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-Receptor blocker enhances the anabolic effect of PTH after osteoporotic fracture

The autonomic nervous system plays a crucial role in regulating bone metabolism,with sympathetic activation stimulating bone resorption and inhibiting bone formation.We found that fractures lead to increased sympathetic tone,enhanced osteoclast resorption,decreased osteoblast formation,and thus hastened systemic bone loss in ovariectomized(OVX)mice.However,the combined administration of parathyroid hormone(PTH)and theβ-receptor blocker propranolol dramatically promoted systemic bone formation and osteoporotic fracture healing in OVX mice.The effect of this treatment is superior to that of treatment with PTH or propranolol alone.In vitro,the sympathetic neurotransmitter norepinephrine(NE)suppressed PTH-induced osteoblast differentiation and mineralization,which was rescued by propranolol.Moreover,NE decreased the PTH-induced expression of Runx2 but enhanced the expression of Rankl and the effect of PTH-stimulated osteoblasts on osteoclastic differentiation,whereas these effects were reversed by propranolol.Furthermore,PTH increased the expression of the circadian clock gene Bmal1,which was inhibited by NE-βAR signaling.Bmal1 knockdown blocked the rescue effect of propranolol on the NE-induced decrease in PTHstimulated osteoblast differentiation.Taken together,these results suggest that propranolol enhances the anabolic effect of PTH in preventing systemic bone loss following osteoporotic fracture by blocking the negative effects of sympathetic signaling on PTH anabolism.

Treatment of Helicobacter pylori with potassium competitive acid blockers:A systematic review and meta-analysis

BACKGROUND Helicobacter pylori(H.pylori)infects over half the global population,causing gastrointestinal diseases like dyspepsia,gastritis,duodenitis,peptic ulcers,GMALT lymphoma,and gastric adenocarcinoma.Eradicating H.pylori is crucial for treating and preventing these conditions.While conventional proton pump inhibitor(PPI)-based triple therapy is effective,there’s growing interest in longer acid suppression therapies.Potassium competitive acid blocker(P-CAB)triple and dual therapy are new regimens for H.pylori eradication.Initially used in Asian populations,vonoprazan(VPZ)has been recently Food and Drug Administration-approved for H.pylori eradication.AIM To assess the efficacy of regimens containing P-CABs in eradicating H.pylori infection.METHODS This study,following PRISMA 2020 guidelines,conducted a systematic review and meta-analysis by searching MEDLINE and Scopus libraries for randomized clinical trials(RCTs)or observational studies with the following command:[("Helicobacter pylori"OR"H pylori")AND("Treatment"OR"Therapy"OR"Eradication")AND("Vonaprazan"OR"Potassium-Competitive Acid Blocker"OR"P-CAB"OR"PCAB"OR"Revaprazan"OR"Linaprazan"OR"Soraprazan"OR"Tegoprazan")].Studies comparing the efficacy of P-CABs-based treatment to classical PPIs in eradicating H.pylori were included.Exclusion criteria included case reports,case series,unpublished trials,or conference abstracts.Data variables encompassed age,diagnosis method,sample sizes,study duration,intervention and control,and H.pylori eradication method were gathered by two independent reviewers.Meta-analysis was performed in R software,and forest plots were generated.RESULTS A total of 256 references were initially retrieved through the search command.Ultimately,fifteen studies(7 RCTs,7 retrospective observational studies,and 1 comparative unique study)were included,comparing P-CAB triple therapy to PPI triple therapy.The intention-to-treat analysis involved 8049 patients,with 4471 in the P-CAB intervention group and 3578 in the PPI control group across these studies.The analysis revealed a significant difference in H.pylori eradication between VPZ triple therapy and PPI triple therapy in both RCTs and observational studies[risk ratio(RR)=1.17,95%confidence interval(CI):1.11-1.22,P<0.0001]and(RR=1.13,95%CI:1.09-1.17,P<0.0001],respectively.However,no significant difference was found between tegoprazan(TPZ)triple therapy and PPI triple therapy in both RCTs and observational studies(RR=1.04,95%CI:0.93-1.16,P=0.5)and(RR=1.03,95%CI:0.97-1.10,P=0.3),respectively.CONCLUSION VPZ-based triple therapy outperformed conventional PPI-based triple therapy in eradicating H.pylori,positioning it as a highly effective first-line regimen.Additionally,TPZ-based triple therapy was non-inferior to classical PPI triple therapy.

