1) trial was designed as a two-stage protocol. We previously reported the first stage, a randomized open-label comparison of exenatide QW to exenatide BID in patients with type 2 diabetes over 30 weeks (17). Both therapies improved glycemic control, and the improvement in A1C observed with exenatide QW treatment was significantly greater than that observed with exenatide BID (−1.9 vs. −1.5%, respectively). Similar improvements in body weight, blood pressure, and fasting lipids were demonstrated with both forms of exenatide therapy. We now describe 52-week results from the second phase of the DURATION-1 trial which examined the safety and efficacy of 1) switching from exenatide BID to exenatide QW after 30 weeks of treatment and 2) continuing exenatide QW treatment for an additional 22 weeks (52 weeks total).     

针刺干预后更年期综合征患者临床症状及β-内啡肽的改变

目的:拟定补肾、调理脏腑、协调阴阳的针刺处方,观察针刺对女性更年期综合征的症状改善及治疗效果。方法:收集1998-06/1999-04山东省中医院女性更年期综合征患者65例,随机抽签法分为针刺组(n=33)和谷维素组(n=32),另在济南第二钢铁厂女工中随机选取20～30岁健康育龄妇女15名作为正常对照组。针刺组拟定补肾、调理脏腑、协调阴阳处方,主穴选取肾俞、足三里、三阴交(均双取);配穴选取内关、神门、太冲(均双取)百会、膻中。阴虚型患者酌加肝俞、太溪、大赫(均双取);阳虚型可酌配脾俞(双取)、关元。平补平泻,留针30min,每10min行针一次。治疗1次/d,连针6d后休息1d,连续治疗4周为1个疗程。谷维素组患者口服谷维素4周,20mg,3次/d。观察治疗前及治疗达1疗程后的Kupperman指数。参照改良的Kupperman指数评定法,Kupperman指数比=治疗1疗程以上的Kupperman指数/治疗前Kupperman指数。显效:Kupperman指数比<25%;有效:25%≤Kupperman指数比≤80%;无效:Kupperman指数比>80%。并于初诊后次日与治疗满1个疗程后3d内的上午8:00～9:00空腹时抽取肘静脉血5mL,采用放免分析法测定β-内啡肽。正常标准对照组抽血时间同患者治疗后时间。结果:针刺组和谷维素组各脱落2例,原因为外出等。针刺组和谷维素组进入结果分析分别为31例和30例,正常对照组全部进入结果分析。①针刺对女性更年期综合征患者潮热出汗、感觉障碍、失眠、易激动、泌尿系统感染、抑郁多疑、眩晕、头痛、关节肌肉痛、心悸、易疲劳、皮肤蚁行感的有效率明显高于谷维素组(P<0.01,P<0.05)。②两组患者治疗后Kupperman指数与治疗前比较显著降低,差异有显著性意义(P<0.05)。针刺组的Kupperman指数下降幅度更大,与谷维素组相比差异有显著性意义(P<0.05)。③针刺组显效4例、有效26例、无效1例,有效率97%;谷维素组显效2例、有效20例、无效8例,有效率73%,针刺组明显优于谷维素组(χ2=4.927,P<0.05)。④治疗前患者血清β-内啡肽水平明显低于正常对照组犤(94.3486±30.8609),(177.1331±43.2032)mg/L,t=7.404,P<0.01犦;针刺治疗后血清β-内啡肽与治疗前比较显著升高犤(136.1452±54.6915),(94.3486±30.8609)mg/L,t=3.632,P<0.05犦。与正常对照组相比差异仍有显著性意义。结论:针刺治疗女性更年期综合征有良好的疗效,在改善各项临床症状方面优于谷维素。患者血清β-内啡肽含量显著低于正常育龄妇女,针刺治疗后明显升高,可能的机制是针灸改善了患者神经内分泌-免疫网络内环境,体现在诱发β-内啡肽的释放增多,导致外周β-内啡肽水平上升。     

补肾健脾化瘀法治疗男性骨质疏松症疼痛的效果

目的:观察补肾健脾基础上加强化瘀药物制成补肾壮骨中药对男性骨质疏松患者疼痛程度的影响。方法:①选择1998-07/2004-07解放军广州军区广州总医院住院及门诊就诊的男性老年性骨质疏松症患者198例,年龄65～83岁。符合骨质疏松症综合诊断评分标准,且均对治疗方案知情同意。②按随机数字表法将患者分为2组;补肾壮骨中药组101例,降钙素组97例。补肾壮骨中药组:均囗服补肾壮骨中药(由生地、山药、山萸肉、泽泻等药物组成,广东一方制药厂生产,批号:980705,100g/包),1包/次,2次/d。降钙素组:均肌肉注射降钙素(诺华公司产品,生产批号980823,990523,011121,50IU/支),其中第1周100IU,1次/d,第2,3,4周100IU,每周2次。两组均治疗4周。③分别于治疗前,治疗1,2,3,4周后及停药后2周记录疼痛强度(共计0～10,0为无痛,10为剧烈疼痛)、疼痛缓解度(共计0～4度,0度为无缓解,4度为完全缓解),计算镇痛有效率:显效(明显缓解 完全缓解),有效(中度缓解),总有效率(显效 有效)。④计量和计数结果差异比较分别采用t检验和χ2检验。结果:男性老年性骨质疏松症患者198例均进入结果分析。①骨质疏松症疼痛强度:补肾壮骨中药组治疗后2,3,4周和停药后2周和降钙素组治疗后1,2,3,4周和停药后2周疼痛强度明显低于治疗前(t=2.35～2.93,P<0.05),补肾壮骨中药组治疗1和2周后疼痛强度明显高于降钙素组(5.32±1.21,3.26±1.32;3.49±1.39,2.21±1.28,t=2.98,2.36,P<0.05)。②骨质疏松症疼痛缓解情况:治疗2周后,补肾壮骨中药组完全缓解率明显低于降钙素组(5.9%,18.6%,χ2=6.25,P<0.05)。补肾壮骨中药组及降钙素组治疗1,3,4周后和停药后2周疼痛完全缓解率、明显缓解率、中度缓解率差异不明显(P>0.05)。③镇痛有效率:治疗2周后,补肾壮骨组镇痛显效率明显低于降钙素组(44.6%,58.8%,χ2=5.721,P<0.05),有效率和总有效率与降钙素组相近(P>0.05)。补肾壮骨中药组和降钙素组治疗4周后和停药后2周镇痛总有效率、显效率、有效率比较,差异不明显(P>0.05)。结论:补肾壮骨中药可明显缓解男性患者骨质疏松症疼痛,作用效果基本与降钙素相当。