Behcet's syndrome (BS) is a complex, heterogeneous disorder. However, classification of its subgroups is still debated. The purpose of this study was to investigate the clinical features and ...aggregation of patients with BS in China, based on manifestations and organ involvements.
This was a cross-sectional study of BS patients in Huadong Hospital of Fudan University between September 2012 and January 2020. We calculated relative risks (RRs) of clinical variables according to sex. Moreover, we conducted a hierarchical cluster analysis applied according to eighteen variables to determine subgroups of patients.
A total of 860 BS patients were included. Male sex was associated with ocular involvement (RR 2.32, 95% CI 1.67, 3.22, P < 0.0001), vascular involvement (RR 2.00, 95% CI 1.23, 3.23, P = 0.004), cardiac lesion (RR 5.46, 95% CI 2.33, 12.77, P < 0.0001), and central nervous system involvement (RR 2.95, 95% CI 1.07, 6.78, P = 0.007) and was negatively associated with genital ulcers (RR 0.84, 95% CI 0.79, 0.91, P < 0.0001). Five clusters (C1-C5) were observed. C1 (n = 307) showed the skin and mucosa type. In C2 (n = 124), all had articular involvement, barely having major organ involvement except for 18 cases with intestinal lesions. In C3 (n = 156), the gastrointestinal type, 144 patients presented with intestinal involvement, and 36 patients with esophageal ulcers. In C4 (n = 142), all subjects presented with uveitis. C5 (n = 131) consisted of 44 patients with cardiac lesions, 58 with vascular involvement, and 26 cases having central nervous system involvement.
Our analysis confirmed sex differences in phenotypes of BS. Cluster analysis identified gastrointestinal, uveitis, and cardiovascular involvement cluster separately in different subsets, which represents the most commonly involved organs. Further research is required to replicate and clarify the patterns of phenotype in BS.
Inflammatory signals from immunological cells may cause damage to intestinal epithelial cells (IECs), resulting in intestinal inflammation and tissue impairment. Interferon‐γ‐inducible protein 16 ...(IFI16) was reported to be involved in the pathogenesis of Behçet's syndrome (BS). This study aimed to investigate how inflammatory cytokines released by immunological cells and IFI16 participate in the pathogenesis of intestinal BS. RNA sequencing and real‐time quantitative PCR (qPCR) showed that the positive regulation of tumor necrosis factor‐α (TNF‐α) production in peripheral blood mononuclear cells (PBMCs) of intestinal BS patients may be related to the upregulation of polo like kinase 1 (PLK1) in PBMCs (P = 0.012). The plasma TNF‐α protein level in intestinal BS was significantly higher than in healthy controls (HCs; P = 0.009). PBMCs of intestinal BS patients and HCs were co‐cultured with human normal IECs (NCM460) to explore the interaction between immunological cells and IECs. Using IFI16 knockdown, PBMC‐NCM460 co‐culture, TNF‐α neutralizing monoclonal antibody (mAb), stimulator of interferon genes (STING) agonist 2′3′‐cGAMP, and the PLK1 inhibitor SBE 13 HCL, we found that PLK1 promotes the secretion of TNF‐α from PBMCs of intestinal BS patients, which causes overexpression of IFI16 and induces apoptosis of IECs via the STING–TBK1 pathway. The expressions of IFI16, TNF‐α, cleaved caspase 3, phosphorylated STING (pSTING) and phosphorylated tank binding kinase 1 (pTBK1) in the intestinal ulcer tissue of BS patients were significantly higher than that of HCs (all P < 0.05). PLK1 in PBMCs of intestinal BS patients increased TNF‐α secretion, inducing IEC apoptosis via activation of the IFI16–STING–TBK1 pathway. PLK1 and the IFI16–STING–TBK1 pathway may be new therapeutic targets for intestinal BS.
Model summarizing interactions between peripheral blood mononuclear cells (PBMCs) of intestinal Behçet's syndrome (BS) and intestinal epithelial cells (IECs). High expression of polo like kinase 1 (PLK1) promoted tumor necrosis factor‐α (TNF‐α) production and secretion from intestinal BS PBMCs that furthers the increase of interferon‐γ‐inducible protein 16 (IFI16) in IECs. IFI16 then induces IEC apoptosis via activation of the STING–TBK1 pathway.
