A Dual-Branch Fusion Network Based on Reconstructed Transformer for Building Extraction in Remote Sensing Imagery.

Automatic extraction of building contours from high-resolution images is of great significance in the fields of urban planning, demographics, and disaster assessment. Network models based on convolutional neural network (CNN) and transformer technology have been widely used for semantic segmentation of buildings from high resolution remote sensing images (HRSI). However, the fixed geometric structure and the local receptive field of the convolutional kernel are not good at global feature extraction, and the transformer technique with self-attention mechanism introduces computational redundancies and extracts local feature details poorly in the process of modeling the global contextual information. In this paper, a dual-branch fused reconstructive transformer network, DFRTNet, is proposed for efficient and accurate building extraction. In the encoder, the traditional transformer is reconfigured by designing the local and global feature extraction module (LGFE); the branch of global feature extraction (GFE) performs dynamic range attention (DRA) based on the idea of top-k attention for extracting global features; furthermore, the branch of local feature extraction (LFE) is used to obtain fine-grained features. The multilayer perceptron (MLP) is employed to efficiently fuse the local and global features. In the decoder, a simple channel attention module (CAM) is used in the up-sampling part to enhance channel dimension features. Our network achieved the best segmentation accuracy on both the WHU and Massachusetts building datasets when compared to other mainstream and state-of-the-art methods.

Umbilical cord mesenchymal stem cell transfusion ameliorated hyperglycemia in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a serious threat to human health and remains incurable. Insulin deficiency seems to be attributed to the progressive failure of pancreatic islet ß-cells and immune cells such as T cells mediated cytotoxicity may be involved in the loss of pancreatic islet ß-cells in T2DM. Targeting on the immune system to maintain functional activity of pancreatic islet ß-cells could be an attractive way to treat T2DM. Mesenchymal stem cells (MSCs) exert potent capacity of immunomodulation. MSCs have been successfully applied for the treatment of several types of autoimmune diseases. So, the aim of this study is to evaluate the safety and potential therapeutic effects of UMSC on T2DM. METHODS: UMSCs were separated, expanded, and identified on the basis of the previous description. 18 patients of T2DM were recruited according to our experimental protocol. UMSC was intravenously transfused three times. All patients were followed up in the first, third, and sixth month. Age, gender, diabetes duration and medications as well as weight, height, and BMI were recorded. Fasting plasma glucose (FPG), postprandial blood glucose (PBG), HbA1c, C-peptide, and subsets of T cells were measured. All adverse reactions were carefully documented. Effective criteria were made and data was analyzed using SPSS 19.0 software. RESULTS: UMSCs were successful obtained. Baseline clinical characteristics between the efficacy and inefficacy groups were not statistically different (p > 0.05). FBG and PBG of the patients in efficacy group were significantly reduced (p < 0.05) after UMSC transfusion. Plasma C-peptide levels and regulatory T (Treg) cell number in the efficacy group were numerically higher after UMSC transfusion; however, the difference of both parameters did not reach significance (p > 0.05). During the treatment course only 4 out of 18 patients (22.2%) had slight transient fever. Up to 6 months after UMSC transfusion, all patients continued to have a feeling of well-being and were physically more active. CONCLUSIONS: UMSC transfusion is safe and well tolerated, effectively alleviates blood glucose, and increases the generation of C-peptide levels and Tregs in a subgroup of T2DM patients. This pilot study provides fundamental data for further study of UMSC transfusion on control of blood glucose as well as morbidity of T2DM in a larger cohort.

Characterization of Th1- and Th2-associated chemokine receptor expression in spleens of patients with immune thrombocytopenia.

