Epsin Nanotherapy Regulates Cholesterol Transport to Fortify Atheroma Regression.

BACKGROUND: Excess cholesterol accumulation in lesional macrophages elicits complex responses in atherosclerosis. Epsins, a family of endocytic adaptors, fuel the progression of atherosclerosis; however, the underlying mechanism and therapeutic potential of targeting Epsins remains unknown. In this study, we determined the role of Epsins in macrophage-mediated metabolic regulation. We then developed an innovative method to therapeutically target macrophage Epsins with specially designed S2P-conjugated lipid nanoparticles, which encapsulate small-interfering RNAs to suppress Epsins. METHODS: We used single-cell RNA sequencing with our newly developed algorithm MEBOCOST (Metabolite-mediated Cell Communication Modeling by Single Cell Transcriptome) to study cell-cell communications mediated by metabolites from sender cells and sensor proteins on receiver cells. Biomedical, cellular, and molecular approaches were utilized to investigate the role of macrophage Epsins in regulating lipid metabolism and transport. We performed this study using myeloid-specific Epsin double knockout (LysM-DKO) mice and mice with a genetic reduction of ABCG1 (ATP-binding cassette subfamily G member 1; LysM-DKO-ABCG1fl/+). The nanoparticles targeting lesional macrophages were developed to encapsulate interfering RNAs to treat atherosclerosis. RESULTS: We revealed that Epsins regulate lipid metabolism and transport in atherosclerotic macrophages. Inhibiting Epsins by nanotherapy halts inflammation and accelerates atheroma resolution. Harnessing lesional macrophage-specific nanoparticle delivery of Epsin small-interfering RNAs, we showed that silencing of macrophage Epsins diminished atherosclerotic plaque size and promoted plaque regression. Mechanistically, we demonstrated that Epsins bound to CD36 to facilitate lipid uptake by enhancing CD36 endocytosis and recycling. Conversely, Epsins promoted ABCG1 degradation via lysosomes and hampered ABCG1-mediated cholesterol efflux and reverse cholesterol transport. In a LysM-DKO-ABCG1fl/+ mouse model, enhanced cholesterol efflux and reverse transport due to Epsin deficiency was suppressed by the reduction of ABCG1. CONCLUSIONS: Our findings suggest that targeting Epsins in lesional macrophages may offer therapeutic benefits for advanced atherosclerosis by reducing CD36-mediated lipid uptake and increasing ABCG1-mediated cholesterol efflux.

Versatile Types of Inorganic/Organic NIR-IIa/IIb Fluorophores: From Strategic Design toward Molecular Imaging and Theranostics.

In vivo imaging in the second near-infrared window (NIR-II, 1000-1700 nm), which enables us to look deeply into living subjects, is producing marvelous opportunities for biomedical research and clinical applications. Very recently, there has been an upsurge of interdisciplinary studies focusing on developing versatile types of inorganic/organic fluorophores that can be used for noninvasive NIR-IIa/IIb imaging (NIR-IIa, 1300-1400 nm; NIR-IIb, 1500-1700 nm) with near-zero tissue autofluorescence and deeper tissue penetration. This review provides an overview of the reports published to date on the design, properties, molecular imaging, and theranostics of inorganic/organic NIR-IIa/IIb fluorophores. First, we summarize the design concepts of the up-to-date functional NIR-IIa/IIb biomaterials, in the order of single-walled carbon nanotubes (SWCNTs), quantum dots (QDs), rare-earth-doped nanoparticles (RENPs), and organic fluorophores (OFs). Then, these novel imaging modalities and versatile biomedical applications brought by these superior fluorescent properties are reviewed. Finally, challenges and perspectives for future clinical translation, aiming at boosting the clinical application progress of NIR-IIa and NIR-IIb imaging technology are highlighted.

Clinical manifestations, antimicrobial resistance and genomic feature analysis of multidrug-resistant Elizabethkingia strains.

