B2 adrenergic receptors and morphological changes of the enteric nervous system in colorectal adenocarcinoma

To study the morphology of the enteric nervous system and the expression of beta-2 adrenergic (B2A) receptors in primary colorectal cancer.METHODSIn this study, we included forty-eight patients with primary colorectal cancer and nine patients for control tissue from the excision of a colonic segment for benign conditions. We determined the clinicopathological features and evaluated the immunohistochemical expression pattern of B2A receptors as well as the morphological changes of the enteric nervous system (ENS). In order to assess statistical differences, we used the student t-test for comparing the means of two groups and one-way analysis of variance with Bonferroni’s post hoc analysis for comparing the means of more than two groups. Correlations were assessed using the Pearson’s correlation coefficient.RESULTSB2A receptors were significantly associated with tumor grading, tumor size, tumor invasion, lymph node metastasis (P < 0.05), while there were no statistically significant associations with gender, CRC location and gross appearance (P > 0.05). We observed, on one hand, a decrease of the relative area for both Auerbach and Meissner plexuses with the increase of the tumor grading, and on the other hand, an increase of the relative area of other nervous elements not in the Meissner plexus or in the Auerbach plexus with the tumor grading. For G1 tumors we found that epithelial B2A area showed an inverse correlation with the Auerbach plexus areas [r(14) = -0.531, P < 0.05], while for G2 tumors, epithelial B2A areas showed an indirect variation with both the Auerbach plexus areas [r(14) = -0.453, P < 0.05] and the Meissner areas [r(14) = -0.825, P < 0.01]. For G3 tumors, the inverse dependence increased for both Auerbach [r(14) = -0.587, P < 0.05] and Meissner [r(14) = -0.934, P < 0.05] plexuses.CONCLUSIONB2A receptors play an important role in colorectal carcinogenesis and can be utilized as prognostic factors. Furthermore, study of the ENS in colorectal cancer may lead to targeted molecular therapies.

Association of β3 Adrenergic Receptor and Peroxisome Proliferator-activated Receptor Gamma 2 Polymorphisms With Insulin Sensitivity:A Twin Study

Objective To study the effect of β3 adrenergic receptor （β3AR） Trp64Arg and peroxisome proliferator activated receptor gamma 2 （PPAR72） Prol2Ala polymorphisms on insulin resistance. Methods One hundred and eight dizygotic twin pairs were enrolled in this study. Microsatellite polymorphism was used to diagnose zygosity of twins. Insulin sensitivity was estimated with logarithm transformed homeostasis model assessment （HOMA）. PCR-RFLP analysis was performed to detect the variants. As a supplement to the sib-pair method, identity by state （IBS） was used to analyze the association of polymorphisms with insulin sensitivity. Results The genotype frequencies of Trp64Trg, Trp64Arg, and Arg64Arg were 72.3%, 23.8%, and 3.9%, respectively, while the genotype frequencies of Pro12Pro, Pro12Ala, and Ala12Ala were 89.9%, 9.6%, and 0.5%, respectively. For β3AR Trp64Arg the interclass co-twin correlations of Waist-to-hip ratio （WHR）, blood glucose （GLU）, and insulin （INS）, homeostasis model assessment insulin resistance index （HOMA-IR） of the twin pairs sharing 2 alleles of IBS were greater than those sharing 0-1 allele of IBS, and HOMA4R had statistic significance. For PPAR3t2 Prol2Ala most traits of twin pairs sharing 2 alleles of IBS had greater correlations and statistic significance in body mass index （BMI）, WHR, percent of body fat （PBF） and GLU, but there were low correlations of either insulin or HOMA-IR of twin pairs sharing 1 or 2 alleles of IBS. The combined effects of the two variations showed less squared significant twin-pair differences of INS and HOMA-IR among twins sharing 4 alleles of IBS. Condusions β3AR Trp64Arg and PPAR）,2 Pro 12Ala polymorphisms might be associated with insulin resistance and obesity, and there might be slight synergistic effects between this two gene loci, and further studies are necessary to confirm this finding.

