维药肉桂子含量测定方法的建立

目的建立HPLC测定维药肉桂子中桂皮醛含量的方法,并定性定量测定肉桂子中的挥发油,合理制定肉桂子的含量测定方法。方法采用依利特C_(18)柱(250mm×4.6mm,5μm);以甲醇-水(45∶55)为流动相;流速:1mL·min~(-1);柱温:35℃;检测波长:285nm。肉桂子挥发油定性定量测定参照2010年版《中国药典》和日本药典(JP16)。结果桂皮醛质量浓度在2.45~34.24μg·mL~(-1)范围内(r=0.999 9)线性关系良好,平均加样回收率为104.10%(RSD=1.44%)。肉桂子挥发油含量(mL·g~(-1))为1.00%~2.88%,平均含量为1.62%;肉桂子挥发油的折光率(20℃)为1.50~1.55。肉桂子挥发油的鉴别实验和纯度实验结果均符合日本药典规定。结论建立的HPLC方法简便易行,准确性、重复性好,可作为测定肉桂子中桂皮醛的定量测定方法。肉桂子挥发油含量可纳入肉桂子质量标准含量测定起草项。     

Clinical effectiveness of adjunctive diode laser on scaling and root planing in the treatment of periodontitis: is there an optimal combination of usage mode and application regimen? A systematic review and meta-analysis

Lasers in Medical Science - This review aims to evaluate the adjunctive clinical effectiveness of diode laser (DL) to scaling and root planing (SRP) in the treatment of periodontitis, and identify...     

3例肺移植术后肺部感染的防治体会

目的总结3例同种异体肺移植术后肺部感染防治的经验和教训。方法2005年6月-2008年10月在非体外循环下右单肺移植术治疗终末期肺气肿1例（受体1）、单肺移植同期对侧肺减容术治疗终末期肺气肿1例（受体2）、体外循环下双肺移植术治疗终末期矽肺1例（受体3）。结果3例手术基本顺利,受体1术后第4天出现移植肺感染,第7天出现急性排斥反应和左侧自体肺感染,术后2年10月伴发左下肺炎性肌纤维母细胞瘤,存活至今。受体2术后第6天出现急性排斥反应,左侧声带麻痹和声音嘶哑,反复并发严重的移植肺细菌感染、霉菌感染和吻合口狭窄;术后9月因双肺严重感染并移植肺慢性排斥反应而死亡。受体3双肺移植术后未出现排斥反应,但多次伴发肺部感染,出现桥脑中央髓鞘溶解症,存活33天。结论合理强度的免疫抑制治疗和合理的抗生素应用是肺移植术后感染防控和患者长期存活的关键,纤维支气管镜是肺移植术后感染防控的有效方法。     

Novel endoscopic multi-firing-clip applicator for endoscopic closure of large colonic perforations

Background: Existing endoclip closure devices have difficulty in closing large colonic perforation. We developed a novel endoscopic multi-firing-clip applicator (EMFCA) system to address these limitations, and report on its initial evaluation.

Material and methods: The functionality and efficacy of the prototype EMFCA equipped with re-openable clamp and preloaded with four clips were assessed using standardized 1.5?cm incisions created in ex-vivo porcine colonic segments. Endoscopic closure of the lacerations with two, three and four clips (n?=?five for each group) was followed by measurement of the leakage pressure of the three groups. Finite element analysis (FEA) was performed to validate the clip behavior and reliability during deployment.

Results: All 15 perforations were sealed without leakage until fully distended. The leakage pressures of colonic lacerations sealed with two, three, and four clips were 26.1?±?2.8?mmHg, 37.3?±?7.3?mmHg and 42.3?±?7.4?mmHg, respectively. The mean operation time to deploy one clip was 25.4?±?5.2?seconds. On FEA, the deformation of the shape of the clip matched that of the intended design, with each clip sustaining a maximum stress of 648.5?MPa without any material failure during deployment.

Conclusions: These initial results confirm the efficacy of the EMFCA prototype system for endoscopic closure of colonic perforations.     

