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.

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.

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.

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.

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.

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.

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.

Huperzine A attenuates nonalcoholic fatty liver disease by regulating hepatocyte senescence and apoptosis: an in vitro study.

OBJECTIVE: This study was undertaken to detect if free fatty acids (FFA) induce hepatocyte senescence in L-02 cells and if huperzine A has an anti-aging effect in fatty liver cells. METHODS: L-02 cells were treated with a FFA mixture (oleate/palmitate, at 3:0, 2:1, 1:1, 1:2 and 0:3 ratios) at different concentrations. Cell viability and fat accumulation rate were assessed by a Cell Counting Kit 8 and Nile Red staining, respectively. The mixture with the highest cell viability and fat accumulation rate was selected to continue with the following experiment. The L-02 cells were divided into five groups, including the control group, FFA group, FFA + 0.1 µmol/L huperzine A (LH) group, FFA + 1.0 µmol/L huperzine A (MH) group and FFA + 10 µmol/L huperzine A (HH) group, and were cultured for 24 h. The expression of senescence-associated ß-galactosidase (SA-ß-gal) was detected by an SA-ß-gal staining kit. The expression levels of aging genes were measured by qRT-PCR. The expression levels of apoptosis proteins were detected by a Western blot. ELISA kits were used to detect inflammatory factors and oxidative stress products. The expression of nuclear factor (NF-κB) and IκBα were detected by immunofluorescence. RESULTS: The FFA mixture (oleate/palmitate, at a 2:1 ratio) of 0.5 mmol/L had the highest cell viability and fat accumulation rate, which was preferable for establishing an in vitro fatty liver model. The expression of inflammatory factors (TNF-α and IL-6) and oxidants Malonaldehyde (MDA), 4-hydroxynonenal (HNE) and reactive oxygen species (ROS) also increased in the L-02 fatty liver cells. The expression levels of aging markers and aging genes, such as SA-ß-gal, p16, p21, p53 and pRb, increased more in the L-02 fatty liver cells than in the L-02 cells. The total levels of the apoptosis-associated proteins Bcl2, Bax, Bax/Bcl-2, CyCt and cleaved caspase 9 were also upregulated in the L-02 fatty liver cells. All of the above genes and proteins were downregulated in the huperzine A and FFA co-treatment group. In the L-02 fatty liver cells, the expression of IκBα decreased, while the expression of NF-κB increased. After the huperzine A and FFA co-treatment, the expression of IκBα increased, while the expression of NF-κB decreased. CONCLUSION: Fatty liver cells showed an obvious senescence and apoptosis phenomenon. Huperzine A suppressed hepatocyte senescence, and it might exert its anti-aging effect via the NF-κB pathway.

High Incidence of Gastrointestinal Ulceration and Cytogenetic Aberration of Trisomy 8 as Typical Features of Behçet's Disease Associated with Myelodysplastic Syndrome: A Series of 16 Consecutive Chinese Patients from the Shanghai Behçet's Disease Database and Comparison with the Literature.

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.

Infliximab associated with life-threatening lung infection in a patient with Behcet disease with intestinal and hematopoietic system involvement: A case report.

RATIONALE: Tumor necrosis factor (TNF-α) participates in the pathophysiology of Behcet's disease (BD) and myelodysplastic syndrome (MDS). Infliximab is recommaned for the most severe type of BD, however, there is little evidence for its effectiveness in BD associated MDS. PATIENT CONCERNS: A 46-year-old female, initially diagnosed with intestinal BD and leukopenia was later diagnosed as MDS. Treatement with infliximab and other immunoregulators lead to life-threatening pneumonia. DIAGNOSIS: Intestinal BD associated with MDS involving trisomy 8. INTERVENTIONS: The patient initially treated with methylprednisolone, thalidomide, cyclosporine A, and infliximab, which lead to severe lung infection. Therefore, the patient was transferred to Intensive Care Unit for life supportive, anti-infection and immune improving therapy. OUTCOMES: The patient survived from the lung infection. With combination of methylprednisolone, thalidomide and cyclosporine A, the patient recovered from her intestinal ulceration and MDS manifestations. LESSONS: Infliximab treatment may not benefit a patient with BD associated with MDS but place the patient at risk of infection.

Different medical expenses incurred by appendiceal cystadenoma in China: Report of three cases.

Appendiceal cystadenoma, the most common type of what has been generally termed 'mucocele' of the appendix, has unique clinical characteristics. In this study, three similar clinical manifestations of appendiceal cystadenoma are presented, with different subsequent management and diverse prognostic outcomes relating to the characteristics of the disease, the wishes of the patients, the medical workers and social factors. In this study, we provide details of three cases of appendiceal cystadenomas.

[Relationship of cysteine-rich protein 61 and NF-kappaB expression with metastasis and prognosis of gastric carcinoma].

OBJECTIVE: To investigate the expression of cysteine-rich protein 61 (Cyr61) and NF-kappaB in gastric carcinoma and its correlation with the clinicopathologic features and survival time. METHODS: RT-PCR was used to validate and detect expression of Cyr61 mRNA in 53 gastric carcinoma specimens and 11 non-tumor gastric mucosa samples. Cyr61 and NF-kappaB protein levels expressed were detected using immunohistochemistry in 99 gastric carcinoma specimens and 25 non-tumor gastric mucosa samples. RESULTS: RT-PCR demonstrated that expression of Cyr61 mRNA was higher in the primary carcinoma (84.6%, 22/26) and the metastatic foci (88.9%, 24/27) than in the non-tumor control samples (5/11; P < 0.05, respectively). Cyr61 gene mRNA expression levels were (2.76 +/- 5.50) x 10(-5), (14.61 +/- 20.64) x 10(-5), and (18.46 +/- 26.38) x 10(-5) by 2(-DeltaCt) in the control mucosa samples, primary carcinomas and metastatic tissues respectively. The level was higher in the primary carcinomas and metastatic tissues than that of the non-tumor gastric mucosa (P < 0.05, respectively); however, there was no significant difference between the metastatic tissues and the primary carcinomas (P > 0.05). Immunohistochemistry revealed that of the 99 cases, there was a high expression of Cyr61 and NF-kappaB protein, 56.6% (56/99) and 55.6% (55/99) respectively. There was correlation of Cyr61 and NF-kappaB protein expressions with the depth of tumor and vascular invasion, as well as the development of lymph node metastasis, and TNM staging (P < 0.05, respectively), besides, the expression of NF-kappaB also correlated with the tumor diameter (P < 0.05). Cyr61 expression was positively correlated with NF-kappaB expression in gastric carcinoma (P < 0.05); the mean survival time in cases with a high expression level of Cyr61 and NF-kappaB protein was significantly shorter than those with a low expression level (P < 0.05). CONCLUSIONS: Expression of Cyr61 and NF-kappaB closely correlated with invasion and metastasis of gastric carcinoma. They may be considered as the biologic behavior indicators for gastric carcinoma.