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.
Background/Aims: Long noncoding RNAs (lncRNAs) have recently emerged as novel and potentially promising therapeutic targets in various cancers. However, the expression pattern and biological function ...of lncRNAs in glioma remain largely elusive. In the present study, we investigated the functional role of an lncRNA, small nucleolar RNA host gene 16 (SNHG16), in glioma. Methods: The expression levels of SNHG16 and miR-4518 were measured using qRT-PCR. The relationship between the levels of SNHG16 and clinicopathologic features were statically analyzed. The levels of proteins were detected using western blot. Bioinformatics analysis and luciferase reporter assays were applied to the analysis of the relationship between SNHG16, miR-4518 and PRMT5. Cell viability and apoptosis were measured using MTT and apoptosis ELISA assay, respectively. Results: SNHG16 was highly expressed in glioma tissues and cell lines, which was related to poorer clinicopathologic features and shorter survival time. Knockdown of SNHG16 inhibits the viability and induces apoptosis of glioma cells. Further investigation revealed that SNHG16 could up-regulate the expression of miR-4518 targeted gene PRMT5 via acting as an endogenous sponge of miR-4518. Moreover, SNHG16 also affects the expression of Bcl-2 family proteins and the activation of PI3K/Akt signaling pathway. Conclusion: Our study revealed a novel SNHG16-miR-4518-PRMT5 pathway regulatory axis in glioma pathogenesis. SNHG16 could be used as a potential therapeutic target in the treatment of glioma.
In order to optimize the technology of the building, the damage identification of the building structure is studied. Firstly, back propagation neural network (BPNN) and information fusion technology ...are used to build neural network models. Secondly, the established model is trained. Finally, the displacement mode, natural frequency, Modal Assurance Criterion (MAC), and three kinds of information fusion with only one characteristic information are used as input data to analyse the results of BPNN identification damage. The results show that when the natural frequency is used as the sensitive feature of damage, the accuracy is the highest. The difference between the network output value and the expected value is the smallest, the network output is the most stable, and the network recognition effect is the best. The network output of a mixture of two damage depths is compared with the output of a single damage depth. The data of the network training set composed of the feature data with damage depth of 20 mm and 5 mm has higher accuracy and more accurate damage recognition. This research provides a reference for the optimization of building survey technology and has certain practical value.
Intestinal Behçet's syndrome (BS) has high morbidity and mortality rates with serious complications. The purpose of this study was to investigate the clinical characteristics and laboratory ...parameters of intestinal and mucocutaneous BS patients and analyze the risk factors of intestinal involvement in BS patients.
A retrospective analysis was used to collect the demographic data and laboratory parameters from 97 intestinal and 154 mucocutaneous BS patients. Univariate and multivariate logistic regression analyses were used to investigate the risk factors of intestinal involvement in BS patients.
The most common clinical manifestations of first onset in intestinal BS patients were oral ulceration (100.00%), followed by genital ulcers (62.89%) and erythema nodule (28.87%), gastrointestinal lesions (28.87%), pseudofolliculitis (25.77%), fever (17.53%), arthritis (16.49%), ocular involvement (5.15%), while the least common were vascular involvement (2.06%) and hematologic involvement involvement (2.06%). The most common intestinal segment involved in intestinal BS patients was terminal ileum (30.9%), followed by ileocecal (18.6%), colon (15.5%). By univariate logistic regression analysis, gender, age at hospitalization, age of disease onset, BDCAF, T-SPOT, fever, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), leukocyte, erythrocyte, hemoglobin (HGB), neutrophil-to-lymphocyte ratio, serum amyloid A, complement 3, albumin, total cholesterol, high-density lipoprotein and interleukin 6 (IL-6) were found all risk factors of intestinal involvement in BS patients (P < 0.05 or P = 0.00). Moreover, gender (male), BDCAF (≥ 2), ESR (≥ 15 mm/H), CRP (> 10 mg/L), HGB (< 130 g/L) and IL-6 (> 7 pg/ml) were found the independent risk factors of intestinal involvement in BS patients (all P < 0.05).
More attention shall be paid to gender, BDCAF, ESR, CRP, HGB and IL-6 in BS patients. When gender (male), BDCAF (≥ 2), ESR (≥ 15 mm/H), CRP (> 10 mg/L), HGB (< 130 g/L) and IL-6 (> 7 pg/ml) being observed, it may reminds that the presence of intestinal involvement in BS patients.
We have developed a robust method for the visual detection of heavy metal ions (such as Hg(2+) and Pb(2+)) by using aptamer-functionalized colloidal photonic crystal hydrogel (CPCH) films. The CPCHs ...were derived from a colloidal crystal array of monodisperse silica nanoparticles, which were polymerized within the polyacrylamide hydrogel. The heavy metal ion-responsive aptamers were then cross-linked in the hydrogel network. During detection, the specific binding of heavy metal ions and cross-linked single-stranded aptamers in the hydrogel network caused the hydrogel to shrink, which was detected as a corresponding blue shift in the Bragg diffraction peak position of the CPCHs. The shift value could be used to estimate, quantitatively, the amount of the target ion. It was demonstrated that our CPCH aptasensor could screen a wide concentration range of heavy metal ions with high selectivity and reversibility. In addition, these aptasensors could be rehydrated from dried gels for storage and aptamer protection. It is anticipated that our technology may also be used in the screening of a broad range of metal ions in food, drugs and the environment.