不同证型失眠症心率变异性的差异分析

目的:探讨失眠症不同证型心率变异性的差异。方法:将137例失眠患者按辨证分型分为肝郁化火、痰热内扰、心脾两虚、心虚胆怯、阴虚火旺5种证候类型,采集一般资料并采集心率变异性(HRV)频域分析法中低频功率(LF)、高频功率(HF)及低高频功率比值(LF/HF),分析中医证型HRV之间的差异。结果:LF方面,心虚胆怯组与肝郁化火组、痰热内扰组及心脾两虚组,阴虚火旺组与肝郁化火组及心脾两虚组之间均存在显著性差异;HF方面,心虚胆怯组与其余四组之间均存在显著性差异;LF/HF方面,阴虚火旺组与肝郁化火组、痰热内扰组及心脾两虚组之间存在显著性差异。结论:不同证型失眠症的心率变异性存在较大差异,心虚胆怯型失眠患者迷走神经活动较强,心虚胆怯型及阴虚火旺型患者更容易出现自主神经系统不平衡状态。     

高职院校护理专业学生临床实习质量评价指标体系的构建

目的构建适合于高职院校护理专业学生临床实习质量评价的指标体系。方法采用德尔菲法进行两轮专家咨询,用专家排序法对指标的重要性进行权重分析。结果专家问卷的回收率为96.67%,专家的权威系数为0.8867,指标的变异系数<0.25,协调系数为0.135～0.310、P<0.01,专业人文素养的权重高于临床护理能力。形成了2个一级指标、14个二级指标、51个三级指标的高职院校护理专业学生临床实习质量评价指标体系。结论高职院校护理专业学生临床实习质量评价指标体系,可用于学生临床实习质量的评价,亦可作为学生实习工作的标准。     

输液加药后微料污染情况调查

本文采用肉眼观察的方法对输液加药后微粒污染的情况进行了调查。共调查３０９瓶加药输液，有肉眼可见微粒者２２４瓶，占７２．５％。其中加安瓿装药物者微粒检出率为５２．０％，加小瓶装药物者微粒检出率为９２．４％。微粒主要是橡胶屑、玻璃屑等。微粒的产生与加药的多少和穿刺瓶塞次数有关     

Functional polyaspartic acid derivatives as eco-friendly corrosion inhibitors for mild steel in 0.5 M H2SO4 solution

To improve the corrosion inhibition efficiency of eco-friendly polyaspartic acid (PASP) for mild steel in acidic solutions, PASP/N-(3-aminopropyl)imidazole (PD-1) and PASP/N-(3-aminopropyl)-imidazole-co-n-dodecylamine (PD-2) were chemically synthesized by the facile ring-opening reaction of polysuccinimide. Inhibition efficiencies of PD-1 and PD-2 for mild steel in a 0.5 M H₂SO₄ solution were investigated by electrochemical measurements (electrochemical impedance and polarization) and the weight loss method. In comparison with PASP, PD-1 and PD-2 show improved inhibition efficiencies due to the functional groups. In particular, PD-2 shows superior corrosion inhibition capacity, and the efficiency is up to 94% at a relatively low concentration of 100 mg L⁻¹ at 298 K, as determined by potentiodynamic polarization measurements. Surface analysis of mild steel with PD-2 as an inhibitor clearly indicates that the inhibitor molecules adsorb on the steel surface and efficiently inhibit the corrosion of mild steel. The present work provides very meaningful results in designing and preparing new polymer inhibitors with high inhibition efficiency.

To improve the corrosion inhibition efficiency of polyaspartic acid (PASP) for mild steel in acidic solutions, PASP/N-(3-aminopropyl)imidazole (PD-1) and PASP/N-(3-aminopropyl)-imidazole-co-n-dodecylamine (PD-2) were synthesized.     

Orthosteric–allosteric dual inhibitors of PfHT1 as selective antimalarial agents

Artemisinin-resistant malaria parasites have emerged and have been spreading, posing a significant public health challenge. Antimalarial drugs with novel mechanisms of action are therefore urgently needed. In this report, we exploit a “selective starvation” strategy by inhibiting Plasmodium falciparum hexose transporter 1 (PfHT1), the sole hexose transporter in P. falciparum, over human glucose transporter 1 (hGLUT1), providing an alternative approach to fight against multidrug-resistant malaria parasites. The crystal structure of hGLUT3, which shares 80% sequence similarity with hGLUT1, was resolved in complex with C3361, a moderate PfHT1-specific inhibitor, at 2.3-Å resolution. Structural comparison between the present hGLUT3-C3361 and our previously reported PfHT1-C3361 confirmed the unique inhibitor binding-induced pocket in PfHT1. We then designed small molecules to simultaneously block the orthosteric and allosteric pockets of PfHT1. Through extensive structure–activity relationship studies, the TH-PF series was identified to selectively inhibit PfHT1 over hGLUT1 and potent against multiple strains of the blood-stage P. falciparum. Our findings shed light on the next-generation chemotherapeutics with a paradigm-shifting structure-based design strategy to simultaneously target the orthosteric and allosteric sites of a transporter.

Plasmodium falciparum is the deadliest species of Plasmodium, responsible for around 50% of human malaria cases and nearly all malarial death (1). Despite intensive malaria-eradication efforts to control the spread of this disease, malaria prevalence remains alarmingly high, with 228 million cases and a fatality tally of 405,000 in 2018 alone (2). The situation has become even more daunting as resistance to the first-line antimalarial agents has emerged and is rapidly spreading. For instance, artemisinin resistance, primarily mediated by P. falciparum Kelch13 (PF3D7_1343700) propeller domain mutations (3, 4), severely compromises the campaign of antimalarial chemotherapy (5–9). Novel antimalarial agents overcoming the drug resistance are therefore urgently needed (10).The blood-stage malaria parasites depend on a constant glucose supply as their primary source of energy (11). P. falciparum hexose transporter 1 (PfHT1; PF3D7_0204700) (12) is transcribed from a single-copy gene with no close paralogue (13) and has been genetically validated as essential for the survival of the blood-stage parasite (14). A possible approach to kill the parasite is to “starve it out” by the chemical intervention of the parasite hexose transporter (13, 15). The feasibility of this approach would depend on the successful development of selective PfHT1 inhibitors that do not affect the activities of human hexose transporter orthologs (e.g., human glucose transporter 1 [hGLUT1]).Previously, Compound 3361 (C3361) (15), a glucose analog, has been reported to moderately inhibit PfHT1 and suppress the growth of blood-stage parasites in vitro (16). Nonetheless, the modest potency and selectivity of C3361 had limited its further development. Structural determination of PfHT1 and human glucose transporters provides an unprecedented opportunity for rational design of PfHT1-specific inhibitors (17–20). While hGLUT1 is the primary glucose transporter in erythrocyte, its structure was determined only in the inward-open state (17). Fortunately, the neuronal glucose transporter hGLUT3, which shares over 80% sequence similarity with hGLUT1, was captured in both outward-open and outward-occluded conformations (18). A reliable homology model of outward-facing hGLUT1 could thus be generated based on the structure of hGLUT3.Comparing the structures of PfHT1 (19, 20) and hGLUT1, we identified an additional pocket adjacent to the substrate-binding site. Coadministration of allosteric and orthosteric drugs is generally applied to tackle drug resistance when these two pockets were spatially separated (21). However, this discovery led to a hypothesis that simultaneously targeting the orthosteric and allosteric sites by tethering a pharmacophore to the carbohydrate core might render selective inhibitors for PfHT1. Based on this hypothesis, we designed a class of small molecules containing a sugar moiety and an allosteric pocket-occupying motif connected by a flexible linker. Among them, TH-PF01, TH-PF02, and TH-PF03 have exhibited selective biophysical and antiplasmodial activities with moderate cytotoxicity. Furthermore, in silico computational simulations also confirmed their binding mode, lending further support to the dual-inhibitor design. Taken together, our studies validated an antimalaria development strategy that simultaneously targets the orthosteric and allosteric sites of PfHT1.