结核多肽壳聚糖纳米粒的制备及表征

采用离子交联法制备壳聚糖纳米粒(CS-NPs)载体,并以粒径和多分散系数(PDI)为主要评价指标优化了工艺参数。通过文献检索,筛选出结核分枝杆菌复合群(Mycobacterium tuberculosis complex,MTC)标准强菌株H37Rv的保护性抗原蛋白Rv0180c(GLDKNKFDIRVVSPDEARRLY),经异硫氰荧光素(FITC)标记后载入优化的空白CS-NPs中,获得结核多肽壳聚糖纳米粒(Pep-CS-NPs)。所得空白CS-NPs的平均粒径、PDI和ζ电位分别为(148.13±2.24)nm、0.197±0.013和(+18.00±0.89)mV;4℃放置28 d,粒径未见显著增大。Pep-CS-NPs的平均粒径、PDI和ζ电位分别为(186.93±8.80)nm、0.254±0.014和(+12.07±1.68)mV,包封率和载药量为(45.20±2.95)%和(12.92±1.12)%。体外释放结果表明,Pep-CS-NPs缓慢释放多肽,48 h累积释放率为56.6%。本试验表明,离子交联法制备载多肽CS-NPs的工艺简便稳定、条件温和,所得制品粒径大小适宜、分布均匀,且具有明显缓释作用,有望作为治疗结核病的新型疫苗。     

Effects of working memory training in patients with Parkinson's disease without cognitive impairment: A randomized controlled trial

ObjectiveTo determine the feasibility and evaluate effects of a computerized working memory (WM) training (WMT) in patients with Parkinson's Disease (PD) on cognitive and clinical outcomes.Methods76 patients with PD without cognitive impairment were randomized to either the WMT group (n = 37), who participated in a 5-week adaptive WMT, or a passive waiting-list control group (CG, n = 39). Patients underwent clinical and neuropsychological examination at baseline, after training, and at 3-months follow-up, with verbal WM and non-verbal WM as primary outcomes. Outcome assessors were blinded for group allocation.ResultsAll WMT participants completed the training successfully and reported high levels of motivation for and satisfaction with the training. Repeated-measures, linear mixed-effects models revealed positive training effects for the WMT group compared to the CG in verbal working memory with a small relative effect size 0.39 [95%CI 0.05; 0.76] for the 3-months follow-up only. No other reliable training effects in cognitive and clinical variables were found for either point of time.ConclusionsIn this randomized controlled trial, WMT was feasible and yielded some evidence for 3-months follow-up training gains in patients with PD. WMT might be an effective intervention to prevent cognitive decline in this patient group, however, more longitudinal studies with longer follow-up periods and more sensitive assessment tools will have to proof this concept.Trial registrationGerman Clinical Trials Register (DRKS00009379).     

Effects of continuous positive airway pressure treatment on aortic stiffness in patients with resistant hypertension and obstructive sleep apnea: A randomized controlled trial

Resistant hypertension (RHT) is associated with obstructive sleep apnea (OSA) and increased aortic stiffness, measured by carotid‐femoral pulse wave velocity (cf‐PWV). We aimed to evaluate in a randomized controlled trial, the effect of Continuous positive airway pressure (CPAP) treatment on cf‐PWV in comparison with a control group in patients with RHT and moderate‐severe OSA. One‐hundred and sixteen patients were randomized to 6‐month CPAP treatment (56 patients) or no therapy (60 patients), while keeping their antihypertensive treatment unchanged. Carotid‐femoral pulse wave velocity was performed at the beginning and end of the 6‐month period. Intention‐to‐treat intergroup differences in cf‐PWV changes were assessed by a generalized mixed‐effects model with the allocation group as a fixed factor and adjusted for age, sex, changes in mean arterial pressure and the baseline cf‐PWV values. Subgroup sensitivity analyses were performed, excluding patients with low CPAP adherence and low cf‐PWV at baseline. CPAP and control groups had similar clinic‐laboratorial characteristics. Patients had a mean cf‐PWV of 9.4 ± 1.6 m/s and 33% presented cf‐PWV > 10 m/s. During treatment, the control group had a mean increase in cf‐PWV of +0.43 m/s (95% confidence interval [CI], +0.14 to +0.73 m/s; p = .005), whereas the CPAP group had a mean increase of +0.03 m/s (95% CI, ?0.33 to +0.39 m/s; p = .87), resulting in a mean difference in changes between CPAP and control of ?0.40 m/s (95% CI, ?0.82 to +0.02 m/s; p = .059). Subgroup analyses did not change the results. In conclusion, a 6‐month CPAP treatment did not reduce aortic stiffness, measured by cf‐PWV, in patients with RHT and moderate/severe OSA, but treatment may prevent its progression, in contrast to no‐CPAP therapy.     

