[Predictive Value of Complete Blood Count and Inflammation Marker on Risk of Recurrence in Children with Henoch-Schönlein Purpura].

OBJECTIVE: To investigate the predictive value of complete blood count (CBC) and inflammation marker on the recurrence risk in children with Henoch-Schönlein purpura (HSP). METHODS: One hundred and thirty-three children with HSP admitted to Cangzhou Central Hospital from February 2017 to March 2019 were enrolled. The clinical data of the children were collected, at the time of admission CBC and C-reactive protein (CRP) were detected. After discharge, the children were followed up for 1 year, the clinical data of children with and without recurrence were compared, and multivariate logistic regression was used to analyze the risk factors affecting HSP recurrence. Receiver operating characteristic (ROC) curve should be drawn and the predictive value of CBC and CRP on HSP recurrence should be analyzed. RESULTS: In the follow-up of 133 children, 8 cases were lost and 39 cases recurred, with a recurrence rate of 31.20% (39/125). The age, skin rash duration, proportion of renal damage at the initial onset, percentage of neutrophils, percentage of lymphocytes, platelet count (PLT), mean platelet volume (MPV) and neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), MPV/PLT ratio (MPR), and CRP level of patients with recurrence were statistically different from those without recurrence (P <0.05). Multivariate logistic regression analysis showed that long skin rash duration, renal damage at the initial onset, increased PLR, high PLT, increased MPV and elevated CRP level were independent risk factors for recurrence in children with HSP (P <0.05). The ROC curve analysis showed that the area under the curve (AUC) of the combination of the four blood and inflammation marker (PLT, MPV, PLR and CPR) in the early prediction of HSP recurrence was 0.898, which was higher than the initial renal damage (AUC=0.687) and persistent skin rash time (AUC=0.708), with a sensitivity of 84.62% and a specificity of 83.72%. CONCLUSION: Observation of CBC and CPR can predict the risk of HSP recurrence early and guide early clinical intervention.

ANGPTL2 promotes VEGF-A synthesis in human lung cancer and facilitates lymphangiogenesis.

Lung cancer is an extremely common cancer and metastatic lung cancer has a greatly low survival rate. Lymphangiogenesis is essential for the development and metastasis of lung cancer. The adipokine angiopoietin-like protein 2 (ANGPTL2) regulates tumor progression and metastasis, although the functions of ANGPTL2 in lung cancer are unknown. Analysis of data from TCGA genomics program, the GEPIA web server and the Oncomine database revealed that higher levels of ANGPTL2 expression were correlated with progressive disease and lymph node metastasis. ANGPTL2 enhanced VEGF-A-dependent lymphatic endothelial cell (LEC) tube formation and migration. Integrin α5ß1, p38 and nuclear factor (NF)-κB signaling mediated ANGPTL2-regulated lymphangiogenesis. Importantly, overexpression ANGPTL2 facilitated tumor growth and lymphangiogenesis in vivo. Thus, ANGPTL2 is a promising therapeutic object for treating lung cancer.

Cigarette smoke-promoted increases in osteopontin expression attract mesenchymal stem cell recruitment and facilitate lung cancer metastasis.

INTRODUCTION: Cigarette smoking is the main risk factor for lung cancer. MSCs in the TME promoting tumor angiogenesis, growth, and metastasis. SIBLING proteins enable cancer cells to extend, invade and metastasize. OBJECTIVES: Cigarette smoke promotes the progression and metastasis of lung cancer, although how this occurs is poorly understood. We evaluated the impact of whether cigarette smoking motivates SIBLING protein expression and is involved in MSC-mediated lung tumor metastasis. METHODS: We investigated the expression of OPN in the Gene Expression Omnibus (GEO) databases and confirmed the results by immunohistochemistry (IHC), qPCR and Western blotting (WB) of lung cancer cells and tissues. The effect of OPN on the recruitment and adhesion of mesenchymal stem cells (MSCs) to lung cancer cells and lung cancers metastasis was investigated by Transwell, adhesion assays. A series of in vitro and in vivo experiments were conducted to demonstrate the mechanisms by which OPN modulates recruitment and adhesion of MSCs to lung cancer cells and lung cancer metastasis. RESULTS: Cigarette smoke extract (CSE) and benzo[α]pyrene (B[α]P) increased levels of OPN expression and facilitated the recruitment and adhesion of MSCs to lung cancer cells via JAK2/STAT3 signaling. We also observed that OPN promotes tumor-associated MSC (TA-MSC) formation through the OPN receptor (integrins αvß1, αvß3, αvß5 or CD44), inducing lung cancer cell migration and invasion. In an orthotopic mouse model of lung cancer, increases in OPN expression promoted by cigarette smoke upregulated MSC recruitment and facilitated lung cancer metastasis. Knockdown of OPN expression inhibited cigarette smoke-induced lung cancer metastasis in vivo. CONCLUSION: Cigarette smoke increases OPN expression through the JAK2/STAT3 signaling pathway to attract MSC cell recruitment and promote lung cancer metastasis. Our findings offer important insights into how lung cancer metastasis develops in smokers.

Genetic Associations of Visfatin Polymorphisms with EGFR Status and Clinicopathologic Characteristics in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common histologic type of lung cancer. Mutations of the epidermal growth factor receptor (EGFR) gene are among the most common genetic alterations in LUAD and are the targets of EGFR tyrosine kinase inhibitors. The enzyme visfatin is involved in the generation of the oxidized form of nicotinamide adenine dinucleotide (NAD+) and regulation of intracellular adenosine triphosphate (ATP), critical processes in cancer cell survival and growth. This study explored the relationship between visfatin single nucleotide polymorphisms (SNPs) with EGFR status and the clinicopathologic development of LUAD in a cohort of 277 Taiwanese men and women with LUAD. Allelic discrimination of four visfatin SNPs rs11977021, rs61330082, rs2110385 and rs4730153 was determined using a TaqMan Allelic Discrimination assay. We observed higher prevalence rates of advanced (T3/T4) tumors and distant metastases in EGFR wild-type patients carrying the rs11977021 CT + TT and rs61330082 GA + AA genotypes, respectively, compared with patients carrying the CC and GG genotypes. EGFR wild-type patients carrying the rs11977021 CT + TT genotypes were also more likely to develop severe (stage III/IV) malignancy compared with patients carrying the CC genotype. An analysis that included all patients found that the association persisted between the rs11977021 CT + TT and rs61330082 GA + AA genotypes and the development of T3/T4 tumors compared with patients carrying the rs11977021 CC and rs61330082 GG genotypes. In conclusion, these data indicate that visfatin SNPs may help to predict tumor staging in LUAD, especially in patients with EGFR wild-type status.

Melatonin interrupts osteoclast functioning and suppresses tumor-secreted RANKL expression: implications for bone metastases.

Cancer-related bone erosion occurs frequently in bone metastasis and is associated with severe complications such as chronic bone pain, fractures, and lower survival rates. In recognition of the fact that the darkness hormone melatonin is capable of regulating bone homeostasis, we explored its therapeutic potential in bone metastasis. We found that melatonin directly reduces osteoclast differentiation, bone resorption activity and promotes apoptosis of mature osteoclasts. We also observed that melatonin inhibits RANKL production in lung and prostate cancer cells by downregulating the p38 MAPK pathway, which in turn prevents cancer-associated osteoclast differentiation. In lung and prostate bone metastasis models, twice-weekly melatonin treatment markedly reduced tumor volumes and numbers of osteolytic lesions. Melatonin also substantially lowered the numbers of TRAP-positive osteoclasts in tibia bone marrow and RANKL expression in tumor tissue. These findings show promise for melatonin in the treatment of bone metastases.

[Bioinformatics Analysis and Verification of Aging-Related Genes of Bone Marrow Mesenchymal Stem Cells in Patients with Acute Myeloid Leukemia].

OBJECTIVE: To screen and verify the differentially expressed genes related with aging of bone marrow mesenchymal stem cells (BM-MSCs) in acute myeloid leukemia (AML) patients by bioinformatics, so as to provide new molecular markers for the research and clinical treatment of AML. METHODS: The gene expression profiling chip related with BM-MSCs in AML patients in our hospital and the gene chip GSE84881 selected from NCBI database GEO were used for data analysis and exploration. The DAVID analysis software was used to perform gene ontology (GO) enrichment analysis and KEGG pathway enrichment analysis. Furthermore, the differentially expressed genes related with aging of BM-MSCs in AML patients were identified. Bone marrow samples were collected and MSCs were amplified in vitro, and RT-PCR was used to verify the differentially expressed genes, which should be further identified with senescence-associated ß-galactosidase staining and MTT cell proliferation assays. RESULTS: A total of 247 differentially expressed genes were screened out by bioinformatics methods, including genes of 132 up-regulated expression and 115 down-regulated expression. Six differentially expressed genes related with aging of BM-MSCs in AML patients were screened out, including the genes of up-regulated expression, COL3A1 (P<0.05), CRYAB (P<0.01), DCN (P<0.05), and the genes of down-regulated expression, including CCL2 (P<0.05), CTSC (P<0.01) and IL6 (P<0.05). These 6 differentially expressed genes were consistent with data from chip assays, and which was significantly correlated with aging of BM-MSCs in AML patients. Meanwhile, the positive rate of senescence-associated ß-galactosidase staining in BM-MSCs of AML patients was significantly different from that of healthy donors (P<0.01). MTT cell proliferation assay showed that BM-MSCs in AML patients had proliferative ability lower than the healthy donors' BM-MSCs. CONCLUSION: The data here suggest novel clues for the clinical research and treatment of BM-MSCs aging in AML patients.