Clinical phenotypes of adult-onset Behçet's syndrome: a comprehensive cross-sectional study in China.

Behçet's syndrome (BS) is a variant vasculitis that can involve multiple organs with inflammatory manifestations. This study aimed to provide a more comprehensive analysis of the clinical phenotypes and characteristics of BS patients. We enrolled 2792 BS patients referred from China nationwide to Huadong Hospital Affiliated to Fudan University from October 2012 to December 2022. Detailed assessments of demographic information, clinical manifestations, laboratory results, gastroscopy, and medical imaging were conducted. Cluster analysis was performed based on 13 variables to determine the clinical phenotypes, and each phenotype was characterized according to the features of BS patients. A total of 1834 BS patients were included, while 958 invalid patients were excluded. The median age at onset was 31 years (IQR, 24-40 years), and the median disease duration was 10 years (IQR, 5-15 years). Eight clusters were identified, including mucocutaneous (n = 655, 35.7%), gastrointestinal (n = 363, 19.8%), articular (n = 184, 10%), ocular (n = 223, 12.2%), cardiovascular (n = 119, 6.5%), neurological (n = 118, 6.4%), vascular (n = 114, 6.2%), and hematological phenotype (n = 58, 3.2%). Ocular (RR = 1.672 (95% CI, 1.327-2.106); P < 0.001), gastrointestinal (RR = = 1.194 (95% CI, 1.031-1.383); P = 0.018), cardiovascular (RR = = 2.582 (95% CI, 1.842-3.620); P < 0.001), and vascular (RR = = 2.288 (95% CI, 1.600-3.272); P < 0.001) involvement were more prevalent in male BS patients, while the hematological (RR = 0.528 (95% CI, 0.360-0.776); P = 0.001) involvement was more common among female patients. BS presents significant heterogeneity and gender differences. The eight phenotypes of BS patients we propose hold the potential to assist clinicians in devising more personalized treatment and follow-up strategies. Key Points • This cluster analysis divided adult-onset BS into eight clinical phenotypes. • BS demonstrates a high level of clinical heterogeneity and gender differences. • Hematologic phenotypes of BS present distinctive clinical characteristics.

PLK1-activating IFI16-STING-TBK1 pathway induces apoptosis of intestinal epithelial cells in patients with intestinal Behçet's syndrome.

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.

Clinical heterogeneity and five phenotypes identified in pediatric Behçet's syndrome: a cohort study from Shanghai Behçet's syndrome database.

OBJECTIVES: Behçet's syndrome (BS) is a rare disease of unknown etiology, with limited reports especially in pediatric BS. The clinical characteristics and phenotypes of pediatric BS as a highly heterogeneous variable vessel vasculitis were investigated in this study. METHODS: A cross-sectional study was conducted to compare clinical variables and descriptive characteristics of BS by age of onset and gender. Cluster analysis was then performed to identify the phenotypes of pediatric BS. RESULTS: A total of 2082 BS patients were included in this study, 1834 adults and 248 children. Compared with adult-onset BS, pediatric BS had a higher incidence of folliculitis [relative risks (RR) and 95% confidence interval (CI) 1.3 (1.0-1.5)], uveitis of the left eye [RR and 95% CI 2.3 (1.0-5.0)], intestinal ulcer complications [RR and 95% CI 2.1 (1.1-4.2)], pericarditis [RR and 95% CI 2.5 (1.0-6.2)], and psychiatric disorders [RR and 95% CI 2.8(1.0-7.9)], while the incidence of thrombocytopenia was lower [RR 0.2 (0.1-1.0)]. Among pediatric BS, females had more genital ulcers, while males were more likely to have skin lesions, panuveitis, vascular involvement, venous lesions, cardiac involvement, and aortic aneurysms. Cluster analysis classified pediatric BS into five clusters (C1-C5): C1 (n = 61, 24.6%) showed gastrointestinal (GI) involvement; C2 (n = 44, 17.7%) was the central nervous system (CNS) type where 23 cases overlapped joint involvement; in C3 (n = 35, 14.1%), all patients presented with arthritis or arthralgia; all patients in C4 (n = 29, 11.7%) manifested ocular involvement, with a few patients overlapping with GI involvement or joint damage; C5 (n = 79, 31.9%) was the mucocutaneous type, presenting both oral ulcers, genital ulcers, and skin lesions. CONCLUSIONS: The clinical features of pediatric and adult BS differ significantly. Male and female pediatric BS also have a distinct demography. Five phenotypes including GI, CNS, joint, ocular, and mucocutaneous types were identified for pediatric BS.

