Jiayi Zhao

Background: In the study, we aimed to uncover potential therapeutic mechanisms concerning M2 macrophage‐derived exosomes in asthma. Methods: Exosomes were isolated from M0Φ‐Exos and M2Φ‐Exos. An ovalbumin (OVA)‐induced asthma mouse model or lipopolysaccharide (LPS)‐induced alveolar epithelial cells (AECs) were created to unravel the therapeutic mechanisms. High‐throughput sequencing was used to search for differentially expressed circRNA. Bioinformation analysis and luciferase report analysis were used to reveal the regulationship among circ‐Eif3c, miR‐15a‐5p, glutathione synthetase (GSS), and suppressor of cytokine signaling 6 (SOCS6). Results: The results showed that M2Φ‐Exos suppressed OVA‐induced inflammatory cytokine secretion and lung injury in mice. Next‐generation sequencing (NGS) showed that circ‐Eif3c was upregulated in M2Φ‐Exos. Circ‐Eif3c downregulation inhibited the therapeutic effect of M2Φ‐Exos. Bioinformation analysis confirmed that miR‐15a‐5p, GSS, and SOCS6 were the downstream targets of circ‐Eif3c, which were confirmed by luciferase report analysis. The overexpression of miR‐15a‐5p or the downregulation of GSS/SOCS6 reversed circ‐Eif3c’s protective effects on LPS‐induced AEC damage. The overexpression of circ‐Eif3c increased the therapeutic effect of M2Φ‐Exos. Conclusion: In conclusion, circ‐Eif3c‐enriched M2Φ‐Exos attenuated airway remodeling by restoring the function of AECs.

MSCs have demonstrated their unique therapeutic potential in early clinical trials for a variety of respiratory diseases in recent years, but their use in the treatment of asthma has rarely been reported. In this study, a chronic murine asthma model that is more similar to clinical asthma was constructed via sustained HDM induction for 70 days, followed by treatment via tail vein injection of MSCs after modeling. The mechanism by which MSCs alleviate airway remodeling was investigated via RNA-seq. The airways on the day following treatment were used to screen for transcriptomic changes resulting from the MSC treatment under study, filtering for differentially expressed genes (DEGs), identifying their enrichment pathways, and finally confirming the DEGs gained via western blotting. After HDM treatment, airway remodeling is reversed, asthma and the HIF-1 signaling pathway are inhibited, and the expression levels of Timp1 and Wnt2b in the fibrosis pathway are also significantly decreased. STRING analysis revealed a reciprocal interaction in their expression, which was also confirmed by western blotting. To verify whether MSCs alleviate airway remodeling by inhibiting Timp1, we constructed MSCs overexpressing Timp1 and evaluated their effects in vitro and in vivo. The ability of MSCs to alleviate airway remodeling was reversed after Timp1 was overexpressed. These findings demonstrate that MSCs alleviate asthma-induced airway remodeling by inhibiting the Timp1‒Wnt2b axis.

Asthma is a chronic inflammatory disturbance of the airways in which many cells and cellular elements are involved. Wheezing, breathlessness, chest tightness, and coughing, especially at night or in the early morning, are typical symptoms of asthma. At present, inhaled corticosteroid (ICS) and long-acting β-agonists (LABAs) are standard treatments for regular management. Oral corticosteroids (OCSs) were recommended for controlling asthma exacerbation but only for a short-term treatment because of the side effects on organs. Biologic therapies have achieved exciting and notable effects in clinical treatment but are not applicable for all phenotypes of asthma. At present, some new approaches are under exploration to lessen side effects and improve curative effects. Studies have revealed that bone marrow mesenchymal stem cells (BMMSCs) hold various curative effects in asthma and may benefit in the long term with high safety. Extracellular vesicles (EVs) enriched in body fluid were characterized as subcomponents of extracellular vesicles and delivered carriers combined with genetic messages in vivo. The therapeutic potential of exosomes has become a research hotspot in many diseases. BMMSC-derived exosomes were considered as the dominant part of BMMSCs in cell-to-cell communications and playing curative effects. Points also hold that BMMSC-Exo could interfere with airway inflammation and airway remolding in asthma via modulating the immune response, regulating gene expression, adjusting the phenotype of macrophage, etc. However, BMMSC-Exo still lacked more clinical trials for evaluating the effects on asthma, and the technology of extraction and purification still needs to be improved for wide use. This review aims to draw the relationship among asthma, BMMSC, and exosome, which may provide innovate ideas for treatment of asthma, and arouse attention about the curative potential of BMMSC-Exo.