Use of Beta-Blocker in Acute ST-Elevation Myocardial Infarction

This paper reported beta-blocker use in 21 STEMI patients over four years. The patients were between 50 - 65 years of age presenting with anterior, lateral, and inferior STEMI (ST-Elevation Myocardial Infarction). Seven of the patients were female, and 14 were male. They presented to an emergency room of a rural hospital that did not provide emergency percutaneous coronary angioplasty/stenting (PTCA/stenting). The hospital is about 70 minutes from a facility that provided PTCA/ stenting—all the patients presented with typical angina chest pain with ST elevation. They are hemodynamic stable. Most patients received Lopressor 35 mg IVP, with one receiving 115 mg in a 5 mg increment. They were chest pain-free and hemodynamically before leaving the ER for the transfer for PTCA/stent. The results demonstrated that beta-blockers are effective in relieving pain in STEMI patients. Further study is needed to determine its efficacy, safety, and how to use it.

Changes of pulmonary beta-adrenergic receptors and their relationship with membranous phospholipid metabolism in endotoxin-induced lung injury in rats

The changes of beta-adrenergic receptors (AARs) in lung tissue in endotoxin-induced acute lung injury was investigated with radioligand bindig assay in rats. The lipid fluidity and phospholipid content of the cellular membrane of lung tissue were measured with fluorescent polarization and high performance liquid chromatography respectively. The findings were as follows:1- Four hours after endotoxin injection, there was a 47% decrease of the maximal binding capacity of fyARsas compared with the control.2. Endotoxin was able to decrease the lipid fluidity and phospholipid content of the pulmonary cellular membrane markedly and at the same time. There was an elevated activity of phospholipase A2 in the pulmonary tissueThese findings suggest that the decrease of the binding capacity of &ARs results in a decrease of the PAR mediated functions, which plays a ro1e in the pathogensis of endotoxin-induced acute lung injury and the activation of phospholipase A2 which is an important factor to reduce the phospholipid content of cell membrane and subsequently to decrease its lipid fluidity, can result in a reduction of the lateral diffusion and rotatory movement of β-ARs and to decrease the chances of β-ARs to bind with the ligands.

AB033.Implication of beta-adrenergic receptor in choroidal neovascularization

Background:We investigated the role of beta-adrenergic receptor(B-AR)on choroidal neovascularization(CNV)in an animal model of age-related macular degeneration in mice.Methods:The angiogenic effect of the B-AR was evaluated in retinal pigment epithelium(RPE)-choroid explants from C57Bl6 mice stimulated with propranolol or isoproterenol(10μM)(respectively antagonist and agonist of the B-AR)during 24 h.Conversely,a classic choroidal neovascularization(CNV)model induced by laser burn in C57Bl6 mice(8 weeks)was used to assess the anti-angiogenic effect of propranolol.In this experiment,mice were treated with intraperitoneal propranolol(6 mg/kg/d)or vehicle(saline solution)daily for 10 days,starting on day 4 after laser burn and until sacrifice(day 14).Immunostaining analysis on retinal flatmounts and cryosections were performed to determine the surface of CNV,the distribution of B-AR and the number and morphology of microglia/macrophages associated with CNV.To explore if the antiangiogenic effect of propranolol involved the modulation of the inflammatory microenvironment associated with CNV,we used RPE primary cells,J774 macrophages cell line and polarized M1 and M2 bone marrow-derived macrophage(BMDM).Choroidal explants treated with conditioned media(CM)from J774 or polarized M1/M2 BMDM pre-treated with propranolol to confirm the anti-angiogenic effect of propranolol.Expression of angiogenic factors was evaluated by RT PCR and Elisa.Results:The expression and distribution of the B-1,B-2 and B-3 adrenergic receptors were localized in the choroid and RPE cells.The stimulation of RPE-choroid explants with isoproterenol increased CNV compared to vehicle,while propranolol decreased CNV.In vivo,propranolol inhibited significantly the levels of VEGF and CNV growth in laser burn model compared to the vehicle.Additionally,the treatment with propranolol decremented the number of activated(amoeboid shape)microglia/macrophages but surprisingly,the number of non-activated microglia/macrophages around the CNV was higher than with the vehicle treatment.In vitro,propranolol modulated the angiogenic balance in macrophages promoting anti-angiogenic factors expression,especially with M2 BMDM.CM from macrophages pre-treated with propranolol reduced CNV on choroidal explants.Conclusions:These ex vivo and in vivo studies highlight the importance of B-adrenergic receptor in the CNV.Propranolol can inhibit CNV by decreasing the levels of VEGF and modulating microglia/macrophages activation.Further work will investigate the role of B-adrenergic receptor on suppression of the inflammatory environment in order to understand the link between neovascularization and inflammation in CNV during age-related macular degeneration.

Impact of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on the mortality in sepsis: A meta-analysis

BACKGROUND The effect of angiotensin-converting enzyme inhibitors(ACEIs)or angiotensin receptor blockers(ARBs)on the mortality of patients with sepsis is not well characterized.AIM To elucidate the association between prior ACEI or ARB exposure and mortality in sepsis.METHODS The PubMed,EMBASE,Web of Science,and Cochrane Library databases were searched for all studies of premorbid ACEI or ARB use and sepsis mortality until November 302019.Two reviewers independently assessed,selected,and ab-stracted data from studies reporting ACEIs or ARBs,sepsis,and mortality.The primary extracted data consisted of premorbid ACEI or ARB exposure,mortality,and general patient data.Two reviewers independently assessed the risk of bias and quality of evidence.RESULTS A total of six studies comprising 281238 patients with sepsis,including 49799 cases with premorbid ACEI or ARB exposure were eligible for analysis.Pre-morbid ACEIs or ARBs exposure decreased the 30-d mortality in patients with sepsis.Moreover,the use of ACEIs or ARBs was associated with approximately a 6%decreased risk of 30-d mortality.CONCLUSION The results of this systematic review suggest that ACEI or ARB exposure prior to sepsis may be associated with reduced mortality.Further high-quality cohort studies and molecular mechanism experiments are required to confirm our results.

Association between Depression, Pressure Pain Sensitivity, Stress and Autonomous Nervous System Function in Stable Ischemic Heart Disease: Impact of Beta-Adrenergic Receptor Blockade

Background: Depression and ischemic heart disease (IHD) are associated with persistent stress and autonomic nervous system (ANS) dysfunction. The former can be measured by pressure pain sensitivity (PPS) of the sternum, and the latter by the PPS and systolic blood pressure (SBP) response to a tilt table test (TTT). Beta-blocker treatment reduces the efferent beta-adrenergic ANS function, and thus, the physiological stress response. Objective: To test the effect of beta-blockers on changes in depression score in patients with IHD, as well as the influence on persistent stress and ANS dysfunction. Methods: Three months of non-pharmacological intervention aiming at reducing PPS and depression score in patients with stable IHD. Beta-blocker users (N = 102) were compared with non-users (N = 75), with respect to signs of depression measured by the Major Depressive Inventory questionnaire (MDI), resting PPS, and PPS and SBP response to TTT. Results: MDI score decreased 30% in non-users (p = 0.005) compared to 4% (p > 0.1) among users (between-group p = 0.003;effect size = 0.4). Resting PPS decreased in both the groups. Among most vulnerable patients with MDI ≥ 15, reductions in MDI score and resting PPS score correlated in non-users, only (r = 0.69, p = 0.007). Reduction in resting PPS correlated with an increase in PPS and SBP response to TTT. Conclusions: Stress intervention in patients with IHD was anti-depressive in non-users, only. Similarly, the association between the reduction in depression, reduction in persistent stress, and restoration of ANS dysfunction was only seen in non-users, suggesting a central role of beta-adrenergic receptors in the association between these factors.