阿伐斯汀联合氯雷他定治疗慢性难治性荨麻疹的多中心随机对照研究

【摘要】 目的 比较阿伐斯汀与阿伐斯汀联合氯雷他定治疗慢性难治性荨麻疹的疗效。方法 2017年3月至2018年12月，于4家中心采用多中心、随机对照的临床研究，联合治疗组慢性难治性荨麻疹患者口服阿伐斯汀胶囊8 mg每日3次及氯雷他定片10 mg每日1次，阿伐斯汀组口服阿伐斯汀胶囊8 mg每日3次及安慰剂10 mg每日1次，治疗4周。分别于治疗前、治疗1、2、4周随访，采集临床指标及记录不良反应事件。根据瘙痒、风团的数目、风团大小、每次发作持续时间、每周发作次数评估症状积分，使用症状积分下降指数（SSRI）评价疗效。采用重复测量的方差分析和χ2检验进行疗效和安全性评价。结果 联合治疗组53例、阿伐斯汀组59例纳入疗效分析。治疗前，两组症状积分、瘙痒视觉模拟评分差异均无统计学意义。治疗2周，联合治疗组痊愈19例、显效10例，有效率54.72%；阿伐斯汀组痊愈15例，显效6例，有效率35.59%。治疗4周，联合治疗组痊愈23例，显效9例，有效率60.38%；阿伐斯汀组痊愈20例，显效2例，有效率37.29%。治疗2、4周，联合治疗组有效率均高于阿伐斯汀组（χ2 = 4.13、5.96，均P < 0.05）。两组各随访时间点的SSRI差异、组间SSRI差异均有统计学意义（F = 8.62、4.38，均P < 0.05）。多变量方差分析，治疗2、4周时，联合治疗组SSRI（0.63 ± 0.05、0.68 ± 0.05）高于阿伐斯汀组（0.47 ± 0.05、0.51 ± 0.05），差异均有统计学意义（均P < 0.05）。联合治疗组发生药物相关性不良反应7例，阿伐斯汀组3例，主要表现为嗜睡、胃部不适、头痛、肝功能异常。结论 阿伐斯汀治疗慢性难治性荨麻疹安全、有效；阿伐斯汀联合氯雷他定可以显著提高疗效。     

强迫症团体认知行为治疗与药物治疗的随机对照研究

目的分析团体认知行为治疗(group cognitive-behavioral therapy,GCBT)对强迫症患者的疗效。方法本研究采用随机对照试验设计,与常规抗强迫药物治疗做对照。将符合入组标准的94例未用药强迫症患者,采用Excel软件中的RAND函数产生随机数字表形成随机分组序列的简单随机分组法,随机分为GCBT组(47例)和药物治疗组(47例)。经12周的结构化GCBT治疗和常规抗强迫药物治疗,采用t检验、卡方检验和方差分析比较2组间Y-BOCS、HAMA14和HAMD24平均减分率和减分值的差异。结果(1)2组基线Y-BOCS及HAMA14评分差异无统计学意义(t=0.281,P=0.779;t=0.795,P=0.429),但GCBT组HAMD24评分显著低于药物治疗组(t=2.316,P<0.05)。2组各有16例患者退出治疗,总脱落率为34%(32/94)。(2)12周治疗结束时,2组患者的Y-BOCS评分较基线显著降低,GCBT组和药物治疗组治疗前后Y-BOCS平均减分率[(37.0±27.4)%比(45.5±22.9)%]和平均减分值[(9.0±6.3)分比(11.0±5.8)分]比较差异无统计学意义[F(1,62)=0.069,P=0.794;F(1,62)=0.001,P=0.975]。GCBT组和药物治疗组的有效率和治愈率差异无统计学意义(χ^2=1.653,P=0.199;χ^2=0.088,P=0.767)。(3)GCBT组HAMA14减分率和减分值与药物治疗组治疗前后比较差异无统计学意义(t=-0.922,P=0.362;t=1.082,P=0.286)。(4)GCBT组HAMD24减分率与药物治疗组治疗前后比较差异无统计学意义,但药物治疗组HAMD24减分值显著高于GCBT组(t=2.239,P=0.029)。结论GCBT与常规抗强迫药物治疗强迫症患者的强迫和焦虑症状的疗效相当,常规药物治疗对抑郁症状的疗效优于GCBT。     

灯盏生脉胶囊联合盐酸多奈哌齐治疗阿尔茨海默病的临床研究

目的 观察灯盏生脉胶囊联合盐酸多奈哌齐对阿尔茨海默病患者认知功能、日常生活能力及安全性的影响。方法 将98例阿尔茨海默病患者随机分为治疗组与对照组各49例; 对照组给予每日口服盐酸多奈哌齐5 mg/次,1次/d,治疗组在对照组的基础上口服灯盏生脉胶囊0.36 g/次,3次/d; 比较2组患者治疗前与治疗3、6月后认知功能评分(MMSE、ADAS-cog)、日常生活能力评分(ADAS-ADL)、血清一氧化氮(NO)、内皮素(ET)水平及不良反应发生率。结果 治疗6月后治疗组MMSE评分为(21.85±2.58)分,对照组为(20.48±2.23)分(P<0.05); 治疗3、6月后治疗组ADAS-cog评分为(45.48±5.94)、(41.57±5.10)分,对照组为(48.69±6.23)、(414.24±5.53)分(P<0.05); 治疗3、6月后治疗组ADAS-ADL评分为(43.91±4.25)、(47.57±3.86),对照组为(41.77±4.44)分、(44.46±5.18)分(P<0.05); 治疗3、6月后治疗组NO水平为(41.95±7.62)、(37.89±5.93)μmol/L,对照组为(45.28±6.68)、(41.55±7.92)μmol/L(P<0.05); 治疗3、6月后治疗组ET水平为(140.48±22.94)、(132.04±10.08)ng/L,对照组为(152.08±17.39)、(143.91±17.60)ng/L(P<0.05); 2组药物不良反应主要有恶心、失眠、头痛、乏力、头晕、腹泻、皮疹,治疗组和对照组药物不良反应发生率分别为20.41%和14.28%(P>0.05)。结论 灯盏生脉胶囊联合盐酸多奈哌齐可提高阿尔茨海默病患者认知功能及日常生活能力,减少神经毒性物质NO、ET的生成,且安全性较好