Regulatory mechanism of FCGR2A in macrophage polarization and its effects on intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) poses a significant health burden, necessitating a deeper understanding of its molecular underpinnings. Transcriptomic analysis reveals 485 differentially expressed genes (DEGs) associated with IDD, underscoring the importance of immune regulation. Weighted gene co-expression network analysis (WGCNA) identifies a yellow module strongly correlated with IDD, intersecting with 197 DEGs. Protein-protein interaction (PPI) analysis identifies ITGAX, MMP9 and FCGR2A as hub genes, predominantly expressed in macrophages. Functional validation through in vitro and in vivo experiments demonstrates the pivotal role of FCGR2A in macrophage polarization and IDD progression. Mechanistically, FCGR2A knockdown suppresses M1 macrophage polarization and NF-κB phosphorylation while enhancing M2 polarization and STAT3 activation, leading to ameliorated IDD in animal models. This study sheds light on the regulatory function of FCGR2A in macrophage polarization, offering novel insights for IDD intervention strategies. KEY POINTS: This study unveils the role of FCGR2A in intervertebral disc (IVD) degeneration (IDD). FCGR2A knockdown mitigates IDD in cellular and animal models. Single-cell RNA-sequencing uncovers diverse macrophage subpopulations in degenerated IVDs. This study reveals the molecular mechanism of FCGR2A in regulating macrophage polarization. This study confirms the role of the NF-κB/STAT3 pathway in regulating macrophage polarization in IDD.

GAS5, a long noncoding RNA, contributes to annulus fibroblast osteogenic differentiation and apoptosis in intervertebral disk degeneration via the miR-221-3p/SOX11 axis.

miR-221-3p has been reported to attenuate the osteogenic differentiation of annulus fibrosus cells (AFs), which has been implicated in intervertebral disk degeneration (IVDD) development. This study aimed to elucidate miR-221-3p's role in osteogenic differentiation and apoptosis of AFs in an IVDD model. After successfully establishing an IVDD rat model by annulus fibrosus needle puncture, AFs were isolated. Bioinformatics, dual-luciferase reporter, and AGO2-RNA immunoprecipitation (RIP) assays predicted and confirmed the potential miR-221-3p lncRNA and gene target. Functional analyses were performed after AF transfection to explore the roles of the identified lncRNA and gene. Western blotting, Alkaline phosphatase (ALP), and Alizarin red and TUNEL staining were performed to investigate AF apoptosis and osteogenic differentiation with different transfections. Compared with AFs isolated from sham rats, IVDD-isolated Afs exhibited stronger osteogenic potential and higher apoptosis rates accompanied by miR-221-3p downregulation. The growth arrest-specific transcript 5 (GAS5) was identified as miR-221-3p's target lncRNA, which was highly expressed in IVDD. GAS5 overexpression facilitated AF apoptosis and osteogenic differentiation, whereas silencing GAS5 had the opposite effect. SRY box-related11 (SOX11) was identified as a downstream miR-221-3p target gene in IVDD. GASS silencing-induced suppression of AF apoptosis and osteogenic differentiation could be reversed by SOX11 overexpression. Our findings uncovered a lncRNA GAS5/miR-221-3p/SOX11 axis in Afs under IVDD, which may help implement novel IVDD therapeutic strategies.

Characteristics and evaluation of atherosclerotic plaques: an overview of state-of-the-art techniques.

Atherosclerosis is an important cause of cerebrovascular and cardiovascular disease (CVD). Lipid infiltration, inflammation, and altered vascular stress are the critical mechanisms that cause atherosclerotic plaque formation. The hallmarks of the progression of atherosclerosis include plaque ulceration, rupture, neovascularization, and intraplaque hemorrhage, all of which are closely associated with the occurrence of CVD. Assessing the severity of atherosclerosis and plaque vulnerability is crucial for the prevention and treatment of CVD. Integrating imaging techniques for evaluating the characteristics of atherosclerotic plaques with computer simulations yields insights into plaque inflammation levels, spatial morphology, and intravascular stress distribution, resulting in a more realistic and accurate estimation of plaque state. Here, we review the characteristics and advancing techniques used to analyze intracranial and extracranial atherosclerotic plaques to provide a comprehensive understanding of atheroma.