BACKGROUND: Elizabethkingia is emerging as an opportunistic pathogen in humans. The aim of this study was to investigate the clinical epidemiology, antimicrobial susceptibility, virulence factors, and genome features of Elizabethkingia spp. METHODS: Clinical data from 71 patients who were diagnosed with Elizabethkingia-induced pneumonia and bacteremia between August 2019 and September 2021 were analyzed. Whole-genome sequencing was performed on seven isolates, and the results were compared with a dataset of 83 available Elizabethkingia genomes. Genomic features, Kyoto Encyclopedia of Genes and Genomes (KEGG) results and clusters of orthologous groups (COGs) were analyzed. RESULTS: The mean age of the patients was 56.9 ± 20.7 years, and the in-hospital mortality rate was 29.6% (21/71). Elizabethkingia strains were obtained mainly from intensive care units (36.6%, 26/71) and emergency departments (32.4%, 23/71). The majority of the strains were isolated from respiratory tract specimens (85.9%, 61/71). All patients had a history of broad-spectrum antimicrobial exposure. Hospitalization for invasive mechanical ventilation or catheter insertion was found to be a risk factor for infection. The isolates displayed a high rate of resistance to cephalosporins and carbapenems, but all were susceptible to minocycline and colistin. Genomic analysis identified five ß-lactamase genes (blaGOB, blaBlaB, blaCME, blaOXA, and blaTEM) responsible for ß-lactam resistance and virulence genes involved in stress adaptation (ureB/G, katA/B, and clpP), adherence (groEL, tufA, and htpB) and immune modulation (gmd, tviB, cps4J, wbtIL, cap8E/D/G, and rfbC). Functional analysis of the COGs revealed that "metabolism" constituted the largest category within the core genome, while "information storage and processing" was predominant in both the accessory and unique genomes. The unique genes in our 7 strains were mostly enriched in KEGG pathways related to microRNAs in cancer, drug resistance (ß-lactam and vancomycin), ABC transporters, biological metabolism and biosynthesis, and nucleotide excision repair mechanisms. CONCLUSION: The Elizabethkingia genus exhibits multidrug resistance and carries carbapenemase genes. This study presents a comparative genomic analysis of Elizabethkingia, providing knowledge that facilitates a better understanding of this microorganism.

ROS-Responsive Nanoparticle Delivery of mRNA and Photosensitizer for Combinatorial Cancer Therapy.

Messenger RNA (mRNA) therapy has shown tremendous potential for different diseases including cancer. While mRNA has been extensively used in cancer vaccine development as antigen or in cancer immunotherapy as immunomodulatory agent, the combination of mRNA therapy with photodynamic therapy has not been explored in cancer treatment. Herein, we report a reactive oxygen species (ROS)-responsive polymeric nanoparticle (NP) platform for first-in-field codelivery of mRNA and photosensitizer for effective cancer treatment. We developed ROS-responsive oligomer-based polymeric NPs and applied them to test a combination of p53 mRNA and indocyanine green (ICG). The ROS-triggered disassembly of the NPs could promote mRNA translation efficiency, whereby p53 expression induced apoptosis of lung tumor cells. Meanwhile, the released ICG could lead to generation of ROS under 808 nm laser irradiation to induce photodynamic therapy. The NP codelivery of p53 mRNA and ICG demonstrated an effective and safe anti-tumor effect in a lung cancer model.

[Distribution and Antibiotic Resistance Analysis of Ocular Bacterial Pathogens at a Tertiary Hospital From 2012 to 2021]. / 某三甲医院2012­2021å¹´çœ¼éƒ¨ç»†èŒæ„ŸæŸ“ç— åŽŸèŒåˆ†å¸ƒåŠè€è¯æ€§åˆ†æž.