Blocking beta 2-adrenergic receptor inhibits dendrite ramification in a mouse model of Alzheimer's disease

Dendrite ramification affects synaptic strength and plays a crucial role in memory. Previous studies revealed a correlation between beta 2-adrenergic receptor dysfunction and Alzheimer＇s disease （AD）, although the mechanism involved is still poorly understood. The current study investigated the potential effect of the selective β2-adrenergic receptor antagonist, ICI 118551 （ICI）, on Aβ deposits and AD-related cognitive impairment. Morris water maze test results demonstrated that the performance of AD-transgenic （TG） mice treated with ICI （AD-TG/ICI） was significantly poorer compared with NaCl-treated AD-TG mice （AD-TG/NaCl）, suggesting that β2-adrenergic receptor blockage by ICI might reduce the learning and memory abilities of mice. Golgi staining and immunohistochemical staining revealed that blockage of the β2-adrenergic receptor by ICI treatment decreased the number of dendritic branches, and ICI treatment in AD-TG mice decreased the expression of hippocampal synaptophysin and synapsin 1. Western blot assay results showed that the blockage of β2-adrener- gic receptor increased amyloid-β accumulation by downregulating hippocampal a-secretase activity and increasing the phosphorylation of amyloid precursor protein. These findings suggest that blocking the β2-adrenergic receptor inhibits dendrite ramification of hippocampal neurons in a mouse model of AD.

应激性心肌病的研究进展

应激性心肌病是以可逆性室壁运动异常为特征的一种心血管综合征,临床表现与急性冠脉综合征相似,但冠状动脉造影显示冠状动脉解剖正常。应激性心肌病的发病机制尚未完全明确,临床诊断不易,标准治疗药物存在争议,因并发症和复发风险导致预后不佳。现总结应激性心肌病的流行病学、发病机制、诊断和治疗方面的最新进展,以期为改善疾病的预后提供思路。

ADRB1基因多态性对比索洛尔疗效影响的Meta分析

目的基于Meta分析评价β_(1)肾上腺素受体(ADRB1)389位点(rs 1801253)基因多态性对比索洛尔疗效的影响。方法通过计算机检索中国知网、维普网、万方数据知识服务平台、Web of Science、PubMed等数据库收集关于ADRB1与比索洛尔研究的文献,检索时间为建库至2023年7月。研究人员对发表的文献进行筛选,并将纳入文献进入质量评价,提取文献数据,对纳入文献结局指标使用Review Manager 5.3软件进行Meta分析。结果最终纳入文献6篇,其中Gly389Gly(GG型)69例,Gly389Arg(GC型)458例,Arg389Arg(CC型)611例。在降收缩压、舒张压及控制心率疗效方面,GG与CC基因型差异无统计学意义(P=0.96,P=0.84,P=0.87),GC与CC基因型差异无统计学意义(P=0.43,P=0.35,P=0.07),GG与GC基因型差异亦无统计学意义(P=0.60,P=0.68,P=0.77)。结论在比索洛尔降压及控制心率方面,ADRB1389位点基因多态性对其疗效影响并不明显。GG、GC及CC 3个基因型之间均未发现明显差异。

The beta-adrenergic blocker carvedilol restores L-type calcium current in a myocardial infarction model of rabbit

