Explore the vast range of titles available.

The advent of nanomedicine requires novel delivery vehicles to actively target their site of action. Here, we demonstrate the development of lung-targeting drug-loaded liposomes and their efficacy, specificity and safety. Our study focuses on glucocorticoids methylprednisolone (MPS), a commonly used drug to treat lung injuries. The steroidal molecule was loaded into functionalized nano-sterically stabilized unilamellar liposomes (NSSLs). Targeting functionality was performed through conjugation of surfactant protein A (SPANb) nanobodies to form MPS–NSSLs–SPANb. MPS–NSSLs–SPANb exhibited good size distribution, morphology, and encapsulation efficiency. Animal experiments demonstrated the high specificity of MPS–NSSLs–SPANb to the lung. Treatment with MPS–NSSLs–SPANb reduced the levels of TNF-α, IL-8, and TGF-β1 in rat bronchoalveolar lavage fluid and the expression of NK-κB in the lung tissues, thereby alleviating lung injuries and increasing rat survival. The nanobody functionalized nanoparticles demonstrate superior performance to treat lung injury when compared to that of antibody functionalized systems.

Background: The contemporary incidence of heart failure (HF) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains unclear. This prospective cohort study was designed to study the incidence and predictors of new-onset HF in CAD patients after PCI (ChiCTR1900023033). Methods: From January 2014 to December 2018, 3,910 CAD patients without HF history undergoing PCI were prospectively enrolled. Demographics, medical history, cardiovascular risk factors, cardiac parameters, and medication data were collected at baseline. Multivariable adjusted competing-risk regression analysis was performed to examine the predictors of incident HF. Results: After a median follow-up of 63 months, 497 patients (12.7%) reached the primary endpoint of new-onset HF, of which 179, 110, and 208 patients (36.0, 22.1, and 41.9%) were diagnosed as having HF with reduced ejection fraction (EF) (HFrEF), HF with mid-range EF (HFmrEF), and HF with preserved EF (HFpEF), respectively. Higher B-type natriuretic peptide (BNP) or E/e′ level, lower estimated glomerular filtration rate (eGFR) level, and atrial fibrillation were the independent risk factors of new-onset HF. Gender (male) and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) prescription were the negative predictors of new-onset HF. Moreover, it was indicated that long-term ACEI/ARB therapy, instead of beta-blocker use, was linked to lower risks of development of all three HF subtypes (HFrEF, HFmrEF and HFpEF). Conclusions: This prospective longitudinal cohort study shows that the predominant subtype of HF after PCI is HFpEF and ACEI/ARB therapy is accompanied with reduced risks of incident HF across three subtypes.

Glucocorticoid (GC) hormone has been commonly used to treat systemic inflammation and immune disorders. However, the side effects associated with long-term use of high-dose GC hormone limit its clinical application seriously. GC hormone that can specifically target the lung might decrease the effective dosage and thus reduce GC-associated side effects. In this study, we successfully prepared human lung-targeting liposomal methylprednisolone crosslinked with nanobody (MPS-NSSLs-SPANb). Our findings indicate that MPS-NSSLs-SPANb may reduce the effective therapeutic dosage of MPS, achieve better efficacy, and reduce GC-associated side effects. In addition, MPS-NSSLs-SPANb showed higher efficacy and lower toxicity than conventional MPS.

Aims Patients with heart failure (HF) are typically designated as having reduced, mid‐range, or preserved ejection fraction (EF) (HFrEF, HFmrEF, or HFpEF, respectively) because of the importance of left ventricular EF (LVEF) on therapeutic decisions and prognosis. However, such designations are not necessarily static, as there are many transitions among the three HF phenotypes during follow‐up. This prospective longitudinal cohort study sought to examine the HF transitions over time and their clinical characteristics, prognosis, and response to medical therapy. Methods and results We identified 1920 patients from a prospective cohort with a primary diagnosis of HF between 1 January 2007 and 31 December 2012. The enrolled HF patients were re‐classified into three groups on the basis of baseline and 1 year follow‐up echocardiography: HF with improved EF (HFiEF), HF with deteriorated EF (HFdEF), and HF with unchanged EF (HFuEF). The primary outcome was 5 year all‐cause mortality. According to 1 year follow‐up echocardiography, 490 (25.5%) were diagnosed as HFiEF, 179 (9.3%) as HFdEF, and 1251 (65.2%) as HFuEF. Ischaemic heart disease was an independent predictor of HFdEF, and beta‐blocker prescription was an independent predictor of HFiEF. During the 5 year follow‐up, patients with HFdEF had higher mortality, whereas patients with HFiEF had lower mortality. After adjustment, HFiEF, compared with HFuEF, was associated with a 62.1% decreased risk for mortality. Finally, the use of beta‐blockers was associated with improved prognosis of patients with HFiEF and HFuEF. Conclusions In this cohort of patients with HF, LVEF is a dynamic factor related to coexisting conditions and drug therapy. HFiEF and HFdEF are distinct HF phenotypes with different clinical outcomes than other phenotypes.

