More and more studies have shown that NOD-like receptor protein 3 (NLRP3) inflammasome has become the regulatory factor of inflammatory response and protective immunity, and the assembly and activation of NLRP3 inflammasomes are closely related to the anti-tumor immunity effect. Depending on the cell type and stimuli, activation of the NLRP3 inflammasome can induce immune cells to become polarized, hyperactive, or pyroptotic, releasing interleukin (IL)-1β and IL-18, which leads to cascade immune or inflammatory responses, and its role in tumor immunity has received extensive attention. Here, we review the mechanisms of the NLRP3 inflammasome enhancing CD8⁺ T cells-mediated anti-tumor immunity by inducing the pyroptosis of tumor cell, the pyroptosis or hyperactive state of dendritic cells (DCs), and the pyroptosis or polarization of the macrophages. Different anti-tumor immune roles of NLRP3 inflammasome activation in tumor cells and immune cells provide new directions for future research and may influence the development of next-generation immunotherapy.

Animals ; Disease Progression ; Kidney Diseases ; physiopathology ; Kidney Glomerulus ; drug effects ; pathology ; Rats ; Renal Agents ; pharmacology ; Renin-Angiotensin System ; drug effects ; Sclerosis

Adult ; Humans ; Leukocytes, Mononuclear ; metabolism ; Lupus Erythematosus, Systemic ; genetics ; Proto-Oncogene Protein c-ets-1 ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the clinicopathologic features, pathogenesis, diagnostic criteria and the relationship between different classification models and prognosis in Chinese patients with DLBCL, and try to look for the most appropriate classification model to predict clinical prognosis and therapeutic responses for Chinese patients with DLBCL.

METHODS181 cases of Chinese DLBCLs diagnosed according to the WHO 2008 classification were collected. Standard two-step Envision method of immunohistochemical staining was used to assess the expressions of CD20, CD3ε, CD79a, CD10, Mum-1, Bcl-6, GCET-1, FOXP1 and Ki-67. The phenotypic classifications were assessed according to the standard of Hans model and Chan model. Data were analyzed by χ(2) test and Life Table survival analysis with the SPSS14.0 statistical package.

RESULTSThe ratio of male to female in this cohort was 1.26:1. The median age of all patients was 57 yrs with the average age of 53.5 yrs. Of 61 cases (33.7%) primarily showed lymph node involvement. Gastrointestinal tract as the most involved extra-nodal organ was observed in 43 cases (35.8%). All patients with complete clinical follow-up materials survived from 1 - 120 months. The patients showed a high risk for death in the initial one and half years. Three year survival rate was 49.7% (90/181). Three year survival of 44 cases received R-CHOP (Rituximab, cyclophosphamide, doxorubicin, vincristine, bolus) was 76.9% (20/26), whereas 61.9% (60/97) in 119 cases received CHOP alone, R-CHOP group showed better prognosis (P = 0.017). All cases expressed one or more pan B cell markers, such as CD20 (176/179, 98.3%) and CD79a (62/77, 80.5%). For Hans model, 78 cases were classified as GCB group, while 103 cases as Non-GCB group. The ratio of Non-GCB to GCB was 1.32 without difference on the survival (P > 0.05). For the Chan's algorithm, 68 cases belonged to GCB subgroup, while 113 cases non-GCB subgroup. The ratio of non-GCB to GCB was 1.66. GCB subtype showed much better prognosis than non-GCB subtype according to Life Table survival analysis (P < 0.05).

CONCLUSIONThe epidemiology and clinicopathologic features of Chinese DLBCLs were similarly with the western cases. Chan's algorithm was a significant tool to predict the cell origin and clinical biology of Chinese DLBCLs.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Algorithms ; Asian Continental Ancestry Group ; Child ; Child, Preschool ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse ; classification ; diagnosis ; pathology ; Male ; Middle Aged ; Models, Theoretical ; Prognosis ; Young Adult

OBJECTIVETo investigate the implications of erythroblasts periodic acid-Schiff (PAS) stain for myelodysplastic syndromes (MDS) dyserythropoiesis, diagnosis and differential diagnosis.

METHODSPAS stain of bone marrow (BM) erythroblasts in 406 MDS patients, 207 non-severe aplastic anemia (NSAA), 144 immune thrombocytopenic purpura (ITP), 67 megaloblastic anemia (MegA), 76 iron deficiency anemia (IDA), 50 paroxysmal nocturnal hemoglobinuria (PNH), and 50 acute erythroid leukemia (AEL) as well as some related laboratory parameters in MDS patients were analyzed retrospectively.