Background Carvedilol, an antagonist of α1- and β-adrenergic receptors, has shown efficacy in reducing all-cause death and arrhythmia death for ischemic heart disease and congestive heart failure in several large-scale trials. It has been found to prevent ventricular remodeling, and recently was reported to reverse down-regulation of Na^+ channel in a chronic heart failure model. This study was conducted to investigate whether carvedilol could reverse the ion remodeling in a myocardial infarction model of rabbit.Methods After the procedure of coronary ligation, animals were randomized to placebo or carvedilol treatment (5 mg/kg). Action potentials, L-type calcium current (I_(ca L)) and the effect of isoproterenol stimulation on I_(ca L) were measured using whole-cell patch method. Evaluation of the expression of calcium channel subunits was carried out by RT-PCR and Western blot. Results The results indicate that mean peak I_(ca L) densities (pA/pF) at +10 mV was reduced in postinfarction myocytes (5.33±0.45, n=25) compared to sham myocytes (6.52±0.21, n=20). Treatment of myocardial infarction rabbits with carvedilol could restore it partially (5.91±0.39, n=20, P<0.05). However, steady-state activation parameters were similar in three groups. With stimulation by isoproterenol (1 μmol/L) I_(ca L) increased in all three groups, but the increase was smaller in postinfarction myocytes. mRNA levels of calcium channel subunit CaA1 gene was decreased but CaB2a, CaB2b and CaB3 mRNA levels did not change after MI. Corresponding change in CaA1 protein was also observed. Conclusions The results demonstrate that carvedilol restores I_(ca L) density and reverse the downregulation of CaA1 postinfarction.

β受体阻滞剂在中青年高血压中的应用

流行病学数据显示,中青年高血压的患病率约为20%,并逐年上升。这可能与中青年人群工作压力大、精神紧张导致的交感神经兴奋有关,主要表现为以舒张压升高为主。中青年高血压与慢性冠心病或脑卒中明显相关,积极治疗可明显降低患者的长期心血管疾病发生率和死亡风险。β受体阻滞剂通过抑制交感神经活性降低血压,更适用于舒张压升高为主的中青年高血压患病人群。本文通过回顾文献分析了中青年高血压的流行病学数据、潜在机制及临床意义,探讨了β受体阻滞剂在中青年高血压患者管理中的主要作用及应用要点,为临床医生治疗中青年高血压提供参考。

Effects of short-acting β-adrenergic blocker on B-type natriuretic peptide at early stage of postresuscitation in rabbits

Postresuscitation myocardial dysfunction is reversible heart failure and B-type natriuretic peptide （BNP） is a biochemical marker of ventricular disorders secreted from ventricle, which can be used to assess the status of left ventricular function. This study investigated the effect of β-adrenergic blocker on concentration of BNP and cardiac function after cardiopulmonary resuscitation in rabbits.

乌拉地尔改善良性前列腺增生患者下尿路症状的有效性评估:系统评价及meta分析

目的:系统评价乌拉地尔在男性良性前列腺增生(BPH)患者下尿路症状(LUTS)治疗中的潜在价值。方法:从PubMed、MEDLINE、Web of science、中国知网、万方数据库中鉴定和收集随机对照试验(RCT)或临床观察性研究。利用RevMan软件进行固定效应模型和随机效应模型的Meta分析。计算合并效应尺度以加权均数差及其95%可信区间(95%CI)表示。结果:共纳入3项短期(1个月内)观察性研究和1项RCT,共142例患者。发现乌拉地尔显著改善了患者的IPSS(MD=-5.57,95%CI:-7.98~-3.16,P<0.00001)、夜尿频率(MD=-0.7,95%CI:-1.16~-0.24,P=0.003)、残余尿率(MD=-6.97;95%CI:-12.57~-1.37,P=0.01)、平均尿流率(MD=2.04;95%CI:0.52~3.56,P=0.008)和最大尿流率(MD=4.29;95%CI:0.58~8.01,P=0.02),而残余尿量(MD=-35.93;95%CI:-78.62~6.76,P=0.10)在患者服药前后无统计学差异。结论:乌拉地尔是一种有效的缓解BPH患者LUTS的药物。但由于目前的RCT研究数量及质量有限,仍需高质量、大规模的RCT研究进一步证实这一结论。