A pan-cancer analysis of the oncogenic role of ATP binding cassette subfamily E member 1 (ABCE1) in human tumors: An observational study.

ATP-binding-cassette subfamily E member 1 (ABCE1) has been identified as an essential component of RNA translation and cell proliferation. However, studies on its role in pan-cancer are limited. Here, we aimed to characterize ABCE1 expression and its potential biological functions in cancer. ABCE1 expression was analyzed using RNA-seq data from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) database, and the Clinical Proteomic Tumor Analysis Consortium database. The prognostic value of ABCE1 was analyzed using clinical survival data from TCGA. We downloaded the immune cell infiltration score of TCGA samples from published articles and online databases and performed a correlation analysis between immune cell infiltration levels, chemokines/chemokine receptors, and ABCE1 expression. We further assessed the association between ABCE1-correlated genes and their functions in pancreatic adenocarcinoma (PAAD). In general, ABCE1 gene expression was upregulated in most tumors. There were significant strong correlations between ABCE1 expression and tumor-infiltrating cells in cancers. Furthermore, RNA transport and ribosome biogenesis were significantly related to ABCE1 expression in PAAD. Our study revealed that ABCE1 may serve as a potential prognostic and immunological pan-cancer biomarker. Moreover, ABCE1 may be used in the development of a novel target for PAAD.

Clinical heterogeneity of ocular Behçet's syndrome versus intestinal Behçet's syndrome: a cross-sectional study from Shanghai Behçet's syndrome database.

BACKGROUND: Behçet's syndrome (BS) is a rare variant vasculitis which can involve the eyes and gastrointestinal systems. However, ocular involvement rarely overlaps with intestinal lesions. This study aimed to compare the clinical characteristics and laboratory parameters of ocular BS and intestinal BS patients in China and analyze the differences between two key phenotypes to verify the heterogeneous conditions in BS patients. METHODS: A retrospective analysis was used to collect the demographic data, clinical characteristics, endoscopic findings, and laboratory parameters from 135 ocular BS and 174 intestinal BS patients. The Mann-Whitney U test and Pearson chi-square or continuity correction was used to analyze the differences between two groups. RESULTS: Among 916 BS patients enrolled in this study, ocular BS and intestinal BS accounted for 14.74% (135 cases) and 19.00% (174 cases), respectively. Ocular and intestinal involvements overlapped in only 7 cases (0.76%). Male gender (74.8% vs. 51.1%, P=0.00), erythema nodosum (45.9% vs. 32.2%, P=0.01), and vascular involvement (6.7% vs. 1.7%, P=0.03) were more frequent in the ocular BS group compared with the intestinal BS group. On the contrary, hematologic involvement (7.5% vs. 0.0%, P=0.00) and fever (17.8% vs. 4.4%, P=0.00) were more frequent in the intestinal BS group compared with the ocular BS group. Additionally, the inflammation markers including ESR [26.5 (16.0-41.5) vs. 9.0 (5.0-15.0) mm/H, P=0.00], CRP [14.8 (4.8-33.0) vs. 4.1 (1.6-8.3) mg/L, P=0.00], serum amyloid A [27.4 (10.8-92.3) vs. 11.3 (6.0-24.0) mg/L, P=0.00], and interleukin 6 [8.4 (1.7-18.7) vs. 1.7 (1.5-3.2) pg/mL, P=0.00] were higher in the intestinal BS group than those in the ocular BS group, respectively. CONCLUSIONS: Ocular BS was more prevalent in male patients and more likely to manifest with erythema nodosum and vascular involvement, while intestinal BS tends to have fever and hematologic disorders with higher inflammation markers. Ocular BS and intestinal BS are two distinct clinical phenotypes and very rarely overlapped.