In this study, we sought to identify differentially expressed proteins in the serum of patients with sarcoidosis or tuberculosis and to evaluate these proteins as markers for the differential diagnosis of sarcoidosis and sputum-negative tuberculosis. Using protein microarrays, we identified 3 proteins exhibiting differential expression between patients with sarcoidosis and tuberculosis. Elevated expression of these proteins was verified using the enzyme-linked immunosorbent assay (ELISA) and was further confirmed by immunohistochemistry. Receiver operating characteristic (ROC) curve, logistic regression analysis, parallel, and serial tests were used to evaluate the diagnostic efficacy of the proteins. Intercellular Adhesion Molecule 1(ICAM-1) and leptin were screened for differentially expressed proteins relevant to sarcoidosis and tuberculosis. Using ROC curves, we found that ICAM-1 (cutoff value: 57740 pg/mL) had an area under the curve (AUC), sensitivity, and specificity of 0.718, 62.3%, and 79.5% respectively, while leptin (cutoff value: 1193.186 pg/mL) had an AUC, sensitivity, and specificity of 0.763, 88.3%, and 65.8%, respectively. Logistic regression analysis revealed that the AUC, sensitivity, and specificity of combined leptin and ICAM-1 were 0.787, 89.6%, and 65.8%, respectively, while those of combined leptin, ICAM-1, and body mass index (BMI) were 0.837, 90.9%, and 64.4%, respectively, which had the greatest diagnostic value. Parallel and serial tests indicated that the BMI-leptin parallel with the ICAM-1 serial was the best diagnostic method, achieving a sensitivity and specificity of 86.5% and 73.1%, respectively. Thus, our results identified elevated expression of ICAM-1 and leptin in serum and granulomas of sarcoidosis patients. ICAM-1 and leptin were found to be potential markers for the diagnosis of sarcoidosis and differential diagnosis of sarcoidosis and sputum-negative tuberculosis.

A higher visit-to-visit variability in low-density lipoprotein cholesterol (LDL-C) is associated with an increased frequency of cardiovascular events. We investigated the association between the visit-to-visit LDL-C variability and all-cause mortality, myocardial infarction (MI), and coronary revascularization in a population with non-obstructive coronary artery disease (CAD). From this retrospective cohort of individuals who underwent coronary angiography from 2006 to 2010, a total of 2.012 consecutive patients with non-obstructive CAD, who underwent three or more LDL-C determinations during the first 2 years, were identified and followed up for 5 years. The variability in the visit-to-visit LDL-C was measured by standard deviation (SD) and coefficient of variation (CV). The risk of all-cause mortality and composite endpoints, MI, and coronary revascularization were evaluated by a multivariable Cox regression analysis. During a 5-year follow-up, a total of 99 (4.92%) mortality cases and 154 (7.65%) cases of composite endpoints were observed. The percentage of subjects who experienced mortality or composite endpoints was higher in those with a higher LDL-C-SD or LDL-C-CV level. The association between the LDL-C variability and clinical endpoints was regardless of possible confounding factors. Among the patients with non-obstructive CAD, a higher visit-to-visit LDL-C variability is associated with increasing all-cause mortality or composite endpoints during the long-term follow-up.

Lung-targeting drugs are thought to be potential therapies of refractory lung diseases by maximizing local drug concentrations in the lung to avoid systemic circulation. However, a major limitation in developing lung-targeted drugs is the acquirement of lung-specific ligands. Pulmonary surfactant protein A (SPA) is predominantly synthesized by type II alveolar epithelial cells, and may serve as a potential lung-targeting ligand. Here, we generated recombinant rat pulmonary SPA (rSPA) as an antigen and immunized an alpaca to produce two nanobodies (the smallest naturally occurring antibodies) specific for rSPA, designated Nb6 and Nb17. To assess these nanobodies' potential for lung targeting, we evaluated their specificity to lung tissue and toxicity in mice. Using immunohistochemistry, we demonstrated that these anti-rSPA nanobodies selectively bound to rat lungs with high affinity. Furthermore, we intravenously injected fluorescein isothiocyanate-Nb17 in nude mice and observed its preferential accumulation in the lung to other tissues, suggesting high affinity of the nanobody for the lung. Studying acute and chronic toxicity of Nb17 revealed its safety in rats without causing apparent histological alterations. Collectively, we have generated and characterized lung-specific nanobodies, which may be applicable for lung drug delivery.

