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.     

Inhibition of indoleamine 2,3-dioxygenase (IDO) enhances elimination of virus-infected macrophages in an animal model of HIV-1 encephalitis

Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting enzyme in the kynurenine pathway of tryptophan metabolism. IDO activity is linked with immunosuppression by its ability to inhibit lymphocyte proliferation, and with neurotoxicity through the generation of quinolinic acid and other toxins. IDO is induced in macrophages by HIV-1 infection, and it is up regulated in macrophages in human brain tissue with HIV-1 encephalitis (HIVE). Using a model of HIVE, we investigated whether IDO inhibitor 1-methyl-d-tryptophan (1-MT) could affect the generation of cytotoxic T lymphocytes (CTLs) and clearance of virus-infected macrophages from the brain. Severe combined immunodeficient mice were reconstituted with human peripheral blood lymphocytes, and encephalitis was induced by intracranial injection of autologous HIV-1-infected monocyte-derived macrophages (MDMs). Animals treated with 1-MT demonstrated increased numbers of human CD3+, CD8+, CD8+/interferon-gamma+ T cells, and HIV-1(gag/pol)-specific CTLs in peripheral blood compared with controls. At week 2 after MDM injection in the basal ganglia, mice treated with 1-MT showed a 2-fold increase in CD8+ T lymphocytes in the areas of the brain containing HIV-1-infected MDMs compared with untreated controls. By week 3, 1-MT-treated mice showed 89% reduction in HIV-infected MDMs in brain as compared with controls. Thus, manipulation of immunosuppressive IDO activity in HIVE may enhance the generation of HIV-1-specific CTLs, leading to elimination of HIV-1-infected macrophages in brain.     

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.     

两种入路腹腔镜下低位直肠腺癌远端直肠离断的效果比较

目的 比较两种入路腹腔镜下低位直肠腺癌远端直肠离断的效果。方法 选取2019年1月－2022年1月该院收治的80例直肠腺癌患者作为研究对象,采用随机数表法分为A组和B组,各40例,A组采用经闭孔神经前入路远端直肠离断的直肠癌根治术,B组采用腹腔镜辅助经肛门全直肠系膜切除术（TME）,比较两组患者的临床疗效。结果 A组术中出血量少于B组,拔出导尿管时间短于B组（P < 0.05）;术后两组患者血清胃动素和胃泌素水平均较术前降低,且A组低于B组（P < 0.05）。A组术后并发症Clavien-Dindo分级为Ⅰ级的多于B组,术后肛门功能（Kirwan分级）优于B组,两组患者比较,差异均有统计学意义（P < 0.05）。结论 采用经闭孔神经前入路远端直肠离断的直肠癌根治术治疗直肠腺癌,可减少术中出血量,缩短术后拔除导尿管时间,促进胃肠动力,保留肛门功能,减轻术后并发症严重程度。     

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.     

近5年我国护理证据总结类论文的方法学质量分析

目的:检索国内相关数据库,参考JBI循证卫生保健研究中心证据总结制作的核心要素,分析护理证据总结类论文的常见方法学问题,为证据总结的撰写和发表提供参考。方法:使用"证据总结"为检索词检索近5年中国知网、万方数据库、维普数据库中发表的证据总结类论文,将其共性问题进行归纳总结并探讨对应的处理策略。结果:经筛选后共纳入证据总结类论文78篇,其循证问题的提出、证据的检索、筛选、评价以及证据的分级和推荐强度的制定等方面均存在一些共性问题。结论:规范证据总结的报告方法将有利于临床科学决策。