RESULTSPAS-positive detection rate was significantly higher in MDS (53.0%) than in NSAA (14.5%), ITP (27.1%) and PNH (16.0%), but was significantly lower in MDS than in AEL (84.0%) (all P = 0.000). There was no significant difference in PAS-positive detection between MDS and MegA (46.3%), or MDS and IDA (40.8%) (P = 0.310, 0.052, respectively). Erythroblasts PAS-positive rate (Median, M = 1%) and PAS-positive scores (M' = 2) was significantly lower in MDS than in AEL (M = 8%; M' = 17), and significantly higher than in NSAA (M = 0%; M' = 0), ITP (M = 0%; M' = 0), PNH (M = 0%; M' = 0), MegA (M = 0%; M' = 0), and IDA (M = 0%; M' = 0) (all P < 0.05). The cut-off value of PAS-positive rate and score for distinguishing MDS from the other groups except AEL were 0.5% and 0.5, with a sensitivity and specificity of 60.8% and 74.4%, respectively. For MDS patients, the percentage of BM erythroid cells was significantly higher in PAS-positive group than in PAS-negative group (P < 0.05), and so were megakaryocyte count, lymphocyte-like micromegakaryocytes count and percentage of micromegakaryocyte (P = 0.002, 0.000, 0.000, respectively). HGB, MCV, MCH and MCHC were significantly lower in PAS-positive group (all P < 0.05), and so was the neutrophil alkaling phosphatase (NALP) (P = 0.000). PAS-positive detection rate, positive rate and score were higher in MDS patients with abnormal karyotype than with normal karyotype, and were also higher in IPSS high/intermediate-risk 2 group than in low/intermidiate-risk 1 group.

CONCLUSIONThe positive reaction of erythroblasts PAS stain is an indicator of dyserythropoiesis. It is helpful to the diagnosis of MDS patients.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Diagnosis, Differential ; Erythroblasts ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; diagnosis ; Periodic Acid-Schiff Reaction ; Retrospective Studies ; Sensitivity and Specificity ; Staining and Labeling ; Young Adult

OBJECTIVETo explore the molecular mechanisms of G(2)/M checkpoint initiated by diallyl disulfide (DADS) in HL-60 cells.

METHODSCell viability was determined by MTT assay. Cell cycle was assayed by flow cytometry. The expression of phospho-p38, Cdc25B and Cdc2, and p38 mRNA were measured by Western blotting and RT-PCR, respectively.

RESULTSAfter treatment with DADS at 5 - 160 micro mol/L for 0 - 72 h, the growth of HL-60 cells were suppressed in a concentration-dependent manner and the inhibitory effect of DADS (20 micro mol/L) was similar to that of ATRA (10 nmol/L) (P > 0.05). Incubation of HL-60 cells with DADS (20 micro mol/L) for 12 h could activate G(2)/M checkpoint and increase the expression of phospho-p38 MAPK, followed by the expression of phospho-Cdc25B and phospho-Cdc2 (P < 0.05). SB202190, a specific inhibitor of p38 MAPK, markedly blocked the phosphorylation of p38 MAPK, Cdc25B and Cdc2 (P < 0.05).

CONCLUSIONDADS could induce the G(2)/M arrest in HL-60 cells which may be involved in the activation of p38 MAP kinase.

Allyl Compounds ; pharmacology ; Blotting, Western ; CDC2 Protein Kinase ; genetics ; metabolism ; Cell Division ; drug effects ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Disulfides ; pharmacology ; Dose-Response Relationship, Drug ; Enzyme Activation ; drug effects ; Flow Cytometry ; G2 Phase ; drug effects ; Gene Expression ; drug effects ; HL-60 Cells ; Humans ; Phosphorylation ; drug effects ; Reverse Transcriptase Polymerase Chain Reaction ; cdc25 Phosphatases ; genetics ; metabolism ; p38 Mitogen-Activated Protein Kinases ; genetics ; metabolism

Previous studies proposed that the synergistic effect of fibroblast growth factor-21 (FGF-21) and insulin may be due to the improvement of insulin sensitivity by FGF-21. However, there is no experimental evidence to support this. This study was designed to elucidate the mechanism of synergistic effect of FGF-21 and insulin in the regulation of glucose metabolism. The synergistic effect of FGF-21 and insulin on regulating glucose metabolism was demonstrated by investigating the glucose absorption rate by insulin resistance HepG2 cell model and the blood glucose chances in type 2 diabetic db/db mice after treatments with different concentrations of FGF-21 or/and insulin; The synergistic metabolism was revealed through detecting GLUT1 and GLUT4 transcription levels in the liver by real-time PCR method. The experimental results showed that FGF-21 and insulin have a synergistic effect on the regulation of glucose metabolism. The results of real-time PCR showed that the effective dose of FGF-21 could up-regulate the transcription level of GLUT1 in a dose-dependent manner, but had no effect on the transcription level of GLUT4. Insulin (4 u) alone could up-regulate the transcription level of GLUT4, yet had no effect on that of GLUT1. Ineffective dose 0.1 mg kg(-1) FGF-21 alone could not change the transcription level of GLUT1 or GLUT4. However, when the ineffective dose 0.1 mg x kg(-1) FGF-21 was used in combination with insulin (4 u) significantly increased the transcription levels of both GLUT1 and GLUT4, the transcription level of GLUT1 was similar to that treated with 5 time concentration of FGF-21 alone; the transcription level of GLUT4 is higher than that treated with insulin (4 u) alone. In summary, in the presence of FGF-21, insulin increases the sensitivity of FGF-21 through enhancing GLUT1 transcription. Vice versa, FGF-21 increases the sensitivity of insulin by stimulating GLUT4 transcription in the presence of insulin. FGF-21 and insulin exert a synergistic effect on glucose metabolism through mutual sensitization.
Animals ; Blood Glucose ; Diabetes Mellitus, Experimental ; metabolism ; Drug Synergism ; Fibroblast Growth Factors ; pharmacology ; Glucose ; metabolism ; Glucose Transporter Type 1 ; metabolism ; Glucose Transporter Type 4 ; metabolism ; Hep G2 Cells ; Humans ; Insulin ; pharmacology ; Insulin Resistance ; Liver ; metabolism ; Mice