PURPOSE: In view of the numerous clinical observations and laboratory studies that suggest a critical role for the spleen in immune thrombocytopenia (ITP) pathophysiology, we aimed to characterize Th1-associated chemokine receptors CXCR3 and CCR5 and Th2-associated chemokine receptor CCR3 in spleens of ITP patients and assess the significance of their differential expression in the clinical setting. METHODS: The histopathology of spleens was observed using hematoxylin-eosin staining (HE), and the positive rate of CXCR3, CCR5 and CCR3 expression in spleens of 24 ITP patients and 12 patients with traumatic splenic rupture as normal controls was detected by immunohistochemistry using the SP method. CXCR3, CCR5 and CCR3 protein expression was analyzed by Western blot and mRNA levels were investigated by real-time polymerase chain reaction (RT-PCR). RESULTS: Reactive hyperplasia could be seen in follicles of the white pulp, the germinal central zone was enlarged and the marginal zone was thickened, the central arteries were thickened and fibrotic, and the density of the capillary vessel was increased in ITP patients. ITP group displayed a higher rate of expression of Th1-associated chemokine receptors CXCR3 and CCR5 (83.3% vs. 75%, 100% vs. 83.3%) but lower rate of expression of Th2-associated chemokine receptor CCR3 (50% vs. 66.7%) compared with the controls (P < 0.05, respectively). Western blot analysis revealed that CXCR3 and CCR5 protein expression was significantly increased in ITP patients while CCR3 was significantly reduced (P < 0.05, respectively). Meanwhile, ITP patients displayed increased mRNA levels of CXCR3 and CCR5 but decreased gene expression of CCR3 (P < 0.05, respectively). CONCLUSION: The data suggested that the abnormal expression of Th1/Th2 chemokine receptors may participate in splenic immune disorder in patients with ITP. Using corresponding inhibitors may inhibit Th1-dominant expression and mitigate the progress of the disease.

Hemophagocytic lymphohistiocytosis after autologous stem cell transplantation in angioimmunoblastic T-cell lymphoma: A case report.

BACKGROUND: Angioimmunoblastic T-cell lymphoma (AITL), a unique subtype of peripheral T-cell lymphoma, has relatively poor outcomes. High-dose chemotherapy with autologous stem cell transplantation (ASCT) can achieve complete remission and improve outcomes. Unfortunately, subsequent T-cell lymphoma-triggered hemophagocytic lymphohistiocytosis (HLH) has a worse prognosis than B-cell lymphoma-triggered HLH. CASE SUMMARY: We here report a 50-year-old woman with AITL who achieved a favorable outcome after developing HLH 2 mo after receiving high-dose chemotherapy/ ASCT. The patient was initially admitted to our hospital because of multiple enlarged lymph nodes. The final pathologic diagnosis, made on biopsy of a left axillary lymph node was AITL (Stage IV, Group A). Four cycles of the following chemotherapy regimen were administered: Cyclophosphamide 1.3 g, doxorubicin 86 mg, and vincristine 2 mg on day 1; prednisone 100 mg on days 1-5; and lenalidomide 25 mg on days 1-14. The interval between each cycle was 21 d. The patient received a conditioning regimen (busulfan, cyclophosphamide, and etoposide) followed by peripheral blood stem cell infusion. Unfortunately, she developed sustained fever and a low platelet count 17 d after ACST, leading to a diagnosis of HLH after ASCT. During treatment, she experienced thrombocytopenia and Pneumocystis carinii pneumonia. The patient was successfully treated with etoposide and glucocorticoids. CONCLUSION: It is possible that development of HLH is related to immune reconstitution after ASCT.

Heterogeneous Myeloid Cells in Tumors.

Accumulating studies highlight a critical role of myeloid cells in cancer biology and therapy. The myeloid cells constitute the major components of tumor microenvironment (TME). The most studied tumor-associated myeloid cells (TAMCs) include monocytes, tumor-associated macrophages (TAMs), dendritic cells (DCs), cancer-related circulating neutrophils, tumor-associated neutrophils (TANs), and myeloid-derived suppressor cells (MDSCs). These heterogenous myeloid cells perform pro-tumor or anti-tumor function, exerting complex and even opposing effects on all stages of tumor development, such as malignant clonal evolution, growth, survival, invasiveness, dissemination and metastasis of tumor cells. TAMCs also reshape TME and tumor vasculature to favor tumor development. The main function of these myeloid cells is to modulate the behavior of lymphocytes, forming immunostimulatory or immunosuppressive TME cues. In addition, TAMCs play a critical role in modulating the response to cancer therapy. Targeting TAMCs is vigorously tested as monotherapy or in combination with chemotherapy or immunotherapy. This review briefly introduces the TAMC subpopulations and their function in tumor cells, TME, angiogenesis, immunomodulation, and cancer therapy.

