Crohn's disease exacerbated by IL-17 inhibitors in patients with psoriasis: a case report.

BACKGROUND: Previous studied revealed that psoriasis and Inflammatory bowel disease (IBD) have highly overlapping epidemiological characteristics, genetic susceptibility loci, disease risk factors, immune mechanisms, and comorbidities. More and more biologics have been used to treat psoriasis and IBD. Interleukin (IL)-17 inhibitors played an important role in the treatment of psoriasis, but induced and aggravated inflammatory bowel disease in some patients. IL-23 inhibitors have shown to be effective to both psoriasis and CD. CASE PRESENTATION: Forty-one year old Chinese male patient who came to the hospital for psoriasis, developed severe gastrointestinal symptoms after using an IL-17 inhibitor, and was diagnosed with Crohn's disease (CD). The patient eventually used an IL-23 inhibitor to relieve both psoriasis and CD. CONCLUSION: IBD patients and psoriasis patients have increased probability of suffering from the other disease. The case that patients had suffered from psoriasis and CD before the use of IL-17 inhibitor is quite rare. This case suggests that physicians need to be careful when treating patients with psoriasis and CD with biologics, and it is necessary to evaluate the gastrointestinal tract.

Intravoxel incoherent motion diffusion-weighted imaging in quantitative evaluation of Ileal Crohn's disease - A comparison with dynamic contrast-enhanced magnetic resonance imaging and ileocolonoscopy.

OBJECTIVES: To investigate the prospective role of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in evaluating terminal ileal Crohn's disease (CD) inflammation quantitatively, compared with quantitative dynamic contrastenhanced magnetic resonance imaging (DCE-MRI) and ileocolonoscopic segmental score. METHODS: Fifty CD patients underwent magnetic resonance enterography (MRE) including IVIM-DWI and quantitative DCE-MRI from Jan. 2017 to Nov. 2019. ADC, D, D* and f value of IVIM-DWI and Ktrans, Kep, and Ve value of DCE-MRI in normal (n = 50) and inflamed bowel segments (n = 50), defined during the clinical MRI analysis, were calculated and compared using Wilcoxon signed-rank tests respectively. Receiver operating characteristic (ROC) analysis was performed. Correlations between IVIM-DWI and DCE-MRI parameters in comparison with ileocolonoscopic segmental score were assessed using Spearman's rank correlation analysis. RESULTS: For IVIM-DWI, ADC, D, D* and f value showed significant differences respectively between normal and inflamed bowel segments (p < 0.05). ADC value presented the highest diagnostic accuracy (AUC = 0.813) and sensitivity (92%), and D value presented the highest specificity (84%) for the evaluation of inflamed bowel segments. For DCE-MRI, Ktrans value presented the highest diagnostic accuracy (AUC = 0.835), the highest sensitivity for Kep value (88%) and the highest specificity for Ve value (96%). ADC, f and Ktrans value had high correlations with ileocolonoscopic score respectively (r = -0.739-0.876, p < 0.01). The logarithm of normalized signal intensity/b-values for IVIM-DWI could also indicate directly the evident difference between the normal and inflamed bowel segments of terminal ileal CD. CONCLUSION: IVIM-DWI will be another promising noninvasive tool to provide precise quantitative-indicators in evaluating inflamed bowel segments of terminal ileal CD with little contrast-agent damage worries.

[A study on the correlation between exercise-induced bronchoconstriction and atopy].

OBJECTIVE: To investigate the correlation between exercise-induced bronchoconstriction and atopy. METHODS: Exercise-induced bronchoconstriction (EIB) was defined by free running asthma screening test. Atopy was defined by serum total IgE level and skin allergen test. Airway hyperreactivity was determined by bronchial provocation test. For a matched pair study, all EIB and some non-EIB students received serum total IgE measurements, skin allergen test and bronchial provocation test. All data were calculated by correlation analysis to investigate the correlation between EIB and atopy. RESULTS: Totally 773 students participated in the free running screening test, and 89 students (11.5%) were diagnosed as having EIB. The serum total IgE level exceeded the normal range in 16 among the 89 EIB students, but in 10 among the 70 non-EIB students. Statistical analysis (χ(2) test) did not support the correlation between atopy and EIB. Fifty EIB students received bronchial provocation test, but only 1 showed airway hyperreactivity. CONCLUSION: There was no correlation between atopy and EIB, and airway hyperreactivity was absent in most of the EIB students.

Higher liver stiffness in patients with chronic congestive heart failure: data from NHANES with liver ultrasound transient elastography.