T lymphocytes are the major components of adaptive immunity in Behçet's syndrome (BS) pathology. However, the precise mechanism of T‐cell‐induced inflammatory condition remains to be determined. We ...applied bulk sequencing of the T‐cell receptor (TCR) β chain in peripheral blood samples from 45 patients with BS and 10 healthy donors as controls. TCR repertoires in BS patients displayed more clonality and less diversity than in healthy donors. Male patients exhibited lower diversity metrics of TCR and had a larger proportion in the top 10 clones than females (p = 0.016). There were no TCR clonality differences in other clinical features, such as age, disease duration, organ involvement, disease severity, and activity. By “Grouping of Lymphocyte Interactions by Paratope Hotspots” (GLIPH2) for antigen prediction, we found distinct 2477 clusters of TCR‐β sequences that potentially recognize similar antigens shared between BS patients. We observed clonal T‐cell expansion in BS patients. Sexual differences in TCR clonal expansion and public TCR groups deserve further study to reveal the underline T‐cell‐mediated immunity in BS.
Bulk sequencing of the TCR repertoires in BS patients displayed more clonality and less diversity than in healthy donors. Male patients exhibited lower diversity metrics of TCR than females. GLIPH2 predicted distinct clusters of TCR‐β sequences in BS patients.
•GB reduced the CI symptoms of banana fruit.•GB enhanced the contents of antioxidant substances.•GB elevated enzyme activities and gene expression of antioxidant enzymes.•GB increased total ...antioxidant capacity.
Chilling injury (CI) represents a physiological disorder caused by improper low temperature management, which affects the postharvest quality and marketing potential of banana fruit. In this study, postharvest application of glycine betaine (GB) can significantly reduce the CI incidence of banana fruit during cold storage, as observed by lower CI index, electrolyte leakage, malondialdehyde (MDA) contents, and higher values of lightness, chlorophyll, soluble sugar contents. Moreover, GB not only increased the antioxidant substances such as total phenolics, glutathione and ascorbic acids (AsA), but also elevated the enzyme activities and gene expression of the antioxidant enzymes including ascorbate peroxidase (APX), catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD). In addition, GB could obviously enhance the total antioxidant capacity of banana fruit under refrigerated storage. Collectively, these findings suggest that GB-attenuated CI incidence in banana fruit during cold storage might be, at least partially, ascribed to the enhancement of antioxidant system involving antioxidant substances, as well as enzyme activities and gene expression of antioxidant enzymes.
•Formation of ionic wind and cooling enhancement mechanism was deeply explored.•Literatures published in the past few years were classified and discussed.•The ongoing challenges were highlighted and ...discussed.
Corona discharge-produced ionic wind has drawn considerable attention as a potential candidate to solve the thermal problems that originate from heat accumulation in small-scale devices, as it has clear advantages over conventional cooling devices. The research and application cases of corona wind technology in the field of local heat transfer enhancement have been increasing in recent years. In this review, the formation process of corona wind and the mechanism of local heat dissipation enhancement are deeply investigated from the perspectives of physics, electricity, and thermodynamics. Related literature published in the past decade that has focused on the application of small-scale corona wind generators (CWGs) in local heat transfer enhancement is classified and discussed. Some important research conclusions are highlighted and used to guide the optimal design of a small-scale corona wind cooling system. The ongoing challenges of the power supply, adverse effects of byproducts, humidity, and electrode deterioration are discussed, and corresponding solutions are put forward. The use of corona wind cooling technology will present opportunities based on the research that has been conducted and its future development tendency.
Epizootic hemorrhagic disease (EHD) is an infectious viral disease caused by epizootic hemorrhagic disease virus (EHDV) and EHDV frequently circulates in wild and domestic ruminants. Sporadic ...outbreaks of EHD have caused thousands of deaths and stillbirths on cattle farms. However, not much is known about the circulating status of EHDV in Guangdong, southern China. To estimate the seroprevalence of EHDV in Guangdong province, 2886 cattle serum samples were collected from 2013 to 2017 and tested for antibodies against EHDV using a competitive ELISA. The overall seroprevalence of EHDV reached 57.87% and was highest in autumn (75.34%). A subset of positive samples were serotyped by a serum neutralization test, showing that EHDV serotypes 1 and 5-8 were circulating in Guangdong. In addition, EHDV prevalence always peaked in autumn, while eastern Guangdong had the highest EHDV seropositivity over the five-year period, displaying apparent temporal-spatial distribution of EHDV prevalence. A binary logistic model analysis indicated a significant association between cattle with BTV infections and seroprevalence of EHDV (OR = 1.70,
< 0.001). The co-infection of different serotypes of EHDV and BTV raises a high risk of potential genomic reassortment and is likely to pose a significant threat to cattle, thus urging more surveillance to monitor their circulating dynamics in China.
