Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel(PTX).However,no intravenous lipid emulsion of PTX has been approved for clinical treatment,and systemic safety profiles have not yet been reported.Here we outline the development of a PTX-loaded tumor-targeting intravenous lipid emulsion(PTX Emul)and describe its characteristics,colloidal stability,and systemic safety profiles in terms of acute toxicity,long-term toxicity,and tox-icokinetics.We also compare PTX Emul with conventional PTX injection.Results showed that PTX Emul exhibited an ideal average particle size(approximately 160 nm)with narrow size distribution and robust colloidal stability under different conditions.Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential.In addition,where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs,including the decreased AUC and increased plasma clearance and volume of distribution,PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose,moderate body weight change,decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose.A fundamental understanding of the systemic safety profiles,high tumor-targeting efficiency,and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer.

Objective:To introduce the Burnt Hand Outcome Tool (BHOT) into China to conduct sinicization, cross-cultural debugging, and test the reliability and validity, thus provide a reference for the evaluation of treatment effect and making of medical decisions of hand burn patients.Methods:The cross-sectional research was conducted. After obtaining the authorization of the original author, the Brislin translation mode was used to literally translate, synthesize, back-translate, and be checked by experts to form the Chinese version of BHOT (C-BHOT) 2. Ten experts in the field of burn rescue and treatment were invited by purpose sampling method to conduct cross-cultural debugging to form C-BHOT 3. A total of 21 hand burn patients who were treated in General Hospital of Ningxia Medical University from January to March 2020 and conformed to the inclusion criteria were selected by accidental sampling method for pre-testing. Then the final version of C-BHOT 4 was formed. Hospitalized patients who met the selection criteria were recruited using accidental sampling, multi-site and cross-regional survey method from May 2020 to March 2021 in General Hospital of Ningxia Medical University, the First Affiliated Hospital of Air Force Medical University, the First Affiliated Hospital of Army Medical University (the Third Military Medical University), and the First Affiliated Hospital of Nanchang University. The survey was performed with the general information questionnaire and C-BHOT 4. Critical ratio method and correlation coefficient method were used for item analysis, Cronbach's α coefficient test tool was used to test internal consistency, test-retest reliability was used to judge the stability of the tool, content validity index analysis tool was used to analyze the content validity, and exploratory factor analysis was used to test the validity of the structure. Data were statistically analyzed with independent sample t test or Pearson correlation analysis. Results:After the sinicization, cross-cultural debugging, and pre-testing, C-BHOT 4 was formed with a total of 20 items. All items were adjusted to positive scoring, and 7 modifications were made on the basis of the original tool. A total of 353 questionnaires were issued in the formal survey, and 344 valid questionnaires were returned, with an effective response rate of 97.45%. In the 344 patients, there were more male patients (297 patients) than female patients (47 patients), with ages of 23 to 57 years. The critical ratios of each item in the item analysis ranged from 5.48 to 12.59 ( P<0.05). There were statistically significant differences in the scores between patients in high-score group and low-score group ( t=-10.72--2.84, P<0.05 or P<0.01). There was significant positive relationship among the scores of each two items and between scores of each item and the overall tool score ( r=0.68-0.71, 0.47-0.63, P<0.05 or P<0.01). In reliability test, the Cronbach's α coefficient of the whole tool was 0.837, and the test-retest reliability was 0.702-0.793. In validity test, the content validity index of whole tool was 0.923. The exploratory factor analysis extracted 3 common factors, and the cumulative variance contribution rate was 76.162%. The comparative fit index in the confirmatory factor analysis was 0.924. Conclusions:After the BHOT tool being sinicized, cross-culturally debugged, pre-tested, and tested for reliability and validity, it was verified that C-BHOT 4 has good reliability and validity in assessing the outcome of Chinese hand burn patients, and therefore can be used as an effective tool for the evaluation.