Identification of miR-4510 as a metastasis suppressor of gastric cancer through regulation of tumor microenvironment via targeting GPC3.

The genes miR-4510 and glypican-3 (GPC3) have reported to be closely associated with tumors, with miR-4510 inversely correlated with GPC3 mRNA and protein in hepatocellular carcinoma samples. Glypican-3-expressing gastric cancer (GPC3-GC), characterized as gastric cancer (GC) expressing GPC3, accounts for 11% of the GC cases. However, the expression and mechanism of action of miR-4510 in GPC3-GC have not been clearly defined. We found that miR-4510 expression in GC tissues was significantly lower than that in the adjacent tissues (p < 0.001). miRNA-4510 expression in GPC3-GC was significantly lower than that in GPC3-negative GC tissue (p < 0.001). Our study confirmed that miR-4510 is inversely correlated with GPC3 in gastric cancer samples and that GPC3 is a direct target gene of miR-4510. The proportion of M2 macrophages in GC with low expression of miR-4510 was significantly increased, while the proliferation of CD8+ T cells was limited. miR-4510 may change the immunosuppressive signals in the tumor microenvironment by downregulating GPC3 and inhibiting gastric cancer cell metastasis. Oxaliplatin treatment may become a specific therapeutic drug for patients with miR-4510 inhibition and GPC3-GC.

Expression of miRNAs derived from plasma exosomes in patients with intestinal Behçet's syndrome.

OBJECTIVES: MicroRNAs (miRNAs) derived from plasma exosomes are potential diagnostic biomarkers. However, little is known about the expression of miRNAs derived from plasma exosomes in patients with intestinal Behçet's syndrome (BS). This study aimed to explore the difference of miRNAs derived from plasma exosomes between intestinal BS patients and healthy people, and further identify potential biomarkers that predict the disease activity of intestinal BS. METHODS: A total of 43 intestinal BS patients and 23 healthy volunteers were enrolled, among whom 23 were active intestinal BS and 20 were stable intestinal BS. The miRNAs expression profiles of plasma exosomes in 3 active intestinal BS patients and 3 healthy volunteers were determined using next-generation high throughput sequencing. Additionally, significantly differentially expressed miRNAs were further analysed by quantitative real-time polymerase chain reaction (qRT-PCR) in a validation cohort of 60 subjects. RESULTS: From the sequencing analysis, 15 miRNAs were identified to be differently expressed (p<0.05). Of these, 13 miRNAs were up-regulated, and 2 were down-regulated in intestinal BS patients compared with healthy volunteers. Furthermore, qRT-PCR analysis confirmed that miR-141-3p was down-regulated and miR-122-5p, miR-150-3p, miR-183-5p, miR-224-5p and miR-342-5p were up-regulated in intestinal BS patients' plasma exosomes. Additionally, the level of miR-141-3p was negatively correlated with disease activity indicators of intestinal BS, while miR-122-5p, miR-150-3p, miR-183-5p, miR-224-5p and miR-342-5p was positively correlated with disease activity indicators of intestinal BS. CONCLUSIONS: Circulating miR-141-3p, miR-122-5p, miR-150-3p, miR-183-5p, miR-224-5p and miR-342-5p derived from plasma exosomes may serve as biomarkers of disease activity in intestinal BS.

CDH17+/CDX2+ Can be Helpful in Providing Support for Small Intestinal Origin Versus Pancreatic or Biliary Origin.

Because of the distinct and complex anatomy of the ampullary region, the exact origin of the periampullary tumors was often difficult to ascertain. In this study, we evaluated 78 patient samples, including 26 small intestinal adenocarcinomas, 35 pancreatic ductal adenocarcinomas, and 17 cholangiocarcinomas by immunohistochemical detection of cadherin-17 (CDH17), CDX2, CK20, and CK19 protein expression. The result showed that CDH17 and CDX2 expression was higher in small intestinal adenocarcinoma (73.1% and 65.4%) than in pancreatic (14.3% and 2.9%) and bile duct (41.2% and 23.5%) cancers, respectively. CK20 expression was low in 78 tumor tissues, but relatively high in small intestinal adenocarcinoma (42.3%). CK19 showed a strong positive expression in all 78 adenocarcinoma tissues. The CDH17-high/CDX2-high pattern was predominantly expressed in small intestinal cancer tissues (75%), whereas the CDH17-low/CDX2-low pattern was observed in pancreatic cancers (63.8%) and bile duct cancers (20.9%). The study concluded that CDH17-high/CDX2-high adenocarcinomas more likely originated from small intestine versus pancreas or bile duct, whereas CDH17-low/CDX2-low ones are more likely of pancreatic origin. The combined use of CDH17 and CDX2 could be helpful in providing support for the histologic origin of periampullary adenocarcinoma.

Plasma exosomes derived from patients with intestinal Behçet's syndrome induce intestinal epithelial cell pyroptosis.

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-1ß 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-1ß 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-1ß (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-1ß (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.

Clinical characteristics and risk factors of intestinal involvement in Behçet's syndrome patients: a cross-sectional study from a single center.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Behçet's disease with latent Mycobacterium tuberculosis infection.

OBJECTIVE: The aim of this study is to examine the clinical features of patients with Behçet's disease (BD) in the presence or absence of latent tuberculosis infection (LTBI). METHODS: This was a retrospective study of 232 consecutive patients with active BD hospitalized between October 2012 and June 2017. LTBI was diagnosed based on the positive T-SPOT.TB assay, negative clinical, and imaging examinations. RESULTS: Among the 232 patients, 68 (29.3%) had LTBI. The frequency, number, and scope of oral ulcers in the BD-LTBI group were significantly more serious than in the non-LTBI group (all P < 0.05). Genital ulcers and eye involvement in the LTBI group were significantly higher than in the non-LTBI group (both P < 0.01). No active TB was diagnosed during follow-up (median, 27.9 months; range, 3-58 months). The patients with LTBI had signs of liver damage compared with the non-LTBI group. In the LTBI group, the frequency of alanine transaminase >2.0, the upper limit of normal, was higher in the rifampicin subgroup compared with the non-rifampicin subgroup (P = 0.033). CONCLUSION: Patients with BD and LTBI had worse clinical features than those with BD without LTBI. Rifampicin might be associated with the damage to liver in BD patients combined with latent TB.

The Tumor-Associated Macrophage-M2-Cancer Cell Complex and the Observation of Heterogeneous Modification of the Morphological Structure of Lung Adenocarcinoma.

OBJECTIVE: The aim of this study was to investigate the effect of the tumor-associated macrophage-m2-cancer cell complex (TAM-M2-CC) on the heterostructural modification of lung adenocarcinoma. METHODS: The expression of CD163+/CD68+ in macrophages in the microenvironment of 161 cases of lung adenocarcinoma was identified by dual immunohistochemistry, and the association between a TAM-M2-CC and its growth, as well as the histological changes in lung adenocarcinoma cells, was assessed. RESULTS: The morphological change of lung adenocarcinoma was related to the number of m2 phenotypes of the macrophages in the microenvironment of lung adenocarcinoma. TAM-M2-CCs were involved in the process of cancer cell recognition, association, and reconstruction. CONCLUSION: The microenvironment of lung adenocarcinoma can affect the phenotypic distinction of macrophages, and the polarization recruitment, zombification, and formation of a TAM-M2-CC, which can also affect the local differentiation of lung adenocarcinoma to a certain extent. The applicable pathogenesis needs to be verified and studied further.

Evaluation of factors for predicting risk of uveitis recurrence in Behcet's disease patients.