Reelin depletion alleviates multiple myeloma bone disease by promoting osteogenesis and inhibiting osteolysis.

Extracellular matrix glycoprotein Reelin is associated with tumor metastasis and prognosis in various malignancies. However, its effects on multiple myeloma (MM) are not fully understood. Here, we investigated the regulatory effects of Reelin on MM and its underlying pathogenic mechanisms. Lentivirus plasmid containing short hairpin RNA targeting Reelin (LV3-Reln) was transfected into SP2/0 cells to knockdown Reelin expression. Flow cytometry assay analyzed cell cycle and apoptosis while Transwell assay evaluated invasiveness. BALB/c mice were inoculated with LV3-Reln-transfected SP2/0 cells to establish MM model. Primary myeloma cells and osteoblasts/osteoclast were isolated from tumor tissue and limb long bones respectively. ELISA examined serum biomarkers and immunohistochemistry detected immunoglobulin light chain expression. Morphological changes and osteoclast/osteoblast differentiation were observed by histological staining. mRNA and proteins expression were determined by qPCR and WB. In vitro studies showed that Reelin depletion regulated osteolysis and osteogenesis balance, cell cycle, invasiveness, and apoptosis in SP2/0 cells. In LV3-Reln mice, tumor growth and invasiveness were suppressed, meanwhile, reduced osteoclast activation and enhanced osteoblast activity were observed. Reelin knockdown alleviated extramedullary morbidity and inhibited spleen immune cell apoptosis by down-regulating CDK5, IL-10, and Cyto-C expression. Furthermore, reduced Reelin expression restrained osteoclast differentiation while promoted osteogenesis in the bone of LV3-Reln mice. This was further supported by down-regulation of osteolytic specific mRNAs and proteins (Trap, Mmp9, Ctsk, Clcn7) and up-regulation of osteogenic specific ones (COL-1, Runx2, ß-Catenin). Reelin exerted important impacts on myeloma development through rebalancing osteolysis and osteogenesis, thus might be a potential therapeutic target for MM.

Predictors of hepatic steatosis in HBeAg-negative chronic hepatitis B patients and their diagnostic values in hepatic fibrosis.

OBJECTIVE: To investigate predictors of hepatic steatosis in HBeAg-negative chronic hepatitis B (CHB) patients and their diagnostic values in hepatic inflammation and fibrosis. METHODS: A total of 106 HBeAg-negative CHB patients with clinically and pathologically proven steatosis and 98 patients without steatosis were recruited into this study. The levels of fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG), cholesterol (CHOL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), globulin (Glb), HBV DNA, body mass index (BMI), homeostatic model assessment of insulin resistance (HOMA-IR) and pathological changes of the liver in inflammation, fibrosis and fatty deposition were examined in all patients. RESULTS: The levels of BMI, HOMA-IR, FBG, insulin, TG, and CHOL were significantly higher in patients with steatosis than those without steatosis (all P<0.05). But ALT, AST and HBV DNA levels were significantly lower in patients with steatosis (all P<0.05). Logistic regression analysis showed that only FINS was a significant predictor for hepatic steatosis (P<0.05); FINS and Glb were significant predictors for hepatic inflammation (all P<0.05); BMI and TC were significant predictors for hepatic fibrosis (all P<0.05). CONCLUSIONS: Hepatic steatosis, a common disease in HBeAg-negative CHB patients, was positively associated with BMI, FBG, FINS, TG, TC, GGT, ALP and HOMA-IR. In these patients, the prevalence of hepatic inflammation and fibrosis was also increased.

Cyclosporine Broadens the Therapeutic Potential of Lenalidomide in Myeloid Malignancies.