Objective To evaluate the occurrence and management of complications following mini- mally invasive percutaneous nephrostolithotomy (MPCNL).Methods The data of 436 cases of MPCNL from December 2001 to March 2005 were reviewed,including 249 male cases and 187 female cases.Their age ranged from 14 to 71 years with a mean of 41.6 years.Of the 436 cases,314 cases had simple nephrolith- iasis,79 had nephrolithiasis combined with upper ureterolithiasis,27 had unilateral upper ureterolithiasis,and 16 had bilateral upper ureterolithiasis.Results Among the 436 cases of MPCNL,complications occurred in 27 cases (6.2%).Of the 27 cases,5 had massive hemorrhage,which was cured by closing meatus of nephric fistula,cleaning out the blood clot within the bladder with instrument and transfusing blood;2 cases had pleural effusion,11 cases had hydroperitoneum,8 eases had renal perforating injury,and they were cured by puncture and drainage;1 case had pyocalix,which was cured by using effective antibiotics,re-punc- turing kidney and postponing pulling out the fistula catheter.Conclusions MPCNL is a minimally inva- sire operation.However,it has obvious risk if the surgeon's skill is not proficient.The improvement in the pre- vention and management of complications can promote the application of this procedure.

Objective Throush identify biochemical characteristics and virulence factors of 2 strains suspected Yersinia pestis(Y.pestis)isolated from the dead Marmota himalayana(M.himalayana)to confirm the nature epidemic focus in Dege County,Sichuan Province.Methods Y.pestis was analyzed by specific staining and shape,culturing characteristics,splitting-test by bacteriophage,test of biochemical characteristics and glycolysis ability,virulence factors,virulence,nutritional requirement,plasmid,genetic test and genetic type. Results The tested strains were Gram staining bacilus.The main biochemical characteristics were Arabinose(+)、 Rhamnose(-),Maltose(+),Melibiose(-),Glycerol(+),Denitrification(+).The virulence factors with FI+.VW+, Pgm+,Pst I+;and with the common 6.0×106,45.0×106,65.0×106 plasmids,also with the virulence-relative plasmid gene.Both their absolutely lethal dose(LD100)in mice were 50 bacteria.The nutritional requirement appeared which were depended on Phenylalanine and Methionine.With the Genomovar 5 genotype characteristics of M.himalayana plague foci of Qinghai-Tibet plateau.The difference between tested strains and Yersinia pseudotubercuosis on the 3 different culture medium was obvious.The tested strains had a Y.pestis' specific 3a fragment,Pst I and FI-Ag,at 22 ℃,the strains could be split by bacteriophage completely.Conclusions According to the diagnostic criteria of plague in China,the 2 suspected strains isolated from Dege County,Sichuan Province ale confirmed as Y.pestis.both with powerful virulenceand with the characteristics of the Y.pestis of M.himahtyana in Qinghai-Tibet plateau plague natural focus.

OBJECTIVE: To investigate the therapeutic effects and mechanisms of Bianyanning on acute pharyngitis in rats, and to provide evidence and experimental data for its clinical application. METHODS: The acute pharyngitis of rats was induced by spraying ammonia directly to their throat. The model rats were randomly divided into model control group, the high-, medium- and low-dose group of Bianyanning, while normal rats were used as control group, 10 in each group. After the corresponding drug treatment, the symptoms and manifestations of each group were observed and recorded; 24 hours after last gavaging, blood samples of each group were collected from the abdominal aorta. The serum contents of interleukin 1-beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were detected by ELISA. HE method was used to observe the characteristic of the lung tissues and the transmission electron microscopy method was used to observe the trachea cilia. RESULTS: After the treatment, compared with the model control group, the high-, medium- and low-dose group of Bianyanning, the symptoms of acute pharyngitis such as inflamed and congestive throat were relieved obviously. The morphological changes of lung and bronchus tissues were apparently improved. The contents of IL-1β and TNF-α in serum were decreased significantly. CONCLUSION Compound Bianyanning can promote the recovering process of acute pharyngitis, improve the morphology of lungs and bronchus, which may be related to inhibiting the releasing of the IL-1β and TNF-α in serum.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Interleukin-1beta ; metabolism ; Pharyngitis ; drug therapy ; immunology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism