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.     

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     

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.     

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.     

前交叉韧带重建术后界面螺钉排异微创治疗1例

前交叉韧带（anterior cruciate ligament,ACL）对维持膝关节稳定性有重要作用,但受伤后的恢复能力很差,且保守治疗效果不佳,不实施重建手术一般无法治愈[1]。关节镜进行前交叉韧带重建手术具有伤口小,位置准确,促进患者早期康复的优点。随着运动医学的发展,前交叉韧带重建手术失败病例也越来越多。现报道1例前交叉韧带重建术后聚醚醚酮 (polyether ether ketone,PEEK)界面螺钉发生排异反应并用微创治疗案例,希望引起临床重视,了解术后排异反应和翻修手术的代替治疗。     

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...     

微创经皮肾镜技术在肾结石开放手术中的应用

目的:评价微创经皮肾镜取石(minimally invasive Pereutaneous nephrolithotomy,MPCNL)技术在特殊肾结石患者开放手术中的应用价值.方法:开放手术中经肾穿刺、扩张,利用输尿管镜碎石、取石治疗8例患者.结果:穿刺均一次成功,一次取尽结石7例,1例残留结石再次经造瘘管取尽,术后恢复理想,无严重并发症发生.结论:肾结石开放手术中配合使用MPCNL技术具有创伤小、提高结石取尽率等优点,特别是在术前估计不足,应急的状况下,术中使用MPCNL技术不失为一种行之有效的补救措施.     

康乃潘胶囊的临床疗效研究

目的：研究康乃潘胶囊治疗疼痛的疗效和不良反应，为临床应用提供依据。方法：选择疼痛原因不同的受试对象，分治疗组和对照组。疼痛强度采用标尺法，治疗组服用康乃潘胶囊，对照组服用曲马多胶囊，记录疼痛开始缓解时间。结果：治疗组对恶性肿瘤所致疼痛的疗效明显优于对照组（ Ｐ＜ ０．００１），而对创伤、手术所致疼痛及神经性疼痛，两组疗效基本相同（ Ｐ＞０．０５），疼痛缓解时间治疗组明显短于对照组（ Ｐ＜ ０．００１）。不良反应发生率两组相近（ Ｐ＞ ０．０５） 。结论：康乃潘胶囊可作为一种速效、高效、安全、无成瘾性镇痛药使用，对疼痛因子持续存在的恶性肿瘤所致疼痛具有良好的镇痛作用，其疗效优于曲马多胶囊。     

福达拉滨联合环磷酰胺治疗多毛细胞白血病1例并文献复习

目的:探讨多毛细胞白血病（HCL）的临床特点及治疗措施。方法:根据患者的临床表现、骨髓细胞形态学及组织化学染色、免疫分型、电镜检查等进行诊断,采用福达拉滨联合环磷酰胺方案治疗,并综合已有文献简述HCL治疗现状及进展。结果:该例患者为经典型HCL,福达拉滨联合环磷酰胺方案治疗后缓解。结论:HCL患者骨髓涂片发现毛细胞、电镜检查、免疫分型对诊断有重要意义,嘌呤核苷酸类似物对其治疗有较高的缓解率。