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Circular RNAs (circRNAs) play important roles in carcinogenesis. Here, we investigated the mechanisms and clinical significance of circ-NOL10, a highly repressed circRNA in breast cancer. Subsequently, we also identified RNA-binding proteins (RBPs) that regulate circ-NOL10. Bioinformatics analysis was utilized to predict regulatory RBPs as well as circ-NOL10 downstream microRNAs (miRNAs) and mRNA targets. RNA immunoprecipitation, luciferase assay, fluorescence in situ hybridization, cell proliferation, wound healing, Matrigel invasion, cell apoptosis assays, and a xenograft model were used to investigate the function and mechanisms of circ-NOL10 in vitro and in vivo. The clinical value of circ-NOL10 was evaluated in a large cohort of breast cancer by quantitative real-time PCR. Circ-NOL10 is downregulated in breast cancer and associated with aggressive characteristics and shorter survival time. Upregulation of circ-NOL10 promotes apoptosis, decreases proliferation, and inhibits invasion and migration. Furthermore, circ-NOL10 binds multiple miRNAs to alleviate carcinogenesis by regulating PDCD4. CASC3 and metadherin (MTDH) can bind directly to circ-NOL10 with characterized motifs. Accordingly, ectopic expression or depletion of CASC3 or MTDH leads to circ-NOL10 expression changes, suggesting that these two RBPs modulate circ-NOL10 in cancer cells. circ-NOL10 is a novel biomarker for diagnosis and prognosis in breast cancer. These results highlight the importance of therapeutic targeting of the RBP-noncoding RNA (ncRNA) regulation network., Graphical abstract, A novel RBP-ncRNA signaling route, formed by two RBPs (MTDH and CASC3), one circRNA (circ-NOL10), three miRNAs (miR-149-5p, miR-330-3p, and miR-452-5p), and the effector PDCD4, is identified. This investigation reveals a ncRNA-mediated mechanism in breast cancer carcinogenesis and provides novel insights for therapeutic targeting of ncRNAs.

The use of an antibiotic with immunomodulatory properties could be fascinating in treating multifactorial inflammatory conditions such as ulcerative colitis (UC). We report our investigations into the immunomodulatory properties of levornidazole, the S-enantiomer of ornidazole, which displayed a tremendous therapeutic potential in UC induced by dextran sodium sulfate (DSS). Levornidazole administration to DSS-colitic mice attenuated the intestinal inflammatory process, with an efficacy better than that shown by 5-amino salicylic acid. This was evidenced by decreased disease activity index, ameliorated macroscopic and microscopic colon damages, and reduced expression of inflammatory cytokines. Additionally, levornidazole displayed anti-inflammatory activity through Caveolin-1-dependent reducing IL-1β and IL-18 secretion by macrophages contributing to its improvement of the intestinal inflammation, as confirmed in vitro and in vivo. In conclusion, these results pointed out that the immunomodulatory effects of levornidazole played a vital role in ameliorating the intestinal inflammatory process, which would be crucial for the translation of its use into clinical settings.

Background: Pre-existing liver disease is a risk factor for the worse prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to evaluate whether chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) affect the expression of viral receptor angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in the liver. Methods: Twelve pairs of matched liver tissues of HCC and para-carcinoma were collected from the First Affiliated Hospital of Zhejiang University School of Medicine. And 20 liver biopsies from CHB patients were collected from Peking University People's Hospital. The expression of ACE2 and TMRPSS2 were detected using immunofluorescence staining, western blot, and RT-qPCR. The effects of hepatitis B virus (HBV) replication or interferon on ACE2 and TMPRSS2 expression were tested in hepatic cell lines. Results: The mRNA expression of TMPRSS2 in HCC tissues was six-fold higher than that of para-carcinoma tissues (P = 0.002), whereas that of ACE2 was not statistically different between HCC and para-carcinoma tissues. Hepatocellular ACE2 expression was detected in 35% (7/20) of CHB patients and mostly distributed in the inflammatory areas. However, there was no difference in TMPRSS2 expression between areas with or without inflammation. IFN-α2b slightly induced ACE2 expression (2.4-fold, P = 0.033) in HepG2 cells but not in Huh-7, QSG-7701, and L-02 cells. IFN-α2b did not affect TMPRSS2 expression in these cell lines. In addition, HBV replication did not alter ACE2 expression in HepAD38 cells. Conclusions: Although HBV replication does not directly affect the expression of ACE2 and TMPRSS2, intrahepatic inflammation and carcinogenesis may increase their expression in some patients, which, in turn, may facilitate SARS-CoV-2 infection in hepatocytes.

Considering the few reported cardiac masses, PET/CT in the imaging workup of cardiac masses is not well established. This retrospective study analyzed the role of 18F-FDG PET/CT imaging in cardiac/pericardial masses. Fifty-nine patients with newly diagnosed cardiac/pericardial masses who underwent PET/CT and transthoracic echocardiography (TTE) were recruited. Echocardiographic and PET/CT characteristics were evaluated for predictive value in differentiating malignant and non-malignant lesions using histologic confirmation as the gold standard. The McNemar test was used to test the differences in sensitivity between PET/CT and TTE. 18F-FDG PET/CT had higher sensitivity in determining the malignancy of cardiac/pericardial masses compared to TTE (sensitivity, 96.6% vs 72.4%, P = .039). However, when pericardial masses were excluded from the analysis, the difference in sensitivity between the two was not statistically significant (sensitivity, 95.6% vs 78.3%, P = .219). 18F-FDG PET/CT identified two malignant pericardial masses missed on TTE, changed the diagnostic orientation of TTE in 15 patients, and found seven patients with extracardiac lesions in 29 malignant patients. PET/CT was an effective additional image modality in patients with suspected malignant cardiac mass for further confirmation and to screen for potential metastasis.

Programmed cell death-ligand 1 (PD-L1) is expressed on tumor cells (TC) and tumor-infiltrating immune cells (IC). We conducted a retrospective study to investigate the relationship between PD-L1 expression on TC/IC and 18F-FDG uptake in patients with surgically resected non-small cell lung cancer (NSCLC). Total 362 NSCLC patients (297 adenocarcinoma and 65 squamous cell carcinoma) who underwent preoperative 18F-FDG-PET/CT imaging were analyzed retrospectively. Immunohistochemistry analysis was performed for PD-L1 expression on TC and IC in NSCLC specimens with 28–8 antibody. The cut-off value of 5% for defining PD-L1 positivity was determined according to previous trials. The association between PD-L1 expression and clinicopathological variables were analyzed, including age, gender, smoking status, tumor diameter, lymph node metastasis, stage and the maximum standardized uptake value (SUVmax). PD-L1 positive expression was 50.8% (184/362) in NSCLC patients. Its positive expression on TC and IC were 24.3% (88/362) and 42.5% (154/362), respectively. SUVmax was significantly higher in patients with PD-L1 positive expression on TC or IC than that with negative. Multivariate analysis demonstrated that PD-L1 expression were correlated with SUVmax. The best cut-off value of SUVmax for PD-L1 expression on TC/IC was 8.5 [area under the curve (AUC) = 0.607, 95% CI 0.549–0.665, P = 0.001, sensitivity 50.5% and specificity 71.4%] determined by ROC curve. High SUVmax is linked to PD-L1 expression on TC and IC in our patients with surgically resected non-small cell lung cancer. 18F-FDG-PET/CT imaging may be used to predict the PD-L1 expression on TC and IC in NSCLC patients.