Objective:To analyze the magnetic resonance imaging (MRI) features of epithelioid glioblastoma (eGBM), and to quantitatively analyze the characteristics of apparent diffusion coefficient (ADC) , perfusion-weighted imaging (PWI) and magnetic resonance spectrum (MRS) of eGBM patients.Methods:The MRI results of eight cases of eGBM confirmed by pathology in the Affiliated Hospital of Qingdao University from October 2016 to November 2018 were analyzed retrospectively. The location, edge, signal, peritumoral edema, adjacent meningeal invasion and enhancement of the patients were observed, and the changes of ADC value, relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV) and the ratio of choline (Cho)/N-acetyl-L-aspartic acid (NAA) were analyzed.Results:Among the eight patients, the main tumors were located in temporal lobe ( n=3), frontal lobe ( n=3) and parietal lobe ( n=2). The boundary of the lesion was clear in six cases and unclear in two cases. The lesions were superficial in five cases and in deep white matter in three cases. Bleeding could be seen in four cases. There were three cases with cystic change and four cases with necrosis, and there was no cystic necrosis only in one case. There was no edema around the lesion in one case, severe edema in five cases and moderate edema in two cases. The adjacent meninge was involved in four cases and the ependyma was involved in one case. Two patients had leptomeningeal metastasis within two months after operation. The average ADC value of tumor parenchyma in eight patients was 7.15×10 -4 mm 2/s, which was 17.6% lower than that of the contralateral side. MRS showed that the ratio of Cho/NAA in the lesions of two patients were 5.27, 0.81. PWI showed that the rCBV in the lesions of two patients was 3.51 ml/100 g and 3.32 ml/100 g, respectively, which was 36% and 29% higher than that of the contralateral side, respectively. And the rCBF of the lesions was 31.5 ml·100 g -1·min -1and 82.1 ml·100 g -1·min -1, respectively, which increased by 49% and 203% respectively compared with the contralateral side. Conclusions:eGBM has the characteristics of superficial location, easy to be cystic, but the wall of the cyst is not smooth and uneven, the boundary of the mass is clear, the adjacent meninges are easy to be involved and the meningeal tail sign appears, and it is easy to be spread by cerebrospinal fluid. ADC value, PWI and MRS can provide some help for preoperative tumor grading.

Objective To explore the value of contrast-enhanced ultrasound (CEUS) in improving the diagnosis ability for xanthogranulomatous cholecystitis ( XGC ) and wall-thickening gallbladder cancer ( GBC) . Methods Forth-three patients with XGCs and 31 patients with wall-thickening GBCs proved by pathology were enrolled in this study ,the features on conventional ultrasound and CEUS were recorded ,and the preliminary diagnosis before and after CEUS were given by doctors . Results Significant differences were found in continuous gallbladder inner wall and arterial blood supplement on conventional ultrasound , 58 .1％ (25/43) had continuous inner wall and 34 .9％ (15/43) had arterial blood flow in XGCs compared to 19 .4％ (6/31) and 100％ in GBCs . On CEUS ,72 .1％ (31/43) demonstrated continuous gallbladder inner wall and 48 .8％ (21/43) had hypoechoic nodules in the wall in XGCs compared to 16 .1％ (5/31) and 19 .4％ (6/31) in GBCs ,respectively ( P <0 .05) . No significant difference was found in intra-calcification , infiltration to adjacent organs ,gallbladder stones and fast-in and fast-out enhanced pattern( P >0 .05) . The area under ROC curve was improved from 0 .701 to 0 .899 after combining with CEUS ( P < 0 .05 ) . Conclusions Conventional ultrasound combining with CEUS could help acquiring more effective ultrasonic information and may improve the differential diagnosis ability of XGCs and GBCs .

