Objective To explore the effects of polymorphisms of Crohn's disease related NOD2 gene and human beta-defensin 2 (hBD-2) on transcription of hBD-2 gene and its mechanism. Methods HEK293T cells were transfected with hBD-2 gene and NOD2 eukaryotic expression plasmid, and were then stimulated with LPS, TNF-α, or BAY 11-7082 (antagonist of NF-κB), respectively. Transcriptional activity of hBD-2 was detected afterwards. Results LPS could suppress transcription of hBD-2 (P=0. 020), which was increased by TNF-α in a dose-dependent manner (P =0. 004). In the presence of LPS, there was sig-nificant difference in transcriptional activity of hBD-2 between wild-NOD2 transfected group and mutated NOD2 (P268S) transfected group (P=0. 008), but there was no significant difference between wild hBD-2 transfected group and mutated hBD-2 transfected group (P=0. 053). With the stimulation of TNF-α (5 ng/ml), there was a significant difference between mutated hBD-2 transfected group and wild hBD-2 transfected group (P=0. 006), but no significant difference between wild-NOD2 transfected and mutated NOD2 transfected group was defected (P = 0. 064). Pretreatment with BAY 11-7082 before TNF-α (5 ng/ml) significantly inhibited the transcriptional activity of hBD-2 (P < 0. 001). Conclusion The poly-morphism of NOD2 affects the innate expression of hBD-2, the polymorphism of site in hBD-2 promoter (-233) may lead to significant decline of the inducible expression of hBD-2, and NF-κB might be a key pathway that NOD2 protein mediates the expression of defensin.

Objective To investigate the association of two single nuclear peptides(SNPs)polymorphisms(rs11209026 and rs11805303)which lies in interleukin-23 receptor(IL23R)gene with susceptibility to inflammatory bowel disease(IBD).Methods The target SNPs were directly sequenced by polymerase chain reaction(PCR)and gene polymorphisms of 50 healthy and 81 patients with IBD (Crohn's disease in 41 patients and ulcerative colitis in 40 patients)were analyzed using chromassoftware.Results The geno-type frequency and allelic frequency of rs11209026 were 7.3%and 3.7%in patients with Crohn's disease respectively,15.0%and 7.5%in patients with ulcerative colitis respectively as well as 14.0%and 7.0%in normal population respectively(all P value＞0.05).The geno-type frequency and allelic frequency of rs11805303 were 22.0%and 52.4%in patients with Crohn's disease respectively,15.0% and 41.2% in patients with ulcerative colitis respectively as well as 34.0%and 59.0%in normal population respectively(all P value＞0.05).But in allelic frequency there was significant difference between ulcerative colitis patients and normal population(P=0.018).The polymorphisms of rs11805303 loci did not correlate with age,gender,disease duration.activity and site in patients with ulcerative colitis.Conclusions IL23R gene polymorphism is not associated with the susceptibility to Crohn's disease.rs11805303 allele may be related with susceptibility to ulcerative colitis.But no correlation was found between the SNP polymorphisms and the clinical characteristic of ulcerative colitis.

16 and the distribution of severe trauma more than 2 anatomic parts.They were randomly divided into two groups:intensive insulin treatment group(n=31)and control group(n=31).Intensive insulin treatment group received insulin with insulin pump in order to maintain blood glucose levels at 4.0-6.1 mol/L,while the control group received routine insulin treatment in order to mmaintain blood glucose levels at 10.0- 11.0 mol/L.Plasma levels of TNF-?,IL-1,IL-6, CRP,APACHEⅡscores and cure rate were analyzed before and after the treatment.Data was expressed as mean?standard deviation.Two- tailed T test and ANOVA were used for comparison in SPSS 10.0,and changes were considered as statistically significant if P value was less than 0.05.Results After the intensive insulin treatment, patient's hemodynamic parameter apparently improved,APACHEⅡscores descended,and the levels of TNF-?, Ib-1,IL-6,CRP all declined,in comparison with control group,there were significant differences. Intensive insulin treatment might improve patient's general condition and decrease complications and mortality of severe multiple trauma.

OBJECTIVETo discuss the effect of calcitonin gene-related peptides (CGRP) on epithelial cadherin (E-cd) expression in human bronchial epithelial cells (HBECs) in vitro.

METHODSThe effect of CGRP on E-cd protein and mRNA expression in both normal and O3-challenged HBECs were determined by immunocytochemistry and RT-PCR. The signal transduction pathways of CGRP were observed by using protein kinase C(PKC) inhibitor (H-7), calmodulin(CaM) inhibitor (W-7) and PKA inhibitor (H-89).

RESULTSCGRP increased E-cd mRNA and protein expressions of normal and O3-challenged HBECs in a dose-dependent manner. CGRP had no effect on cytoplasm E-cd expression. Pre-treatment with H-89, H-7 and W-7, the up-regulatory effect of CGRP on E-cd expression was partly abolished.

CONCLUSIONCGRP increased in cytomembrane E-cd expression of normal and O3-challenged HBECs in a dose-dependent manner. E-cd expression on HBECs was strengthened by CGRP via PKA, PKC and CaM pathways.

Bronchi ; cytology ; Cadherins ; metabolism ; Calcitonin Gene-Related Peptide ; administration & dosage ; pharmacology ; Cell Line ; Epithelial Cells ; drug effects ; metabolism ; Humans ; Ozone ; RNA, Messenger ; genetics

OBJECTIVETo investigate the diagnostic methods and reasonable treatment of Peutz-Jeghers syndrome (PJS).

METHODSClinical data of six patients with PJS were reviewed.