Adipokines in atherosclerosis: unraveling complex roles.

Adipokines are biologically active factors secreted by adipose tissue that act on local and distant tissues through autocrine, paracrine, and endocrine mechanisms. However, adipokines are believed to be involved in an increased risk of atherosclerosis. Classical adipokines include leptin, adiponectin, and ceramide, while newly identified adipokines include visceral adipose tissue-derived serpin, omentin, and asprosin. New evidence suggests that adipokines can play an essential role in atherosclerosis progression and regression. Here, we summarize the complex roles of various adipokines in atherosclerosis lesions. Representative protective adipokines include adiponectin and neuregulin 4; deteriorating adipokines include leptin, resistin, thrombospondin-1, and C1q/tumor necrosis factor-related protein 5; and adipokines with dual protective and deteriorating effects include C1q/tumor necrosis factor-related protein 1 and C1q/tumor necrosis factor-related protein 3; and adipose tissue-derived bioactive materials include sphingosine-1-phosphate, ceramide, and adipose tissue-derived exosomes. However, the role of a newly discovered adipokine, asprosin, in atherosclerosis remains unclear. This article reviews progress in the research on the effects of adipokines in atherosclerosis and how they may be regulated to halt its progression.

Wearable Sensor-Based Monitoring of Environmental Exposures and the Associated Health Effects: A Review.

Recent advances in sensor technology have facilitated the development and use of personalized sensors in monitoring environmental factors and the associated health effects. No studies have reviewed the research advancement in examining population-based health responses to environmental exposure via portable sensors/instruments. This study aims to review studies that use portable sensors to measure environmental factors and health responses while exploring the environmental effects on health. With a thorough literature review using two major English databases (Web of Science and PubMed), 24 eligible studies were included and analyzed out of 16,751 total records. The 24 studies include 5 on physical factors, 19 on chemical factors, and none on biological factors. The results show that particles were the most considered environmental factor among all of the physical, chemical, and biological factors, followed by total volatile organic compounds and carbon monoxide. Heart rate and heart rate variability were the most considered health indicators among all cardiopulmonary outcomes, followed by respiratory function. The studies mostly had a sample size of fewer than 100 participants and a study period of less than a week due to the challenges in accessing low-cost, small, and light wearable sensors. This review guides future sensor-based environmental health studies on project design and sensor selection.

Metabolism Characteristics of Mycoplasma pneumoniae Infection in Asthmatic Children.

PURPOSE: Studies have shown that Mycoplasma pneumoniae (Mp) infection can aggravate symptoms in asthmatics. However, the mechanism by which Mp infection exacerbates asthma remains unclear. Metabolomics can help identify the mechanism of Mp aggravating asthma in children, thereby providing more a potential target for improving clinical treatment programs. In this article, we analyzed the metabolic level of patients to explain how Mp aggravates asthma in children. METHODS: We divided the subjects into the asthma, Mp infection, asthma combined with Mp infection and healthy groups. Patients' peripheral blood was collected for metabolic and interaction analysis. Cytokine levels were measured via serum and exhaled breath condensate (EBC). RESULTS: A total of 150 participating subjects were divided into four groups after exclusion. We found out that there were different metabolic pathways between the healthy and disease groups. The major pathways of both asthma and asthma combined with Mp infection were valine, leucine and isoleucine biosynthesis; malate-aspartate shuttle was the main differential pathway for Mp infection. Moreover, even though three disease groups involved 81 metabolites at the same time, compared with asthma combined with Mp infection, 2 single disease groups still involved different amino acid pathways (phenylalanine, tyrosine and tryptophan biosynthesis; valine, leucine and isoleucine biosynthesis). Interaction analysis showed that Mp infection in asthmatic patients not only activated cytokines, but also activated Toll-like receptors (TLRs) 2 and 6. Finally, the levels of interleukin (IL)-4, IL-8, IL-13 and tumor necrosis factor-α in EBC with asthma combined with Mp infection were significantly higher than the 2 single disease groups. CONCLUSIONS: Mp infection in asthmatic children can cause changes in the levels of various amino acids in the body, which were enriched in the pathways such as valine, leucine and isoleucine biosynthesis. Palmitic acid can activate TLR2, and iloprost reduces IL-10 levels, ultimately leading to the increased airway inflammation.