Objective: To study the molecular epidemiology and genetic variation of coxsackievirus B5 (CV-B5) in certain areas in China. Methods: MEGA 6.0 software was used to analyze the complete VP1 region of CV-B5 isolated strains from certain areas of China by retrieving the GenBank nucleotide database. Besides, the phylogenetic tree was constructed, the homology of nucleotide and amino acids were calculated and the rate of evolution was estimated. Results: A total of 189 Chinese CV-B5 isolated strains were included in this study. Most of Chinese CV-B5 isolated strains belonged to genotype C, accounted for 90.5%. Compared with the genotype A, the homology of nucleotide sequences and amino acid sequences of complete VP1 region of 189 Chinese isolated strains were 79.8%-82.8% and 92.6%-97.9%, respectively; moreover, the nucleotide and the amino acid homology of 189 Chinese CV-B5 isolated strains among themselves ranged from 80.3% to 100.0% and ranged from 91.5% to 100.0%, respectively. The estimated rate of evolution of the CV-B5 was 4×10^-3 substitutions/site/year. Conclusions The majority of CV-B5 isolated strains belonged to genotype C, and subgenotype C1 and C2 were co-circulating together in certain areas of China.

Given the Ebola outbreak in West Africa and the risks of spread to other regions, a rapid, sensitive and simple method for the detection of the Ebola virus (EBOV) is of great significance for the prevention and control of Ebola. We developed a simple colorimetric isothermal multiple self-matching initiated amplification (IMSA) for rapid detection of the Zaire subtype of the Ebola virus (EBOV-Z). This method employed six primers that recognized seven sites of the EBOV-Z nucleoprotein gene for amplification of nucleic acids under isothermal conditions at 63 degrees C for 1 h. Amplification products were detected through visual inspection of color change by pre-addition of hydroxyl naphthol blue dye. Relative sensitivity was validated by detection of serial tenfold dilutions of virus-like particles containing the partial EBOV-Z nucleoprotein gene and mock clinical sample. Specificity of IMSA was validated by detection of the plasma of 30 healthy volunteers, the dengue virus, and Japanese encephalitis virus. IMSA had comparable sensitivity to Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and cross-reaction with human plasma or other viruses was not observed. Reverse transcription-isothermal multiple self-matching initiated amplification (RT-IMSA) was also evaluated and compared in parallel with the commercial RT-qPCR kit for detection of EBOV-suspected samples of human blood in Sierra Leone. Sensitivity and specificity of the RT-IMSA was 91.4% and 100%, respectively. These data suggest that RT-IMSA is a valuable tool for the detection of the EBOV with the distinct advantages of simplicity and low cost compared with RT-qPCR.
Colorimetry ; methods ; DNA Primers ; genetics ; Ebolavirus ; genetics ; isolation & purification ; Hemorrhagic Fever, Ebola ; diagnosis ; virology ; Humans ; Nucleic Acid Amplification Techniques ; methods

Objective To evaluate the effect of the integrated strategy in prevention and control of intestinal nematodiasis in Hongze County,so as to provide the evidence for formulating the control strategies and measures in the future. Methods Since 1995,the integrated strategy has been carried out for intestinal nematodiasis,and the measures included deworming,health ed?ucation,safe water,sanitation and environmental remediation. The effects of the integrated strategy were evaluated by the inves?tigations of the prevalence of soil?transmitted nematodiasis,awareness of health knowledge and behaviors of residents. Results From 1995 to 2014,601 900 person?times were administrated with deworming medication and the coverage rate of villages and towns was 100%. The benefit rate of safe water was 100%. The popularity rate of harmless toilets was 92.77%. The prevalence of intestinal nematodiasis decreased from 26.04%in 1995 to 0.56%in 2014,and the difference had statistical significance(χ2=693.54,P < 0.01). The awareness rate of health knowledge and correct rate of health behaviors increased from 43.13% and 40.94%in 1995 to 98.00%and 96.80%in 2012,respectively(χ2=181.97 and 182.14 respectively,P<0.01). Conclusion The prevalence of intestinal nematodiasis has been controlled effectively through the integrated strategy in Hongze County ,Jiang?su Province.