SNA001 is a novel recombinant human thyroid stimulating hormone (rhTSH). rhTSH has long been approved in several countries to facilitate monitoring and ablation of thyroid carcinoma without hypothyroidism caused by thyroid hormone withdrawal (THW). To assess the safety, tolerance, pharmacokinetics and pharmacodynamics properties of SNA001, the two-period (SNA001 period and THW period), dose-ascending study in well-differentiated thyroid cancer (DTC) patients was designed.Three doses (0.45 mg, 0.9 mg, and 1.35 mg) of SNA001 were intramuscularly injected, twice in the SNA001 period to stimulate iodine-131 uptake and thyroglobulin (Tg) release. Twenty-four hours after the last dose of SNA001, iodine-131 (111~185MBq) was administrated, followed by whole-body scan (WBS) 48 hours later. THW period began just after SNA001 washout and lasted for about 3~6 weeks. When TSH level was above 30 mU/L, iodine-131 (111~185MBq) was administrated, followed by a WBS and Tg detection 48 hours later.Twenty-four DTC patients after thyroidectomy were enrolled, mean peak concentrations of SNA001 in 0.45 mg, 0.9 mg, 1.35 mg groups were 18.5, 26.7, and 37.0 ng/mL (about 244.7, 354.2 and 489.6 mU/L) respectively, within 28~32 hours after first dose of SNA001. SNA001 was metabolized in a dose-dependent manner. The results of WBS and Tg release in the SNA001 period were compared with those in THW period. Compared to Tg level in baseline, the Tg levels in SNA001 and THW periods were increased, with 78% of subjects showing higher Tg levels in the THW period. 100% of the patients had concordant qualitative results of the scans within two periods in three groups. Symptoms of hypothyroidism were relieved in the SNA001 period compared with THW period, though there was no significant difference in most of the scale scores. There were no serious adverse events related to SNA001, the most common adverse event were gastrointestinal symptoms, of mild and transient nature.Thus, SNA001 promises to be a safe and effective method to stimulate iodine-131 uptake and Tg secretion during monitoring and ablation for DTC without the disadvantages of incidental hypothyroidism.

Key Points Common progenitor cells exist in clonally related concomitant chronic lymphocytic leukemia and acute myeloid leukemias. CLL cells dedifferentiated to clonally related myeloid cells posttransplantation.

OBJECTIVES This study aimed to investigate the diagnostic value of ultrasound in children with perforation of congenital choledochal cysts. METHODS Eligible patients recruited from January 2004 to December 2018 in our hospital were enrolled in this retrospective study. A total of 59 cases of congenital choledochal cysts with perforation were defined as the perforation group, and 100 cases of congenital choledochal cysts without perforation with similar symptoms were defined as the control group. Clinical features were analyzed and compared between the groups. The differential efficacy of varied diagnostic criteria was evaluated by a receiver operating characteristic analysis. RESULTS Significant differences were found between the groups with respect to clinical characteristics (abdominal pain, vomiting, fever, and abdominal distention; all P

Background: Primary open-angle glaucoma (POAG) is a very common disorder, and it is the second leading cause that results in blindness worldwide after cataracts. Previous studies have reported that dorzolamide/timolol-fixed combination (DTFC) can be used in treating POAG. However, there are still inconsistent results. Thus, this study will systematically investigate the efficacy and safety of DTFC on POAG. Methods: A comprehensive search will be carried out in Cochrane Library, MEDLINE, EMBASE, CINAHI, ACMD, China National Knowledge Infrastructure, and WANGFANG database from origin to the present. There are no limitations related to the language and publication status. Only randomized controlled trials that assessed the efficacy and safety of DTFC for the treatment of POAG will be included. Two researchers will independently undertake record selection, data extraction, and study quality assessment. Any divisions will be solved by discussion with a third researcher. We will perform statistical analysis using RevMan 5.3 software Results: This study will summarize the present evidence to identify the efficacy and safety of DTFC in treating POAG through mean intraocular pressure, best corrected visual acuity, contrast sensitivity, bioelectric activity of the retina, rate of progression of glaucoma, quality of life, and adverse events. Conclusions: The results of this study will provide evidence of DTFC for the treatment of POAG. Systematic review registration: INPLASY202040120.

We report a rare case of pancreatic collision tumor of solid pseudopapillary tumor and neuroendocrine tumor in a 43-year-old woman. A pancreatic mass was found by abdominal ultrasound. A mainly cystic mass with solid component progressive enhancement was revealed using abdominal enhanced CT. Staging 18F-FDG PET/CT demonstrated a pancreatic tail mass with an increased uneven 18F-FDG uptake. Distal pancreatectomy was performed. Postoperatively, the mass was diagnosed as pancreatic collision tumor of solid pseudopapillary tumor and neuroendocrine tumor.

To develop and validate a nomogram that incorporates the gallbladder morphology, hepatic elasticity, and demographic information for the prediction of biliary atresia (BA) in children.A total of 294 consecutive patients under the age of 70 days with cholestasis and suspected symptoms of BA were enrolled in this study, who were divided into a training cohort (150 patients) and a validation cohort (144 patients). Ultrasonography and two-dimensional shear wave elastography were performed for each patient prior to knowing the final diagnosis. Multivariate logistic regression was used to analyze the gallbladder morphologic feature in the sonogram (absence of gallbladder, small gallbladder, lower postprandial gallbladder contractibility, or abnormal gallbladder wall), hepatic elasticity and clinical data from the training cohort, and a diagnostic nomogram for BA was subsequently developed. The performance of the nomogram was respectively evaluated with respect to the discrimination and calibration in every cohort.The multivariate analysis showed that the factors of age (p = 0.009), gallbladder morphology (p = 0.001) and hepatic elasticity (p0.001) could serve as independent predictive factors to differentiate between BA and other causes of cholestasis. The nomogram incorporating these three parameters showed good discrimination and satisfactory calibration, indicating a better performance compared to using only the gallbladder morphologic features and hepatic elasticity. The observed area under the receiver operator characteristic curve in the training cohort and validation cohort was 0.939 (p0.001) and 0.942 (p0.001), respectively, with a sensitivity of 95.5% and a specificity of 83.4% in the combined cohort.The established nomogram shows a favored and improved predictive value for the diagnosis of BA.

Acute promyelocytic leukemia (APL) therapy involves the compounds cytotoxic to both malignant tumor and normal cells. Relapsed APL is resistant to subsequent chemotherapy. Novel agents are in need to kill APL cells selectively with minimal toxicity. DDX5 has been recognized to be a novel target to suppress acute myeloid leukemia (AML). However, the role of DDX5 remains elusive in APL. Here a DDX5-targeting fully human monoclonal autoantibody named after 2F5 was prepared. It is demonstrated that 2F5 selectively inhibited APL cell proliferation without toxicity to normal neutrophil and tissues. Moreover, 2F5 was confirmed to induce G0/G1 phase arrest in APL cells, and promote APL cell differentiation combined with decreased DDX5 expression and increased reactive oxygen species (ROS) production. Knockdown of DDX5 by siRNA also inhibited proliferation, promoted cell differentiation and enhanced ROS production in APL cells. However, the ROS inhibitor reversed the effects of 2F5 on DDX5 and ROS in APL cells. Thus, we conclude that DDX5-targeting 2F5 inhibits APL cell proliferation, and promotes cell differentiation via induction of ROS. 2F5 showed the therapeutic value of fully human monoclonal autoantibody in APL, which provides a novel and valid approach for treatment of relapse/refractory APL.

Background. Recently, P16INK4a expression has been shown to be correlated with cancer-specific survival (CSS) in penile squamous cell carcinoma (SCC). Therefore, we performed this meta-analysis to clarify the prognostic value of P16INK4a for penile SCC. Methods. A systematic search was performed in PubMed, Embase, and Web of Science to identify all relevant articles up to May 25, 2017. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of included studies were pooled to estimate the prognostic value. Trial sequential analysis (TSA) was performed to assess the quantity and strength of survival evidence. Results. Five retrospective studies consisting of 323 cases were finally included. We found that P16INK4a positive expression was significantly associated with a better CSS of penile SCC (HR=0.45, 95%CI: 0.30-0.67, P Conclusions. P16INK4a positive expression is independently associated with improved CSS for patients with penile SCC.

A 48-year-old woman was experiencing abdominal pain and melena for 3 months. Because of these symptoms combined with increased level of tumor marker CA125, possible abdominal malignancy was considered, and an FDG PET/CT was performed to assess occult tumor. The images revealed multiple hypermetabolic lesions along the peritoneal surface. Pathological examination after biopsy demonstrated low-grade epithelioid peritoneal mesothelioma.

SUMMARY Canonical NF-κB signaling is constitutively activated in acute myeloid leukemia (AML) stem cells and is required for maintenance of the self-renewal of leukemia stem cells (LSCs). However, any potential role for NF-κB non-canonical signaling in AML has been largely overlooked. Here, we report that stabilization of NF-κB-inducing kinase (NIK) suppresses AML. Mechanistically, stabilization of NIK activates NF-κB non-canonical signaling and represses NF-κB canonical signaling. In addition, stabilization of NIK-induced activation of NF-κB non-canonical signaling upregulates Dnmt3a and downregulates Mef2c, which suppresses and promotes AML development, respectively. Importantly, by querying the connectivity MAP using up- and downregulated genes that are present exclusively in NIK-stabilized LSCs, we discovered that verteporfin has anti-AML effects, suggesting that repurposing verteporfin to target myeloid leukemia is worth testing clinically. Our data provide a scientific rationale for developing small molecules to stabilize NIK specifically in myeloid leukemias as an attractive therapeutic option., Graphical abstract

Quantification of anti-HBs and anti-HBc predicts the risk of HBV reactivation (HBVr) in lymphoma patients receiving rituximab treatment. However, it remains unclear whether the quantification is predictive of HBVr in leukemia patients undergoing immunosuppression.and patients: Clinical and laboratory data of the leukemia patients with resolved HBV infection diagnosed between January 2013 and March 2018 were retrospectively collected. Data series of HBV seromarkers and HBV DNA levels before the patients receiving chemotherapy and/or hematopoietic stem cell transplantation (HSCT) and during follow-up duration were analyzed.In total, 533 leukemia patients with resolved HBV infection were included. The incidences of HBVr were 5.7% (25/441) and 2.2% (2/92) in patients receiving HSCT and chemotherapy, respectively. In patients receiving HSCT, acute lymphoid leukemia had a significantly higher incidence of HBVr than acute myeloid leukemia (8.9% vs 3.9%, P 0.05). The incidence varied almost zero to 40% due to the differences in the profiles of HBV antibodies. High anti-HBs (cut-off of 79.2 IU/L) or low anti-HBc levels (cut-off of 4.475, S/CO) at baseline were associated with a low risk of HBVr. Anti-HBe status did not affect the incidence of HBVr. However, the cut-offs were only predictive of HBVr in the patients who had negative anti-HBe.The baseline profiles of HBV antibodies are predictive of the risk of HBVr in leukemia patients undergoing immunosuppression. However, seronegative anti-HBe is a prerequisite for using baseline anti-HBs and anti-HBc quantification to predict HBVr risk.

Meckel diverticulum is one of the most important causes of small bowel bleeding in children. Reports suggest that ultrasonography can be used as an alternative examination for children with negative radionuclide scanning results or children with atypical clinical manifestations. To evaluate the diagnostic accuracy of high-frequency ultrasound in children with bleeding Meckel diverticulum. We collected the data of children who were admitted to our hospital for the main symptom of bloody stool from February 2006 to December 2017. Ultrasonography was performed in all children. The final diagnosis was confirmed by pathological analysis or clinical follow-up observation. We evaluated the diagnostic performance of ultrasonography according to the final diagnosis. A total of 784 eligible children were enrolled in the study. Presenting symptoms or findings included black and red stool in 528 (67.3%), bright red stool in 51 (6.5%) and obscure or occult bloody stool in 205 (26.1%). Anemia was diagnosed in 489 (62.4%). Ultrasonography diagnosed Meckel diverticulum with a sensitivity of 93.6% (95% confidence interval [CI] 91.0–95.6%) and a specificity of 98.1% (95% CI 95.9–99.3%). High-frequency ultrasound diagnosis of Meckel diverticulum in children has high sensitivity and specificity.

Elevated expression of autoantibodies is a hallmark of immune dysregulation in glaucoma and may cause retinal ganglion cell apoptosis and immune-mediated nerve damage, thus contributing to the development of blindness. The cause of autoantibody upregulation remains unclear. Th17 cells are shown to promote autoimmunity and Ig production. Here, we demonstrate that the serum levels of interleukin (IL)-17A and IL-21 are comparable between glaucoma patients and non-glaucoma controls. However, the levels of Th17-promoting cytokines, such as tumour necrosis factor (TNF) IL-6, are higher in glaucoma patients than in controls. Subsequently, we demonstrate that glaucoma patients present upregulated levels of Th17 cells that are quiescent directly ex vivo. Interestingly, compared to the Th17 cells from non-glaucoma subjects, the Th17 cells from glaucoma patients present similar IL-17A production capacity but significantly higher IL-21 production capacity. Given that IL-21 is also described as a specific cytokine of follicular helper T cells, the Ig production by B cells following co-incubation with circulating Th17 cells is investigated. Th17 cells from glaucoma patients present significantly enhanced potential to promote Ig production than the Th17 cells from controls. Both glaucoma patient Th17 cells and control Th17 cells require IL-17A and IL-21 for Ig production. Overall, results from this study suggest that Th17 cells from glaucoma patients present elevated capacity to stimulate Ig production.

Tamoxifen resistance presents a prominent clinical challenge in endocrine therapy for hormone sensitive breast cancer. However, the underlying mechanisms that contribute to tamoxifen resistance are not fully understood. In this study, we established a tamoxifen resistant MCF-7 cell line (MCF-7-Tam-R) by continuously incubating MCF-7 cells with 4-OH-tamoxifen. We found that melanoma cell adhesion molecule (MCAM/CD146), a unique epithelial-to-mesenchymal transition (EMT) inducer, was significantly up-regulated at both mRNA and protein levels in MCF-7-Tam-R cells compared to parental MCF-7 cells. Mechanistic research demonstrated that MCAM promotes tamoxifen resistance by transcriptionally suppressing ER alpha expression and activating the AKT pathway, followed by induction of EMT. Elevated MCAM expression was inversely correlated with recurrence-free and distant metastasis-free survival in a cohort of 4142 patients with breast cancer derived from a public database, particularly in the subgroup only treated with tamoxifen. These results demonstrate a novel function of MCAM in conferring tamoxifen resistance in breast cancer. Targeting MCAM might be a promising therapeutic strategy to overcome tamoxifen resistance in breast cancer patients. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.

Alzheimer's disease (AD) is a progressive disease and the predominant cause of dementia. Common symptoms include short-term memory loss, and confusion with time and place. Individuals with AD depend on their caregivers for assistance, and may pose a burden to them. The acetylcholinesterase (AChE) enzyme is a key target in AD and inhibition of this enzyme may be a promising strategy in the drug discovery process. In the present study, an inhibitory assay was carried out against AChE using total alkaloidal plants and herbal extracts commonly available in vegetable markets. Subsequently, molecular docking simulation analyses of the bioactive compounds present in the plants were conducted, as well as a protein‑ligand interaction analysis. The stability of the docked protein‑ligand complex was assessed by 20 ns molecular dynamics simulation. The inhibitory assay demonstrated that Uncaria rhynchophylla and Portulaca oleracea were able to inhibit AChE. In addition, molecular docking simulation analyses indicated that catechin present in Uncaria rhynchophylla, and dopamine and norepinephrine present in Portulaca oleracea, had the best docking scores and interaction energy. In conclusion, catechin in Uncaria rhynchophylla, and dopamine and norepinephrine in Portulaca oleracea may be used to treat AD.

A 69-year-old woman had gradually worsening abdominal discomfort over a year. A pancreatic mass was revealed by abdominal CT. The patient underwent FDG PET/CT for staging, which demonstrated the hypermetabolic pancreatic mass with multiple liver metastases. The lesion was pathologically confirmed as pancreatic adenosquamous carcinoma after biopsy.

More and more evidence indicates that circular RNAs (circRNAs) have important roles in several diseases, especially in cancers. However, their involvement remains to be investigated in breast cancer. Through screening circRNA profile, we identified 235 differentially expressed circRNAs in breast cancer. Subsequently, we explored the clinical significance of two circTADA2As in a large cohort of triple-negative breast cancer (TNBC), and performed functional analysis of circTADA2A-E6 in vitro and in vivo to support clinical findings. Finally, we evaluated the effect of circTADA2A-E6 on miR-203a-3p and its target gene SOCS3. We detected two circRNAs, circTADA2A-E6 and circTADA2A-E5/E6, which were among the top five differentially expressed circRNAs in breast cancer. They were consistently and significantly decreased in a large cohort of breast cancer patients, and their downregulation was associated with poor patient survival for TNBC. Especially, circTADA2A-E6 suppressed in vitro cell proliferation, migration, invasion, and clonogenicity and possessed tumor-suppressor capability. circTADA2A-E6 preferentially acted as a miR-203a-3p sponge to restore the expression of miRNA target gene SOCS3, resulting in a less aggressive oncogenic phenotype. circTADA2As as promising prognostic biomarkers in TNBC patients, and therapeutic targeting of circTADA2As/miRNA/mRNA network may be a potential strategy for the treatment of breast cancer.

Background Melanoma is defined as a highly mutational heterogeneous disease containing numerous alternations of the molecule. However, due to the phenotypically and genetically heterogeneity of malignant melanoma, conventional clinical characteristics remain restricted or limited in the ability to accurately predict individual outcomes and survival. This study aimed to establish an accurate gene expression signature to predict melanoma prognosis. Methods In this study, we established an RNA sequencing-based 12-gene signature data of melanoma patients obtained from 2 independent databases: the Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. We evaluated the quality of each gene to predict survival conditions in each database by employing univariate and multivariate regression models. A prognostic risk score based on a prognostic signature was determined. This prognostic gene signature further classified patients into low-risk and high-risk groups. Results Based on a prognostic signature, a prognostic risk score was determined. This prognostic gene signature further divided the patients into low-risk and high-risk groups. In the chemotherapy and radiotherapy groups of the TCGA cohort and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) expression group in the GEO cohort, patients in the low-risk group had a longer survival duration compared to patients in the high-risk group. Nevertheless, the immunotherapy group in the TCGA database and neuroblastoma RAS viral oncogene homolog (NRAS) expression group in the GEO database had no significant differences in statistics. Moreover, this gene signature was associated with patient prognosis regardless of whether the Breslow depth was greater than or less than 3.75 mm. Stratified gene set enrichment analysis (GSEA) revealed that certain immune-related pathways, such as the T-cell signaling pathway, chemokine signaling pathway, and primary immunodeficiency, were significantly enriched in the low-risk group of both TCGA and GEO cohorts. This information implied the immune-related properties of the 12-gene signature. Conclusions Our study emphasizes the significance of the gene expression signature in that it may be an indispensable prognostic predictor in melanoma and has great potential for application in personalized treatment.

Thyroid metastasis from hepatocellular carcinoma (HCC) is very rare. We present a case of a 41-year-old man with a markedly elevated serum α-fetoprotein (2,297 ng/mL) and a left neck mass 6 months after a hepatolobectomy for a primary HCC. F-FDG PET/CT imaging showed a focal uptake in the left thyroid lobe corresponding to a mass. The patient underwent a left hemithyroidectomy. Subsequent pathology confirmed HCC metastasis to the thyroid.

Inflammaging induces osteoporosis by promoting bone destruction and inhibiting bone formation. TRAF3 limits bone destruction by inhibiting RANKL-induced NF-κB signaling in osteoclast precursors. However, the role of TRAF3 in mesenchymal progenitor cells (MPCs) is unknown. Mice with TRAF3 deleted in MPCs develop early onset osteoporosis due to reduced bone formation and enhanced bone destruction. In young mice TRAF3 prevents β-catenin degradation in MPCs and maintains osteoblast formation. However, TRAF3 protein levels decrease in murine and human bone samples during aging when TGFβ1 is released from resorbing bone. TGFβ1 induces degradation of TRAF3 in murine MPCs and inhibits osteoblast formation through GSK-3β-mediated degradation of β-catenin. Thus, TRAF3 positively regulates MPC differentiation into osteoblasts. TRAF3 deletion in MPCs activated NF-κB RelA and RelB to promote RANKL expression and enhance bone destruction. We conclude that pharmacologic stabilization of TRAF3 during aging could treat/prevent age-related osteoporosis by inhibiting bone destruction and promoting bone formation., Increased inflammation during ageing promotes osteoporosis by activating osteoclast function and inhibiting osteoblasts. Here, the authors show that TGFβ1 release from bone matrix during ageing induces degradation of TRAF3 in mesenchymal progenitor cells, leading to reduced osteoblast differentiation and increased osteoclast formation, and suggesting that pharmacological stabilization of TRAF3 could ameliorate age-related osteoporosis.

A 41-year-old woman presented with abdominal distention, inappetence, and rapid emaciation for 1 month. Diffuse bulky gastric wall thickening with lymph nodes enlargement and peritoneal nodules were revealed using abdominal CT. Staging F-FDG PET/CT performed after admission demonstrated intensely diffuse FDG uptake in stomach, FDG-avid lymph nodes, and peritoneal nodular lesions. Postoperatively, these lesions were diagnosed as diffuse large B-cell lymphoma.