Simultaneous placement of short implants (≤ 8 mm) versus standard length implants (≥ 10 mm) after sinus floor elevation in atrophic posterior maxillae: a systematic review and meta-analysis.

PURPOSE: The objective of this meta-analysis was to compare the clinical outcomes of using short implants (≤ 8 mm) inserted with osteotome sinus floor elevation (OSFE) and standard implants (≥ 10 mm) inserted with sinus floor elevation (SFE) in atrophic posterior maxillae with insufficient residual bone height (RBH). METHODS: An electronic search was performed on PubMed, EMBASE, and the Cochrane Library from 1994 to July 2022, in combination with a manual search of references in relevant articles. Randomized controlled trials (RCTs) that compared the clinical results between short and standard implant placement with SFE were included. The primary outcomes were implant survival rate and marginal bone loss (MBL); the secondary outcome was complication rate. RESULTS: Three RCTs were included, totaling 138 short and 156 standard implants. The results of the meta-analysis showed no significant differences between the short and standard implant groups in survival rate (RR = 1.02, 95% CI 0.96-1.08, p = 0.570), MBL (MD = - 0.13, 95% CI - 0.32 to 0.07, p = 0.190) and complication rate (intra-surgical complication: RR = 1.14, 95% CI 0.46-2.83, p = 0.770; post-operative complication: RR = 1.34, 95% CI 0.71-2.55, p = 0.370). CONCLUSIONS: Using short implants (≤ 8 mm) combined with OSFE might be an alternative to standard implants (≥ 10 mm) with SFE when the RBH of the posterior maxilla is insufficient. Based on a short-term clinical observation, short implants with OSFE show good results in terms of survival rate, MBL, and complication incidence.

Blood Eosinophil Endotypes across Asthma and Chronic Obstructive Pulmonary Disease (COPD).

Background: Eosinophils were common inflammatory cells involved in the occurrence and development of various inflammatory diseases. Multiple recent studies have pointed to the increasingly important role of eosinophils in respiratory diseases. This article aims to compare the expression differences of blood eosinophil counts between asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO). Methods: Patients with asthma, COPD, and ACO who were seen in the First Affiliated Hospital of Guangzhou Medical University from January 2012 to June 2019 were included. We collected information such as age, gender, diagnosis, the eosinophil counts from the medical records. Moreover, the levels of 10 cytokines in the plasma of each group were detected by using the Meso Scale Discovery method. Results: We included 9787 patients with asthma, 15806 patients with COPD, and 831 ACO patients. From our results, it can be first found that eosinophil levels were age-related in the three diseases (asthma and ACO: p < 0.001; COPD: P = 0.001); in asthma and COPD, the number of eosinophils in males was more significant than that in females (asthma: p < 0.001; COPD: p = 0.012). Second, asthma patients had higher blood eosinophil counts than those with COPD and ACO (p < 0.001). Moreover, we found out that eosinophil levels were highly expressed in the stable group of all three diseases. Finally, we found that most cytokines in ACO patients showed a downward trend when the level of eosinophils was low, whereas the results were reversed in asthma patients; 7 cytokines had similar trends in COPD and ACO patients. Conclusions: In conclusion, eosinophils have their own unique endotypes in asthma, COPD, and ACO patients, which were reflected in the fluctuation of their levels and changes in cytokine secretion.

Clinical Efficacy of Sanfeng Tongqiao Diwan in the Treatment of Allergic Rhinitis: A Randomized Controlled Trial.