厄贝沙坦通过调节NLRP3表达在糖尿病肾病大鼠中的保护作用

目的 观察糖尿病肾病大鼠中NLRP3(NOD-like receptor protein 3)的表达,并在沉默NLRP3和以血管紧张素受体抑制剂(ARB)厄贝沙坦干预后观察NLRP3及炎症和纤维化因子的表达变化,探讨厄贝沙坦对糖尿病肾病大鼠的保护作用。方法 雄性SD大鼠随机分成5组:对照(Control)组、模型(Model)组、空载(Model+Blank)组、NLRP3沉默(Model+NLRP3 Sh)组、ARB(Model+ARB)组,分别在糖尿病肾病模型建立后8周、12周处死大鼠并收集肾脏组织。实时荧光定量PCR检测NLRP3、半胱氨酸天冬氨酸蛋白酶-1(Caspase-1)、核因子κB(NF-κB)P65和波形蛋白(Vimentin)的mRNA表达水平;Western blot检测NLRP3、P65、热休克蛋白47(heat shock protein 47,HSP47)和Vimentin的蛋白表达水平;免疫荧光法观察NLRP3、Caspase-1和Vimentin的表达;PAS、PASM和Masson染色观察肾脏病理改变。结果 与对照组比较,模型组及空载组NLRP3、Caspase-1、P65和Vimentin mRNA的表达升高(均P<0.05),NLRP3、Caspase-1、P65、HSP47和Vimentin的蛋白表达升高(均P<0.05)。与模型组及空载组相比,NLRP3沉默组及ARB组的上述指标表达均下调(均P<0.05),模型组与空载组以上指标之间差异无统计学意义。病理染色结果显示NLRP3沉默和厄贝沙坦干预可减轻糖尿病肾病大鼠肾脏损害,减轻肾小球肥大、肾小球硬化、系膜扩张、间质纤维化。结论 糖尿病肾病大鼠肾脏NLRP3信号通路被激活,且炎性和纤维化因子表达上调。厄贝沙坦可阻断NLRP3信号通路,减轻肾脏损害。天然免疫受体NLRP3可能成为治疗糖尿病肾病的新靶点。

氟比洛芬酯对胸腔镜右肺叶切除术患者单肺通气期间肺功能的影响

目的观察氟比洛芬酯对胸腔镜右肺叶切除术患者采用封堵器行单肺通气期间肺氧合功能、呼吸力学及肺部并发症的影响。方法选择择期全麻下行胸腔镜右肺叶切除术采用封堵器行单肺通气的患者60例,男25例,女35例,年龄35~64岁,BMI 18~28 kg/m^(2),ASAⅠ或Ⅱ级。采用随机数字表法将患者分为两组:氟比洛芬酯组(F组)和对照组(C组),每组30例。F组在麻醉诱导前15 min静注氟比洛芬酯1.0 mg/kg,C组不予处理。于麻醉诱导前20 min(T_(0))、单肺通气30 min(T_(1))、单肺通气60 min(T_(2))、双肺通气15 min(T_(3))时抽取桡动脉血行血气分析,计算氧合指数(OI)并记录SpO_(2)。记录T_(1)、T_(2)时的气道峰压(Ppeak)、气道平台压(Pplat)、肺动态顺应性(Cdyn)和无效腔气量与潮气量之比(V_(D)/V_(T))。记录单肺通气期间低氧血症发生情况、补救例数、术后转ICU例数、术后72 h内肺不张、急性肺损伤和肺炎发生情况。结果与C组比较,F组T_(1)时SpO_(2)、T_(1)—T_(3)时PaO_(2)和OI、T_(1)、T_(2)时Cdyn明显升高(P<0.05);T_(1)、T_(2)时Ppeak和V_(D)/V_(T)、T_(2)时Pplat明显降低(P<0.05)。两组无一例单肺通气期间发生低氧血症和补救、术后转入ICU、术后72 h内发生肺不张、急性肺损伤和肺炎。结论对胸腔镜右肺叶切除术采用封堵器行单肺通气的患者,麻醉诱导前静注氟比洛芬酯有助于改善单肺通气期间肺氧合功能,优化呼吸力学参数。

预先单肺通气联合呼吸暂停对支气管封堵器用于胸腔镜手术单肺通气时肺萎陷的影响

目的 探讨预先单肺通气(OLV)联合呼吸暂停对支气管封堵器(BB)用于胸腔镜手术行OLV时肺萎陷的影响。方法 选择择期行胸腔镜下左肺段或肺叶切除术的患者75例,随机分为预先OLV组(A组)、呼吸暂停组(B组)和预先OLV联合呼吸暂停组(C组),每组25例。记录3组打开胸膜到肺完全萎陷的时间、外科医生满意度、进胸前准备时间、OLV时间、手术时间和OLV开始至胸膜打开后20 min内低氧血症[经皮动脉血氧饱和度(SpO_(2))<90%]的发生情况;记录3组胸膜腔开放即刻(T_0)、胸膜腔开放后1 min (T_1)、5 min (T_2)、10 min (T_3)和20 min (T_4)的肺萎陷评分(LCS)。结果 与A组和B组比较,C组肺完全萎陷时间明显缩短,外科医生满意度明显提高,差异均有统计学意义(P <0.05),A组和B组肺完全萎陷时间和外科医生满意度比较,差异均无统计学意义(P> 0.05);与A组比较,B组T0时点LCS低于A组,而在T_1时点,则明显高于A组,C组T_(1)、T_(2)、T_(3)和T_(4)时点LCS明显高于A组和B组,差异均有统计学意义(P <0.05);C组T2时点SpO_(2)明显低于A组和B组,差异有统计学意义(P <0.05)。结论 对于用BB行OLV的胸腔镜手术患者,预先使用OLV联合呼吸暂停,可以改善非通气侧肺的肺萎陷效果,缩短了肺完全萎陷时间,提高了外科医生满意度,且OLV的早期LCS更高,但仍需监测OLV期间的SpO_(2)。

真实世界中伊伐布雷定在急性心肌梗死住院患者中使用状况的单中心回顾性分析

目的 分析本中心急性心肌梗死住院患者伊伐布雷定的使用状况。方法 回顾性分析2019年1月至2020年4月天津市人民医院1 021例急性心肌梗死住院患者的临床资料,连续选取其中100例资料完整的使用伊伐布雷定、合用或未合用美托洛尔缓释片的患者作为观察组,另外连续选取同期100例使用美托洛尔缓释片、未使用伊伐布雷定的患者作为对照组。比较两组患者的基线特征、治疗前后心率、收缩压和舒张压变化;分析观察组伊伐布雷定的使用原因;描述观察组伊伐布雷定和美托洛尔缓释片的剂量调整情况;记录观察组中与伊伐布雷定相关的不良反应。结果 两组患者的前壁心肌梗死和非ST段抬高型心肌梗死比例、Killip心功能分级Ⅰ和Ⅱ级比例、治疗前心率、收缩压和舒张压、治疗前左心室射血分数、主动脉内球囊反搏植入比例、肌酸激酶峰值和B型利钠肽峰值比较,差异均有统计学意义(均为P<0.01)。对照组治疗前后心率、收缩压和舒张压变化均有统计学差异(均为P<0.001);观察组治疗前后心率变化有统计学差异(P<0.001),收缩压和舒张压变化无统计学差异(均为P>0.05)。观察组使用伊伐布雷定的主要原因为医生担心患者血压偏低或心功能不能耐受β受体阻滞剂。观察组初始有89例(89.0%)患者合用了美托洛尔缓释片,伊伐布雷定和美托洛尔缓释片的剂量呈“此消彼长”的变化,未出现与伊伐布雷定相关的严重不良反应。结论 本中心的数据表明,在临床实践中伊伐布雷定通常用于心率偏快、血压偏低、合并心功能不全的急性心肌梗死患者,特别是前壁心肌梗死患者。通过与β受体阻滞剂联合使用,调整剂量,可以安全、有效地控制急性心肌梗死患者住院期间心率。

