BF-30 effectively inhibits ciprofloxacin-resistant bacteria in vitro and in a rat model of vaginosis

Bacterial infections are becoming increasingly difficult to treat due to the increasing number of multidrug-resistant strains. Cathelicidin-BF (BF-30) is a cathelicidin-like antimicrobial peptide and exhibits broad antimicrobial activity against bacteria. In the present study, the antibacterial activity of BF-30 against ciprofloxacin-resistant Escherichia coli and Staphylococcus aureus was examined, and the protective effects of this peptide against these bacteria in rats with bacterial vaginosis were identified for the first time. The data showed that BF-30 had effective antimicrobial activities against ciprofloxacin-resistant E. coli and S. aureus. The minimal inhibitory concentrations for both bacterial strains were 16 μg/ml, and the minimal bactericidal concentrations were 64 and 128 μg/ml, respectively. A time course experiment showed that the CFU counts rapidly decreased after BF-30 treatment, and the bacteria were nearly eliminated within 4 h. BF-30 could reduce the fold change (CFU/ml) in local colonization by drug-resistant E. coli and S. aureus to 0.01 at a dose of 0.8 mg/kg/day in the rats’ vaginal secretions. In addition, BF-30 induced membrane permeabilization and bound to the genomic DNA, interrupting protein synthesis. Taken together, our data demonstrate that BF-30 has potential therapeutic value for the prevention and treatment of bacterial vaginosis.     

Ultrasmall bimodal nanomolecules enhanced tumor angiogenesis contrast with endothelial cell targeting and molecular pharmacokinetics

Nonintrusive and precise imaging for tumor angiogenesis is critical in accurate assessment of cancer diagnosis and prognosis. However, reticulo-endothelial system (RES) capture and inadequate accumulation remain major bottlenecks for current nanoparticle to retain at tumor angiogenesis site. Herein, we report the ultrasmall contrast agent (cNGR-Au:Gd@GSH NMs) could accumulate at tumor vasculature site and enhance the tumor angiogenesis-contrast. It is demonstrated that by loading Au and Gd atom into the naturally-occurring glutathione (GSH) shell with cNGR peptide modification, cNGR-Au:Gd@GSH NMs exhibit the high X-ray photon absorption, longer rotational correlation time and efficient tumor vascular endothelia cell targeting. In vivo studies further indicate the cNGR-Au:Gd@GSH NMs prominently enhance tumor angiogenesis-contrast both on the computed tomography (CT) and magnetic resonance imaging (MRI) modalities by escaping the RES capture and target delivering. Our data imply that the cNGR-Au:Gd@GSH NMs may serve as the high-efficiency contrast agent to assess tumor angiogenesis in a nonintrusive technique.     

Inhibition of hypoxia-induced proliferation of pulmonary arterial smooth muscle cells by a mTOR siRNA-loaded cyclodextrin nanovector

The proliferation of pulmonary arterial smooth muscle cells (PASMCs) is a key pathophysiological component of vascular remodeling in pulmonary arterial hypertension (PAH), an intractable disease, for which pharmacotherapy is limited and only slight improvement in survival outcomes have achieved over the past few decades. RNA interference provides a highly promising strategy to the treatment of this chronic lung disease, while efficient delivery of small interfering RNA (siRNA) remains a key challenge for the development of clinically acceptable siRNA therapeutics. With the aim to construct useful nanomedicines, the mammalian target of rapamycin (mTOR) siRNA was loaded into hybrid nanoparticles based on low molecular weight (Mw) polyethylenimine (PEI) and a pH-responsive cyclodextrin material (Ac-aCD) or poly(lactic-co-glycolic acid) (PLGA). This hybrid nanoplatform gave rise to desirable siRNA loading, and the payload release could be modulated by the hydrolysis characteristics of carrier materials. Fluorescence observation and flow cytometry quantification suggested that both Ac-aCD and PLGA nanovectors (NVs) may enter PASMCs under either normoxia or hypoxia conditions as well as in the presence of serum, with uptake and transfection efficiency significantly higher than those of cationic vectors such as PEI with Mw of 25 kDa (PEI25k) and Lipofectamine 2000 (Lipo 2k). Hybrid Ac-aCD or PLGA NV containing siRNA remarkably inhibited proliferation and activated apoptosis of hypoxic PASMCs, largely resulting from effective suppression of mTOR signaling as evidenced by significantly lowered expression of mTOR mRNA and phosphorylated protein. Moreover, these hybrid nanomedicines were more effective than commonly used cationic vectors like PEI25k and Lipo 2k, with respect to cell growth inhibition, apoptosis activation, and expression attenuation of mTOR mRNA and protein. Therefore, mTOR siRNA nanomedicines based on hybrid Ac-aCD or PLGA NV may be promising therapeutics for diseases related to hypoxic abnormal growth of PASMCs.     

Simultaneous detection of acetaminophen and 4-aminophenol with an electrochemical sensor based on silver–palladium bimetal nanoparticles and reduced graphene oxide

In this paper, Ag–Pd bimetallic nanoparticles uniformly distributed on reduced graphene oxide (rGO) were synthesized by redox reaction between Pd²⁺, Ag⁺and GO, and were characterized by X-ray diffractometry, field emission scanning electron microscopy, electrochemical impedance spectroscopy and thermal gravimetric analyses. A novel electrochemical sensor was constructed based on these nanocomposites using glassy carbon as a substrate. Under optimal conditions, the linear ranges were 0.50–300.00 μM for PA and 1.00–300.00 μM for 4-AP, with the detection limits of 0.23 μM for PA and 0.013 μM for 4-AP, respectively. This sensor was successfully applied to the determination of PA in pharmaceutical formulations and gave satisfactory results with a lower detection limit, wider linear range and good reproducibility.