Objective: To analyze the distribution of ocular bacterial pathogens and their antibiotic resistance status at a tertiary-care hospital and to provide a reference for the appropriate use of antibiotics. Methods: Retrospective analysis was conducted with bacteria isolated from the ophthalmic samples sent for lab analysis at a tertiary-care hospital from 2012 to 2021. The suspected bacterial strains were identified with automated systems for microbial identification and susceptibility analysis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometer. VITEK 2 Compact, an automated microbial identification and antibiotic susceptibility analysis system, was used for antimicrobial susceptibility testing. Results: A total of 1556 ophthalmology bacteria culture samples were collected, 574 of which showed bacterial growth, presenting an overall positive rate of 36.89%. Of the isolated bacteria, Gram-positive cocci, Gram-positive bacilli, Gram-negative bacilli, and Gram-negative cocci accounted for 63.15% (377/597), 18.76% (112/597), 17.09% (102/597), and 1.00% (6/597), respectively. Among the bacteria isolated in different years over the course of a decade, Gram-positive cocci always turned out to be the main cause of eye infections. Of the Gram-positive cocci, 73.47% (277/377) were isolated from patients with endophthalmitis, with the most important species being Staphylococcus epidermidis, which was followed by Streptococcus viridans. The rest, or 26.53% (100/377), of the Gram-positive cocci were isolated from patients with external eye infections, with the main isolated strains being Staphylococcus epidermidis, Streptococcus viridans, and Staphylococcus aureus. More than 70% of Staphylococcus epidermidis isolated from both endophthalmitis and external eye infections were resistant to methicillin. No strains resistant to vancomycin, linezolid, or tigecycline were detected. Staphylococcus epidermidis isolated from patients with external eye infections had a low rate of resistance to levofloxacin (2/27 or 7.41%), whereas those isolated from patients with endophthalmitis had a higher resistance rate (43/127 or 33.86%). The difference in drug resistance rate between the two groups was statistically significant (P<0.05). Conclusion: The chief ocular bacterial pathogens identified in a tertiary-care hospital were Gram-positive cocci, among which, Staphylococcus epidermidis was the most common species. The Staphylococcus epidermidis identified in the hospital had a high rate of resistance to oxacillin, but remained highly sensitive to vancomycin, linezolid, and tigecycline. The endophthalmitis caused by Staphylococcus epidermidis in the hospital can be treated empirically with vancomycin and then the treatment plan can be further adjusted according to the results of the drug susceptibility test. However, the establishment of the breakpoint of drug susceptibility test is mainly based on the model of bloodstream infection and has limited reference value for the treatment of eye infection. The required drug distribution concentration at the infection site can be achieved by dose increase or local administration.

Clonal Dissemination of Antifungal-Resistant Candida haemulonii, China.

Candida haemulonii, a relative of C. auris, frequently shows antifungal resistance and is transmissible. However, molecular tools for genotyping and investigating outbreaks are not yet established. We performed genome-based population analysis on 94 C. haemulonii strains, including 58 isolates from China and 36 other published strains. Phylogenetic analysis revealed that C. haemulonii can be divided into 4 clades. Clade 1 comprised strains from China and other global strains; clades 2-4 contained only isolates from China, were more recently evolved, and showed higher antifungal resistance. Four regional epidemic clusters (A, B, C, and D) were identified in China, each comprising ≥5 cases (largest intracluster pairwise single-nucleotide polymorphism differences <50 bp). Cluster A was identified in 2 hospitals located in the same city, suggesting potential intracity transmissions. Cluster D was resistant to 3 classes of antifungals. The emergence of more resistant phylogenetic clades and regional dissemination of antifungal-resistant C. haemulonii warrants further monitoring.

Evaluation of the Autof ms1000 mass spectrometry for rapid clinical identification of filamentous fungi.