This study aimed to investigate the predictive factors for uveitis recurrence (UR) risk in Behcet's disease (BD) patients. BD patients (n=164) with a history of uveitis were recruited, and demographic data, clinical features, and laboratory tests were recorded. Uveitis was defined as anterior uveitis, intermediate uveitis, posterior uveitis, panuveitis referring to the "International Uveitis Study Group recommendations for the evaluation of intraocular inflammatory disease". In total, there were 70 UR patients and 94 non-UR patients. Compared to non-UR patients, UR patients appeared to be older and presented with increased uveitis occurrence rate and times within 3 months, oral ulcers occurrence rate, as well as higher concentrations of triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), and serum amyloid A (SAA). Multivariate logistic model disclosed that uveitis occurrence times within 3 months, oral ulcers, TG, LDL, and SAA independently predicted higher risk of UR. Furthermore, receiver operating characteristic curve analysis showed that the combination of uveitis occurrence times within 3 months, oral ulcers, TG, LDL, and SAA exhibited a high predictive value for UR risk with an area under the curve of 0.983 (95%CI: 0.969-0.998). In conclusion, uveitis occurrence times within 3 months, oral ulcers, TG, LDL, and SAA might be potential predictive factors for UR risk in BD patients, which can help in prevention and management of the disease.

Clinical characteristics and factors influencing the prognosis of Behçet's disease complicated with vascular involvement.

Background: Vascular Behçet's disease (VBD) might involve all sizes of arterial and venous vessels. Major vascular involvement caused the primary death in Behçet's syndrome (BS). We aimed to investigate the clinical characteristics and factors influencing the prognosis of VBD. Patients and methods: A retrospective analysis of the prospectively collected data of the Shanghai BS database from October 2012 to October 2018 was conducted. Patients who were diagnosed with BS and merged with venous thrombosis, arterial aneurysms, and arterial stenosis/occlusions were enrolled. Results: There were 47 patients with vascular involvement among 836 BS patients, 38 males and 9 females. The numbers of patients with venous thrombosis, arterial aneurysm, and arterial stenosis/occlusion were 25 (53.2 %), 21 (44.7 %), and 12 (25.5 %), respectively. Nearly half of the venous thromboses were located in limbs (n = 22, 46.8 %). Arterial aneurysm was the main form of arterial lesion. Most of the patients (93.6 %) were treated with corticosteroids and immunosuppressants. Late onset of BS or with arterial involvement had lower treatment response. Therapy with biological agents had significantly better results than that in the group without biological treatment (94.1 % vs. 80 %, P = 0.005). Conclusions: VBD showed a male preponderance and more than half of the patients presented with venous thrombosis. Late onset and arterial involvement were associated with poor prognosis. Therapy with biological agents is a viable alternative treatment to improve the prognosis.

Evaluation of factors for predicting risk of uveitis recurrence in Behcets disease patients

This study aimed to investigate the predictive factors for uveitis recurrence (UR) risk in Behcet's disease (BD) patients. BD patients (n=164) with a history of uveitis were recruited, and demographic data, clinical features, and laboratory tests were recorded. Uveitis was defined as anterior uveitis, intermediate uveitis, posterior uveitis, panuveitis referring to the "International Uveitis Study Group recommendations for the evaluation of intraocular inflammatory disease". In total, there were 70 UR patients and 94 non-UR patients. Compared to non-UR patients, UR patients appeared to be older and presented with increased uveitis occurrence rate and times within 3 months, oral ulcers occurrence rate, as well as higher concentrations of triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), and serum amyloid A (SAA). Multivariate logistic model disclosed that uveitis occurrence times within 3 months, oral ulcers, TG, LDL, and SAA independently predicted higher risk of UR. Furthermore, receiver operating characteristic curve analysis showed that the combination of uveitis occurrence times within 3 months, oral ulcers, TG, LDL, and SAA exhibited a high predictive value for UR risk with an area under the curve of 0.983 (95%CI: 0.969−0.998). In conclusion, uveitis occurrence times within 3 months, oral ulcers, TG, LDL, and SAA might be potential predictive factors for UR risk in BD patients, which can help in prevention and management of the disease.

An immune-related gene pairs signature predicts overall survival in serous ovarian carcinoma.