This study proposed to investigate the function of miR-19a/ACSL axis in hypoxia/reoxygenation (H/R)-induced myocardial injury and determine whether metformin exerts its protective effect via ...miR-19a/ACSL axis. Firstly, bioinformatics analysis of data from Gene Expression Omnibus (GEO) database indicated that miR-19a was downregulated in patients with myocardial infarction (MI) compared to that in control group. H/R model was constructed with AC16 cells in vitro. qRT-PCR assay revealed that miR-19a was downregulated in H/R-treated AC16 cells. Then, CCK-8 assay demonstrated that upregulation of miR-19a significantly alleviated H/R-induced decline of cell viability. Moreover, bioinformatics prediction, western blotting and dual-luciferase reporter assays were performed to check the target genes of miR-19a, and ACSL1 was determined as a downstream target gene of miR-19a. Besides, the analysis based on Comparative Toxicogenomics Database (CTD) suggested that metformin targeting ACSL1 can be used as a potential drug for further research. Biological function experiments in vitro revealed that H/R markedly declined the viability and elevated the apoptosis of AC16 cells, while metformin can significantly mitigate these effects. Furthermore, overexpression of miR-19a significantly strengthened the beneficial effect of metformin on H/R-induced AC16 cells injury, which can be reversed by upregulation of ACSL1. In conclusion, metformin can alleviate H/R-induced cells injury via regulating miR-19a/ACSL axis, which lays a foundation for identifying novel targets for myocardial I/R injury therapy.
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•H/R elevates the apoptosis of AC16 cells, while metformin alleviates this effect.•Metformin alleviates H/R-induced cells injury via regulating miR-19a/ACSL1 axis.•miR-19a mimic possible alleviates myocardial injury by improving cell viability.
Extra‐large‐pore zeolites for processing large molecules have long been sought after by both the academia and industry. However, the synthesis of these materials, particularly extra‐large‐pore pure ...silica zeolites, remains a big challenge. Herein we report the synthesis of a new extra‐large‐pore silica zeolite, designated NUD‐6, by using an easily synthesized aromatic organic cation as structure‐directing agent. NUD‐6 possesses an intersecting 16×8×8‐membered ring pore channel system constructed by four‐connected (Q4) and unusual three‐connected (Q3) silicon species. The organic cations in NUD‐6 can be removed in nitric acid to yield a porous material with high surface area and pore volume. The synthesis of NUD‐6 presents a feasible means to prepare extra‐large pore silica zeolites by using assembled aromatic organic cations as structure‐directing agents.
The right template: An extra‐large‐pore silica zeolite was prepared using small, easily synthesized aromatic organic cations as the structure‐directing agent. It possesses an intersecting 16×8×8‐membered ring pore system and shows large specific surface area and pore volume after removal of organic templates.
This study aimed to investigate the characteristics of Chinese patients with Behçet disease (BD) and myelodysplastic syndrome (MDS) and explore the role played by trisomy 8. This was a retrospective ...study of patients with BD and MDS from the Shanghai Behçet’s disease database who were diagnosed between October 2012 and July 2017. There were 805 patients with BD and 16 also had MDS. Trisomy 8 was examined in patients with BD-MDS and some patients with gastrointestinal (GI) BD. Patients with BD and MDS (16/805; 2%) were more likely to be female and older; display fever and intestinal lesions; have lower leukocyte count, hemoglobin, platelet count; and show higher C-reactive protein and erythrocyte sedimentation rate (ESR) than patients with BD without MDS (all P<0.05). Trisomy 8 was common (81.3%) in patients with BD-MDS. Ulcers in the ileocecal region were more frequently seen in intestinal patients with BD-MDS than in BD without MDS (90.0% versus 48.9%; P=0.032). GI ulceration is common in patients with BD-MDS. Cytogenetic aberrations, especially trisomy 8, may play a role in the pathogenesis of intestinal involvement in patients with BD-MDS.
Background:
Intestinal Behçet’s syndrome is a major cause of morbidity and mortality in Behçet’s syndrome.
Objectives:
Current treatment challenges remain in refractory intestinal Behçet’s syndrome, ...when patients failed first and second-line therapies.
Design:
We reported the efficacy and safety profiles of tofacitinib in patients with moderate-severe intestinal Behçet’s syndrome in a retrospective single-center study.
Methods:
Treatment with glucocorticoids, immunosuppressors, or even anti-TNFα monoclonal antibodies (mAbs) had previously failed. Primary outcomes were clinical remission or low disease activity and endoscopic healing.
Results:
We included 13 patients; 11 were administered tofacitinib 5 mg twice daily, and 2 took tofacitinib 5 mg once daily. Nine patients achieved clinical remission after a mean treatment duration of 10.1 ± 7.0 months, and the other four had low disease activity. Follow-up endoscopy was available in 11 patients: 5 had achieved mucosal healing; the other 4 achieved marked mucosal improvement. Prednisone dosage was significantly reduced, from 30 (interquartile range: 20–30) mg/d to 2.5 (interquartile range: 0–12.5) mg/d (p < 0.001). No serious adverse event was observed.
Conclusion:
Tofacitinib could be an efficacious and generally well-tolerated option in patients with intestinal Behçet’s syndrome refractory to conventional agents, even anti-TNFα mAbs.
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