A Novel and Rapid Smear Cytomorphology Detection Strategy Based on Upconversion Nanoparticles Immunolabeling Integrated with Wright's Staining for Accurate Diagnosis of Leukemia.

Background: Accurate, sensitive, and rapid identification of leukemia cells in blood and bone marrow is of paramount significance for clinical diagnosis. An integrative technique combining traditional cytomorphology with immunophenotyping was proposed to improve the diagnostic efficiency in leukemia. On account of high photostability, biocompatibility, and signal-to-background ratio, upconversion nanoparticles (UCNPs) as luminescent labels have drawn substantial research scrutiny in immunolabeling. Methods: To achieve simultaneous determination, NaYF4:Yb,Er UCNPs were coupled with CD38 antibodies to construct immunofluorescence probes that were developed to bind to diffuse large B cell lymphoma (DLBCL) cells, followed by Wright's staining that has been widely used in clinical work for morphological diagnosis. Further, the experimental conditions were optimized, such as medium, slice-making method, antibody dosage, incubation time, etc. Results: The cell morphology and immunolabeling could be observed simultaneously, and its simple operation rendered it a possibility for clinical diagnosis. The developed immunolabeling assay could achieve DLBCL cell counting with high reproducibility and stability, and the detection limit was as low as 1.54 cell/slice (>3 σ/s). Moreover, the proposed method also realized real blood and bone marrow sample analysis, and the results were consistent with the clinical diagnosis. Conclusion: Overall, this strategy can be carried out after simple laboratory training and has prospective biomedical applications in leukemia classification, diagnosis validation, and differential diagnostics.

Photoredox-Catalyzed Radical-Radical Cross-Coupling of Sulfonyl Chlorides with Trifluoroborate Salts.

Sulfones are widely found in natural products and drug molecules. Here, we disclose a strategy for direct synthesis of sulfone compounds with diverse structures by visible-light-catalyzed radical-radical cross-coupling of sulfonyl chlorides and trifluoroborate salts. Allyl, benzyl, vinyl, and aryl trifluoroborates can be successfully cross-coupled with (hetero)aryl and alkyl sulfonyl chlorides, respectively. This strategy features redox neutrality, good substrate generality, simple operation, and benign reaction conditions.

Highly Sensitive Lanthanide-Doped Nanoparticles-Based Point-of-Care Diagnosis of Human Cardiac Troponin I.

INTRODUCTION: Cardiac troponin I (cTnI) has been regarded as a gold standard for early diagnosis and prognosis monitoring of acute myocardial infarction (AMI) in clinical practice. Owing to its low concentration in blood, accurate determination of cTnI often requires high sensitivity. However, current established point-of-care (POC) assays are insufficient to meet clinically analytical requirements due to their low sensitivity. METHODS: To this end, we established a highly sensitive and reliable POC lateral flow strip based on lanthanide-doped nanoparticles (NPs) for cTnI determination in human blood samples. The capture of cTnI on the lateral flow strip was performed in a sandwich assay, where Eu3+-doped vanadate nanoparticles (GdVO4:30% Eu NPs) were used as luminescent probes to allow quantification. RESULTS: Our platform realized the analytical sensitivity enhancement with limit-of-detection (LOD) as low as 17 pg mL-1 for cTnI detection, which was lower than the commercial counterpart; meanwhile, it displayed high specificity, excellent reproducibility and outstanding accuracy for analyzing clinical serum samples. CONCLUSION: Overall, this strategy provided an ultrasensitive, cost-effective and user-friendly platform for on-site cTnI detection, demonstrating the prospect of lanthanide-doped NPs-based POC diagnosis of disease-related biomarkers.

Hyperglycemia is a strong predictor of poor prognosis in COVID-19.

AIMS: The objective of this study is to explore the association between documented diabetes, fasting plasma glucose (FPG), and the clinical outcomes of Coronavirus disease 2019 (COVID-19). METHODS: This retrospective study included 255 patients with COVID-19. Of these, 214 were admitted to isolation wards and 41were admitted to intensive care units (ICUs). Demographic, clinical, treatment, and laboratory data were collected and compared between ICU and non-ICU patients. Multivariable logistic regression models were used to explore the risk factors associated with poor clinical outcomes (ICU admission or death). RESULTS: There were significant changes in several clinical parameters in ICU patients (leukopenia, lymphopenia, elevated D-dimer, as well as higher levels of FPG, cardiac troponin, serum ferritin, IL-6, and high-sensitivity C-reactive protein)compared with non-ICU patients. The prevalence of known diabetes was substantially higher in ICU than non-ICU patients (31.7% vs. 17.8%, P = 0.0408). Multivariable regression analysis showed that a history of diabetes [odds ratio (OR), 0.099; 95% confidence interval (CI), 0.016-0.627; P = 0.014], high FPG at admission (OR, 1.587; 95% CI, 1.299-1.939, P < 0.001), high IL-6 (OR, 1.01; 95% CI, 1.002-1.018, P = 0.013), and D-dimer higher than 1 mg/L at admission (OR, 4.341; 95% CI, 1.139-16.547, P = 0.032) were independent predictors of poor outcomes. Cox proportional hazards analysis showed that compared with FPG < 7 mmol/L, FPG levels of 7.0-11.1 mmol/L and ≥ 11.1 mmol/L were associated with an increased hazard ratio (HR) for poor outcome (HR, 5.538 [95% CI, 2.269-13.51] and HR, 11.55 [95% CI, 4.45-29.99], respectively). CONCLUSION: Hyperglycemia and a history of diabetes on admission predicted poor clinical outcomes in COVID-19.

High-intensity focused ultrasound treatment for patients with unresectable pancreatic cancer.

BACKGROUND: High-intensity focused ultrasound (HIFU) is a non-invasive method of solid tissue ablation therapy. However, only a few studies have reported the effect of HIFU for unresectable pancreatic cancer. This study aimed to evaluate the clinical benefits, survival time and complications associated with the use of HIFU ablation in patients with unresectable pancreatic cancer. METHODS: Twenty-five patients with unresectable pancreatic cancer were enrolled in our study. All patients received HIFU therapy for tumors at least once. The therapeutic effects of HIFU was evaluated in terms of Karnofsky performance status (KPS) scores, pain relief, serum CA19-9, and imaging by B-US and CT before and after the therapy. We also recorded median overall survival time and complications caused by the treatment. RESULTS: In the 25 patients, KPS scores were above 60, and increased KPS was observed in 23 patients after treatment. Pain relief occurred in 23 patients. Serum CA19-9 levels were significantly reduced one month after HIFU treatment and became negative in 5 patients. B-US revealed enhanced tumor echogenicity in 13 patients and decreased tumor blood supply in 9. Tumor necrosis was confirmed by CT in 8 patients one month after HIFU treatment. The median overall survival time was 10 months, and the 1-year survival rate was 42%. No severe complications were observed after HIFU treatment. CONCLUSION: HIFU can effectively relieve pain, increase KPS, decrease tumor growth and prolong the survival time of patients with unresectable pancreatic cancer.

Highly enantioselective conjugate addition of aldehydes to nitroolefins catalyzed by chiral bifunctional sulfamides.

Chiral bifunctional sulfamides were found to be highly efficient organocatalysts for the conjugate addition of aldehydes to nitroolefins in the presence of base additives.