The immunomodulatory drug lenalidomide is used for the treatment of certain hematologic malignancies, including myelodysplastic syndromes (MDS). Lenalidomide interacts with cereblon (CRBN), a component of the CRL4CRBN E3 ubiquitin ligase complex, leading to ubiquitination and subsequent degradation of substrates, such as transcription factor Ikaros (Ikaros family zinc finger 1, IKZF1). With a genome loss of function screen, we recently identified two novel pathways mediated by lenalidomide in MDS. In this review, we summarized the major findings of these two pathways and their clinical implications. Depletion of G protein-coupled receptor 68 (GPR68) or an endogenous calcineurin (CaN) inhibitor, regulator of calcineurin 1 (RCAN1), reversed the inhibitory effect of lenalidomide on MDSL cells, an MDS cell line. Intriguingly, both GPR68 and RCAN1 expression levels were upregulated in MDSL cells after treatment with lenalidomide that was dependent on diminishment of IKZF1, indicating that IKZF1 functioned as a transcription repressor for GPR68 and RCAN1. Mechanistic studies revealed that upregulation or activation of GPR68 induced a Ca2+/calpain pro-apoptotic pathway, while upregulation of RCAN1 inhibited the CaN pro-survival pathway in MDSL cells. Notably, the pharmacological CaN inhibitor, cyclosporine, enhanced the sensitivity to lenalidomide in MDS as well as acute myeloid leukemia (AML). Surprisingly, pretreatment with lenalidomide reversed the immunosuppressive effects of cyclosporine on T lymphocytes. Our studies suggest that lenalidomide mediates degradation of IKZF1, leading to derepression of GPR68 and RCAN1 that activates the Ca2+/calpain pro- apoptotic pathway and inhibits the CaN pro-survival pathway, respectively. Our studies implicate that cyclosporine extends the therapeutic potential of lenalidomide to myeloid malignancies without compromising immune function.

Cyclosporine enhances the sensitivity to lenalidomide in MDS/AML in vitro.

Our previous study revealed that expression of G protein-coupled receptor 68 (GPR68) was upregulated in MDSL cells, a cell line representing myelodysplastic syndromes (MDS), in response to lenalidomide (LEN), and mediated a calcium/calpain proapoptotic pathway. Isx, a GPR68 agonist, enhanced the sensitivity to LEN in MDSL cells. The fact that Isx is not a U.S. Food and Drug Administration-approved drug prompts us to look for alternative candidates that could enhance the sensitivity of LEN in MDS as well as other hematologic malignancies, such as acute myeloid leukemia (AML). In the study described here, we found that regulator of calcineurin 1 (RCAN1), an endogenous inhibitor of calcineurin (CaN), was upregulated in MDSL cells in response to LEN, possibly through degradation of IKZF1. Consistently, cyclosporin (Cys), a pharmacological inhibitor of CaN, inhibited the activity of CaN and induced apoptosis in MDSL cells, indicating that CaN provided a prosurvival signal in MDSL cells. In addition, Cys enhanced the cytotoxic effect of LEN in MDS/AML cell lines as well as primary bone marrow cells from MDS patients and AML patient-derived xenograft models. Intriguingly, pretreatment with LEN reversed the suppressive effect of Cys on T-cell activation. Our study suggests a novel mechanism of action of LEN in mediating cytotoxicity in MDS/AML via upregulation of RCAN1, thus inhibiting the CaN prosurvival pathway. Our study also suggests that Cys enhances the sensitivity to LEN in MDS/AML cells without compromising T-cell activation.

Loss of Reelin suppresses cell survival and mobility in non-Hodgkin lymphoma.