支气管封堵器在左侧肺叶切除术后行右侧肺部分切除术患者肺隔离中的临床应用

目的:探讨左侧肺叶切除术后行右侧肺部分切除术患者的临床特征及肺隔离方法效果。方法:选取2022年5月至2023年11月首都医科大学附属北京友谊医院胸外科收治的5例行左侧肺叶切除术后再行右侧肺部分切除术的患者。术前评估患者胸部CT除外下呼吸道解剖异常,全麻诱导后使用单腔气管插管联合支气管封堵器行肺隔离,采用短暂停通气结合术侧肺阻塞技术行单肺通气。术中均采用保护性肺通气策略,观察肺隔离成功、单肺通气时高气道峰压、低氧血症发生情况及处理方法。结果:5例患者均无右肺上叶开口解剖变异,使用支气管封堵器行肺隔离完成手术治疗,其中2例患者行右肺隔离,2例患者行选择性右肺上叶隔离,1例患者行选择性右肺中下叶隔离。2例行选择性右肺上叶隔离患者中,1例患者需降低单肺通气时潮气量以利于右肺上叶的显露。另1例单肺通气后出现高气道峰压,调整呼吸模式后未见好转且脉搏血氧饱和度进行性下降,在窒息氧合下完成肿物切除。5例患者单肺通气时均未发生低氧血症,术后随访均无麻醉并发症。结论:支气管封堵器可安全用于左侧肺叶切除术后再次行右肺部分切除手术患者的肺隔离,但术前应仔细评估右肺上叶开口位置是否存在变异,选择合理的肺隔离方案,并有相应处理预案。

5种β受体拮抗剂类药物中的N-亚硝基类杂质的含量研究

目的测定普萘洛尔、美托洛尔、阿替洛尔、艾司洛尔、比索洛尔原料药/制剂中N-亚硝基类杂质含量,明确其含量的关注阈值。方法采用超高效液相色谱-四极杆/静电场轨道阱高分辨质谱技术。以ACE Excel 3 C18-AR为色谱柱,以含0.01 mol/L乙酸铵的0.2%甲酸溶液-甲醇为流动相进行梯度洗脱,流速为0.60 mL/min,柱温为40℃,进样量为5μL;以可加热的电喷雾离子源为离子源,以全扫描-选择离子监测模式进行正离子扫描。采用该法对10家企业生产的15批β受体拮抗剂类药物原料药/制剂中N-亚硝基类杂质含量进行测定,并采用Discovery Studio软件对待测杂质进行毒性预测和关注阈值估算。结果5种β受体拮抗剂类药物中,N-亚硝基普萘洛尔、N-亚硝基美托洛尔、N-亚硝基阿替洛尔、N-亚硝基艾司洛尔、N-亚硝基比索洛尔检测质量浓度的线性范围分别为1.01~503.38、1.02~508.38、0.97~483.63、1.11~554.27、1.05~523.92 ng/mL(r>0.999),定量限分别为1.04、0.25、0.05、0.55、1.05 ng/mL,检测限分别为0.52、0.08、0.02、0.17、0.52 ng/mL,精密度、重复性、加样回收率、稳定性、耐用性试验的RSD均小于7.5%(n=6或n=5)。15批样品中,除1批样品外,其余批次均检出了N-亚硝基普萘洛尔(1.07~8.91 ng/mg)、N-亚硝基美托洛尔(1.43~3.37 ng/mg)、N-亚硝基阿替洛尔(1.33 ng/mg)、N-亚硝基艾司洛尔(0.19 ng/mg)、N-亚硝基比索洛尔(1.27 ng/mg)。经预测,上述5种杂质有不同程度的生育毒性、致突变性、致癌性,关注阈值分别为1.0、0.4、4.3、0.2、46.7 ng/mg。结论所建方法简单快捷、灵敏度高、专属性强,估算的关注阈值明确,可用于多种β受体拮抗剂类药物中N-亚硝基类杂质的含量控制。

