Background In patients with vitiligo, an increased reactive oxygen species (ROS) level has been proved to be a key player during disease initiation and progression in melanocytes. Nevertheless, ...little is known about the effects of ROS on other cells involved in the aberrant microenvironment, such as keratinocytes and the following immune events. CXCL16 is constitutively expressed in keratinocytes and was recently found to mediate homing of CD8+ T cells in human skin. Objective We sought to explicate the effect of oxidative stress on human keratinocytes and its capacity to drive CD8+ T-cell trafficking through CXCL16 regulation. Methods We first detected putative T-cell skin-homing chemokines and ROS in serum and lesions of patients with vitiligo. The production of candidate chemokines was detected by using quantitative real-time PCR and ELISA in keratinocytes exposed to H2 O2 . Furthermore, the involved mediators were analyzed by using quantitative real-time PCR, Western blotting, ELISA, and immunofluorescence. Next, we tested the chemotactic migration of CD8+ T cells from patients with vitiligo mediated by the CXCL16-CXCR6 pair using the transwell assay. Results CXCL16 expression increased and showed a positive correlation with oxidative stress levels in serum and lesions of patients with vitiligo. The H2 O2 -induced CXCL16 expression was due to the activation of 2 unfolded protein response pathways: kinase RNA (PKR)–like ER kinase–eukaryotic initiation factor 2α and inositol-requiring enzyme 1α–X-box binding protein 1. CXCL16 produced by stressed keratinocytes induced migration of CXCR6+ CD8+ T cells derived from patients with vitiligo. CXCR6+ CD8+ T-cell skin infiltration is accompanied by melanocyte loss in lesions of patients with vitiligo. Conclusion Our study demonstrated that CXCL16-CXCR6 mediates CD8+ T-cell skin trafficking under oxidative stress in patients with vitiligo. The CXCL16 expression in human keratinocytes induced by ROS is, at least in part, caused by unfolded protein response activation.
Background Previous studies have shown that individuals with schizophrenia have a greater risk for psoriasis than a typical person. This suggests that there might be a shared genetic etiology between ...the 2 conditions. We aimed to characterize the potential shared genetic susceptibility between schizophrenia and psoriasis using genome-wide marker genotype data. Methods We obtained genetic data on individuals with psoriasis, schizophrenia and control individuals. We applied a marker-based coheritability estimation procedure, polygenic score analysis, a gene set enrichment test and a least absolute shrinkage and selection operator regression model to estimate the potential shared genetic etiology between the 2 diseases. We validated the results in independent schizophrenia and psoriasis cohorts from Singapore. Results We included 1139 individuals with psoriasis, 744 with schizophrenia and 1678 controls in our analysis, and we validated the results in independent cohorts, including 441 individuals with psoriasis (and 2420 controls) and 1630 with schizophrenia (and 1860 controls). We estimated that a large fraction of schizophrenia and psoriasis risk could be attributed to common variants ( h2SNP = 29% ± 5.0%, p = 2.00 × 10−8 ), with a coheritability estimate between the traits of 21%. We identified 5 variants within the human leukocyte antigen ( HLA ) gene region, which were most likely to be associated with both diseases and collectively conferred a significant risk effect (odds ratio of highest risk quartile = 6.03, p < 2.00 × 10−16 ). We discovered that variants contributing most to the shared heritable component between psoriasis and schizophrenia were enriched in antigen processing and cell endoplasmic reticulum. Limitations Our sample size was relatively small. The findings of 5 HLA gene variants were complicated by the complex structure in the HLA region. Conclusion We found evidence for a shared genetic etiology between schizophrenia and psoriasis. The mechanism for this shared genetic basis likely involves immune and calcium signalling pathways.
To address the limitations of silicone stents, we designed a hinged self-expandable covered metallic stent. The aim of this study was to evaluate the safety and efficacy of the customized stents in ...clinical applications.
This was a retrospective analysis. Under conscious sedation and local anesthesia, the stents were implanted or removed by interventional radiologists, with fluoroscopic guidance.