Reelin, a secreted glycoprotein, was recently demonstrated to be involved in the pathogenesis of cancer. However, its oncogenic activities in non-Hodgkin lymphoma (NHL) remain unclear. Therefore, we aimed to evaluate the functional role of reelin in NHL, and the underlying molecular mechanisms. In the present study, we analyzed reelin expression in lymphoma tissues and cell lines using immunohistochemistry, immunofluorescence staining, qRT-PCR and western blotting. Then, the expression of Reelin was silenced with short hairpin RNA (shRNA)-expressing plasmid in the NHL cell line A20. The effects of Reelin depletion on cell growth, migration and invasion in vitro were determined by CCK-8 and transwell assays. Flow cytometry was used to examine the cell cycle status and cellular apoptosis. Hoechst 33258 fluorescence staining was used to analyze morphologic changes caused by apoptosis. The second messenger, cAMP was analyzed by ELISA. In addition, we used nude mice to evaluate the tumorigenic ability of reelin. Aberrant upregulated levels of mRNA and protein of reelin were observed in lymphoma tissues and cell lines. Knockdown of reelin suppressed lymphoma growth, migration and invasion ability of A20. Furthermore, reelin depletion induced cell cycle arrest in G0/G1 phase and promoted apoptosis of A20 cells. Further analysis indicated that knockdown of reelin downregulated the expression of CDK5 and IL-10 and activated caspase-3 in shReelin group. ELISA assay showed cAMP at a lower level in shReelin group. SQ22536, a cAMP pathway inhibitor, treated A20 cells and revealed likely effects. The tumor size in a mouse model injected shReelin was significantly smaller than controls. There results suggest that reelin played essential roles in the development of lymphoma and might be a potential drug target in lymphoma.

Clinical presentation of hemophagocytic lymphohistiocytosis in adults is less typical than in children.

OBJECTIVE: Hemophagocytic lymphohistiocytosis in adults is largely underdiagnosed. To improve the rate and accuracy of diagnosis in adults, the clinical and laboratory characteristics of hemophagocytic lymphohistiocytosis were analyzed in and compared between adults and children in a Chinese cohort. METHOD: Data from 50 hemophagocytic lymphohistiocytosis patients, including 34 adults and 16 children who fulfilled the 2004 hemophagocytic lymphohistiocytosis diagnostic criteria, were collected and analyzed. RESULTS: 1. Etiological factors: The proportion of Epstein-Barr virus infection was lower in adults compared with children, whereas fungal infection and natural killer/T cell lymphoma were more frequent in adults (P<0.05). 2. Clinical manifestations and laboratory findings: Over 90% of adults and pediatric patients presented with fever, thrombocytopenia and high serum ferritin levels. However, in adults, the proportions of hepatomegaly, splenomegaly and jaundice were much lower (P<0.01) than in children, and serous cavity effusion was more frequent in adult patients (P<0.05). More children had hemoglobin <90 g/L, total bilirubin >19 mmol/L and lactate dehydrogenase >500 U/L compared with adults (P<0.05). 3. The time interval from the onset of symptoms to clinical diagnosis was significantly shorter in pediatric patients than in adults (P<0.05). CONCLUSIONS: Certain clinical features were different between the two groups. The less characteristic clinical presentation of hemophagocytic lymphohistiocytosis in adults may make the disease more difficult to diagnose. Our findings suggest that hemophagocytic lymphohistiocytosis should be considered when an adult patient presents with the above-mentioned symptoms.

Predictive value of microRNAs as novel biomarkers in detection of lymphoma.

MicroRNAs (miRNAs) have attracted many attentions in lymphoma diagnostic research. The inconsistence of diagnostic performance in these existed literatures leading us to conduct this meta-analysis. In order to have a scientific and reliable study, all related articles were screened from Medline, Embase, CNKI and other databases. The sensitivity and specificity of each involved research were used to plot the summary receiver operator characteristic (SROC) curve and calculate the area under the curve (AUC). The QUADAS-2 tool was applied to estimate the quality of included studies. In addition, Deeks' funnel plot asymmetry test was performed to estimate publication bias. Overall, 14 studies from 6 articles were included to evaluate the whole test performance. The overall pooled results were as follows: sensitivity was 0.91 (95% CI: 0.83-0.95), specificity was 0.84 (95% CI: 0.75-0.90), the AUC was 0.93 (95% CI: 0.91-0.95), positive likelihood ratio-PLR was 5.5 (95% CI: 3.5-8.8), negative likelihood ratio-NLR was 0.11 (95% CI: 0.06-0.21), and diagnostic odds ratio-DOR was 50 (95% CI: 19-128). In summary, results from meta-analysis showed that miRNAs analysis might significantly increase the diagnostic accuracy of lymphoma. Further massive prospective studies still needed to validate our conclusion before clinical application.