This study attempted to evaluate the feasibility of 99m Tc-labeled glucarate ( 99m Tc-GLA) imaging in non-small cell lung cancer (NSCLC) and the potential tumor uptake mechanism. Cell lysates from two NSCLC cell lines, H292 and H1975, were immunoblotted with anti-glucose transporter 5 (GLUT5) antibody for Western blotting. Thereafter, the two cell lines were used to examine cellular uptake of 99m Tc-GLA with or without fructose. SPECT/CT imaging studies were performed on small animals bearing H292 and H1975 tumors. Biodistribution studies were also conducted to achieve accurate tissue uptake of this tracer in two tumor models. Hematoxylin & eosin (H&E) staining and GLUT5, Ki67 and cytokeratin-7 (CK-7) immunohistochemistry (IHC) analysis were further investigated on tumor tissues. In Western blotting, H292 cells showed higher levels of GLUT5 compared to the H1975 cells. Meanwhile, the in vitro cell assays indicated GLUT5-dependent uptake of 99m Tc-GLA in H292 and H1975 cells. The fructose competition assays showed a significant decrease in 99m Tc-GLA uptake by H292 and H1975 cells when fructose was added. The 99m Tc-GLA accumulation was as much as two-fold higher in H292 implanted tumors than in H1975 implanted tumors. 99m Tc-GLA exhibited rapid clearance pharmacokinetics and reasonable uptake in human NSCLC H292 (1.69±0.37 ID%/g) and H1975 (0.89±0.06 ID%/g) implanted tumors at 30min post injection. Finally, the expression of GLUT5, Ki67 and CK-7 on tumor tissues also exhibited positive correlation with the in vitro cell test results and in vivo SPECT/CT imaging results in xenograft tumors. Both in vitro and ex vivo studies demonstrated that the uptake of 99m Tc-GLA in NSCLC is highly related to GLUT5 expression. Imaging and further IHC results support that 99m Tc-GLA could be a promising SPECT imaging agent for NSCLC diagnosis and prognosis evaluation.

Seven ideal health metrics were defined by AHA to monitor cardiovascular health. This study aimed to investigate the impact of ideal cardiovascular health behaviors and factors on the development of hypertension in prehypertensive subjects.Thirty-two thousand eight-hundred and eighty-seven participants with prehypertension were included in the study after excluding for preexisting stroke, myocardial infarction or malignancy. Cox proportional hazards regression was used to calculate hazard ratios and 95% confidence intervals [CI] for the development of hypertension.During a follow-up of 52.2 months, 15,500 prehypertensive participants developed hypertension. The cumulative incidence of hypertension decreased with the number of ideal health metrics increased. It was 78.61%, 71.08%, 63.15%, 56.07% and 61.62% in prehypertensive individuals carrying ≤ 1, 2, 3, 4 and ≥ 5 ideal health behaviors or factors, respectively. After adjustment for age, gender, family history of hypertension, alcohol consumption, resting heart rate, plasma triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein, the risk ratios of incident hypertension in the subjects who carried 2, 3, 4, and ≥ 5 ideal health metrics were 0.833 (95%CI: 0.789-0.880), 0.710 (95%CI: 0.672-0.749), 0.604 (95%CI: 0.568-0.642), and 0.581 (95%CI: 0.524-0.643), respectively, in comparison to those with ≤ 1 ideal health metric. A similar trend was also observed in male and female populations. Poor health metrics, including body mass index, diet (salt intake), physical activity, total cholesterol, and smoking, were predictors for the development of hypertension in prehypertensive individuals.Ideal cardiovascular health behaviors and factors are protective factors to prevent the progression from prehypertension to hypertension.

To investigate the relationship between relapse and the levels of the residual amount of HBV DNA in serum at cessation in chronic hepatitis B patients meeting 2008 Asian Pacific Association for the Study of the Liver (APASL) nucleos(t)ide analogs (NAs) cessation criteria.A total of 72 chronic hepatitis B patients who took NAs and had reached 2008 APASL cessation criteria entered the study. Patients were followed up for 6 months or longer after antiviral therapy was stopped. Serum HBV DNA level at cessation was detected by a highly sensitive polymerase chain reaction assay with detection limitation of 2 IU/mL.Of all the 72 patients, 42 patients (65.3%) relapsed after NA cessation. The detectable rate of the trace amount of HBV DNA at cessation was 41.7% by highly sensitive polymerase chain reaction reagents. The detectable rate of patients with consolidation treatment duration of18 months was higher than that with consolidation duration of ≥18 months (47.5% vs. 15.4%, P=0.034), and the detectable rate of patients with HBeAg seroconversion within 6 months of treatment was lower than that of ≥6 months (25.0% vs. 61.5%, P=0.036). The residual amount of HBV DNA and detectable rate at cessation showed significant differences between relapsed and nonrelapsed patients (130.4±420.90 vs 44.6±155.16 IU/mL, P=0.004; 55.3% vs. 16.0%, P=0.001). The cutoff value predicting relapse was 2.24 IU/mL, with a sensitivity of 0.553 and specificity of 0.840.Residual amount of HBV DNA in serum at NA cessation is associated with HBV relapse. The cutoff value predicting relapse was 2.24 IU/mL, with a sensitivity of 0.553 and specificity of 0.840.

A 32-year-old woman presented with 3 months' history of rapid enlargement of the left breast and superficial ulceration. Staging F-FDG PET/CT performed after admission demonstrated a hypermetabolic mass in the left breast, with smaller hypermetabolic areas in the left axillary and internal mammary lymph nodes, as well as in the sternum. Postoperatively, the mass was diagnosed as metaplastic squamous cell carcinoma of the breast.

Background Renal arteriovenous malformation is an aberrant vascular connection between the renal artery and vein. Acquired renal arteriovenous malformation (arteriovenous fistulae) accounts for approximately 70% of renal arteriovenous abnormalities. Congenital renal arteriovenous malformation, relatively rare, can result in significant hematuria which may require arterial embolization or nephrectomy. Case presentation A 64-year-old Asian man presented to the Urology department in our hospital with gradual left scrotal swelling for 2 years. Ultrasound and computed tomography showed an irregular mass in the upper pole of his left kidney. Digital subtraction angiography confirmed cirsoid-type left renal arteriovenous malformation combined with left renal vein ostial stenosis. After digital subtraction angiography and selective segmental renal artery embolization, the varicocele was obviously alleviated. Conclusions The etiology diagnosis of varicocele is not always straightforward, and renal arteriovenous malformation should be considered in the differential diagnosis of varicocele and renal mass. Renal arteriovenous malformation is difficult to distinguish from renal tumor according to varicocele and computed tomography presentation, while magnetic resonance imaging and digital subtraction angiography help to make a definite diagnosis and selective renal angiographic embolization is one of the best treatments for renal arteriovenous malformation.

Fibronectin (FN) is a widely expressed molecule that can participate in development of osteoarthritis (OA) affecting cartilage, meniscus, and synovial membrane (SM). The alternatively spliced isoforms of FN in joint tissues other than cartilage have not been extensively studied previously. The present study compares FN splice variation in patients with varying degrees of osteoarthritic change. Joint tissues were collected from asymptomatic donors and patients undergoing arthroscopic procedures. Total RNA was amplified by PCR using primers flanking alternatively spliced Extra Domain A (EDA), Extra Domain B (EDB) and Variable (V) regions. EDB+, EDB− and EDA− and V+ variants were present in all joint tissues, while the EDA+ variant was rarely detected. Expression levels of EDB+ and EDV+ variants were similar in cartilage, synovium, and meniscal tissues. Synovial expression of V+ FN in arthroscopy patients varied with degree of cartilage degeneration. Two V− isoforms, previously identified in cartilage, were also present in SM and meniscus. Fibronectin splicing in meniscus and SM bears striking resemblance to that of cartilage. Expression levels of synovial V+ FN varied with degree of cartilage degeneration. V+ FN should be investigated as a potential biomarker of disease stage or progression in larger populations. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:556–562, 2015.