Of 24 patients with benign main bronchial stenosis, stents were successfully placed in 21 (87.5%). The low-pressure balloon before dilation failed in 1 case (4.17%) of left main bronchial cicatricial stenosis. In 2 other cases (8.33%), stent placement was abandoned. Stents were successfully removed between 29 and 103 days after the procedure. After stent removal, the follow-up lasted for at least 12 months. Restenosis occurred only in 1 case (4.55%) owing to bronchial collapse 3 days after stent removal. Dyspnea occurred in another case (4.55%) at 2 months after retrieval; recurrence was confirmed using bronchoscopy, leading to a left pneumonectomy.
The described procedure is safe and easy to be performed and avoids the use of intubation, bronchoscopy, and general anesthesia.
Objectives This study investigated the feasibility of noninvasive renal sympathetic denervation (RSD) by using the novel approach of extracorporeal high-intensity focused ultrasound (HIFU). ...Background Catheter-based RSD has achieved promising clinical outcomes. Methods Under the guidance of Doppler flow imaging, therapeutic ablations (250 W × 2 s) were performed by using extracorporeal HIFU on the bilateral renal nerves (36.3 ± 2.8 HIFU emissions in each animal) in a mean 27.4-min procedure in 18 healthy canines of the ablation group. Similar procedures without acoustic energy treatment were conducted in 5 canines of the sham group. The animals were killed on day 6 or 28. Blood pressure (BP), plasma noradrenaline (NA) level, and renal function were determined on days 0, 6, and 28. Pathological examinations were performed on all retrieved samples. Results All of the animals survived the treatment. After ablation, BP and NA significantly decreased compared with the baseline values (BP changed −15.9/−13.6 mmHg, NA changed −55.4% p < 0.001 28 days after ablation) and compared with the sham group on days 6 and 28. Ablation lesions around the renal artery adventitia were observed on day 6. A histological examination revealed the disruption of nerve fibers, necrosis of Schwann cells and neurons, and apparent denervation on day 28. No procedure-related complications were observed. Conclusions Effective RSD was successfully achieved by using the extracorporeal HIFU method in canines. Thus, noninvasive HIFU may be further explored as an important and novel strategy for RSD.
Background After pulsed dye laser (PDL) treatment, facial lateral port-wine stains (PWS) clear quicker and more completely than central PWS do. Objective We sought to investigate whether the ...difference in the efficacy of the treatment between central and lateral facial PWS was related to different histologic manifestations. Method Thirteen patients with PWS had biopsies and underwent PDL treatments in both central and lateral areas of the face. The hypothesis was tested by correlating the PWS response to PDL with the depth and diameter of the PWS vessels. The clinical efficacy was assessed by chromameter 2 months after the final PDL treatment, whereas diameter and depth of PWS vessels were measured in biopsy specimens. Results All patients were treated on central and lateral facial sites. The chromameter evaluation showed that the average blanching rate was 34.01% and 8.68% for lateral and central facial sites, respectively ( P < .05), which suggests a better response to PDL treatment in the lateral than in the central area. Histologic manifestations showed that vessels in the lateral regions were primarily located in the papillary dermis, whereas in the central regions they were extensively distributed from the dermis into the subcutaneous tissue. Limitations The small number of cases included in this study and the lack of follow-up longer than 2 months constitute limitations. Conclusion Lateral facial PWS respond better to PDL than PWS located in the central face. Differences in vessel location and diameter may be responsible for the variations in PWS response to PDL.