Role of five small nucleotide polymorphisms in the VEGF gene on the susceptibility to osteosarcoma and overall survival of patients.

The present study aimed to investigate the association between five common small nucleotide polymorphisms (SNPs) in the VEGF gene and the risk of osteosarcoma. An additional aim was to investigate the role of these five SNPs on the prognosis of osteosarcoma. A total of 186 patients with osteosarcoma and 186 age- and sex-matched healthy controls were enrolled into the present study. A polymerase chain reaction-restriction fragment length polymorphism assay was conducted to determine the incidence of the VEGF-2578 C/A, -1156 G/A, +1612 G/A, +936 C/T and -634 G/C polymorphisms. Conditional logistic regression analyses revealed that individuals carrying the -634 GG genotype possessed a significantly increased risk of osteosarcoma, with an adjusted odds ratio [(95% confidence interval (CI)] of 2.00 (1.07-3.75). In the Cox proportional hazards model, subsequent to adjusting for potential confounding factors, patients with osteosarcoma carrying the -634 GG genotype were found to demonstrate a shorter overall survival time (hazard ratio, 3.10; 95% CI, 1.17-8.38). The VEGF-634 G/C polymorphism may therefore be used as a genetic marker for the prediction of the risk and clinical outcome of osteosarcoma.

Identification of therapeutic target genes with DNA microarray in multiple myeloma cell line treated by IKKß/NF-κB inhibitor.

PURPOSE: To explore the mechanism of resistance to IKKß inhibitor in multiple myeloma (MM) cells and uncover novel therapeutic targets for MM. METHODS: We downloaded the microarray data (GSE8476) from GEO (Gene Expression Omnibus) database. The data were derived from the human MM cells lines (L363 cells) treated with IKKß inhibitor MLN120b (MLN) for eight, 12 and 24 hours. Furthermore, we applied the Search Tool for the Retrieval of Interacting Genes (STRING) and Expression Analysis Systematic Explorer (EASE) database to construct protein-protein interaction networks and identified over-represented pathway among DEGs (differentially expressed genes). RESULTS: We obtained 108 DGEs in 8h vs. 12h group and 101 ones in 8h vs. 24h group. Most of DGEs were found to be involved in biological regulation. The significant pathways were Ig A pathway and the CAMs pathways. In addition, 24 common DGEs were found in the networks of the two groups such as ICAM 3 and SELL. CONCLUSION: Intercellular adhesion molecule 3 and SELL may be potential targets in multiple myeloma treatment in the future.

Cyclic adenosine monophosphate involvement in low-dose cyclophosphamide-reversed immune evasion in a mouse lymphoma model.

Lymphoma cells mobilize many mechanisms to evade the immune system. There is substantial evidence that CD4(+)CD25(+) regulatory T cells (Tregs) play a key role in the control of immune evasion. Tregs can transfer cyclic adenosine monophosphate (cAMP) to effector T cells, suggesting an association between Tregs' immune-evasion role and the intracellular cAMP pathway. In this study, we used A20 B-cell lymphoma mice as aggressive tumor models to investigate the mechanism of the depletion of Tregs by low-dose cyclophosphamide (CY, 20 mg/kg). The tumor-bearing mice had longer survival times and slower tumor growth rates following treatment with CY, but its effects were temporary. Along with the depletion of Tregs by low-dose CY treatment, the expression of interleukin-2 (IL-2) in T effector cells increased, and intracellular cAMP concentrations in immune cells decreased. Our study demonstrates the ability of low-dose CY to reverse Tregs-mediated immune evasion in a mouse model. The changes in intracellular cAMP concentrations correlated with the upregulation of effector T cells and the downregulation of Tregs, indicating the close association of cAMP analogs and low-dose CY in the immune therapy of B-cell lymphoma.

[Expression of CXCR3 and CCR5 chemokine receptor in spleens of patients with primary immune thrombocytopenia].

