Nanoparticle-based drug delivery systems for the treatment of cardiovascular diseases.

Cardiovascular disease is the most common health problem worldwide and remains the leading cause of morbidity and mortality. Despite recent advances in the management of cardiovascular diseases, pharmaceutical treatment remains suboptimal because of poor pharmacokinetics and high toxicity. However, since being harnessed in the cancer field for the delivery of safer and more effective chemotherapeutics, nanoparticle-based drug delivery systems have offered multiple significant therapeutic effects in treating cardiovascular diseases. Nanoparticle-based drug delivery systems alter the biodistribution of therapeutic agents through site-specific, target-oriented delivery and controlled drug release of precise medicines. Metal-, lipid-, and polymer-based nanoparticles represent ideal materials for use in cardiovascular therapeutics. New developments in the therapeutic potential of drug delivery using nanoparticles and the application of nanomedicine to cardiovascular diseases are described in this review. Furthermore, this review discusses our current understanding of the potential role of nanoparticles in metabolism and toxicity after therapeutic action, with a view to providing a safer and more effective strategy for the treatment of cardiovascular disease.

Biosafety risk assessment and risk control of clinical laboratory in designated hospitals for treating COVID-19 in Chongqing, China.

BACKGROUND: If a nucleic acid preservation solution containing viral inactivators is used, the biosafety risk in the process of detecting the nucleic acid of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will be low. Patients infected with SARS-CoV-2 are sent to designated hospitals for treatment in China, except for detecting nucleic acid of SARS-CoV-2, other laboratory tests such as bacterial culture may also be carried out while the patients are being treated. However, in addition to nucleic acid testing, biosafety risks in the testing of these items for patients with coronavirus disease 2019 (COVID-19) might be ignored. Therefore, we identified and evaluated risks in these detection processes and formulated appropriate, but not excessive control measures for biosafety risk, to improve the work efficiency and prevent biosafety accidents. METHODS: Biosafety risks in all laboratory tests for COVID-19 patients were identified and evaluated according to the risk severity and occurrence probability. Subsequently, the corresponding control measures for biosafety risk were formulated according to the identified risk. Hereafter, risk monitoring was carried out. RESULTS: More than 32 risks in the entire laboratory testing process were identified and evaluated, and the residual risk after the implementation of the control measures was acceptable. CONCLUSIONS: The biosafety risk assessment of laboratories in designated hospitals for treating COVID-19 should be re-implemented before testing specimens for COVID-19 patients. Risk management by risk monitoring is even more important, as it can prevent the occurrence of biosafety incidents and can continuously improve risk management.

Meta-analysis on aspirin combined with low-molecular-weight heparin for improving the live birth rate in patients with antiphospholipid syndrome and its correlation with d-dimer levels.

BACKGROUND: Antiphospholipid antibody syndrome (APS) is a systemic, autoimmune, prothrombotic disease characterized by persistent antiphospholipid antibodies, thrombosis, recurrent abortion, complications during pregnancy, and occasionally thrombocytopenia. At present, there is no consensus on the treatment of this disease. Long-term anticoagulation is recommended in most cases in patients with thrombotic APS. This study aimed to evaluate whether aspirin combined with low-molecular-weight heparin (LMWH) can improve the live birth rate in antiphospholipid syndrome and its correlation with D-dimer. METHODS: The data were retrieved from the WanFang Data, CBM, VIP, CNKI, the Cochrane Library, PubMed, EMBASE, OVID, and Web of Science databases. We collected data on randomized controlled trials of aspirin combined with LMWH in the treatment of pregnant women with APS. The "Risk of Bias Assessment" tool and the "Jadad Scale" provided by the Cochrane Collaboration were used to evaluate the risk of bias and quality of the collected literature. The risk ratio (RR) and its 95% confidence interval (CI) were determined using Statase-64 software. RESULTS: In this study, a total of 11 studies were included, comprising a total of 2101 patients. The live birth rate in pregnant women with APS was higher on administration of aspirin combined with LMWH than with aspirin alone (RR = 1.29, 95% CI = 1.22-1.35, P < .001). d-dimer concentration in plasma predicted the live birth rate, which was higher below the baseline than above it (RR = 1.16, 95% CI = 1.09-1.23, P < .001). The subgroup analysis of the live birth rate was carried out based on the course of treatment, and the results were consistent with the overall results. Begg funnel plot test revealed no publication bias. Sensitivity analysis showed that deleting any study did not affect the results. CONCLUSION: Aspirin combined with LMWH for APS may improve live birth rate, and detection of d-dimer levels in APS pregnant women may predict pregnancy complications and guide the use of anticoagulants.