The aberrant expression in some of the circadian clock-related proteins is associated with the pathogenesis of immune disorders.5 On the basis of results of Fig E1, we reasoned that one or some of ...the circadian clock-related proteins interfered with the expression of Foxp3 in CD4+ T cells. ...after treating with ACC, we isolated CD4+ T cells from the mouse intestine; the cells were analyzed by chromatin immunoprecipitation assay. Occurrence of food allergy after the career of day-/night-shift rotation Time (y) Patients with food allergy Percent Participants, n 668 668 40 Sex: male/female, n 334/334 334/334 20/20 Age (y), mean ± SD 38.5 ± 16 37.8 ± 15 38.8 ± 18 Total food allergy patients 86 (12.9) 26 (3.9)low * 0 Allergen distribution    Fish 18 (20.9) 5 (19.2) 0 Shell fish 12 (13.9) 3 (11.5) 0 Milk 11 (12.8) 3 (11.5) 0 Tree nuts 10 (11.6) 3 (11.5) 0 Soy 10 (11.6) 1 (3.8) 0 Fruit 8 (9.3) 6 (23.1) 0 Sesame seed 6 (6.9) 0 0 Wheat 6 (6.9) 0 0 Egg 6 (6.9) 5 (19.2) 0 Peanut 5 (5.8) 5 (19.2) 0 With other allergies    Asthma 1 (0.15) 1 (0.15)  Allergic rhinitis 2 (0.3) 0  Allergic dermatitis 1 (0.15) 2 (0.3)  Serum vitamin D (ng/mL) 30.8 ± 1.9 30.5 ± 1.3  Serum cortisol (ng/mL) 19.8 ± 2.4 20.2 ± 2.3  Height (m) 1.59 ± 0.06 1.58 ± 0.06  Weight (kg) 61.5 ± 3.5 60.6 ± 3.2  BMI (kg/m2) 24.2 ± 2.8 23.9 ± 2.1  Specific IgE (kU/L) 15.3 ± 21.6 <0.35 12.5 ± 18.2 <0.35 <0.35 Regulatory T cells (%) 2.14 ± 2.06 5.95 ± 5.14 2.28 ± 2.35 6.28 ± 7.29 6.68 ± 6.26 Serum IL-4 (pg/mL) 45.8 ± 25.9 12.6 ± 18.6 39.5 ± 31.3 9.8 ± 15.4 10.5 ± 8.6 SPT diameter (mm) 6.58 ± 4.87 2.11 ± 1.14 5.74 ± 3.85 1.86 ± 1.47 1.17 ± 1.08 1-2 5 5.8 3-4 70 81.4 5-6 9 10.5 >7 1 1.2 Table I Clinical features of human subjects Some patients were allergic to more than 1 allergen.
Objectives The purpose of this study was to examine the association of different levels of occupational, commuting, and leisure-time physical activity and heart failure (HF) risk. Background The role ...of different types of physical activity in explaining the risk of HF is not properly established. Methods Study cohorts included 28,334 Finnish men and 29,874 women who were 25 to 74 years of age and free of HF at baseline. Baseline measurement of different types of physical activity was used to predict incident HF. Results During a mean follow-up of 18.4 years, HF developed in 1,868 men and 1,640 women. The multivariate adjusted (age; smoking; education; alcohol consumption; body mass index; systolic blood pressure; total cholesterol; history of myocardial infarction, valvular heart disease, diabetes, lung disease, and use of antihypertensive drugs; and other types of physical activity) hazard ratios of HF associated with light, moderate, and active occupational activity were 1.00, 0.90, and 0.83 (p = 0.005, for trend) for men and 1.00, 0.80, and 0.92 (p = 0.007, for trend) for women, respectively. The multivariate adjusted hazard ratios of HF associated with low, moderate, and high leisure-time physical activity were 1.00, 0.83, and 0.65 (p < 0.001, for trend) for men and 1.00, 0.84, and 0.75 (p < 0.001, for trend) for women, respectively. Active commuting had a significant inverse association with HF risk in women, but not in men, before adjustment for occupational and leisure-time physical activity. The joint effects of any 2 types of physical activity on HF risk were even greater. Conclusions Moderate and high levels of occupational or leisure-time physical activity are associated with a reduced risk of HF.
There are few evidences of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell (WBC) in differentiating active Crohn's disease (CD) from intestinal lymphoma (IL), ...intestinal tuberculosis (ITB) and Behcet's syndrome (BD). This study is designed to investigate potential differential capacity of the 3 biomarkers between these disorders.
A hospital-based case-control study was performed. A total of 29 active CD, 25 IL, 30 ITB and 17 BD patients were collected. Laboratory parameters were drawn from the first blood test results on admission.
