OBJECTIVE: To study the protective effect of asiaticoside against hyperoxia-induced bronchopulmonary dysplasia in neonatal rats based on the microRNA-155 (miR-155)/suppressor of cytokine signaling-1 (SOCS1) axis. METHODS: Neonatal rats were randomly divided into a control group, a model group, a low-dose asiaticoside group (10 mg/kg), a middle-dose asiaticoside group (25 mg/kg), a high-dose asiaticoside group (50 mg/kg), and a budesonide group (1.5 mg/kg), with 12 rats in each group. All rats except those in the control group were exposed to a high concentration of oxygen for 14 days to establish a neonatal rat model of bronchopulmonary dysplasia. The low-, middle-, and high-dose asiaticoside groups were given asiaticoside at different doses by gavage, and those in the budesonide group were given budesonide aerosol treatment. Hematoxylin and eosin staining was used to observe lung tissue development and measure radial alveolar count (RAC) and mean linear intercept (MLI). Superoxide dismutase (SOD) and malondialdehyde (MDA) detection kits were used to measure the levels of SOD and MDA in lung tissue. ELISA was used to measure the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Quantitative real-time PCR was used to measure the mRNA expression of miR-155 and SOCS1 in lung tissue. Western blotting was used to measure the protein expression of SOCS1 in lung tissue. RESULTS: Compared with the control group, the model group had the symptoms of bronchopulmonary dysplasia such as a disordered structure of lung tissue, enlargement of alveolar fusion, uneven alveolar septa, enlargement of average alveolar space, and a reduction in alveolar number. The model group also had significant increases in MLI, MDA level in lung tissue, serum levels of IL-6 and TNF-α, and miR-155 level in lung tissue (P<0.05) and significant reductions in RAC, SOD level, and mRNA and protein expression of SOCS1 in lung tissue (P<0.05). Compared with the model group, the low-, middle-, and high-dose asiaticoside groups and the budesonide group had significant improvement in the above symptoms of bronchopulmonary dysplasia, significant reductions in MLI, MDA level in lung tissue, serum levels of IL-6 and TNF-α, and miR-155 level in lung tissue (P<0.05), and significant increases in RAC, SOD level, and mRNA and protein expression of SOCS1 in lung tissue (P<0.05). Asiaticoside improved the above symptoms and indices in a dose-dependent manner. There were no significant differences in the above indices between the high-dose asiaticoside and budesonide groups (P>0.05). CONCLUSIONS Asiaticoside can alleviate inflammation injury induced by hyperoxia in neonatal rats and improve the symptoms of bronchopulmonary dysplasia in a dose-dependent manner, possibly by down-regulating the expression of miR-155 and up-regulating the expression of SOCS1.
Animals ; Animals, Newborn ; Bronchopulmonary Dysplasia ; Hyperoxia ; Lung ; MicroRNAs ; Rats ; Triterpenes

Aim To observe the effect of epidurally application of osthole on the model of nucleus pulposusinduced inflammatory radicular pain and the expression of p38 MAPK signaling related pathway in the spinal dorsal horn of rats.Methods The model of radicular pain was generated by putting nucleus pulposus to the L5 dorsal root ganglion (DRG).50％ MWT was measured using Von Frey filaments to calculate mechanical pain threshold before and after operation.50 μL of 20 g · L-1 osthole was administered epidurally in group Ost and 50 μL of 100 mL · L-1 DMSO in group DMSO at postoperative day (POD).The expression of phosphorylated p38 (p-p38),IL-18 and IL-18R in the lumbar spinal dorsal horn was detected by Western blot.IL-18 mRNA was assessed by real-time PCR.Results The mechanical pain threshold significantly decreased after operation (P ＜ 0.05),while the expression of protein p-p38 MAPK,IL-18,IL-18R and IL-18 mRNA was significantly different.Compared with DMSO group,50％ MWT was significantly increased and accompanied with the decrease of protein p-p38,IL-18,IL-lgR and IL-18 mRNA in Ost group after drug administration (P ＜ 0.05).The correlation analysis between protein concentration of p38 MAPK and IL-18 mRNA showed that the Spearman correlation coefficient was 0.9 (P ＜ 0.05).Conclusion p-p38 and IL-18 of spinal dorsal horn participate in the rat model with inflammatory radicular pain induced by nucleus pulposus,and IL-18R plays a role in maintenance of the pain.Osthole administered epidurally in the early stage of pain could alleviate the pain for a long time,which may be related with inhibiting p38 MAPK signaling related pathways.

Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. Trial Registration ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.
Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; China ; Cyclophosphamide ; administration & dosage ; Doxorubicin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Follicular ; drug therapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Rituximab ; therapeutic use ; Vincristine ; administration & dosage

Most Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) patients often show rapid recurrence and development of ABL kinase domain (KD) mutation after tyrosine kinase inhibitor (TKI) treatment. To further investigate the mechanism of Ph(+) ALL fast relapse after TKI treatment, ABL KD mutation in 35 Chinese Ph(+) ALL with TKI resistance was detected by direct sequencing. The results showed that 77.1% (27/35) Ph(+) ALL patients with TKI resistance had ABL KD mutation and 55.6% (15/27) Ph(+) ALL patients with ABL KD mutation had T315I. Interestingly, 77.8% (21/27) Ph(+)ALL showed ABL mutation G: C→A:T, including T315I, E255K and E459K. Furthermore, all the Ph(+) ALL patients with two or more ABL KD mutations collaborated with complex chromosome abnormality and all the TKI-resistant Ph(+) ALL patients, whose karyotype progressed from simple t (9;22) into complex, developed ABL KD mutation. Moreover, the expression level of uracil-DNA glycosylase UNG2, which inhibits G:C→A:T transition in genomic DNA, decreased in Ph(+) ALL with TKI-resistance compared to that in newly diagnosis Ph(+) ALL. It is concluded that there is a high frequent ABL KD G:C→A:T mutation and a high genomic instability in Chinese TKI-resistant Ph(+) ALL. In addition, the decreased UNG2 expression in TKI-resistant Ph(+) ALL probably contributes to their high rate of ABL KD G:C→A:T mutation.
Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; DNA Glycosylases ; genetics ; Drug Resistance, Neoplasm ; genetics ; Female ; Humans ; Male ; Middle Aged ; Point Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Protein Kinase Inhibitors ; pharmacology ; Uracil-DNA Glycosidase ; genetics

Aged ; Humans ; Hypercalcemia ; complications ; Liver Neoplasms ; complications ; Lymphoma ; complications ; Male

OBJECTIVETo investigate the clinical features and to identify the DAX-1 gene mutation in a Chinese kindred with X-linked adrenal hypoplasia congenital(AHC).

METHODSClinical data and peripheral blood samples were obtained from the affected individuals and their relatives. The genomic DNA was isolated from whole blood. Four pairs of primers were used to amplify the two exons of the DAX-1 gene, and PCR products were purified and sequenced directly. Sequencing results were compared to the human DAX-1 sequence in the public database.

RESULTSA novel hemizygous frameshift mutation (428delG) in exon 1 of the DAX-1 gene was found in both patients (the index case and his cousin). Some clinical features such as the age of onset were different although these 2 patients carried the same mutation. Three females in the family, including the mothers of the 2 patients and their grandmother were carriers of this mutation. No such mutation was detected in other healthy persons in the family.

CONCLUSIONThe result suggested that X-linked AHC in the kindred was caused by a novel mutation of 428delG in the DAX-1 gene, and the same mutation can give rise to variable phenotypes.

Adolescent ; Adrenal Hyperplasia, Congenital ; genetics ; pathology ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; DAX-1 Orphan Nuclear Receptor ; DNA-Binding Proteins ; genetics ; Female ; Genetic Diseases, X-Linked ; genetics ; pathology ; Humans ; Male ; Mutation ; Pedigree ; Phenotype ; Receptors, Retinoic Acid ; genetics ; Repressor Proteins ; genetics ; Sequence Analysis, DNA

This study was aimed to investigate the biological characteristics of osteoblasts from patients with myelodysplastic syndrome (MDS) and their supportive capacity for hematopoiesis in vitro. A two-dimensional culture system was constructed by using osteoblasts derived from human marrow mesenchymal stem cells (MSC); MSCs were isolated from bone marrow of MDS patients and normal individuals and were cultured; the third passage of MSCs were induced into osteoblasts which were treated with mitomycin C and confluenced into a feeder layer. Ficolled bone marrow mononuclear cells were obtained from normal individuals and seeded into the two-dimensional culture system to culture in vitro without exogenous cytokines. By using colony-forming assay, the ability of the two-dimensional system to culture HPCs was observed. The cytokine expression of osteoblasts from MDS patient bone marrows in mRNA level was detected by RT-PCR and was compared with human osteoblast cell line hFOB1.19. The results showed that the osteoblasts from MDS patients could support short-term survival of GM-CFC in condition without exogenous cytokines, that is, osteoblasts played a crucial role in regulation of HPC growth. The results of RT-PCR clearly demonstrated that the osteoblast cell line hFOB1.19 expressed SCF, IL-6, SDF-1alpha, G-CSF and GM-CSF. The same expression patterns of above cytokines were also seen in osteoblasts derived from BM-MSCs of MDS patients and normal individuals, but these cells did not express GM-CSF. It is concluded that the biological characteristics of osteoblasts from bone marrow of MDS patients are generally not different from those of osteoblasts from normal bone marrow. Both of them can support GM -CFC to form colonies in vitro, it may be associated with expressing important related cytokines by osteoblasts.
Cytokines ; metabolism ; Granulocyte-Macrophage Colony-Stimulating Factor ; metabolism ; Granulocyte-Macrophage Progenitor Cells ; cytology ; Hematopoietic Stem Cells ; cytology ; Humans ; Interleukin-6 ; metabolism ; Myelodysplastic Syndromes ; metabolism ; pathology ; Osteoblasts ; metabolism ; physiology ; RNA, Messenger ; metabolism ; Stem Cell Factor ; metabolism