OBJECTIVE: To study CXCR3 and CCR5 chemokine receptor expression in spleens of patients with primary immune thrombocytopenia (ITP) and its clinical significance. METHODS: The splenectomy specimens from 10 ITP patients (ITP group) and 8 patients with traumatic splenic rupture (normal control group) were studied. Immunohistochemistry (IHC) was used to study the positive rate of CXCR3 and CCR5. Western blot was performed to detect CXCR3 and CCR5 protein expression, while real-time polymerase chain reaction (RT-PCR) was conducted to analyze their mRNA expression. RESULTS: The positive rate of CXCR3 and CCR5 were both higher in ITP group (90% and 100%, respectively) than those in control group (75% and 87.5%, respectively)(P < 0.05). The differences were statistically significant (P < 0.05). Protein and mRNA level of CXCR3 in ITP group were 3.0 and 3.5 times as high as those in control group, respectively. Those of CCR5 in ITP group were 1.2 and 1.7 times as high as those in control group, respectively. CONCLUSION: High expression of CXCR3 and CCR5 may play a part in the splenic immune disorders in patients with ITP.

Clinical presentation of hemophagocytic lymphohistiocytosis in adults is less typical than in children

OBJECTIVE: Hemophagocytic lymphohistiocytosis in adults is largely underdiagnosed. To improve the rate and accuracy of diagnosis in adults, the clinical and laboratory characteristics of hemophagocytic lymphohistiocytosis were analyzed in and compared between adults and children in a Chinese cohort. METHOD: Data from 50 hemophagocytic lymphohistiocytosis patients, including 34 adults and 16 children who fulfilled the 2004 hemophagocytic lymphohistiocytosis diagnostic criteria, were collected and analyzed. RESULTS: 1. Etiological factors: The proportion of Epstein-Barr virus infection was lower in adults compared with children, whereas fungal infection and natural killer/T cell lymphoma were more frequent in adults (P<0.05). 2. Clinical manifestations and laboratory findings: Over 90% of adults and pediatric patients presented with fever, thrombocytopenia and high serum ferritin levels. However, in adults, the proportions of hepatomegaly, splenomegaly and jaundice were much lower (P<0.01) than in children, and serous cavity effusion was more frequent in adult patients (P<0.05). More children had hemoglobin <90 g/L, total bilirubin >19 mmol/L and lactate dehydrogenase >500 U/L compared with adults (P<0.05). 3. The time interval from the onset of symptoms to clinical diagnosis was significantly shorter in pediatric patients than in adults (P<0.05). CONCLUSIONS: Certain clinical features were different between the two groups. The less characteristic clinical presentation of hemophagocytic lymphohistiocytosis in adults may make the disease more difficult to diagnose. Our findings suggest that hemophagocytic lymphohistiocytosis should be considered when an adult patient presents with the above-mentioned symptoms.

Cyclic adenosine monophosphate signal pathway in targeted therapy of lymphoma.

OBJECTIVE: To review the role of cyclic adenosine monophosphate (cAMP) signal pathway in the pathogenesis of lymphoma and explore a potential lymphoma therapy targeted on this signaling pathway. DATA SOURCES: The data cited in this review were mainly obtained from the articles listed in Medline and PubMed, published from January 1995 to June 2009. The search terms were "cAMP" and "lymphoma". STUDY SELECTION: Articles regarding the role of the cAMP pathway in apoptosis of lymphoma and associated cells and its potential role in targeted therapy of lymphoma. RESULTS: In the transformation of lymphocytic malignancies, several signal pathways are involved. Among of them, the cAMP pathway has attracted increasing attention because of its apoptosis-inducing role in several lymphoma cells. cAMP pathway impairment is found to influence the prognosis of lymphoma. Targeted therapy to the cAMP pathway seems to be a new direction for lymphoma treatment, aiming at restoring the cAMP function. CONCLUSIONS: cAMP signal pathway has different effects on various lymphoma cells. cAMP analogues and phosphodiesterase 4B (PDE4B) inhibitors have potential clinical significance. However, many challenges remain in understanding the various roles of such agents.