Some individuals claim that they are very sensitive to pain, whereas others say that they tolerate pain well. Yet, it is difficult to determine whether such subjective reports reflect true ...interindividual experiential differences. Using psychophysical ratings to define pain sensitivity and functional magnetic resonance imaging to assess brain activity, we found that highly sensitive individuals exhibited more frequent and more robust pain-induced activation of the primary somatosensory cortex, anterior cingulate cortex, and prefrontal cortex than did insensitive individuals. By identifying objective neural correlates of subjective differences, these findings validate the utility of introspection and subjective reporting as a means of communicating a first-person experience.
Objectives
Intestinal Behçet’s syndrome (IBS) has high morbidity and mortality rates with serious complications. The purpose of this study was to investigate the expression of pyroptosis-related ...proteins in the intestinal tissues of IBS patients and explore the role of plasma exosomes derived from IBS patients in the pyroptosis of intestinal epithelial cells.
Method
Immunohistochemistry was used to investigate the expression of nucleotide-binding domain-like receptor protein 3 (NLRP3), caspase-1, and gasdermin D (GSDMD). Quantitative real-time PCR was employed to measure the mRNA levels of IL-1β and IL-18 in the intestinal tissues. Plasma exosomes were isolated and observed by transmission electron microscopy. The exosomes were co-cultured with intestinal epithelial cells in vitro. Western blot was used to measure the expression of pyroptosis-related proteins including NLRP3, full-length GSDMD, N-terminal GSDMD, pro-caspase-1, and cleaved caspase-1. The levels of IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay. Cell death was measured by using the lactate dehydrogenase (LDH) release assay.
Results
Expression of NLRP3 (12.2% ± 1.2%, 8.1% ± 0.9%,
t
= 4.692,
p
= 0.009), caspase-1 (24.6% ± 2.1%, 4.2% ± 1.8%,
t
= 12.842,
p
= 0.000), and GSDMD (16.6% ± 1.9%, 9.8% ± 1.3%,
t
= 5.194,
p
= 0.007) were significantly increased in the intestinal tissues of patients with IBS compared with normal control (NC) group, respectively. The relative mRNA levels of IL-1β (
t
= 4.308,
p
= 0.005) and IL-18 (
t
= 3.096,
p
= 0.021) in the intestinal tissues were significantly higher in IBS patients than in NC group, while the protein levels of IL-1β (
t
= 3.873,
p
= 0.018) and IL-18 (
t
= 4.389,
p
= 0.012) were also significantly increased, which was consistent with the results of the relative mRNA levels. Moreover, we found that exosomes from IBS patients significantly induced pyroptosis of intestinal epithelial cells via the activation of NLRP3 inflammasome in vitro experiments.
Conclusions
Plasma exosomes derived from IBS patients may induce pyroptosis of intestinal epithelial cells via the activation of NLRP3 inflammasome.
Key Points
•The role of exosomes in IBS is first reported in this study.
• In this study, we explored the mechanism that plasma exosomes derived from IBS patients may induce pyroptosis of intestinal epithelial cells via the activation of NLRP3 inflammasome.
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.
Behçet's disease (BD) can involve any site of the alimentary canal. There has been research concerning intestinal BD. Nevertheless, the entire digestive tract not yet been studied extensively. ...Therefore, the purpose of study was to describe the prevalence, location, clinical features and possible risk factors of BD with gastrointestinal tract ulcer. This was a cross-sectional observational study that included 1232 consecutive BD patients who routinely underwent endoscopy upon their wishes. The clinical symptoms, endoscopic findings, and histologic features of BD with gastrointestinal ulcer and negative Helicobacter pylori (Hp) were identified. We found that 22.16% (273/1232) BD patients had ulcers of the alimentary tract. At presentation, 61.54% (168/273) patients were asymptomatic. Isolated gastroduodenal involvement is an extremely usual event. The second was the pairwise combination between bowel segments, and 24 cases involved three segments at the same time. One patient suffered from total gastrointestinal tract involvement. Inflammation was the most common histopathologic feature 77.60% (142/183). The 273 BD patients with gastrointestinal ulcer were at greater risk of having archenteric symptoms (OR 0.070, P < 0.001), fever (OR 0.115, P = 0.047), high CRP (OR 0.994, P = 0.027) and BDCAF level (OR 0.590, P = 0.010). Uveitis correlates negatively with gastrointestinal involvement in BD patients (OR 3.738, P = 0.011). BD could affect the upper gastrointestinal tract independently. Endoscopy should be conducted in all patients in whom a diagnosis of BD is entertained, especially in patients with higher CRP, disease activity and fever. While, BD patients with uveitis correlates negatively with gastrointestinal involvement.
Considering the wall smoothness and mechanical continuity of conical tubular vascular grafts, the conical tubular vascular graft with continuous variable cross-sections (CVC) has been successfully ...woven on the basis of the equal-cover-factor principle. However, the tubular wall property and its effect on water permeability is still unknown, which is one of the fundamental properties for woven vascular grafts. In this study, a series of CVC conical tubular prototypes with different conical degrees and typical fabric weaves were prepared, and their wall features and the water permeability along the tubular walls were measured. And then, the study investigated the uniformity of the wall structure as well as the relationship among water permeability, and porosity and pore sizes. The results show that these samples have statistically uniform pore features and water permeability along the graft wall, but both the pore features and the permeability are sensitive to the conical degree as well as fabric weaves. Moreover, the water permeability has a significant parabolic relationship with the pore size, while there is no significant dependence on the porosity. These results demonstrate advantages of the CVC tubular vascular graft produced in the equal-cover-factor principle, and will facilitate the development of the CVC woven tubular vascular graft.