Rationale: Heparin-induced thrombocytopenia (HIT), a potentially devastating form of drug-induced thrombocytopenia, occurs in patients receiving heparin for thrombosis prevention or treatment. An isolated HIT is characterized by decreased platelet counts without thrombosis, which are atypical and difficult to clinically find. Symptoms and clinical findings: A 33-year-old female patient’s admission examination revealed elevated D-dimer levels. After prophylactic anticoagulation using low-molecular weight heparin, her blood platelet counts were rapidly decreased, whereas her D-dimer levels increased, followed by presentations of chest tightness, abdominal pain, and skin itching without thrombosis. After excluding all the other causes of thrombocytopenia, HIT was suspected. Her 4Ts score was 5 points, and enzyme-linked immunoassay for platelet factor 4 (PF4)/heparin antibodies was positive, indicating isolated HIT. Diagnoses, interventions, and outcomes: The patient was diagnosed with advanced lung cancer presenting with isolated HIT. We immediately stopped low-molecular weight heparin and initiated rivaroxaban for anticoagulation. We administered thrombopoietin (TPO) and avatripopal maleate tablets to increase blood platelet counts, whereas intravenous immunoglobulin (IVIG) was administered to stimulate her immune system. The patient’s thrombocytopenia was successfully treated without thrombosis and bleeding complications. Lessons: Rivaroxaban is a potential option for tumor preventive anticoagulation and HIT treatment. Early HIT identification is necessary. After identification, the 4Ts score as well as PF4/heparin antibodies should be assessed and appropriate anticoagulants selected based on patients’ conditions.

Icariin is a major bioactive component extracted from Epimediumbrevicornum Maxim, which has various biological attributessuch as anti-inflammatory and antioxidative activities, and immune regulation.

Background: Venous thrombosis (VTE) is a high-incidence disease that affects different systems of the body, but no comparative studies have been conducted to explore its incidence in different systems in patients with the coexistence of multiple diseases. Primary care is a medical institution that has the first contact with patients’ conditions. The majority of outpatients suffer from multiple diseases, and they are more prone to VTE, which is of significance and requires investigation. At the same time, we observed that the primary care patients’ cognition level of VTE is insufficiency at present, and the prevention and management of VTE in China is still in its infancy. Most studies focus on whether doctors and nurses are clear about the diagnosis and manifestations of VTE, however, few studies on patients’ cognitive level and influencing factors of symptoms and prevention of VTE. Therefore, it is necessary to study the causes of cognitive deficiency of VTE from the perspective of patients, conduct targeted cognitive and behavioral interventions, and finally achieve the purpose of improving the effect of VTE prevention and management. Aim: This study aimed to explore the risk factors, cognitive level and cognitive potential influence factors of VTE in outpatients of primary care in Shanghai, as well as which diseases, are more likely to promote occurrence of VTE among patients with multiple diseases. Methods: A total of 710 patients were included in the analysis. Shanghai in China is divided into urban and suburban areas by their geographical location, and a random sample of 10 primary care areas was investigated, including 5 urban areas and 5 suburban areas. The Padua scale and the VTE cognitive level-related knowledge test scale were used for the investigation. Statistical software was used to conduct univariate Pearson correlation analysis and multivariate logistic regression analysis for VTE high-risk factors among outpatients of primary care. Furthermore, the high-risk factors for VTE and the types of chronic disease in patients with multiple diseases were subjected to subgroup analyses. t-test was used to statistically analyze cognitive level of VTE and the potential influence factors related to the patients’ VTE cognitive level. Results: Univariate analysis of risk factors for VTE in 710 outpatients showed that age (χ²=83.895, P< 0.001), education (χ²=8.324, P=0.004), region (χ²=63.936, P< 0.001), chronic disease (χ²=18.198, P< 0.001) and the coexistence of multiple diseases (χ²=61.347, P< 0.001) were the main risk factors for VTE risk in patients. Logistic multivariate regression analysis showed that age, region, chronic diseases and the coexistence of multiple diseases were independent risk factors for VTE risk in patients. The correlation between high risk of VTE in patients with multiple diseases and various types of chronic diseases was further analyzed by logistic multivariate regression. The results showed that diabetes mellitus (OR=1.636 [95% CI, 1.030– 2.599], P=0.037), cerebral infarction (OR=8.484 [95% CI, 4.615– 15.597], P< 0.001), coronary heart disease (OR=2.987 [95% CI, 1.699– 5.252], P< 0.001), intracerebral hemorrhage (OR=15.130 [95% CI, 4.707– 48.630], P< 0.001), respiratory diseases (OR=3.470, [95% CI, 1.428– 8.43], P=0.006) and malignant tumors (OR=4.576, [95% CI, 1.85– 11.315], P=0.001) were independent risk factors for VTE among patients with co-existing diseases, and the risks from high to low were cerebral hemorrhage>cerebral infarction>malignant tumor>respiratory system disease>coronary heart disease> diabetes. In addition, patients’ age (t=6.869, P< 0.001), region (t=3.420, P< 0.001), education level (t=− 7.341, P< 0.001), chronic disease (t=5.875, P< 0.001), BMI (t=6.404, P=0.012), smoking (t=4.152, P=0.042) were related to the VTE cognitive level. Conclusion: General practitioners should pay close attention to independent risk factors for VTE among patients in routine outpatient care, especially patients with co-existing diseases with independent risk for VTE, placing them high risk of VTE. At the same time, health education and other measures should be strengthened to improve the patients’ awareness and cognitive level of VTE to prevent the occurrence of VTE and its related complications.