A 73-year-old man presented with fatigue and anorexia and underwent FDG PET/CT scan to evaluate a right lung nodule revealed by a chest CT. The FDG PET/CT not only showed that the lung nodule was hypermetabolic but also revealed that there was significantly increased activity in the region of the duodenum. The findings were suspected as primary duodenal malignancy with metastases. However, an upper gastrointestinal tract endoscopic examination with further culture led to a diagnosis of duodenal cryptococcosis.

This study retrospectively evaluated the effect of lutein supplement (LS) on patients with non-proliferative diabetic retinopathy (NPDR). A total of 72 patients with NPDR were included in this study. All patients received Zeaxanthin during the study period. In addition, 36 patients also received LS and were assigned to the treatment group, while the other 36 patients did not receive LS and were assigned to the control group. All patients were treated for a total of 4 months. The endpoints included visual acuity (VA), contrast sensitivity (CS), and glare sensitivity (GS). In addition, any adverse events were also assessed. All endpoints were measured before and after 4-month treatment. Before treatment, there were no significant differences in VA (P = .75), CS (P = .71), and GS (P = .73) between two groups. After 4-month treatment, there were still no significant differences in all endpoints of VA (P = .66), CS (P = .58), and GS (P = .61) between two groups. No adverse events were recorded in either group. The results of this retrospective study showed that LS may not benefit for patients with NPDR after 4-month treatment. More high quality randomized controlled trials should still be needed to warrant the results of this study.

Background Numerous studies have reported the efficacy of fenofibrate for patients with diabetic retinopathy (DRP). No systematic review has, however, addressed its efficacy for DRP. Thus, this systematic review will firstly evaluate the efficacy and safety of fenofibrate for patients with DRP. Methods This study will search the following databases: PUMBED, EMBASE, CINAHI, ACMD, CENTRAL, CBM, CNKI, VIP, and WANGFANG, along with grey literature from inception to the present. We will accept randomized controlled trials on evaluating the efficacy and safety of fenofibrate for DRP. The primary outcome is the progression of DRP. The secondary outcomes are vision loss, development of diabetic macular edema, aggravation of hard exudates, quality of life, and any adverse events. Methodological quality of each included study will be assessed by using Cochrane Collaboration risk of bias tool. In addition, Grading of Recommendations Assessment, Development and Evaluation tool will also be used to evaluate the overall strength of the evidence. Two independent reviewers will conduct all procedures of study selection, data extraction, and methodological assessment. Any disagreements will be consulted with a third reviewer. RevMan 5.3 software will be used to pool data and to carry out the meta-analysis if it is possible. Results In present study, we anticipate to find a considerable number of published studies presenting evidence on efficacy and safety of fenofibrate for DRP. Conclusion The findings of this systematic review will provide latest evidence of fenofibrate for patients with DRP. Dissemination and ethics The findings of this scoping review will be disseminated in print, conferences, or by peer-reviewed journals. No ethical approval is needed for this systematic review, because it is a literature-based study. Systematic review registration PROSPERO CRD42019121869.

Background Previous clinical trials have reported that ranibizumab can be used to treat diabetic retinopathy (DR) effectively. However, no study has been conducted to evaluate its efficacy for patients with DR systematically. Thus, this study will specifically and systematically assess the efficacy and safety of ranibizumab for DR. Methods Cochrane Library, EMBASE, PUBMED, Web of Science, Google Scholar, Cumulative Index to Nursing and Allied Health Literature, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database will be searched from inceptions to the March 20, 2019 for studies related to the topic. This study will only consider publicly released randomized controlled trials for evaluating the effect and safety of ranibizumab for DR. No language restrictions will be imposed for all databases search. Methodological quality of each included trial will be assessed by Cochrane risk of bias tool. Statistical analysis will be performed by Stata 12.0 software. Results This study will provide recent summary evidence of ranibizumab for DR. Primary outcomes include percentages with retinopathy improvement, and cumulative probabilities for retinopathy worsening. Secondary outcome consist of visual function, best-corrected visual acuities, central subfield thickness, total macular volume, peripheral visual field loss, retinal neovascularization, and adverse events. Conclusion The findings of this study may provide theoretical basis for clinical practice refer and may benefit more patients with DR.

The predictive value of cumulative blood pressure (BP) on all-cause mortality and cardiovascular and cerebrovascular events (CCE) has hardly been studied. In this prospective cohort study including 52,385 participants from the Kailuan Group who attended three medical examinations and without CCE, the impact of cumulative systolic BP (cumSBP) and cumulative diastolic BP (cumDBP) on all-cause mortality and CCEs was investigated. For the study population, the mean (standard deviation) age was 48.82 (11.77) years of which 40,141 (76.6%) were male. The follow-up for all-cause mortality and CCEs was 3.96 (0.48) and 2.98 (0.41) years, respectively. Multivariate Cox proportional hazards regression analysis showed that for every 10 mm Hg·year increase in cumSBP and 5 mm Hg·year increase in cumDBP, the hazard ratio for all-cause mortality were 1.013 (1.006, 1.021) and 1.012 (1.006, 1.018); for CCEs, 1.018 (1.010, 1.027) and 1.017 (1.010, 1.024); for stroke, 1.021 (1.011, 1.031) and 1.018 (1.010, 1.026); and for MI, 1.013 (0.996, 1.030) and 1.015 (1.000, 1.029). Using natural spline function analysis, cumSBP and cumDBP showed a J-curve relationship with CCEs; and a U-curve relationship with stroke (ischemic stroke and hemorrhagic stroke). Therefore, increases in cumSBP and cumDBP were predictive for all-cause mortality, CCEs, and stroke.

The diagnosis of adult onset Still's disease (AOSD) is non‑specific, and requires the exclusion of other diseases including infectious, inflammatory and malignant diseases. The current study aimed to summarize the imaging characteristics of fluorodeoxyglucose (18F‑FDG) positron emission tomography (PET)/computerized tomography (CT) in patients with AOSD. The 18F‑FDG PET/CT characteristic observations of 32 patients with definite AOSD were retrospectively reviewed based on visual interpretation and the semi‑quantitative index of standard uptake value of maximum (SUVmax). Among 32 patients, no normal case was observed. Abnormal FDG accumulation by the spleen, bone marrow and lymph nodes was the main observation of the PET/CT images. Totals of 27 (84.4%) and 26 cases (81.3%) were identified with diffusely elevated FDG uptake by the spleen and bone marrow, respectively, and the average SUVmax was 4.2±1.1 and 4.6±0.6, respectively. A total of 20 cases (62.5%) showed lymphadenopathy with FDG uptake, with the range of SUVmax from 2.2‑13.9. In addition, 7 patients (21.9%) were observed to exhibit effusion without FDG uptake, 1 case presented with abnormal FDG uptake by the skin, and another by the right shoulder joint. In addition, no abnormally elevated FDG uptake by the liver or large vessels was observed. Due to non‑specific imaging features, 18F‑FDG PET/CT could not be directly helpful in diagnosing AOSD. However, 18F‑FDG PET/CT serves important roles in evaluating the involved extent of AOSD, and guiding the biopsy of lymph nodes, bone marrow or other tissues, which may aid in the development of novel clinical management strategies.