Nanobody (Nb) is a promising vector for targeted drug delivery. This study aims to identify an Nb that can specifically target the lung by binding human pulmonary surfactant protein A (SP-A). Human lung frozen tissue sections were used for 3 rounds of biospanning of our previously constructed Nb library for rat SP-A to establish a sub-library of Nb, which specifically bound human lung tissues. Phage-ELISA was performed to screen the sub-library to identify Nb4, which specifically bound human SP-A. The binding affinity Kd of Nb4 to recombinant human SP-A was 7.48 × 10 −7 M. Nb4 (19 kDa) was stable at 30 °C–37 °C and pH 7.0–7.6 and specifically bound the SP-A in human lung tissue homogenates, human lung A549 cells, and human lung tissues, whereas didn’t react with human liver L-02 cells, kidney 293T cells, and human tissues from organs other than the lung. Nb4 accumulated in the lung of nude mice 5 minutes after a tail vein injection of Nb4 and was excreted 3 hours. Short-term exposure (one month) to Nb4 didn’t cause apparent liver and kidney toxicity in rats, whereas 3-month exposure resulted in mild liver and kidney injuries. Nb4 may be a promising vector to specifically deliver drugs to the lung.

Rotaviruses cause acute diarrhea worldwide. Previous studies of rotavirus diarrhea in China found that rotavirus infection is the most common cause of severe diarrhea in young children. In the present study, surveillance of rotavirus diarrhea was conducted involving 9549 children aged <5 years who were admitted for treatment of diarrhea at 11 sentinel hospitals in China from August 2003 through July 2007. Group A rotavirus was detected in 3749 (47.8%) of the 7846 fecal specimens by using enzyme-linked immunosorbent assay. Rotavirus isolates were characterized by reverse-transcriptase polymerase chain reaction to determine G and P genotypes. All the strains that are common worldwide were detected; G3P[8] was the most common. An unusual G5 strain was detected in 2 specimens. Of all episodes of rotavirus diarrhea, 94% occurred during the first 2 years of life, peaking at 6–23 months of age. Our findings indicate that globally common rotavirus strains continue to be a major cause of severe childhood diarrhea in China. Introduction of routine immunization with effective rotavirus vaccines would substantially reduce this burden

Background. Human bocavirus (HBoV) was recently discovered in children with respiratory tract disease and gastroenteritis. The causative role of HBoV in human gastroenteritis remains uncertain, and, to our knowledge, no previous case-control study has studied the relationship between HBoV and gastroenteritis. Methods. We conducted a case-control study that examined stool samples from 397 children with diarrhea and from 115 asymptomatic control subjects. HBoV was detected using polymerase chain reaction. Real-time polymerase chain reaction was used to quantify the HBoV loads in case and control groups. Common enteric viruses were examined using enzyme-linked immunosorbent assays, polymerase chain reaction, and reverse-transcription polymerase chain reaction. Results. At least 1 viral agent was discovered in 60.2% of cases. HBoV was detected in 14 samples, and 9 were coinfected with either rotavirus (7 of 14 samples) or human calicivirus (2 of 14). Many (8 [57.1%] of 14) of the HBoV infections occurred during September-December 2006. Most (12 [85.7%]) of the HBoV-infected children were 7–18 months of age. The percentage of children with HBoV infection did not differ significantly between case patients and control subjects (3.5% vs. 3.5%), and the statistical analysis did not support a correlation between HBoV infection and more-severe clinical symptoms. The viral load differences between the 2 groups were not statistically significant (P = .09, by log-normal Student's t test). In addition, the VP1/VP2 partial gene of HBoV from case patients and control subjects showed minimal sequence variation. Conclusions. A single genetic lineage of HBoV was revealed in persons in China. Despite its high prevalence in stool samples, our study does not support a causative role of HBoV in gastroenteritis.