BACKGROUND: Ovarian cancer has the highest death rate of all fatal gynecological cancers. Increasing evidence has depicted the correlation between serous ovarian carcinoma prognosis and immune signature. Therefore, the aim of this study is to develop a robust prognostic immune-related gene pairs (IRGPs) signature for estimating overall survival (OS) of HGSOC. METHODS: Gene expression profiling and clinical information of serous ovarian carcinoma patients were derived from three public data sets, divided into training and validation cohorts. Immune genes significantly associated with prognosis were selected. RESULTS: Among 1,534 immune genes, a 20 IRGPs signature was built which was significantly associated with OS in the training cohort (P=1.44×10-14; hazard ratio [HR] =3.05 [2.26, 4.10]). In the validation datasets, the IRGPs signature significantly divided patients into high- vs low- risk groups considering their prognosis (P=4.30×10-3; HR =1.48 [1.13, 1.95]) and was prognostic in multivariate analysis. Functional analysis showed that several biological processes, including EMT and TGF-ß related pathways, enriched in the high-risk group. Macrophages M2 was significantly higher in the high-risk group compared with the low-risk group. CONCLUSION: We successfully constructed a robust IRGPs signature with prognostic values for serous ovarian carcinoma, providing new insights into post-operational treatment strategies.

Ulcerative intestinal tuberculosis case as a complication of treatment by infliximab for intestinal Behçet's disease: A case report.

RATIONALE: Intestinal Behçet's disease (BD) is characterized by intestinal ulcerations and gastrointestinal symptoms. Ulcerative intestinal tuberculosis (TB) is usually with dyspepsia, abdominal pain, vomiting, and weight loss. The 2 diseases exhibit similar clinical manifestations, but the most critical aspects of their clinical courses and required treatments are not at all similar. PATIENT CONCERNS: We present a case in which a patient with intestinal Behçet's disease developed a de novo ulcerative intestinal TB infection after the start of anti-tumor necrosis factor-α treatment. This was despite histopathologic examination without caseous necrosis granuloma and negative for acid-fast staining and latent TB screen. DIAGNOSES: Intestinal Behçet's disease and intestinal TB. INTERVENTIONS: The patient was treated with quadruple antituberculous chemotherapy, comprising rifapentine, isoniazid, ethambutol, and pyrazinamide. OUTCOMES: At follow-up about 3 months, the therapy of oral antituberculous drugs and thalidomide was continued and the patient's condition had stabilized. LESSONS: This case illustrates the importance of closely monitoring patients who are on infliximab for possible onset of TB, even without abdominal symptoms, and with negative screening results for latent TB.

An immune-related gene signature predicts prognosis of gastric cancer.

BACKGROUND: Although the outcome of patients with gastric cancer (GC) has improved significantly with the recent implementation of annual screening programs. Reliable prognostic biomarkers are still needed due to the disease heterogeneity. Increasing pieces of evidence revealed an association between immune signature and GC prognosis. Thus, we aim to build an immune-related signature that can estimate prognosis for GC. METHODS: For identification of a prognostic immune-related gene signature (IRGS), gene expression profiles and clinical information of patients with GC were collected from 3 public cohorts, divided into training cohort (n = 300) and 2 independent validation cohorts (n = 277 and 433 respectively). RESULTS: Within 1811 immune genes, a prognostic IRGS consisting of 16 unique genes was constructed which was significantly associated with survival (hazard ratio [HR], 3.9 [2.78-5.47]; P < 1.0 × 10). In the validation cohorts, the IRGS significantly stratified patients into high- vs low-risk groups in terms of prognosis across (HR, 1.84 [1.47-2.30]; P = 6.59 × 10) and within subpopulations with stage I&II disease (HR, 1.96 [1.34-2.89]; P = 4.73 × 10) and was prognostic in univariate and multivariate analyses. Several biological processes, including TGF-ß and EMT signaling pathways, were enriched in the high-risk group. T cells CD4 memory resting and Macrophage M2 were significantly higher in the high-risk risk group compared with the low-risk group. CONCLUSION: In short, we developed a prognostic IRGS for estimating prognosis in GC, including stage I&II disease, providing new insights into the identification of patients with GC with a high risk of mortality.