In active CD group, the level of CRP was 20.2 ± 4.26 mg/dL, which was statistically lower than IL (59.9 ± 10.8 mg/dL, P < 0.0001). Similarly, the level of ESR reached its lowest point in active CD group (23.8 ± 3.18 mm/hr), compared with 46.6 ± 6.46 mm/hr in IL group (P = 0.0002). CRP showed a possible diagnostic value in differentiation of IL from active CD (odds ratio = 1.028, P = 0.046). CRP also exhibited a superior ability (area under curve AUC = 0.821) than ESR (AUC = 0.797) and CRP+ESR (AUC = 0.800) in distinguishing active CD from IL. The optimal cutoff value was 19.7 mg/dL, and the sensitivity and specificity were 62.1% and 96.0%, respectively.
A significant decreased level of CRP and ESR was confirmed in active CD compared with IL. Current study demonstrated a possible differential value of CRP between active CD and IL. Further studies would be performed to validate their clinical significances.
Background Aberrant airway epithelial remodeling is one of the cardinal histopathologic features of inflammatory airway diseases, but whether it alters the mucociliary apparatus remains unknown. ...Objective We sought to investigate the morphologic pattern of motile cilia and ciliogenesis-associated makers in hyperplastic nasal epithelium from nasal polyps (NPs) both in vivo and in vitro. Methods Biopsy specimens obtained from patients with NPs (n = 44) and inferior turbinate from healthy control subjects (n = 38) were analyzed by using scanning electron microscopy, immunofluorescence staining, single-cell (cytospin) staining, quantitative real-time PCR, and human nasal epithelial stem/progenitor cell culture and differentiation. Results Abnormal cilia architecture (untidy, overly dense, and lengthened) was more commonly observed in patients with NPs by using scanning electron microscopy. Ectopic lengthened cilia were visualized by means of immunofluorescence (patients with NPs: 6.33 μm 5.51-7.43 μm vs control subjects: 3.73 μm 3.50-4.27 μm, P < .0001), at the site of epithelial hyperplasia in isolated single cells (patients with NPs: 6.55 ± 0.23 μm vs control subjects 4.89 ± 0.24 μm, P < .0001), and in differentiated ciliated cells derived from human nasal epithelial stem/progenitor cells (patients with NPs: 9.20 ± 0.56 μm vs control subjects: 5.21 ± 0.37 μm, P < .0001). Ciliary beat frequency was found to be significantly slower in patients with NPs than control subjects in vitro . Both protein and mRNA levels of ciliogenesis-associated markers (centrosomal protein 110 CP110, forkhead box J1 Foxj1, and P73 isoform with an N-terminal transactivation domain TAp73) were significantly increased in patients with NPs versus those seen in control subjects and were positively correlated with cilia length. Conclusion For the first time, this study demonstrates for that motile cilia impairment is a co-condition of epithelial hyperplasia in patients with NPs, and this impairment of function is a likely cause of chronic mucosal inflammation or infection (eg, biofilm) observed in patients with chronic rhinosinusitis.
Background Port-wine stain (PWS) is a congenital, progressive vascular malformation but the pathogenesis remains incompletely understood. Objective We sought to investigate the activation status of ...various kinases, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, AKT, phosphatidylinositol 3-kinase, P70 ribosomal S6 kinase, and phosphoinositide phospholipase C γ subunit, in PWS biopsy tissues. Methods Immunohistochemistry was performed on 19 skin biopsy samples from 11 patients with PWS. Results c-Jun N-terminal kinase, extracellular signal-regulated kinase, and P70 ribosomal S6 kinase in pediatric and adult PWS blood vessels were consecutively activated. Activation of AKT and phosphatidylinositol 3-kinase was found in many adult hypertrophic PWS blood vessels but not in infants. Phosphoinositide phospholipase C γ subunit showed strong activation in nodular PWS blood vessels. Limitation Infantile PWS sample size was small. Conclusion Our data suggest a subsequent activation profile of various kinases during different stages of PWS: (1) c-Jun N-terminal and extracellular signal-regulated kinases are firstly and consecutively activated in all PWS tissues, which may contribute to both the pathogenesis and progressive development of PWS; (2) AKT and phosphatidylinositol 3-kinase are subsequently activated, and are involved in the hypertrophic development of PWS blood vessels; and (3) phosphoinositide phospholipase C γ subunit is activated in the most advanced stage of PWS and may participate in nodular formation.
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