A simple, rapid and sensitive colorimetric reverse-transcription loop-mediated isothermal amplification (RT-LAMP) was developed for rapid detection of Middle East respiratory syndrome coronavirus (MERS-CoV). The method employed six primers that recognized sequences of a nucleocapsid gene for amplification of nucleic acids under isothermal conditions at 63 degrees C for 60 min. Products were detected through a LA-320c Loopamp Turbidimeter (real-time RT-LAMP) or visual inspection of color change by pre-addition of Hydroxynaphthol Blue dye (visual RT-LAMP). Specificity of RT-LAMP was validated by detection of several human coronaviruses and common respiratory viruses. MERS-CoV real-time RT-LAMP had a linear correlation (R2) of 0.995 at 10(3)-10(6) copies. The limit of detection of real-time RT-LAMP, visual RT-LAMP and quantitative real-time PCR was 500, 1000 and 100 copies/reaction, respectively. The established RT-LAMP assay was demonstrated to be a rapid screening tool for MERS-CoV infection, and could be suitable in resource-limited clinical sites and for field studies.
Coronavirus Infections ; virology ; DNA Primers ; genetics ; Humans ; Middle East Respiratory Syndrome Coronavirus ; classification ; genetics ; isolation & purification ; Nucleic Acid Amplification Techniques ; methods ; Reverse Transcription

OBJECTIVETo develop a simple, rapid and sensitive colorimetric reverse-transcription loop-mediated isothermal amplification (RT-LAMP) for rapid detection of coxsackievirus A6 (CV-A6) based on the colour chang of hydroxy naphthol blue (HNB).

METHODSThe method employed a set of six primers that recognized sequences of VP1 gene for amplification of nucleic acid under isothermal conditions at 63 °C for 50 min. The products were detected through visual inspection of color change by the pre-addition of HNB dye. The specificity was validated by detecting a collection of different human enteroviruses. The sensitivity of this assay was evaluated by serial dilutions of RNA molecules from in vitro transcription of CV-A6 VP1 gene, and compared with real-time RT-PCR (rRT-PCR) in parallel. This assay was evaluated with 92 clinical specimens from patients with hand-foot-mouth disease.

RESULTSA positive color (sky blue) was only observed in the preparation of CV-A6, whereas none of the other 23 kinds of human enteroviruses showed a color change. The HNB based RT-LAMP showed a sensitivity of 100 copies/reaction, which was at the same level as that of the rRT-PCR. The result of RT-LAMP in analysis of 92 clinical specimens was consistent with that of the rRT-PCR. The kappa correlation between the two methods was 1 and both of the sensitivity and specificity of the RT-LAMP assay were 100%.

CONCLUSIONThe established RT-LAMP assay had good specificity and sensitivity and thus demonstrated to be a promising screening tool for CV-A6 infection. It also has the potential to be used in resource-limited clinical sites and field study.

Colorimetry ; Coloring Agents ; chemistry ; DNA Primers ; Enterovirus ; isolation & purification ; Hand, Foot and Mouth Disease ; virology ; Humans ; Indicators and Reagents ; chemistry ; Naphthalenesulfonates ; chemistry ; Nucleic Acid Amplification Techniques ; Real-Time Polymerase Chain Reaction ; Reverse Transcription ; Sensitivity and Specificity

Objective To construct and express ribonuclease-resistant virus-like particles containing the RNA fragmengts of MERS-CoV N gene.Methods The coat protein and maturase gene of E.coli bacteriophage MS2 was amplified by PCR,then the gene was cloned into pET32a to construct the intermediate vector pET32MS.The gene fragments harboring MERS-CoV N gene and beta-actin was cloned into the downstream of pET32MS to construct the prokaryotic expression vector p32MS-EMC-Beta.The recombinant plasmid p32MS-EMC-Beta was transformed into E.coli BL21 (DE) competent cells and induced with IPTG.The virus-like particles were obtained after purification.RNase digestion test and stability test were carried out to observe the stability of the particles.Results The RNase-resistant virus-like particles which was able to express the gene fragments containing MERS-CoV N gene and beta-actin were successfully produced and were shown to be stored stable for 30 days at 37℃.Conclusion The virus-like particles with high safety and stability can be used as positive standards and quality controls in the application of MERS-CoV detection.