β受体阻滞剂应用于小儿充血性心力衰竭的系统评价与Meta分析

目的 系统评价β受体阻滞剂对小儿充血性心力衰竭患者的疗效,为临床用药提供证据。方法 从PubMed、Embase、the Cochrane Library及CNKI、万方、维普数据库中检索相关前后对照试验与随机对照试验,检索时限自建库起至2023年10月31日。结局指标有左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)、左心室舒张末期内径(LVDD)、左心室收缩末期内径(LVSD)、N端B型脑钠肽(NT-proBNP)、心率、血压及心功能改善情况。结果 共纳入20项符合标准的研究,包含1 068例患儿,包括扩张型心肌病、心内膜弹力纤维增生。Meta分析显示,在常规心力衰竭药物治疗的基础上,使用β受体阻滞剂(琥珀酸美托洛尔、比索洛尔及卡维地洛),对改善患儿LVEF[MD=13.06,95%CI(11.67,14.45),P <0.001]、LVFS [MD=6.96,95%CI(6.54,7.37),P <0.001]、LVDD [MD=-6.43,95%CI(-7.58,-5.28),P <0.001]和LVSD [MD=-8.30,95%CI(-8.83,-7.76),P <0.001]效果显著;也可改善患儿血压、心率、NT-proBNP和心功能。结论 在常规心力衰竭药物治疗的基础上使用β受体阻滞剂的联合方案可提高小儿充血性心力衰竭患者的心功能及改善心力衰竭症状,推荐将β受体阻滞剂积极应用于该类患儿的常规治疗方案中。

异种器官移植排斥反应及其预防治疗策略

异种器官移植是解决人类器官短缺问题的潜在方案。在过去的上百年里,异种器官移植经历了早期尝试和不断进步,目前已进入新的高速发展阶段,取得了一系列的成果,但异种器官移植排斥反应的管理较同种异体器官移植排斥反应更为棘手。为此,研究者们开发出了一系列免疫抑制策略,如使用基因修饰猪供体、使用传统和新型免疫抑制药、将供体猪的胸腺与供器官一同移植等,以实现调整受体免疫系统反应,降低排斥反应强度并延长移植物存活时间。本文就异种器官移植排斥反应发生机制、预防和治疗策略的相关研究进行评述,以期为促进异种器官移植的进一步发展提供参考。

富硫废水中稳定生物单质硫效果与机制研究

为提高含硫废水同步脱氮除硫工艺中生物单质硫回收率,开展了富硫废水中稳定生物单质硫效果与机制研究。在富硫废水(S^(2-)质量浓度300 mg/L)和贫硫废水(S^(2-)质量浓度200、100 mg/L)中添加阻断剂硫代硫酸钠进行脱氮除硫实验。结果表明,富硫废水中稳定组(加30 mg/L阻断剂)在60 h时单质硫积累量达到68.79 mg/L,比未稳定组(不添加阻断剂)高25.34 mg/L,单质硫稳定率达58.31%,单质硫回收率为36.84%;而贫硫废水(S^(2-)质量浓度为200、100 mg/L)中单质硫不稳定,单质硫稳定率仅11.2%、14.14%,且回收率低(15.71%、12.39%)。可见,阻断剂在富硫废水中实现了稳定生物单质硫。此外,阻断剂有利于反硝化菌和脱氮硫杆菌增殖积累,富硫废水下高比例的脱氮硫杆菌可促进单质硫稳定。阻断剂抑制了硫代硫酸盐和硫酸盐的生成,使硝酸盐得到更多电子(稳定组比未稳定组多得19.76 mmol/L电子),促进了单质硫的生成,实现了生物单质硫稳定。该技术可为废水中生物单质硫的回收与利用提供理论基础。