Prognostic significance of pretreatment neutrophil-to-lymphocyte ratio in patients with laryngeal cancer: a systematic review and meta-analysis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has been shown to be associated with the progression of laryngeal cancer (LC), but studies have reported inconsistent results. We systematically evaluated the effect of the pretreatment NLR on the prognosis of LC in the meta-analysis. METHOD: The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched from January 1, 2000 to September 10, 2019, to identify studies investigating the relationship between the NLR and outcomes in LC patients. The fixed-effects model was used to assess the pooled hazard ratio (HR), along with the 95% confidence interval (95% CI). RESULTS: A total of 105 records were obtained through the databases and 12 studies enrolling 3710 patients were included in the meta-analysis. The pooled overall survival (OS, HR = 1.76, 95% CI 1.53-2.03, P < 0.001), progression-free survival (PFS, HR = 1.72, 95% CI 1.38-2.13, P < 0.001) and disease-free survival (DFS, HR = 1.66, 95% CI 1.33-2.07, P < 0.001) indicated that a higher NLR led to a poorer prognosis for patients with LC. In terms of publication year, country, cutoff value, cutoff method, treatment modality, statistical model and NOS score, subgroup analyses consistently showed a worse OS in patients with an elevated NLR. Additionally, there was no significant difference among the subgroups (all P for heterogeneity > 0.05). CONCLUSION: An elevated pretreatment NLR is significantly associated with poorer prognosis in patients with LC. NLR values are easily obtained from routinely collected blood samples and could assist clinicians in determining the prognosis of LC patients.

Prognostic value of ATPase family, AAA+ domain containing 2 expression in human cancers: A systematic review and meta-analysis.

BACKGROUND: ATPase family, AAA+ domain containing 2 (ATAD2) is also known as AAA+ nuclear coregulator cancer-associated protein or PRO2000. ATAD2 has been reported as a prognostic factor in different cancer types, but the association between ATAD2 high expression and survival is still unclear. Thereby, this meta-analysis was performed to evaluate the prognostic value of ATAD2 high expression in human cancers. METHODS: All of the studies included were retrieved from PubMed, EMBASE, and Cochrane Library electronic databases. The clinical outcomes were evaluated by calculating hazard ratio (HR) with their 95% confidence interval (CI). RESULTS: Thirteen studies including 2689 patients were eligible for this analysis. The pooled results showed that ATAD2 over-expression was significantly associated with shorter overall survival (OS) (HR = 2.32, 95% CI = 1.77-3.02), as well as shorter recurrence-free survival (RFS), disease-free survival (DFS), and disease-specific survival (DSS) (HR = 1.83, 95% CI = 1.51-2.23) among human cancers. Subgroup analyses for OS were implemented in terms of region, tumor type, and sample size and the results were coincident with overall pooled results. Begg funnel plot and Egger test showed the presence of publication bias for OS. Sensitivity analysis indicated that both results were not affected for removing any study. CONCLUSION: ATAD2 would be likely to act as a prognostic biomarker for the patients of different cancer types and provide a guide on clinical treatment. Prospective clinical studies are needed to support these findings.

Graphdiyne-Based One-Step DNA Fluorescent Sensing Platform for the Detection of Mycobacterium tuberculosis and Its Drug-Resistant Genes.

The accurate and early detection of Mycobacterium tuberculosis (Mtb) is of great significance for the clinical diagnosis and treatment of tuberculosis. In this work, we report a facile method for the controllable synthesis of a novel few-layered two-dimensional graphdiyne nanosheet (GDY NS) with a thickness of only ∼0.9 nm via an electrochemical lithium-intercalation strategy, which possesses a prominent fluorescence quenching effect. The few-layered GDY NS with its strong adsorptivity for single-stranded DNA is first proposed as a new fluorescent sensing platform for the real-time detection of DNA with excellent specificity, multiplicity, and superhigh sensitivity (limit of detection as low as 25 pM). This sensing platform can be further applied for the Mtb detection from clinical samples and the identification of drug-resistant mutants with a low background and a high signal-to-noise ratio. Herein, we provide a potential basis for the clinical development of rapid, sensitive, and accurate substitutes for the molecular diagnosis of Mtb and its drug-resistant genes.

Prognostic significance of programmed cell death ligand 1 expression in patients with ovarian carcinoma: A systematic review and meta-analysis.

BACKGROUND: Programmed cell death ligand 1 (PD-L1) overexpression has been reported to be associated with poor prognosis in several human cancers. However, studies on the prognostic value of PD-L1 expression in ovarian carcinoma (OC) remain controversial. This meta-analysis aimed to evaluate comprehensively the prognostic value of PD-L1 in OC. METHODS: Electronic databases, including PubMed, EMBASE, and the Cochrane Library, were searched up until March 28, 2018. Hazard ratio (HR), along with 95% confidence interval (CI), was used to analyze the included outcomes. RESULTS: A total of 10 studies with 1179 OC patients were included in this meta-analysis. There was no significant correlation between PD-L1 expression and overall survival (OS) (HR 1.23, 95% CI 0.85-1.79) and progression-free survival (PFS) (HR 0.88, 95% CI 0.52-1.47) of OC patients. However, the subgroup analysis suggested that positive PD-L1 expression was significantly associated with poor OS (HR 1.66, 95% CI 1.08-2.55) and PFS (HR 2.17, 95% CI 1.31-3.61) among OC patients from Asian countries. Increased PD-L1 expression was also a favorable factor for OS (HR 0.73, 95% CI 0.53-0.99) and PFS (HR 0.58, 95% CI 0.45-0.75) in OC patients from non-Asian regions. No evidence of publication bias was detected by the Egger linear regression test and Begg funnel plot. Sensitivity analyses suggested that the results of this meta-analysis were robust. CONCLUSIONS: The results indicated that PD-L1 expression may be a negative predictor for prognosis of OC patients from Asian countries, and a good predictor for favorable prognosis of OC patients from non-Asian countries. PD-L1 expression has potential to be a prognostic biomarker to guide clinicians for the selection of individuals who may get clinical benefit from anti-PD-1/PD-L1 immunotherapy. Prospective clinical studies are needed to support these findings.

Heavily Graphitic-Nitrogen Self-doped High-porosity Carbon for the Electrocatalysis of Oxygen Reduction Reaction.

Large-scale production of active and stable porous carbon catalysts for oxygen reduction reaction (ORR) from protein-rich biomass became a hot topic in fuel cell technology. Here, we report a facile strategy for synthesis of nitrogen-doped porous nanocarbons by means of a simple two-step pyrolysis process combined with the activation of zinc chloride and acid-treatment process, in which kidney bean via low-temperature carbonization was preferentially adopted as the only carbon-nitrogen sources. The results show that this carbon material exhibits excellent ORR electrocatalytic activity, and higher durability and methanol-tolerant property compared to the state-of-the-art Pt/C catalyst for the ORR, which can be mainly attributed to high graphitic-nitrogen content, high specific surface area, and porous characteristics. Our results can encourage the synthesis of high-performance carbon-based ORR electrocatalysts derived from widely-existed natural biomass.