BACKGROUND: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has revolutionized microbial identification. However, there is a lack of data on its performance in identifying filamentous fungi. The objective of our study was to evaluate the accuracy of the Autof ms1000 mass spectrometry for identifying filamentous fungi in the clinical microbiology laboratory. RESULTS: Among 106 samples tested using the Autof ms1000 system, 101 (95.28%) were identified at the genus or species level, and 81 (76.41%) were accurately identified at the species level. Additionally, we developed a new rapid formic acid extraction method with simple pretreatment for filamentous fungi that saved time and provided accurate results. CONCLUSIONS: The Autof ms1000 mass spectrometer proved to be a valuable tool for identifying filamentous fungi. However, upgrading the database is recommended for correctly identifying rare strains.

[Application of Rapid Detection Method Based on NG-Test® CARBA 5 in Bloodstream Infections Associated With Carbapenem-Resistant Enterobacterales].

Objective: To compare the consistency and accuracy of a rapid test method and a traditional test method for pathogen identification, antimicrobial susceptibility and carbapenemase type identification of positive blood culture samples. Methods: A total of 51 positive blood culture samples of bloodstream infection (BSI) were collected between March 2022 and May 2022. All samples were found to be "positive for Gram-negative bacilli" according to the blood smear results. The rapid method was adopted to perform rapid antimicrobial susceptibility test (RAST) and analysis of the positive blood culture samples. According to the RAST result interpretation standards, NG-Test® CARBA 5 was used for rapid carbapenemase detection of the imipenem-resistant strains and the results were confirmed by PCR. In addition, mass spectrometry, VITEK 2 Compact drug sensitivity analysis, and carbapenemase type identification were performed with the colonies cultured with positive samples according to the traditional method. Results: In the identification of bacteria, the rapid method and the traditional method had 100% consistency rate in the identification results of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. In the antimicrobial susceptibility test, the consistency rate between the results of the two methods was high and the consistency rate for results for susceptibility to imipenem was 100%. In the identification of carbapenemase type, 18 serinase-producing strains and 3 metal-ß-lactamase-producing strains of Enterobacterales were detected by the traditional method. With the rapid method, 18 Klebsiella pneumoniae carbapenemase (KPC)-producing strains, 2 New Delhi metallo-betalactamase (NDM)-producing strains, and 1 imipenem enzyme (IMP)-producing strain were identified in the blood culture samples by using a testing kit. Compared with the PCR results, the sensitivity and specificity of the rapid test for determining carbapenemase types were 100%. In this study, we investigated a rapid method for bacteria and carbapenemase type identification of positive blood culture specimens and found that the turnaround time (TAT) of the rapid method was reduced by 1.94 days on average in comparison with the TAT of the traditional method. Conclusion: The rapid method established in the study can effectively shorten the TAT for pathogenic microorganism identification and antimicrobial susceptibility test of blood culture samples, and the joint report of colloidal gold carbapenemase type identification results can provide a reference for clinicians to use antibiotics appropriately and accurately manage multi-drug resistant bacterial infections.

Highly Twisted Conformation Thiopyrylium Photosensitizers for In Vivo Near Infrared-II Imaging and Rapid Inactivation of Coronavirus.

Despite significant effort, a majority of heavy-atom-free photosensitizers have short excitation wavelengths, thereby hampering their biomedical applications. Here, we present a facile approach for developing efficient near-infrared (NIR) heavy-atom-free photosensitizers. Based on a series of thiopyrylium-based NIR-II (1000-1700 nm) dyads, we found that the star dyad HD with a sterically bulky and electron-rich moiety exhibited configuration torsion and significantly enhanced intersystem crossing (ISC) compared to the parent dyad. The electron excitation characteristics of HD changed from local excitation (LE) to charge transfer (CT)-domain, contributing to a ≈6-fold reduction in energy gap (ΔEST ), a ≈10-fold accelerated ISC process, and a ≈31.49-fold elevated reactive oxygen species (ROS) quantum yield. The optimized SP@HD-PEG2K lung-targeting dots enabled real-time NIR-II lung imaging, which precisely guided rapid pulmonary coronavirus inactivation.

Evaluation of a Cryptococcus capsular polysaccharide detection FungiXpert LFA (lateral flow assay) for the rapid diagnosis of Cryptococcosis.

Cryptococcus is an opportunistic pathogenic fungus and is the major cause of fungal meningitis. The cryptococcal antigen (CrAg) lateral flow assay (LFA) is an immunochromatographic test system that has simplified diagnosis as a point-of-care test. In this study, we evaluated the diagnostic performance of Cryptococcal capsular polysaccharide detection FungiXpert (Genobio Pharmaceutical, Tianjin, China) using serum and cerebrospinal fluid (CSF) samples for the diagnosis of cryptococcosis and investigated the cross-reaction of the assays to pathogenic fungi and bacterium by comparing it to the U.S. Food and Drug Administration (US FDA)-approved IMMY CrAg LFA. Eighty CSF and 119 serum/plasma samples from 158 patients were retrospectively collected to test for qualitative or semi-quantitative detection of CrAg. Cross-reaction of the assays was tested using 28 fungi and 1 bacterium. Compared to IMMY CrAg LFA, the FungiXpert LFA demonstrated 99.1% sensitivity and 98.9% specificity in the qualitative test. In the 96 semi-quantitative CrAg assay results, 39 (40.6%) test titers of FungiXpert LFA were 1-2 dilutions higher than those of IMMY CrAg LFA. The Intraclass Correlation Coefficient of the Semi-quantitative results of CrAg titer tests via the two assays was 0.976. Similar to IMMY CrAg LFA, FungiXpert LFA showed cross-reactivity with Trichosporon asahii. Compared with the IMMY CrAg LFA, the FungiXpert LFA showed an equal, yet, excellent performance. However, it is important to note that these two assays have potential cross-reactivity to T. asahii when diagnosing patients. FungiXpert LFA is a rapid screening method for the effective and practical diagnosis and treatment of cryptococcosis. LAY SUMMARY: The FungiXpert LFA was developed to diagnose fungal meningitis caused by Cryptococcus yeasts, by using serum or cerebrospinal fluid. It was compared to an existing lateral flow assay (LFA). The FungiXpert LFA performed well in qualitative and semi-quantitative tests.

Molecular epidemiology and antifungal susceptibilities of Cryptococcus species isolates from HIV and non-HIV patients in Southwest China.

To investigated the molecular epidemiology and in vitro antifungal susceptibility of Cryptococcus isolates from West China Hospital from HIV and non-HIV patients between 2009 and 2015. A total of 132 C. neoformans and C. gattii were subjected to antifungal susceptibility testing by E-test method. Among the 132 isolates, 42 C. neoformans and C. gattii were analyzed by mating type and URA5-RFLP. A total of 113 C. neoformans and C. gattii were subjected to multi-locus sequence typing (MLST). MLST results revealed that ST5 was the major molecular type. The wild-type (WT) phenotype was seen in 91.5-100% of C. neoformans isolates for amphotericin B, 5-flucytosine, fluconazole, and voriconazole. However, 72.3% (94/130) of C. neoformans isolates were non-wild-type (non-WT) to itraconazole by E-test method. In the sixth study year, the geometric mean, MIC50 and MIC90 of fluconazole were the highest (P < 0.001). Among 132 patients. 52 were coinfected with HIV and 80 were HIV-negative. Isolates from HIV and non-HIV patients showed no differences in susceptibility to amphotericin B (P = 0.544), 5-flucytosine (P = 0.063), fluconazole (P = 0.570), voriconazole (P = 0.542), and itraconazole (P = 0.787). Our study showed that Cryptococcus in southwest China showed a low degree of genetic diversity. The increased MIC values of fluconazole are noted. Cryptococcus isolates from HIV and non-HIV patients have shown no differences in susceptibility to five antifungal agents.

Comparing three different phenotypic methods for accurate detection of carbapenemase-producing Enterobacterales.