新型降血压药奈必洛尔研究进展

奈必洛尔是新型选择性 β 受体阻滞剂 ,是一种兼有血管扩张作用的新型降压药物。主要介绍其药效学、药代动力学、疗效、耐受性和国内外对其合成工作的研究进展。

β-受体阻滞剂在儿童慢性心功能不全中的应用

目的 探讨β-肾上腺能受体阻滞剂对儿童慢性心功能不全的治疗作用,方法 将40例慢性心功能 不全患儿随机分为常规组(n=20)和美托洛尔组(n=20),治疗前和治疗后6个月采用高效液相色谱--电化学法 测定血浆去甲肾上腺素(NE)、肾上腺素(E);放射性配体结合分析法测定外周血淋巴细胞β-受体密度(Bmax);X 线胸片测心胸比率(CTR);彩色多普勒超声仪测心脏左室射血分数(EF),左室心肌重量指数(LVMI)。结果 ①心 衰患儿血浆NE、E水平较正常对照组显著升高,心功能Ⅲ、Ⅳ级者较心功能Ⅱ级者升高明显,心功能越差,升高越明 显,差异有显著意义(F值分别为10.57、17.48,P均<0.05);Bmax显著降低,心功能越差降低越显著,与正常对照 组比较差异有显著性(F=11.39,P<0.05)。②10例LVMI正常的患儿血浆NE、E水平显著升高,Bmax显著降 低;30例LVMI增高患儿,血浆NE、E水平升高及Bmax降低更明显,但与LVMI正常组比较无明显差异。Bmax 与LVMI呈显著负相关(r=-0.395,P<0.01)。③与治疗前相比,常规组治疗6个月后,血浆NE、E水平降低明显 (t=2.203、2.54,P均<0.05),Bmax、EF、CTR及LVMI无明显变化(P均>0.05);美托洛尔组治疗前后比较, Bmax、EF明显升高,差异有显著性(t=9.95、7.19,P均<0.001),NE、E、CTR、LVMI明显降低,差异有统计学意 义(t=6.

围术期美托洛尔对老年非心脏手术病人血流动力学及心肌缺血的影响

目的：比较围术期关托洛尔（metoprolol）对老年非心脏手术病人血流动力学和心肌缺血的影响。方法：30例60～75岁拟行择期非心脏手术病人被随机分为metoprolol组和对照组，每组15例。Metoprolol组病人于麻醉诱导前和气管插管后分别静脉注射0．5mg和1．5mgmetoprolol。围术期监测：①血流动力学指标为有创血压、HR和心率-收缩压乘积（rate—pressure product，RPP）；②心肌缺血发作指标为ECGⅡ，V5导联ST段偏移幅度及持续时间。心肌缺血被规定为ST段上抬≥0．2mv或下移≥0．1mv，至少持续1min；③心肌损伤指标为心肌钙蛋白Ⅰ（cardiac troponinⅠ，cTnⅠ）的释放；④反映metoprolol心血管和呼吸副作用的指标为HR〈50次／分发生率、阿托品用量和气道峰压。结果：两组病人在麻醉诱导后气管插管前，HR和RPP明显低于麻醉前基础值，但组问差异无统计学意义（P〉0．05）；气管插管期对照组HR和RPP明显高于基础值（P〈0．05）和metoprolol组同时点值（P〈0．05）；心肌缺血发生率对照组为30％，metoprolol组为13％（P〈0．05）；麻醉前没有检测到1例病人的血清cTnⅠ，手术开始2h后，可检测到对照组5例（30％），metoprolol组2例（13％）病人的血清cTnⅠ（P〈0．01）。HR〈50次／分发生率和阿托品平均用量组间差异无统计学意义（P〉0．05），但腹腔手术病人被牵拉内脏时．心动过缓发生率在metoprolol组有增高倾向。Metoprolol没有引起明显的气道压升高。结论：麻醉诱导前和气管插管后小量分次静脉注射总量2mg metoprolol可以使老年非心脏手术病人心肌耗氧降低，血流动力学稳定，心肌缺血和心肌损伤发生率降低。当metoprolol用于腹腔手术病人时，应注意牵拉内脏可能引起较高的心动过缓发生率和需要用较高荆量的阿托品治疗。