Bronchial asthma is a common chronic airway disease, and long-term management of asthma is the focus and difficulty of clinical treatment. Glucocorticoids are often used as the first choice for the treatment of asthma. However, the occurrence of hormone dependence, hormone resistance, local and systemic adverse reactions caused by hormone application also brings problems for the treatment of asthma. Finding safe and effective new therapeutic drugs is an important research direction at present. Icariin is the effective ingredient of traditional Chinese medicine Epimedium. It has various biological activities such as anti-inflammatory, anti-oxidative stress, and immune regulation. It has high safety and has a wide range of clinical applications. Icariin has the characteristics of multi-target intervention in the treatment of asthma. This article reviews recent studies in order to provide new research directions for further therapeutic drug development.

This study focused on using “General Practitioners–Specialists” (GP-S) mode to teach the patients with asthma to master inhalation skills. 200 patients with asthma being admitted to the respiratory department of Shanghai Changhai Hospital were included in the study from January to December in 2018. There were 100 cases in the control group and 100 cases in the experimental group. The control groups received routine instruction and the experimental group adopted GP-S mode education, respectively, to learn mastering dry powder inhaler skills. The level of mastery and errors in the use of inhaled medications were recorded after each guidance. After four times’ instruction in two different ways, the patient’s mastery of inhalation skills gradually improved. After the guidance through the GP-S mode, the incidence of inhalation errors after each times instruction was 67%, 28%, and 7%, respectively. The later one was significantly lower than the previous one (67% vs. 28%, χ² = 30.496, p < 0.001; 28% vs. 7%, χ² = 15.273, p < 0.001). After twice instructions, the GP-S mode was associated with the lower incidence of inhaler device operating errors versus the regular guidance method (10% vs. 26%, χ² = 8.672, p = 0.005); the same as the third guidance (2% vs. 11%, χ² = 6.664, p = 0.018). Similarly, after thrice instructions, the incidence of inhalation method errors in the GP-S mode group was significantly lower than the regular guidance mode group (4% vs. 15%, χ² = 7.037, p = 0.018), and there was still existing statistical difference of inhalation method errors between the two groups after four times instructions (3% vs. 11%, χ² = 4.916, p = 0.049). General Practitioners–Specialists mode can effectively improve the patient’s mastery of inhalation skills, which significantly reduced the incidence of errors in the use of inhaled drugs and improved the overall management effectivity of asthma and patients’ compliance.

Melanoma is one of the most highly metastatic, aggressive and fatal malignant tumors in skin cancer. This study employs bioinformatics to identify key microRNAs and target genes (TGs) of plasma extracellular vesicles (pEVs) and their diagnostic and prognostic significance in melanoma. The gene expression microarray dataset (GSE100508) was downloaded from the Gene Expression Omnibus database. Differential analysis of miRNAs in pEVs was performed to compare melanoma samples and healthy samples. Then, TGs of the differential miRNAs (DE-miRNAs) in melanoma were selected, and differential genes were analyzed by bioinformatics (including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment, protein–protein interaction network and prognostic analysis). A total of 55 DE-miRNAs were found, and 3,083 and 1,351 candidate TGs were diagnostically correlated with the top ten upregulated DE-miRNAs and all downregulated DE-miRNAs, respectively. Prognostic analysis results showed that high expression levels of hsa-miR-550a-3p, CDK2 and POLR2A and low expression levels of hsa-miR-150-5p in melanoma patients were associated with significantly reduced overall survival. In conclusion, bioinformatics analysis identified key miRNAs and TGs in pEVs of melanoma, which may represent potential biomarkers for the early diagnosis and treatment of this cancer.