BACKGROUND: Early identification of carbapenemase-producing Enterobacterales (CPE) is highly essential to prevent their dissemination within health care settings. OBJECTIVE: This study aimed to compare 3 reported phenotypic assays for detecting carbapenemase-producing Enterobacterales (CPE). METHODS: 151 Enterobacterales isolates were collected, the sensitivity and specificity of each test was determined, with molecular genotype serving as the gold standard. The phenotypic evaluations were performed using EDTA-synergistic carbapenem inactivation method (esCIM), EDTA-carbapenem inactivation method (eCIM), and enzyme inhibitor enhancement experiment (EIE). RESULTS: The concordance rate was 98% for the EIE for the detection of KPC producer, and 100% for the esCIM and eCIM. Sensitivity differed among the 3 methods, and all assays had excellent sensitivity exceeding 90% for detecting metallo-ß-lactamases (MBLs). The specificity of the eCIM, esCIM and EIE was 100%, 100% and 95%. Both eCIM and esCIM were unsatisfactory in detecting multi-enzyme strains (MBL and class A serine carbapenemase) (0/6). However, EIE increased the positive number to six (6/6). CONCLUSIONS: The eCIM, esCIM and EIE can be used to accurately detect and distinguish carbapenemase and is suitable for routine use in most clinical microbiology laboratories.

PTX3 gene polymorphism associated with cryptococcosis in HIV-uninfected Chinese patients.

BACKGROUND: For Chinese Han populations, cryptococcosis are more likely to occur in HIV-uninfected patients instead of HIV-infected patients compared with other countries and regions, implying that there may be genetic predisposing factors for cryptococcosis in the Chinese Han populations. However, the retail mechanism has not been clarified. OBJECTIVES: We aimed to conduct an association analysis between the single nucleotide polymorphisms (SNPs) of pattern recognition receptors (PRR) genes and the susceptibility to cryptococcosis in HIV-uninfected Chinese patients, which may provide new genetic predisposing factors for early-risk prediction of disease, individualised treatment and prognosis monitoring. PATIENTS/METHODS: Using the SNaPshot SNP typing technique, eight SNPs of PRR genes (Dectin-2, Dectin-1, PTX3, CXCL8, IL12B, IFIH1, TLR1 and CD209) were typed on 97 HIV-uninfected cryptococcosis patients and 120 healthy controls who admitted to West China Hospital, Sichuan University, China, from 1 March 2018 to 30 December 2018. The results were analysed by the SHEsis software and SPSS 20.0 software. RESULTS: It was found that that PTX3 rs2305619 polymorphism was associated with cryptococcosis in HIV-uninfected patients. Compared with the GG genotype, AA genotype increased the risk of cryptococcosis in HIV-uninfected patients (p = .015, OR, 2.579; 95% CI, 1.202-5.535). In the immunocompetent patients, the AA genotype had a higher risk (p = .002, OR, 4.399; 95% CI, 1.745-11.088). Further verification found that the plasma PTX3 level of the AA genotype was significantly higher than the GA or GG genotype (60.28 ± 16.12 vs 7.32 ± 0.79, p < .001). CONCLUSIONS: PTX3 rs2305619 polymorphism was associated with cryptococcosis in HIV-uninfected Chinese patients. The AA genotype increased the risk of cryptococcosis, and its plasma PTX3 level was significantly higher than that of GA or GG genotype.

Development of a fluorescent DNA nanomachine for ultrasensitive detection of Salmonella enteritidis without labeling and enzymes.