Objective: To explore the clinical effect of Sanfeng Tongqiao Diwan in the treatment of allergic rhinitis. Methods: Allergic rhinitis patients included in this study were randomly divided into control group and study group for 7 days of treatment. The control group was treated with Tongqiao Biyan Pian, while the study group was treated with Sanfeng Tongqiao Diwan. Results: After 7 days of treatment, the total effective rate of Sanfeng Tongqiao Diwan was 75.76%, which was higher than that of Tongqiao Biyan Pian (65.62%). The scores of visual analogue scale (VAS), symptom relief, Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Epworth sleepiness scale (ESS) in both groups were significantly improved before and after treatment (P < 0.05), and the improvement was most significant 24 hours after treatment. The adverse reactions in both groups were low. Conclusion: Sanfeng Tongqiao Diwan can significantly alleviate the symptoms and improve the quality of life of patients with allergic rhinitis, with less adverse reactions.

Efficacy and safety of Sanfeng Tongqiao Diwan in patients with allergic rhinitis: a single-arm clinical trial in China.

Background: Traditional Chinese medicine (TCM) has a long history and its own characteristics in the treatment of allergic rhinitis. In this study, the efficacy and safety of patients with allergic rhinitis treated with Sanfeng Tongqiao Diwan were observed to support the clinical medication of patients with allergic rhinitis. Methods: A total of 61 patients with allergic rhinitis aged 12-70 years from the First Affiliated Hospital of Guangzhou Medical University were included in this study. All the patients were treated with Sanfeng Tongqiao Diwan for a period of 7 days. Return visits were carried out 24 hours after the first medication, the 4th day of medication, and the 7th day of medication, during which the efficacy and safety were assessed. Results: The effective rates of Sanfeng Tongqiao Diwan at 24 hours, 4 days, and 7 days were 49.2%, 60.7%, and 65.6%, respectively. Comparing the severity of various symptoms after treatment to baseline, significant differences were found in nasal secretion (2.95±0.67 vs. 2.26±1.30, P<0.001), stuffy nose (5.66±2.95 vs. 3.34±2.57, P<0.001), mucosa congestion (7.08±1.82 vs. 4.23±2.28, P<0.001), running nose (5.21±1.81 vs. 2.90±1.89, P<0.001), and sneezing (3.00±0 vs. 1.92±1.45, P<0.001). The full symptom scores showed progressive decline during treatment, measuring 20.21±5.13 at baseline and 12.02±6.47 at 7 days (P<0.001). Compared to the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score of 64.61±30.27 at baseline, statistical significance (P<0.001) was found at 24 hours, 4 days, and 7 days, measuring 43.11±28.01, 40.74±28.6, and 39.97±40.48, respectively. The incidence rate of adverse events (AEs) was 3.3% (2/61), with no serious AEs. Conclusions: In this study, the use of Sanfeng Tongqiao Diwan is effective in the treatment of allergic rhinitis patients, especially in patients with severe symptoms. Although the treatment system of TCM is different from that of Western medicine, the application of TCM will provide a new direction for the treatment of chronic diseases. Follow-up studies with an increased sample size are required for verification.

Corrigendum: Low Frequency Ultrasound With Injection of NMO-IgG and Complement Produces Lesions Different From Experimental Autoimmune Encephalomyelitis Mice.

[This corrects the article DOI: 10.3389/fimmu.2021.727750.].

SNHG1 functions as an oncogenic lncRNA and promotes osteosarcoma progression by up-regulating S100A6 via miR-493-5p.

The mechanism behind the aberrant expression of S100A6 in osteosarcoma is seldom reported so far. This study sought to explore the regulatory axis targeting S100A6 involved in osteosarcoma progression. Clinical samples collected from osteosarcoma patients were used to detect the expressions of SNHG1, miR-493-5p, and S100A6 by western bolt analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The effects of S100A6 on proliferation and osteogenic differentiation were investigated by the CCK-8 assay, colony formation assay, Ethynyl deoxyuridine staining, matrix mineralization assay, and alkaline phosphatase assay. The potential of lncRNAs/miRNAs targeting S100A6 was identified by the bioinformatics approach, and the results were verified by the dual luciferase assay and RNA immunoprecipitation assay. Both and rescue experiments were performed to investigate the regulatory relationship between the identified lncRNAs and S100A6. The results showed that S100A6 is highly expressed in osteosarcoma. S100A6 overexpression not only increases the proliferation but also reduces the osteogenic differentiation of osteosarcoma cells, while S1006A silence exerts the opposite effects. Then, SNHG1 is identified to directly interact with miR-493-5p to attenuate miR-493-5p binding to the 3'-untranslated region of S100A6. Notably, S100A6 silence partially rescues the effect of SNHG1 overexpression on proliferation and osteogenic differentiation of osteosarcoma cells. Furthermore, the suppressive role of SNHG1 silence in the growth of osteosarcoma xenograft tumors is countered by S100A6 overexpression. Collectively, this study reveals that S100A6 plays an important role in osteosarcoma progression, and SNHG1 promotes S100A6 expression by competitively sponging miR-493-5p.