BACKGROUND: Liver stiffness in patients with chronic congestive heart failure (CCHF) is poorly understood and liver ultrasound transient elastography (LUTE) is a new non-invasive method to detect this condition. In this cross-sectional study we explored liver stiffness and secondary congestive hepatopathy in patients with CCHF detected by LUTE. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES 2017-2018) were analyzed. All participants undergoing LUTE and without liver disease were included, among whom, 110 participants were diagnosed with CCHF. The cut-off values of stiffness for fibrosis and cirrhosis were above 7.65 and 13.01 kPa, respectively. Data regarding liver stiffness were compared between the participants with and without CCHF. RESULTS: Among patients with CCHF, the median liver stiffness was 6.0 kPa, above 7.65 kPa in 32.7% of patients, and above 13.01 kPa in 14.6% of patients. The mean liver stiffness was 5.0 kPa in the control group and was significantly lower than that of patients with CCHF (P<0.001). The ratio of serum albumin/globulin (A/G) gradually decreased according to the liver stiffness of patients with CCHF (P=0.03). CONCLUSIONS: Patients with CCHF had higher liver stiffness values than controls, nearly one-third had substantial fibrosis, and more than one in seven patients progressed to cirrhosis. The A/G ratio may be a potential biomarker for liver stiffness caused by CCHF.

Nlrp3 Deficiency Alleviates Angiotensin II-Induced Cardiomyopathy by Inhibiting Mitochondrial Dysfunction.

Inflammation has been considered a key component in the pathogenesis and progression of angiotensin II- (Ang II-) induced cardiac hypertrophy and related cardiomyopathy. As a vital mediator of inflammation, the role of the Nlrp3 inflammasome in Ang II-induced cardiomyopathy remains unclear. This study was aimed to determine whether Nlrp3 inflammasome activation and its downstream pathway were involved in Ang II-induced cardiomyopathy. We established an Ang II infusion model in both wild-type and Nlrp3-/- mice to determine the contribution of Nlrp3 to cardiac function. Cardiac fibrosis was determined by Masson's trichrome staining, real-time PCR, and TUNEL assay; cardiac function was assessed by echocardiography. Nlrp3 inflammasome activation and related downstream cytokines were measured by Western blotting and enzyme-linked immunosorbent assays; mitochondrial dysfunction was examined by transmission electron microscopy and real-time PCR. We found that Ang II-infused mice showed impaired cardiac function, as evidenced by increased cardiac fibrosis, apoptosis, inflammation, and left ventricular dysfunction. However, these alterations were significantly alleviated in the mice with Nlrp3 gene deletion. Moreover, Ang II-infused mice showed increased Nlrp3 inflammasome activity relative to that of the cytokines IL-1ß and IL-18, increased reactive oxygen species, mitochondrial abnormalities, and decreased mtDNA copy number and ATP synthase activity. These molecular and pathological alterations were also attenuated in Nlrp3 deficient mice. In conclusion, Nlrp3 inflammasome-induced mitochondrial dysfunction is involved in Ang II-induced cardiomyopathy. Nlrp3 gene deletion attenuated mitochondrial abnormalities, cardiac inflammation, oxidative stress, and fibrosis and thus alleviated heart dysfunction and hypertrophy. Targeting the Nlrp3 inflammasome and/or mitochondria may be a therapeutic approach for Ang II-induced cardiac diseases.

Combination of active targeting, enzyme-triggered release and fluorescent dye into gold nanoclusters for endomicroscopy-guided photothermal/photodynamic therapy to pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most devastating malignancies in patients, and there is an urgent need for an effective treatment method. Herein, we report a novel gold nanocluster-based platform for confocal laser endomicroscopy-guided photothermal therapy (PTT)/photodynamic therapy (PDT) for PDAC, which consists of four components: the PTT-carrier gold nanocluster, an active targeting ligand U11 peptide, a Cathepsin E (CTSE)-sensitive PDT therapy prodrug, and a CTSE-sensitive imaging agent (cyanine dye Cy5.5). Due to the strong coupling among cross-linked gold nanoparticles (AuNPs), the surface plasmon resonance peak of nanoclusters shifts to the near-infrared (NIR) region, thus making the nanoclusters useful in the effective PTT therapy. In the system, the labeling of nanoclusters with U11 peptide can distinctly increase their affinity and accelerate their uptake by pancreatic cancer cells. Cell apoptosis staining demonstrates that, upon incorporation of the uPAR-targeted unit, the antitumor efficacy of CTSE-sensitive nanocluster AuS-U11 is significantly enhanced with respect to that of the non-targeted nanocluster AuS-PEG and the insensitive nanocluster AuC-PEG. In vivo and ex vivo optical imaging confirms the high accumulation of AuS-U11 in the in situ pancreatic tumor model. Therapeutic studies further show that the combination of active targeting for tumor tissue, enzyme-triggered drug release of 5-ALA and fluorescent dye Cy5.5 in nanoclusters AuS-U11 could achieve optimal therapeutic efficacy with endomicroscopy-guided photothermal/photodynamic therapy with minimal side effects. As a consequence, the delicate gold nanocluster concept provides a promising strategy to enhance the therapy efficiency in the most challenging PDAC treatment.