The T-SPOT.TB assay used for screening and monitoring of latent tuberculosis infection in patients with Behçet's disease pre- and post-anti-TNF treatment: A retrospective study.

BACKGROUND: Patients undergoing anti-tumor necrosis factor (TNF) treatment are more susceptible to latent tuberculosis infection (LTBI). The aim of the current study was to determine the rate of active tuberculosis (TB) in patients with Behçet's disease (BD) pre- and post-anti-TNF treatment and to evaluate the long-term efficacy of LTBI screening as primary prophylaxis in China. METHODS: This retrospective study included BD patients eligible for anti-TNF therapy at a single institution in Fudan University, China. On the basis of the results of T-SPOT.TB assay, chest radiograph, and history of exposure to TB, patients were screened and regularly followed up at 3-months interval. RESULTS: Eighty-nine BD patients with mean disease duration of 87.5 ± 86.1 months were included. Their median duration of anti-TNF therapy was 10.6 months; 51 patients were treated with Infliximab, 38 with Etanercept, and four with Adalimumab. While 84 patients received a consecutive single anti-TNF drug therapy, five patients switched to a second drug. Twelve patients demonstrated positive results in LTBI screening: three had history of TB exposure and nine were solely T-SPOT.TB-positive patients. Before anti-TNF treatment, LTBI treatment was initiated in 11 patients, and one patient refused treatment. With a median follow-up period of 27.9 months, we observed only one case (1.1%) of intestinal TB during Infliximab treatment. CONCLUSION: Regardless of anti-TNF treatment, long-term screening via T-SPOT.TB assay might represent a more sensitive approach to identify BD patients with LTBI. As a secondary prophylaxis, the LTBI treatment is effective in a country with high risk of TB.

LI-cadherin and CDX2: Useful Markers in Metastatic Gastrointestinal Adenocarcinoma Cells in Serous Cavity Effusion.

OBJECTIVE: The aim of this study was to investigate the expression and significance of liver-intestine cadherin (LI-cadherin) and CDX2 (caudal-type homeobox transcription factor 2) in cytology specimens of metastatic gastrointestinal adenocarcinoma in serous cavity effusion. MATERIALS AND METHODS: The serous cavity effusion samples that were suspected of tumor metastasis in the last 5 years were made into paraffin-imbedded cell blocks, a total of 180 cases, including 97 cases of pleural effusion, 78 cases of ascites, and 5 cases of pericardial effusion. The expressions of LI-cadherin and CDX2 were detected by immunohistochemical staining in cell blocks and primary tumor tissues; thereafter, the specificity and sensitivity were analyzed. RESULTS: The positive expressions of LI-cadherin and CDX2 in 63 cases of gastrointestinal adenocarcinoma cells were 65.1% (41/63), 61.9% (39/63), respectively. Of 11 cases of pancreaticobiliary duct cancers, only one case (9.09%) was weakly positive for LI-cadherin and CDX2 expressions, and 107 cases of non-digestive tract cancers were all negative. In 57 matched-pair samples of cell blocks and primary gastrointestinal adenocarcinoma tissues, the positive expressions of LI-cadherin and CDX2 were 64.9% (37/57), 61.4% (35/57), respectively, in cells, and 82.5% (47/57), and 77.2% (44/57), respectively, in tissues. Positive correlation was observed between the expressions of LI-cadherin and CDX2 in metastatic gastrointestinal adenocarcinoma cells (P<0.05). Both LI-cadherin and CDX2 expressions demonstrated positive correlation in cells with paired cancer tissues (P<0.05). The positive expression reached 80.7% with at least one positive marker in the total cell samples through combined detection of LI-cadherin and CDX2, increased by 15.8% and 19.3% compared with using either of the markers alone. CONCLUSIONS: Combined use of LI-cadherin and CDX2 can improve the accuracy in the diagnosis of metastatic adenocarcinoma cells in serous cavity effusion and provide some bases of histologic origin because of their high sensitivity and specificity.