葛根素及心得安局部应用对家兔脑软膜微循环的影响

本研究采用颅骨开窗法,直接观察了局部滴加葛根素(5%,0.1ml)及心得安(0.5%,0.1ml)对麻醉兔脑软膜微循环的影响。结果发现,葛根素及心得安可分别使微动脉的管径增加41%及37%(P 均<0.01),血流速度增加分别为10%及11%(P 均<0.05),同时,毛细血管开放数目增多。但对微静脉影响较小。葛根素及心得安扩张微动脉,增加血流速度的作用呈浓度依赖性。

体外短波热疗联合前列腺灸及哈乐治疗非细菌性前列腺炎和前列腺痛疗效观察

目的探讨慢性非细菌性前列腺炎(CNP)和前列腺痛(PD)的治疗方法。方法应用体外短波热疗联合前列腺灸及α1A-肾上腺素能受体阻滞剂哈乐治疗CNP和PD患者26例,疗程8周。观察治疗前后前列腺炎症状评分(CPSI)与最大尿流率(MFR)变化。结果有效率为80.8%。治疗前后CPSI和MFR均有显著改善(P<0.05)。结论体外短波热疗联合前列腺灸及哈乐治疗CNP和PD安全有效。

ADRB2 Gln27Glu基因多态性对经皮冠状动脉介入术后β受体阻滞剂临床疗效的影响

目的:探讨β2肾上腺素能受体(ADRB2)Gln27Glu基因多态性对经皮冠状动脉介入术(PCI)后β受体阻滞剂临床疗效的影响。方法:收集广东省人民医院PCI术后接受β受体阻滞剂治疗的冠心病患者384例,采用TaqMan基因分型技术检测ADRB2 Gln27Glu基因型,分析Gln27Glu基因多态性对主要不良心脏事件(MACE)的影响。结果:基因型分布频率符合Hardy-Weinberg平衡(P>0.05),各基因型患者间的一般临床特征没有显著差异(P>0.05);各基因型患者使用β受体阻滞剂种类的构成无显著差异(2=9.196,P>0.05);Cox单因素分析显示,左主干病变、糖尿病和高血压是发生MACE的相关因素,相对危险度分别为2.661(95%CI:1.122～6.307)、2.431(95%CI:1.127～5.242)和2.980(95%CI:1.128～7.871),均P<0.05。ADRB2 Gln27Glu基因多态性对MACE没有显著影响,相对危险度为1.408(95%CI:0.650～3.053),P>0.05。结论:ADRB2 Gln27Glu基因多态性与PCI术后接受β受体阻滞剂治疗患者的临床疗效无明显相关性。

国产盐酸特拉唑嗪治疗高血压病100例疗效观察

选择Ⅰ或Ⅱ期高血压病患者１００例用国产盐酸特拉唑嗪片治疗与另５０例高血压病患者使用美国Ａｂｂｏｔｔ公司产盐酸特拉唑嗪片（高特灵）治疗，并进行疗效对比观察。结果发现，国产盐酸特拉唑嗪片总有效率为９０％，高特灵总有效率为８３％，两组间疗效无明显差异（Ｐ＞０．０５）。均无明显副作用，对脂代谢呈有益作用，可视为治疗高血压病较好的药物。