Peptide Receptor-Targeted Fluorescent Probe: Visualization and Discrimination between Chronic and Acute Ulcerative Colitis.

The inflammatory activity of ulcerative colitis plays an important role in the medical treatment. However, accurate and real-time monitoring of the colitis activity with noninvasive bioimaging method is still challenging, especially in distinguishing between chronic and acute colitis. As a good receptor, the oligopeptide transporter (PepT1) is overexpressed in the colonic epithelial cells of chronic ulcerative colitis, which can deliver tripeptide KPV (Lys-Pro-Val, the C-terminal sequence of α-MSH) into cytosol in the intestine. Herein, we report a PepT1 peptide receptor-targeted fluorescent probe, dicyanomethylene-4H-pyran (DCM)-KPV, with the strategy of conjugating the KPV into the DCM chromophore. The diagnostic fluorescent probe bestows a specific receptor-targeted interaction with PepT1 through the KPV moiety, possessing several beneficial characteristics, such as efficient long emission, low photobleaching, negligible cytotoxicity, and high cytocompatibility in living cells. We build the overexpressed PepT1 on the cytomembrane of ulcerative colitis model Caco-2 cell as the efficient receptor to accumulate the targeted tripeptide KPV in the cytoplasm and nucleus. With the co-localization of DCM-KPV and the DNA-specific fluorophore, DAPI, the specifically long emission from chromophore DCM and efficient receptor-targeted peptide KPV, the fluorescent probe of DCM-KPV makes a breakthrough to the direct noninvasive observation of the accumulation in colon inflammation regions via intestinal mucosa, even successfully distinguishing the chronic, acute ulcerative colitis and normal groups. Compared with the traditional unenhanced magnetic resonance imaging and hematoxylin and eosin (H&E) staining, we make full use of exploiting the specific target-receptor interaction between the tripeptide unit, KPV, and the oligopeptide transporter, PepT1, for sensing selectivity. The desirable diagnostic ability of DCM-KPV can guarantee the real-time tracking and visualization of the role of intracellular KPV on ulcerative colitis, which provides an alternative to replace the time-consuming and tissue sampling-invasive H&E staining diagnosis.

Measurement of single-kidney glomerular filtration function from magnetic resonance perfusion renography.

Glomerular filtration rate (GFR) describes the flow rate of filtered fluid through the kidney, and is considered to be the reference standard in the evaluation of renal function. There are many ways to test the GFR clinically, such as serum creatinine concentration, blood urea nitrogen and SPECT renography, however, they're all not a good standard to evaluate the early damage of renal function. In recent years, the improvement of MRI hardware and software makes it possible to reveal physiological characteristics such as renal blood flow or GFR by dynamic contrast enhancement magnetic resonance perfusion renography (DEC MRPR). MRPR is a method used to monitor the transit of contrast material, typically a gadolinium chelate, through the renal cortex, the medulla, and the collecting system. This review outlines the basics of DCE MRPR included acquisition of dynamic MR perfusion imaging, calculation of the contrast concentration from signal intensity and compartment models, and some challenges of MRPR method faced in prospective clinical application.

Diagnostic values of combination of free running asthma screening test and total serum allergen IgE level in children with asthma.

BACKGROUND: A free running asthma screening test is usually used for screening exercise-induced bronchoconstriction. The total serum allergen IgE level can reveal the patient's atopy characteristics. Our study is to evaluate the diagnostic values of the combination of the two tests in asthmatic children and compare this new diagnostic method with the International Study of Asthma and Allergies in Childhood (ISSAC) questionnaires and the bronchial provocation test, which are popular diagnostic tool for pediatric asthma. METHODS: A total of 773 school children were recruited in this study. The children's asthma was diagnosed by means of a combination of the free running asthma screening test and total serum allergen IgE level. The new diagnostic method value was assessed using receiver operating characteristic (ROC) curves and compared with other diagnostic tools such as ISSAC questionnaires and the bronchial provocation test. RESULTS: The AUC of this new diagnostic method was higher than 0.9. When the cut-off value of total serum allergen IgE level was ≥ 47 KU/L, the sensitivity and the specificity were 71.4% and 85.1%, respectively, which were better than those of either the ISSAC questionnaires or bronchial provocation test. CONCLUSION: The combination of the free running asthma screening test and total serum allergen IgE level may be an effective diagnostic tool for children's asthma.