Simultaneous detection of acetaminophen and 4-aminophenol with a highly sensitive electrochemical sensor based on silver–palladium bimetal nanoparticles and reduced graphene oxide.     

海南省新生儿G6PD缺乏症筛查十年回顾分析

目的寻找海南省人群葡萄糖-6-磷酸脱氢酶(G6PD)缺乏症发病情况和基因突变特点。方法对海南省2007至2016年出生的914520名新生儿的干血斑使用荧光斑点法进行G6PD活性筛查。初筛可疑标本召回使用G6PD/6-磷酸葡萄糖脱氢酶(6GPD)比值法进行确诊,对2016年确诊为G6PD缺乏的患儿的3012份干血斑使用多色探针荧光PCR熔解曲线法进行基因分型。结果海南省10年间在914520例新生儿中初筛阳性36314例,确诊了26370例G6PD缺乏,发病率为2.88%(26370/914520)。以民族划分,汉族人群G6PD发病率2.80%(21688/774555)。黎族人群发病率3.45%(4292/124419),黎族和汉族发病率比较,差异具有统计学意义(χ^2=161.261,P=0.000)。苗族人群发病率3.31%(212/6401),苗族和汉族发病率相比较差异具有统计学意义(χ^2=6.104,P=0.013)。其他民族人群发病率为1.95%(178/9145),与汉族发病率相比较差异具有统计学意义(χ^2=24.283,P=0.000)。在3012例G6PD确诊病例中共检出13种基因突变,其中c.1376 G>T、c.1388 G>A、c.95 A>G和c.1024 C>T突变合并约占91.74%。其中经基因测序发现16种基因型以外的2种突变,即c.86C>T和c.1311C>T。结论海南省新生儿人群G6PD发病率高,G6PD发病有民族和地域差异。海南省人群基因突变主要以c.1376G>T、c.1388G>A、c.95 A>G和c.1024 C>T为主。     

Consistency evaluation of Liferiver,Yaneng, Darui,and the Cobas 4800 test for high-risk human papillomavirus screening

BackgroundIn recent years, several high‐risk human papillomavirus (HR‐HPV) tests have been developed. The assay capabilities need to be systematically reviewed. Here, we compared the clinical sample performance of three novel HR‐HPV assays (Liferiver, Yaneng, and Darui) based on different platforms with the widely adopted cobas4800 test.MethodsA total of 346 cervical swabs from women who were screened for cervical cancer were analyzed for the presence of 14 HR‐HPV genotypes. The distinction between the four assays was investigated by the genotyping and direct sequencing.ResultsThe positive rates of the four assays ranged from 61.56% to 64.16%. The overall concordance was 88.15%. The Yaneng assays displayed the best sensitivity (100%) and specificity (98.43%). The sensitivity (98.17%) and specificity (98.43%) of the Darui assay were superior to those of the cobas4800 test (97.72% and 93.70%, respectively). The Liferiver assay displayed comparable sensitivity with the cobas4800 test (95.89% and 97.72%, respectively). The specificity of the cobas4800 was lower than that of the Liferiver assay (93.70% vs. 97.64%).ConclusionsThe three novel HR‐HPV assays displayed good agreement with the cobas4800 test. The analytical performance of all four fulfilled the requirements of sensitivity and specificity for HR‐HPV detection.     

西宁地区常温下肝门阻断切肝术的临床研究

目的研究西宁地区常温下肝切除术中阻断入肝血流方式、阻断时间对“安全切肝”,尤其是肝癌合并有乙肝、肝硬化者的临床意义。方法选择临床和病理确诊的肝脏肿瘤及肝包虫病人共10例行手术治疗。结果本组10例肝脏手术均获成功(1例术后7天因肝衰死亡),根据病例的不同情况采用了三种肝血流阻断方法。结论采取常温下阻断肝血流的方法,减少肝脏切除术中大出血,同时尽可能减少入肝血流阻断的时间以减少和避免术后发生衰竭,为“安全切肝”提供了有力的技术保障。     

司库奇尤单抗治疗中重度斑块状银屑病的近期疗效及安全性观察

【摘要】 目的 观察司库奇尤单抗治疗中重度斑块状银屑病的近期疗效及安全性。方法 2019年6 - 11月收集就诊于河南省人民医院皮肤科的中重度斑块状银屑病患者36例,给予司库奇尤单抗单药皮下注射治疗,300 mg/次,分别于基线、第1、2、3、4周注射1次,随后每4周1次,分别于第4、8、12周时记录患者银屑病皮损面积和严重度指数（PASI）,观察药物不良反应。结果 36例患者均接受至少12周的治疗。4周时,8例达PASI75,其中3例达PASI90,1例达PASI100;8周时,26例达PASI75,其中16例达PASI90,4例达PASI100;12周时,32例达PASI75,其中26例达PASI90,8例达PASI100。所有患者均未发生严重感染或恶性肿瘤等严重药物不良反应,1例腹部皮下注射后出现腹痛、腹胀,持续3 d后症状消失;1例患者出现扁桃体炎,之后原有皮损处出现湿疹样改变;1例颈部出现化脓性淋巴结炎。结论 司库奇尤单抗治疗中重度斑块状银屑病疗效显著,不良反应较少,是中重度斑块状银屑病患者新的治疗选择之一。     

定量脑电图在脑血管病临床应用中的进展

定量脑电图是近年临床中常用的无创实时脑功能监测手段。脑血管病后神经网络受损所 致的神经电生理传导改变可通过皮层脑电图记录并总结出其规律性,结合计算机技术给予定量处理, 可为卒中的发展、预后以及卒中后抑郁、卒中后认知功能障碍的评估方面提供客观依据。现从定量脑 电图在卒中和卒中后相关疾病的特点及临床应用方面作一综述。