A capture probe complex containing a specific Salmonella enteritidis (S. enteritidis) aptamer and partly hybridized signal trigger sequence was designed with the ability to directly detect viable S. enteritidis. In the presence of the target S. enteritidis, single-stranded trigger sequences were liberated and in turn reacted with hairpins I, II, and III to initiate the triple strand migration reaction; this in turn produced numerous hairpin I·II·III complexes with scaffolds of copper nanoparticles (CuNPs) and replaced the trigger sequence which initiated the next cycle of triple migration reaction. Cyclically, the reuse of the trigger sequences and the successive, cascading production of scaffolds of CuNPs achieved the synthesis of highly fluorescent CuNPs, thus providing significantly enhanced fluorescent signals to achieve ultrasensitive detection of live S. enteritidis as low as 25 CFU/mL with a linear range of detection from 50 to 104 CFU/mL with an emission wavelength at 590 nm. By integrating the triple cascade strand migration amplification with recyclable trigger sequences, aptamer-based target recognition, and self-protection mediated by CuNPs hairpin scaffolds, this is the first report on a non-labeled, non-enzymatic, modification-free, and DNA extraction-free ultrasensitive fluorescent biosensor for the direct detection of live Salmonella, which is distinguished from dead Salmonella. It also provides a new strategy to detect viable bacteria by applying the CuNPs, thus extending the application of metal nanoparticles. Graphical abstract.

Proteomic Analysis and NIR-II Imaging of MCM2 Protein in Hepatocellular Carcinoma.

Targeted therapy of hepatocellular carcinoma (HCC) is essential for improved therapies. Therefore, identification of key targets specifically to HCC is an urgent requirement. Herein, an iTRAQ quantitative proteomic approach was employed to identify differentially expressed proteins in HCC tumor tissues. Of the upregulated tumor-related proteins, minichromosome maintenance 2 (MCM2), a DNA replication licensing factor, was one of the most significantly altered proteins, and its overexpression was confirmed using tissue microarray. Clinicopathological analysis of multiple cohorts of HCC patients indicated that overexpression of MCM2 was validated in 89.8% tumor tissues and strongly correlated with clinical stage. Furthermore, siRNA-mediated repression of MCM2 expression resulted in significant suppression of the HepG2 cell cycle and proliferation through the cyclin D-dependent kinases (CDKs) 2/7 pathway. Finally, the first small molecule-based MCM2-targeted NIR-II probe CH1055-MCM2 was concisely generated and subsequently evaluated in mice bearing HepG2 xenografts. The excellent imaging properties such as good tumor uptake and high tumor contrast and specificity were achieved in the small animal models. This analytical strategy can determine novel accessible targets of HCC useful for imaging and therapy.

[Antibiotic Resistance and Risk Factors for Mortality of Blood Stream Infections (BSIs) with Escherichia coli in Patients with Hematological Malignancies].

OBJECTIVE: To analyze the risk factors for mortality of blood stream infections (BSIs) caused by Escherichia coli in the patients with hematological malignancies. METHODS: There were 110 Escherichia coli BSIs patients with hematological malignancies included in recent five years. Among them,77 cases had BSIs caused by extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli (ESBL-EC group),while 33 cases had BSIs with non-ESBL-producing Escherichia coli (non-ESBL-EC group). The antibiotic resistance and clinical features were compared between the two groups,and the risk factors for death within 30 d were analyzed. RESULTS: Less than 10% of the isolates were resistant to carbapenems and amikacin. Between ESBL-EC group and non-ESBL-EC group,the clinical symptoms,prior use of antibiotics or antifungal agents,risk factors for infection,30 d mortality rates were not significantly different (P>0.05). A logistic regression analysis confirmed that non remission of hematologic malignancies (odds ratio=9.575,95% confidence interval 1.546-59.312,P=0.015) and inappropriate initial antibiotic therapy (odds ratio=8.806,95% confidence interval 1.527-50.772, P=0.015) were independent risk factors for 30 d mortality. CONCLUSION: The use of effective antimicrobial treatment as early as possible could reduce the risk of death for hematological malignancies patients suffering Escherichia coli BSIs.

Preclinical Study on GRPR-Targeted (68)Ga-Probes for PET Imaging of Prostate Cancer.