Umbilical cord blood metabolomics: association with intrauterine hyperglycemia.

BACKGROUND: Intrauterine hyperglycemia can harm a fetus's growth and development, and this can be seen in the umbilical cord blood metabolism disorder. However, the metabolites and metabolic mechanisms involved in the condition remain unknown. METHODS: Targeted metabolomics using liquid chromatography and MetaboAnalyst were conducted in this study to explore differences in metabolites and metabolic pathways between individuals with hyperglycemia or well-controlled gestational diabetes mellitus (GDM) and healthy controls. RESULTS: Univariate analysis found that the hyperglycemic and healthy control groups differed in 30 metabolites, while the well-controlled GDM and the healthy control groups differed only in three metabolites-ursodeoxycholic acid, docosahexaenoic acid, and 8,11,14-eicosatrienoic acid. Most of these metabolic variations were negatively associated with neonatal weights. Further research showed that the variations in the metabolites were primarily associated with the metabolic pathways of linoleic acid (LA) and alpha-linolenic acid (ALA). CONCLUSION: Gestational hyperglycemia and well-controlled GDM, which may play a major role by inhibiting the LA and ALA metabolic pathways, have detrimental effects on cord blood metabolism. IMPACT: The main point of this paper is that intrauterine hyperglycemia has a negative effect on cord blood metabolism mainly through the linoleic acid and alpha-linolenic acid metabolic pathways. This is a study to report a new association between well-controlled GDM and cord blood metabolism. This study provides a possible explanation for the association between intrauterine hyperglycemia and neonatal adverse birth outcomes.

Low Frequency Ultrasound With Injection of NMO-IgG and Complement Produces Lesions Different From Experimental Autoimmune Encephalomyelitis Mice.

Neuromyelitis optica spectrum disorder (NMOSD), a relapsing autoimmune disease of the central nervous system, mainly targets the optic nerve and spinal cord. To date, all attempts at the establishment of NMOSD animal models have been based on neuromyelitis optica immunoglobulin G antibody (NMO-IgG) and mimic the disease in part. To solve this problem, we developed a rodent model by opening the blood-brain barrier (BBB) with low frequency ultrasound, followed by injection of NMO-IgG from NMOSD patients and complement to mice suffering pre-existing neuroinflammation produced by experimental autoimmune encephalomyelitis (EAE). In this study, we showed that ultrasound with NMO-IgG and complement caused marked inflammation and demyelination of both spinal cords and optic nerves compared to blank control group, as well as glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP4) loss of spinal cords and optic nerves compared to EAE mice and EAE mice with only BBB opening. In addition, magnetic resonance imaging (MRI) revealed optic neuritis with spinal cord lesions. We further demonstrated eye segregation defects in the dorsal lateral geniculate nucleus (dLGN) of these NMOSD mice.