血管紧张素转化酶抑制剂或血管紧张素Ⅱ受体阻滞剂联合糖皮质激素治疗IgA肾病疗效观察

目的探讨血管紧张素转化酶抑制剂(ACEI)或血管紧张素Ⅱ受体阻滞剂(ARB)联合糖皮质激素治疗IgA肾病患者的临床疗效。方法选择2019年10月至2022年10月安阳地区医院收治的125例IgA肾病患者为研究对象。将患者随机分为对照组(n=62)和观察组(n=63),对照组患者给予ACEI或ARB类药物治疗,观察组患者在对照组的基础上加用丙酸氟替卡松吸入气雾剂治疗,2组患者均连续治疗3个月。比较2组患者治疗后的效果。分别于治疗前后检测2组患者24 h尿蛋白定量、肾功能指标血肌酐(Scr)、肾小球滤过率(GFR)和血常规指标白细胞计数(WBC)、血红蛋白(HGB)水平、血小板计数(PLT)。记录2组患者治疗期间不良反应发生情况。结果对照组和观察组患者治疗总有效率分别为54.84%(34/62)、84.13%(53/63),观察组患者治疗总有效率显著高于对照组(χ^(2)=12.669,P<0.05)。治疗前2组患者24 h尿蛋白定量、Scr、GFR比较差异无统计学意义(P>0.05)。对照组患者治疗前后24 h尿蛋白定量比较差异无统计学意义(P>0.05),观察组患者治疗后24 h尿蛋白定量显著低于治疗前(P<0.05);2组患者治疗后Scr显著低于治疗前,GFR显著高于治疗前(P<0.05)。治疗后,观察组患者24 h尿蛋白定量显著低于对照组(P<0.05);2组患者Scr、GFR比较差异无统计学意义(P>0.05)。2组患者治疗前后WBC、HGB、PLT水平比较差异均无统计学意义(P>0.05)。2组患者治疗过程中均未出现糖耐量异常、类固醇性糖尿病、血压升高等不良反应。结论丙酸氟替卡松吸入气雾剂联合ACEI或ARB类药物治疗IgA肾病患者,可降低24 h尿蛋白定量,有助于肾功能的改善,疗效显著,且不会对患者造成血液系统损伤,安全性较高。

外用β受体阻滞剂和脉冲燃料激光治疗低、中风险血管瘤的效果对比

目的比较外用β受体阻滞剂和激光治疗低、中风险血管瘤的效果。方法将2018年10月—2021年9月本院收治的262例低、中风险婴幼儿血管瘤患者根据治疗方式分为脉冲燃料激光组(85例)、外用0.5%噻马洛尔组(91例)和外用2%卡替洛尔组(86例)。对比各组的疗效。脉冲燃料激光治疗采用595nm PDL联合1064nm Nd:钇铝石榴石(yttrium aluminum garnet,YAG),每月1次,持续治疗1~6月。其余两组将外用β受体阻滞剂湿敷于瘤体上,持续30min,每日湿敷2次。结果总有效率方面,激光组与噻马洛尔组的差异不明显,无统计学意义(P>0.05),但与卡替洛尔组相比,组间差异显著,有统计学意义(P<0.05)。激光组疗程为(3.47±1.46)月,明显快于外用β受体阻滞剂组,组间差异显著,有统计学意义(P<0.05)。噻马洛尔组的疗程(9.33±5.80月)较卡替洛尔组(5.57±2.57月)长,但噻马洛尔组有效率(85.4%)较卡替洛尔组(79.3%)高。三组血管瘤疗效与性别、风险等级没有相关性。浅表性血管瘤的疗效明显优于混合性。结论无论是脉冲燃料激光还是外用β受体阻滞剂均对低、中风险血管瘤有效。激光治疗较外用β受体阻滞剂控制快、疗程短。建议尽早开始治疗,最好在出生3月以内,并坚持用药保证一定的疗程,使治疗效果达到最优。

高血压心率管理临床结果悖论——心率控制改善高血压治疗有结局吗?

流行病学研究证明心率增快是心血管疾病风险及死亡的独立危险因子,亦是高血压发病及死亡的独立危险因子。有效的心率控制(措施和目标)有望为高血压患者带来巨大获益。然而,使用β受体阻滞剂降低心率并未能使得高血压患者获得额外收益。这一临床悖论值得深入探讨。