Endometriosis is a common multifactorial disease caused by an interaction between multiple gene loci and environment. Four genome-wide association studies (GWASs) of endometriosis have identified several single-nucleotide polymorphisms (SNPs) associated with endometriosis. However, results from independent replication studies with different populations are inconsistent. The present study aims to evaluate whether the GWAS-derived susceptibility loci are correlated with the risk of the development of ovarian endometriosis in North Chinese women. This case-control study comprised 580 patients with ovarian endometriosis and 606 matched control women. Three SNPs were selected for this association study including rs10965235 in CDKN2BAS, rs2235529 located in LI NC00339-WNT4, and rs 12700667 in an intergenic region on 7p 15.2. The results show that the G/A genotype of rs 12700667 can significantly increase the risk of developing ovarian endometriosis when compared with the G/G genotype (odds ratio [OR] = 1.57, 95% confidence interval [CI] = 1.23–2.00). Similarly, the carriers with A allele showed a higher risk of ovarian endometriosis than those with G allele (OR = 1.23, 95% CI = 1.12–1.68). The study suggests that the endometriosis-associated genetic polymorphisms (rs 12700667) from GWAS be associated with the risk of developing ovarian endometriosis in North Chinese women.

To investigate the mechanism and prognosis of occult hepatitis B virus (HBV) infection (OBI) at a molecular level among healthy young adults, the presence of HBV DNA in 1176 sera samples collected from healthy young people after neonatal vaccination was assessed by nested polymerase chain reaction (PCR) using specific primers designed for the X and S regions of the HBV genome. Full-length HBV DNA from 9 patients with OBI (OB1-OB9) was cloned and sequenced. Deletions in the pre-S, basal core promoter (BCP), core (C) and polymerase (P) regions were observed. The data indicate that there is still a substantial risk of OBI in China despite neonatal vaccination. All deletions that were observed in the pre-S, BCP, C and P regions play a direct or indirect role in OBI. The presence of a deletion mutation in the pre-S1 region was considered to play a pivotal role in hepatocarcinogenesis and was found to increase the risk of hepatocellular carcinoma in the cohorts studied.

OBJECTIVE To examine the intraocular pressure-lowering efficacy and safety of travoprost 0.004% and pilocarpine 1% in Chinese patients with primary angle-closure (PAC) and primary angle-closure glaucoma (PACG) after laser iridotomy in China. PATIENTS AND METHODS Thirty patients with PAC or PACG after laser iridotomy were randomized into this double-masked, parallel-group study. Qualified patients had a mean intraocular pressure (IOP) between 21 and 35 mm Hg; inclusive at 9 AM at eligibility visit and previously undergone laser peripheral iridotomy at least 30 days before screening visit. Patients were treated with travoprost 0.004% once daily or pilocarpine 1% 4 times daily for 12 weeks after appropriate washout of glaucoma medications. Efficacy and safety evaluations were conducted at weeks 4, 8, and 12. IOP measurements were performed at 9 AM and 4 PM at baseline and week 12 visits, except at the weeks 4 and 8, when the IOP measurement was undertaken respectively at 9 AM or 4 PM only. The degree and distribution of peripheral anterior synechiae was evaluated by gonioscopy at baseline and week 12, respectively. RESULTS Both the treatment groups showed statistically significant IOP reductions from baseline, except for the results of pilocarpine group at 4 PM in week 12. Travoprost demonstrated a statistically superior IOP reduction (7.6 mm Hg) compared with pilocarpine (1.9 mm Hg; P=0.04) at 4 PM over the 12-week period. There was no difference in peripheral anterior synechiae degree and distribution in week 12 from baseline for both treatment groups. No serious adverse event was found in both the groups. CONCLUSIONS Travoprost 0.004% once daily provides effective IOP-lowering efficacy with significantly greater IOP reduction from baseline when compared with pilocarpine 1% 4 times daily at 4 PM over the 12-week period. Travoprost 0.004% once daily is safe and well tolerated in PAC or PACG patients.

Despite the demonstrated clinical efficacy of CD20 monoclonal antibody (mAb) for lymphoma therapy, the in vivo mechanisms of tumor depletion remain controversial and variable. To identify the molecular mechanisms responsible for lymphoma killing by CD20 mAb in a homologous system amenable to mechanistic studies and genetic manipulation, a mouse lymphoma model was developed using primary tumor cells from a C57BL/6 Eμ-cMyc transgenic mouse and mouse antimouse CD20 mAbs. CD20 mAb treatment of syngeneic mice with adoptively transferred lymphomas prevented tumor development or significantly prolonged mouse survival depending on tumor volume, mAb dose, and treatment timing. Cooperative FcγRIV, FcγRIII, and FcγRI interactions mediated optimal lymphoma depletion by CD20 mAb in vivo, whereas clodronate-mediated depletion of macrophages eliminated the therapeutic benefit of CD20 mAb. Although CD20 mAbs activated complement in vitro and in vivo, normal and malignant B-cell depletion was induced through C1q- and C3-independent mechanisms. Thus, the ability of CD20 mAbs to deplete malignant B cells in vivo required FcγR-dependent use of the innate mononuclear cell immune system. These findings allow for mechanism-based predictions of the biologic outcome of CD20 mAb therapy and treatment optimization.

NOD mice deficient for B lymphocytes from birth fail to develop autoimmune or type 1 diabetes. To assess whether B cell depletion influences type 1 diabetes in mice with an intact immune system, NOD female mice representing early and late preclinical stages of disease were treated with mouse anti-mouse CD20 mAbs. Short-term CD20 mAb treatment in 5-wk-old NOD female mice reduced B cell numbers by ∼95%, decreased subsequent insulitis, and prevented diabetes in >60% of littermates. In addition, CD20 mAb treatment of 15-wk-old NOD female mice significantly delayed, but did not prevent, diabetes onset. Protection from diabetes did not result from altered T cell numbers or subset distributions, or regulatory/suppressor T cell generation. Rather, impaired CD4+ and CD8+ T cell activation in the lymph nodes of B cell-depleted NOD mice may delay diabetes onset. B cell depletion was achieved despite reduced sensitivity of NOD mice to CD20 mAbs compared with C57BL/6 mice. Decreased B cell depletion resulted from deficient FcγRI binding of IgG2a/c CD20 mAbs and 60% reduced spleen monocyte numbers, which in combination reduced Ab-dependent cellular cytotoxicity. With high-dose CD20 mAb treatment (250 μg) in NOD mice, FcγRIII and FcγRIV compensated for inadequate FcγRI function and mediated B cell depletion. Thereby, NOD mice provide a model for human FcγR polymorphisms that reduce therapeutic mAb efficacy in vivo. Moreover, this study defines a new, clinically relevant approach whereby B cell depletion early in the course of disease development may prevent diabetes or delay progression of disease.

Although intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy after hepatocellular carcinoma, there are limited data available on PET/CT imaging in ICC. This retrospective study analyzed the role of PET/CT imaging in the evaluation of ICC.FDG PET/CT findings were reviewed in 65 patients with histologically confirmed ICC. PET/CT was evaluated based on visual interpretation and the semiquantitative index of SUVmax and tumor-to-normal liver tissue ratio (TNR), which were consequently further analyzed and correlated with tumor localization, differentiation, size, and serum levels of tumor markers. Forty-five cases also underwent abdominal MRI examinations.Nineteen patients had hilar ICC, whereas 46 patients had peripheral ICC. Sixty cases of ICC showed elevated FDG uptake with an average SUVmax of 8.3 ± 4.7 and TNR of 3.1 ± 1.7. Five cases located in the hilum were false negative on PET/CT imaging. Compared with hilar ICC, SUVmax and TNR of peripheral ICC were significantly higher (P0.05). FDG accumulation correlated with the degree of ICC differentiation. SUVmax and TNR correlated with tumor size, whereas there was no correlation observed with serum levels of carbohydrate antigen 19-9. The sensitivity, specificity, and accuracy of PET/CT and MRI in the diagnosis of regional lymph node metastases were 70.0% versus 50%, 91.7% versus 83.3%, and 81.8% versus 68.2%, respectively. PET/CT upstaged 12.3% and downstaged 3.1% of cases and had no impact on patient management in the remaining 84.6% of cases.Combination of FDG PET/CT and abdominal MRI might improve the diagnostic accuracy for ICC.