Efficacy of air purifier therapy for patients with allergic asthma

Objectives: This study aimed to evaluate the efficacy of air purifier therapy for patients with allergic asthma. Methods: Thirty-eight subjects were categorized under two groups namely treatment group and control group. All subjects were under 18 years of age and they had been clinically diagnosed with allergic asthma. The treatment group used high efficiency particulate air (HEPA) purifiers for six consecutive months, and the control group did not use the air filters. Particulate matter (PM) data and dust samples (from bedding and a static point) were collected from the subjects’ bedrooms before they started using the air purifiers and each month thereafter. Simultaneously, the subjects were asked to complete a questionnaire for the Asthma Control Test (ACT) or Childhood Asthma Control Test (C-ACT). Fractional exhaled nitric oxide (FENO) tests were performed at the start and end of the study. The concentrations of Der p1 and Der f1 were measured in the dust samples. Results: (1) After utilizing the air purifier, the concentrations of house dust mite (HDM) allergens (Der p1+ Der f1) in the dust samples decreased. In addition, the PMindoor/outdoor values significantly decreased. (2) The ACT and C-ACT scores in the treatment group maintained a steady significant upward trend. (3) At the end of the study, the FENO levels in both groups were lower, although the differences were not significant. Conclusions: It is witnessed that HEPA air purifiers can decrease indoor HDM allergen and PM levels and improve the quality of life for allergic asthma patients (AU)

A Stable Cell Line Expressing Clustered AChR: A Novel Cell-Based Assay for Anti-AChR Antibody Detection in Myasthenia Gravis.

Cell-based assays (CBAs) and radioimmunoprecipitation assay (RIPA) are the most sensitive methods for identifying anti-acetylcholine receptor (AChR) antibody in myasthenia gravis (MG). But CBAs are limited in clinical practice by transient transfection. We established a stable cell line (KL525) expressing clustered AChR by infecting HEK 293T cells with dual lentiviral vectors expressing the genes encoding the human AChR α1, ß1, δ, ϵ and the clustering protein rapsyn. We verified the stable expression of human clustered AChR by immunofluorescence, immunoblotting, and real-time PCR. Fluorescence-activated cell sorting (FACS) was used to detect anti-AChR antibodies in 103 MG patients and 58 healthy individuals. The positive results of MG patients reported by the KL525 was 80.6% (83/103), 29.1% higher than the 51.4% (53/103) of RIPA. 58 healthy individuals tested by both the KL525 CBA and RIPA were all negative. In summary, the stable expression of clustered AChR in our cell line makes it highly sensitive and advantageous for broad clinical application in CBAs.

Clinical application of fractional exhaled nitric oxide and nasal nitric oxide levels for the assess eosinophilic inflammation of allergic rhinitis among children.

BACKGROUND: Allergic rhinitis is one of the most common nasal inflammatory diseases among children. Assessment of clinical symptoms, skin prick test and serum immunoglobulin E (IgE) are common methods used to diagnose allergic rhinitis and assess inflammation degree in clinical settings. However, via blood tests assess eosinophils inflammation is invasive, and may cause fear in children. It makes have burden of the diagnosis of allergic rhinitis. Nasal nitric oxide (nNO) and fractional exhaled nitric oxide (FeNO) are noninvasive, inexpensive, and can provide immediate results. These methods may therefore be preferable to assess the inflammation of allergic rhinitis. METHODS: This study was a retrospective analysis. We recruited 61 children with allergic rhinitis from November 2019 to March 2020. The participants were assessed using the FeNO and nNO tests. We also administered questionnaires and carried out traditional allergen and blood tests. We analyzed the relationship between diagnosis results and FeNO and nNO levels before and after the treatment of allergic rhinitis, to investigate the clinical application of FeNO and nNO levels for assess eosinophilic inflammation of allergic rhinitis in children. RESULTS: We observed a significant association both FeNO, nNO level with eosinophils, total IgE. In different levels of eosinophils (EOS), the correlation of detection parameters had obvious change. FeNO and nNO levels were obvious higher compared to pre-treatment. CONCLUSIONS: Using NO concentration can indicates the extent of allergic inflammation and can measure allergy treatment effects combine other influence indexes. The combined use of FeNO and nNO levels may be a useful method for assess the degree of eosinophilic inflammation of allergic rhinitis in children.

Experimental mouse model of NMOSD produced by facilitated brain delivery of NMO-IgG by microbubble-enhanced low-frequency ultrasound in experimental allergic encephalomyelitis mice.