Gastrin-releasing peptide receptor (GRPR) targeted positron emission tomography (PET) is a highly promising approach for imaging of prostate cancer (PCa) in small animal models and patients. Developing a GRPR-targeted PET probe with excellent in vivo performance such as high tumor uptake, high contrast, and optimal pharmacokinetics is still very challenging. Herein, a novel bombesin (BBN) analogue (named SCH1) based on JMV594 peptide modified with an 8-amino octanoic acid spacer (AOC) was thus designed and conjugated with the metal chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA). The resulting NODAGA-SCH1 was then radiolabeled with (68)Ga and evaluated for PET imaging of PCa. Compared with (68)Ga-NODAGA-JMV594 probe, (68)Ga-NODAGA-SCH1 exhibited excellent PET/CT imaging properties on PC-3 tumor-bearing nude mice, such as high tumor uptake (5.80 ± 0.42 vs 3.78 ± 0.28%ID/g, 2 h) and high tumor/muscle contrast (16.6 ± 1.50 vs 8.42 ± 0.61%ID/g, 2 h). Importantly, biodistribution data indicated a relatively similar accumulation of (68)Ga-NODAGA-SCH1 was observed in the liver (4.21 ± 0.42%ID/g) and kidney (3.41 ± 0.46%ID/g) suggesting that the clearance is through both the kidney and the liver. Overall, (68)Ga-NODAGA-SCH1 showed promising in vivo properties and is a promising candidate for translation into clinical PET-imaging of PCa patients.

Clinical Evaluation of the Newly Developed HISCL-5000 Analyzer on Detection of Hepatitis B Virus Markers in West China Hospital.

BACKGROUND: Detection of serum hepatitis B virus (HBV) markers is important for rapid screening and diagnosis of HBV infection. In this study, the newly launched HISCL-5000 analyzer (Sysmex Corporation, Kobe, Japan) was appraised in parallel with the MODULAR E170 (Roche Diagnostics, Penzberg, Germany), with regard to the detection of serological HBV markers in China for comparing and evaluating their results and capability. METHODS: In this study, a total of 5,662 clinical serum samples were tested with the two automated systems. Among them, 1,266 samples were assessed for HBsAg, 1,000 for anti-HBs, 1,301 for HBeAg, 1,007 for anti-HBe, and 1,088 for anti-HBc. Reproducibility performance of HISCL-5000 was assayed four times per day for five days consecutively. For qualitative results between the two analyzers, the concordance rates and kappa coefficients were calculated. Spearman's rank correlation analysis was performed for quantitative results. RESULTS: The HISCL-5000 detection mode showed excellent reproducibility with total CVs of less than 5.0%. Concordance between the two analyzers was 99.92% for HBsAg, 95.90% for anti-HBs, 100% for HBeAg, 99.30% for anti-HBe, and 98.62% for anti-HBc. Kappa values between the qualitative results of five HBV markers were 0.998, 0.906, 1.0, 0.983, and 0.969, respectively. For anti-HBs, linear regression analysis demonstrated a good correlation between HISCL-5000 and MODULAR E170 with an R2 value of 0.887. Spearman's correlation coefficients of 0.892, 0.644, -0.609, and -0.700 were observed for the other four markers, HBsAg, HBeAg, anti-H1Be, anti-HBc, respectively. CONCLUSIONS: The newly launched HISCL-5000 displayed high agreement with the more matured MODULAR E170 on screening and diagnosing HBV infection in a clinical laboratory of West China Hospital.

Clinical Characteristics, Laboratory Identification, and In Vitro Antifungal Susceptibility of Yarrowia (Candida) lipolytica Isolates Causing Fungemia: a Multicenter, Prospective Surveillance Study.

Our case series showed that uncomplicated Yarrowia lipolytica fungemia might be treated with catheter removal alone. The Vitek 2 YST identification (ID) card system, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and internal transcribed spacer and 25S nuclear ribosomal DNA (nrDNA) gene sequencing provided reliable identification. All isolates had low MICs to voriconazole, echinocandins, and amphotericin B.