INTRODUCTION Three-phase bone scintigraphy using technetium-99m-methylene diphosphonate is used to diagnose skeletal lesions, whereas single-photon emission computed tomography/computed tomography (SPECT/CT) improves the diagnostic accuracy of bone disease. We investigated the usefulness of SPECT/CT combined with three-phase bone scintigraphy over three-phase bone scintigraphy alone in assessing suspected bone tumors in patients with no malignant history. MATERIALS AND METHODS Forty-eight patients (30 men and 18 women; mean age, 43.3 ± 20.1 years; age range, 11-82 years) with suspected bone tumors who underwent technetium-99m-methylene diphosphonate three-phase bone scintigraphy and SPECT/CT between July 2008 and August 2013 were retrospectively reviewed. The lesion from each patient was resected or biopsied for pathological confirmation of the diagnosis within 3 weeks of the bone scan. All images were interpreted by two experienced nuclear medicine physicians who had not been involved in the selection of data for the present study. The reviewers were aware of the patient's sex, age, and the lesion's site but were unaware of the results of other imaging modalities, such as radiography, MRI, and laboratory tests. In cases of discrepancy regarding the interpretations, a consensus was reached after mutual discussion. The diagnostic ability of three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy was compared with pathological results using the χ(2)-(test, with P-values less than 0.05 indicating significant differences. Agreement between three-phase bone scintigraphy alone or SPECT/CT combined with three-phase bone scintigraphy with pathological results was evaluated using κ scores. RESULTS Pathological results from the 48 lesions of all patients revealed 32 malignant bone tumors and 16 benign lesions. On using three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy for the differential diagnosis of bone lesions, we found sensitivities to be 96.9 and 100%, specificities to be 31.2 and 81.3%, positive predictive values to be 73.8 and 91.4%, and negative predictive values to be 83.3 and 100%, respectively. The diagnostic accuracies of three-phase bone scintigraphy alone and SPECT/CT combined with three-phase bone scintigraphy were 75.0 and 93.8%, respectively (χ(2) = 5.057; P = 0.025). κ Scores for the agreement of three-phase bone scintigraphy and SPECT/CT combined with three-phase bone scintigraphy with pathological results were 0.333 (P = 0.005) and 0.850 (P < 0.0001), respectively. CONCLUSION Compared with three-phase bone scintigraphy, the diagnostic accuracy of SPECT/CT combined with three-phase bone scintigraphy was higher. SPECT/CT combined with three-phase bone scintigraphy is beneficial over three-phase bone scintigraphy for the differential diagnosis of suspected bone tumors in patients with no malignant history.

Immune complex (IC)-mediated tissue inflammation is controlled by stimulatory and inhibitory IgG Fc receptors (FcγRs). Systemic lupus erythematosus is a prototype of IC-mediated autoimmune disease; thus, imbalance of these two types of FcγRs is probably involved in pathogenesis. However, how and to what extent each FcγR contributes to the disease remains unclear. In lupus-prone BXSB mice, while stimulatory FcγRs are intact, inhibitory FcγRIIB expression is impaired because of promoter region polymorphism. To dissect roles of stimulatory and inhibitory FcγRs, we established two gene-manipulated BXSB strains: one deficient in stimulatory FcγRs (BXSB.γ−/−) and the other carrying wild-type Fcgr2b (BXSB.IIBB6/B6). The disease features were markedly suppressed in both mutant strains. Despite intact renal function, however, BXSB.γ−/− had IC deposition in glomeruli associated with high-serum IgG anti-DNA Ab levels, in contrast to BXSB.IIBB6/B6, which showed intact renal pathology and anti-DNA levels. Lymphocytes in BXSB.γ−/− were activated, as in wild-type BXSB, but not in BXSB.IIBB6/B6. Our results strongly suggest that both types of FcγRs in BXSB mice are differently involved in the process of disease progression, in which, while stimulatory FcγRs play roles in effecter phase of IC-mediated tissue inflammation, the BXSB-type impaired FcγRIIB promotes spontaneous activation of self-reactive lymphocytes and associated production of large amounts of autoantibodies and ICs.

Summary Background The diagnosis of primary cutaneous lymphoma (PCL) is currently based on clinical and histological findings and/or relatively invasive procedures such as bone marrow and fine-needle lymph node biopsies. Although computed tomography (CT) is a noninvasive imaging modality that is widely used for staging in patients with lymphoma, it cannot provide information about malignant cutaneous lesions. Objectives To investigate the usefulness of 18F-fluorodeoxyglucose (FDG)–positron emission tomography (PET) in the management of PCL. Methods We retrospectively analysed 31 FDG-PET studies in 19 patients with PCL [15 T-cell non-Hodgkin lymphoma (NHL) and four B-cell NHL]. There were 10 men and nine women (age range 23–84 years, mean ± SD 54 ± 16). Eleven FDG-PET studies were performed for initial staging and 20 FDG-PET studies were performed for restaging following therapy. Results of FDG-PET were compared with those of CT. Clinical parameters and/or biopsy results of lesions served as reference for the accuracy of PET and CT in evaluating local and metastatic lesions. Results For the initial staging, FDG-PET had a sensitivity of 82% for the evaluation of local disease and 80% for the detection of distant metastasis. The corresponding values for CT were 55% and 100%, respectively. For restaging of cutaneous lymphoma, FDG-PET had a sensitivity of 86% and specificity of 92% for local recurrence/residual disease and a sensitivity of 100% and specificity of 100% for distant metastasis. The corresponding values for CT were 50% and 83% for local recurrence/residual disease and 100% and 67% for distant metastasis. Conclusions FDG-PET has a potential value for initial staging and restaging following therapy in patients with PCL. FDG-PET has higher diagnostic value than CT in the detection both of local disease and distant metastasis.

Primary adrenal lymphoma is an extremely rare entity. Only 70 cases have been reported in the English literature. Most of the patients are elderly men with bilateral adrenal masses without extraadrenal involvement. The most common presenting symptoms are fever, weight loss, lumbar pain, and/or symptoms of adrenal insufficiency. Of the cases reported, CT, ultrasound, and MRI were the imaging modalities used to describe the lesions. FDG PET has been used successfully to differentiate benign and malignant adrenal masses. The authors report a 67-year-old man diagnosed as having primary bilateral adrenal lymphoma and having no evidence of extraadrenal spread who was evaluated from the time of diagnosis to complete remission with FDG PET scanning. The literature of this unusual neoplasm is reviewed in detail.

A 71-year-old man presented with a progressive right knee pain which persisted for 6 months and was not relieved by pain medications. He had a history of lung squamous carcinoma 1 year ago. X-ray and magnetic resonance imaging (MRI) revealed hyperostosis, degenerative changes, and occupancy lesions of the right patella. The patient underwent Tc methylene diphosphonate (Tc-MDP) bone scan and single photon emission tomography/computed tomography (SPECT/CT), which showed abnormal metabolism of the right patella with bone destruction and soft tissue swelling. Finally, patellectomy was taken and pathology confirmed patella metastasis from lung squamous carcinoma.