衍生化β-环糊精手性固定相液相色谱拆分和测定药片中的阿替洛尔对映体

以有序介孔材料（ SBA-15）为基质，制备了一种二硝基苯醚化β-环糊精键合 SBA-15液相色谱手性固定相（NESP）。优化了流动相和温度等色谱条件，在极性有机溶剂模式下，采用实验室自制的手性柱，实现了阿替洛尔对映体的快速拆分。优化的流动相组成为乙腈/甲醇/冰醋酸/三乙胺（90：10：2.5：3.0，v / v / v / v），流速为0.5 mL / min，柱温为20℃，检测波长为275 nm。在上述色谱条件下，阿替洛尔对映体的分离度为1.73，分析时间约为20 min。阿替洛尔药片经甲醇提取并直接进样分析，实现了阿替洛尔片剂中对映体含量的测定。阿替洛尔的两对映体的质量浓度在2.5-100 mg / L 范围内呈良好的线性关系（r 分别为0.9992和0.9989）。采用标准添加法测得两对映体在片剂中的回收率为94.60％-97.24％。样品测定结果的日内和日间相对标准偏差（ RSD）分别不大于0.92％和1.86％（n =5）。按3倍信噪比确定出最小检测质量浓度为0.2 mg / L。该方法简便、选择性好、回收率较高，自制环糊精手性柱可降低测试成本，在手性药物的快速质量监测和药代动力学研究中具有良好的应用前景。

坦索罗辛单药治疗后加用索利那新对良性前列腺增生体膀胱过度活动症的疗效观察

目的观察男性良性前列腺增生伴下尿路症状患者在接受坦索罗辛治疗后仍然存在的膀胱过度活动症加用索利那新的治疗作用。方法选取大于50岁的的良性前列腺增生伴下尿路症状患者,均先接受4周的坦索罗辛0.2mg治疗,再次评估时仍然有OAB症状者纳入本组观察,予索利那新5mg+坦索罗辛0.2mg治疗4周。观察项目包括国际前列腺症状评分(IPSS)、生活质量指数(QOL)、膀胱活动症症状评分(OABSS)、最大尿流率(Qmax)和残余尿量(PVR)等。结果 112例患者接受坦索罗辛治疗,治疗4周后62例(55.4%)符合纳入标准,58例完成研究,平均年龄67.2岁。IPSS评分(14.4到10.8)、QOL指数(4.4到3.2)及OABSS(6.1到3.9)显著提高,虽然IPSS储尿期症状评分显著改善(10.8到7.4),IPSS排尿期症状无显著改变,治疗前后Qmax和PVR无明显变化。结论男性良性前列腺增生伴下尿路症状患者在接受坦索罗辛治疗后仍然存在的膀胱过度活动症中加用索利那新安全有效。

β肾上腺素受体阻滞剂的研究进展

β受体阻滞剂广泛应用于心血管疾病和非心血管疾病的治疗,然而,该类药物的作用机制存在明显差异,且目前并没有完全阐释清楚。奈比洛尔是第三代β受体阻滞剂中的一种新药。它是该类药物中唯一的既具有心肌选择性,又能通过间接地产生一氧化氮使血管舒张的药物。现回顾β受体阻滞剂的发展,探讨目前已知的关于β受体阻滞剂的作用机制,评价该类药物并对它们在临床应用中的差异做基础研究。

琥珀酸美托洛尔缓释片联合氯沙坦钾片治疗老年慢性心力衰竭的效果

目的观察琥珀酸美托洛尔缓释片联合氯沙坦钾片治疗老年慢性心力衰竭的疗效、安全性和耐受性。方法选取72例老年慢性心力衰竭患者,随机分为对照组及治疗组,每组36例,对照组采用氯沙坦钾片治疗,治疗组在常规治疗及氯沙坦钾片基础上加用琥珀酸美托洛尔缓释片,治疗6个月,观察2组治疗前后一般状况、心功能情况、不良反应。结果两组治疗后较治疗前心功能均有明显改善(P<0.05)。治疗后,治疗组左室射血分数(LVEF)、左室舒张末期内径(LVEDD)、B型钠尿肽(BNP)情况优于对照组,差异有统计学意义(P<0.01),治疗组总有效率为97.2%,对照组总有效率为75.0%,差异有统计学意义(P<0.01)。两组均未发生严重的药物不良反应。结论琥珀酸美托洛尔缓释片联合氯沙坦钾片治疗老年慢性心力衰竭疗效、安全性及耐受性良好。