Although optic neuritis and myelitis are the core clinical characteristics of neuromyelitis optica spectrum disorders (NMOSD), appropriate animal models of NMOSD with myelitis and optic neuritis are lacking. we developed a mouse model of NMOSD by intravenously injecting 100 µg neuromyelitis optica immunoglobulin G antibody (NMO-IgG) and complement into experimental allergic encephalomyelitis (EAE) mice after reversible blood-brain barrier (BBB) opening by microbubble-enhanced low-frequency ultrasound (MELFUS). Animals were assessed by histopathology. We found noticeable inflammation and demyelination concomitant with the loss of aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) expression in the spinal cord, brain and optic nerve, as well as human IgG and C9neo deposition. Thus, with the help of MELFUS, we established an NMOSD mouse model with the core lesions of NMOSD by applying a considerably lower dose of human NMO-IgG, which may help identify the pathogenesis and facilitate the development of other neuroimmune disease models in the future.

Increased MMP8 Levels in Atopic Chronic Obstructive Pulmonary Disease: A Study Testing Multiple Immune Factors in Atopic and Non-Atopic Patients.

Objective: The aim of this study was to analyse the level of serum matrix metalloproteinases (MMPs) in atopic and non-atopic COPD patients, providing guidance for clinical practice and theory for atopic COPD. Methods: Blood samples from 50 adult male patients with COPD, including 17 atopic and 33 non-atopic patients, were submitted for detection of MMP8, MMP9, surfactant associated protein D (SPD), noradrenaline (NE), leukotriene (LT) B4, recombinant proteoglycan (PRG4), Phadiatop sIgE, and tIgE levels. Patients' Modified Medical Research Council Dyspnea Scale (mMRC), COPD Assessment Test (CAT), pulmonary function test results, FeNO, blood cell ratio and induced sputum were collected. Results: The level of serum tIgE in patients with atopic COPD [1876.00 kU/l (760.50, 5347.00)] was significantly higher than in patients with non-atopic COPD [377.00 kU/l (93.50, 581.50), P < 0.001]. The MMP8 levels in atopic COPD (1600 ± 1181 ng/mL) were significantly higher than in non-atopic COPD (973.3 ±921.5 ng/mL, P = 0.0494), but there was no significant difference in MMP9, SPD, NE, LTB4, and PRG4 levels between the two groups. In atopic COPD patients, the rate of leukocyte (rs = 0.63, P < 0.001) and neutrophil (rs = 0.54, P < 0.05) were positively correlated with MMP8 levels, while lymphocyte rate was negatively correlated with MMP8 (rs = -0.70, P < 0.001) and MMP9 levels (rs = -0.54, P < 0.05). Optimal scale analysis showed that NE was most closely related to the basophil rate from induced sputum and FeNO levels (Cronbach's alpha = 85.1%). Interestingly, all atopic COPD patients with mMRC ≥2, CAT ≥ 10, and CCQ ≥16 exhibited MMP8 levels >1000 ng/mL. Conclusion: In general, tIgE and MMP8 levels were higher in atopic COPD patients than in non-atopic patients. NE levels were closely correlated with the basophil rate of induced sputum and FeNO levels, which may play an important role in the pathogenesis and development of atopic COPD.

Discovery of a subgenotype of human coronavirus NL63 associated with severe lower respiratory tract infection in China, 2018.

Human coronavirus NL63 (HCoV-NL63) is primarily associated with common cold in children, elderly and immunocompromised individuals. Outbreaks caused by HCoV-NL63 are rare. Here we report a cluster of HCoV-NL63 cases with severe lower respiratory tract infection that arose in Guangzhou, China, in 2018. Twenty-three hospitalized children were confirmed to be HCoV-NL63 positive, and most of whom were hospitalized with severe pneumonia or acute bronchitis. Whole genomes of HCoV-NL63 were obtained using next-generation sequencing. Phylogenetic and single amino acid polymorphism analyses showed that this outbreak was associated with two subgenotypes (C3 and B) of HCoV-NL63. Half of patients were identified to be related to a new subgenotype C3. One unique amino acid mutation at I507 L in spike protein receptor binding domain (RBD) was detected, which segregated this subgenotype C3 from other known subgenotypes. Pseudotyped virus bearing the I507 L mutation in RBD showed enhanced entry into host cells as compared to the prototype virus. This study proved that HCoV-NL63 was undergoing continuous mutation and has the potential to cause severe lower respiratory disease in humans.