RESULTSRepeated abdominal pain, intussusception and intestinal polyp with bleeding were main manifestations. Four patients father,three patients grandfather and one patients mother were diagnosed with PJS. Three patients had family history of cancer. Case 4 and case 5 underwent laparotomy for many times because of intussusceptions caused by polyps or recurrent abdominal pain. Case 1 and case 4 had polyps synchronous with adenoma, and case 2 had polyp with gastric cancer. Main treatment included polyp resection and partial small intestinal and colon resection.

CONCLUSIONSPatients with PJS have family history of cancer and a high incidence of polyp recurrence of small intestine. Surgical intervention is the first choice regimen. Surveillance should be emphasized on gastrointestinal tract and other potential malignant organs in PJS patients.

Adolescent ; Adult ; Female ; Humans ; Intestine, Small ; surgery ; Male ; Pedigree ; Peutz-Jeghers Syndrome ; diagnosis ; genetics ; surgery

OBJECTIVETo study the effect of Tangshenkang Granule (TG) containing serum on renal mesangial cells' (RMCs) proliferation and TGF-β1/Smad2/3 pathway in the high glucose condition.

METHODSTwelve SD rats were randomly divided into four groups, i.e., the low dose TG group, the middle dose TG group, the high dose TG group, and the blank control group, 3 in each group. After 7-day gastrogavage via portal vein blood, rats were sacrificed and their serum samples were collected. RMCs were cultured in common rat serum and TG containing serum respectively. The proliferation of mesangial cells was determined by methly thiazolyl tetrazolium (MTT) assay to determine the optimal TG containing serum concentration. Expression levels of TGF-β1 mRNA and protein were determined by real time quantitative PCR and ELISA. Smad2/3 protein expression and phosphorylation were determined by Western blot and immunofluorescence.

RESULTSTG containing serum at different doses could inhibit high glucose induced RMC cells' proliferation, TGF-β1 over-expression and Smad2/3 phosphorylation.

CONCLUSIONTG containing serum could inhibit high glucose induced RMC cells' proliferation, and its mechanism might be possibly associated with inhibiting TGF-β1/Smad2/3 signaling pathway.

Animals ; Cell Proliferation ; Drugs, Chinese Herbal ; pharmacology ; Glucose ; Mesangial Cells ; Phosphorylation ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Serum ; Signal Transduction ; Smad2 Protein ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVE: To explore the role of vasoactive intestinal peptide (VIP) on LPS-induced MMP-9 expression by alveolar macrophages (AM) in rats. METHODS: LPS-induced cultured Wistar rats AMs were treated with different concentrations of VIP (10(-10) to approximately 10(-6) mol/L) for 24 h. AMs and the supernatant were collected to measure the MMP-9 expression and activity by RT-PCR and gelatin zymography, respectively. Results The MMP-9 activity and expression of LPS-induced AMs were significantly higher than those in the control group (P < 0.01). VIP (10(-9) to approximately 10(-6) mol/L) down-regulated LPS-induced MMP-9 activity and its expression. The effects were diminished by H-7 and W-7, an antagonist of protein kinase C (PKC) and calmodulin (CaM) (P < 0.01). CONCLUSION VIP can decrease LPS-induced MMP-9 activity and its expression, which may be related to protein kinase C and calmodulin pathway. VIP may have protective roles in the lung injury.
Animals ; Calmodulin ; metabolism ; Cells, Cultured ; Down-Regulation ; Female ; Lipopolysaccharides ; Macrophages, Alveolar ; cytology ; metabolism ; Male ; Matrix Metalloproteinase 9 ; biosynthesis ; genetics ; Protein Kinase C ; metabolism ; Rats ; Rats, Wistar ; Vasoactive Intestinal Peptide ; pharmacology

AIMTo explore the effects of calcitonin-gene-related peptide (CGRP) on LPS-induced MMP-9 secretion by alveolar macrophages (AM) in vitro.

METHODSThe supernatant of LPS-induced Wistar rat AM from different intervention groups were collected to measure the activity by gelatin zymography.

RESULTS(Only secreting a small amount of MMP-9 with unstimulated AM, LPS stimulated MMP-9 production in a concentration-dependent manner (p < 0.01). (2) The activity of MMP-9 in CGRP intervention groups at different levels were significantly lower than those in non-intervention group (p < 0.01). (3) The inhibiting effects of CGRP were diminished by H-7 and W-7, an antagonist of protein kinase C (PKC) and calmodulin (CaM) (p < 0.05).

CONCLUSIONThese data suggested that CGRP involved in the MMP-9 secretion by AM, partly, via PKC and CaM pathway.

Animals ; Cells, Cultured ; Female ; Lipopolysaccharides ; adverse effects ; Macrophages, Alveolar ; secretion ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Rats ; Rats, Wistar ; Receptors, Calcitonin Gene-Related Peptide ; metabolism

OBJECTIVETo study the clinical features of hyperparathyroidism due to parathyroid tumors, and evaluate the efficiency of surgical management.

METHODSTwenty-two patients with hyperparathyroidism resulted from parathyroid tumors were reviewed. The age ranged from 32 to 79 years, 9 males and 13 females. Recurrent laryngeal nerve was routinely exposed, and procedures were performed in normal tissue in initial surgery. Additional selective neck dissection of levels II, III, IV, and VI was taken in the cases with recurrent cancer. Local flaps were used to repair the esophageal defects after resecting tumors. The recurrent laryngeal nerves of 4 cases had to be sacrificed because they were embedded in the tumor tissues despite the nerves had normal function before operation. Prophylactic tracheostomy was performed in 5 cases.

RESULTSEight cases were identified pathologically as parathyroid carcinoma, of them four with neck metastasis, and 14 cases as parathyroid adenoma after surgery. Their PTH dropped to normal level within two hours after surgery and hypercalcemia disappeared in two days postoperatively. The PTH and serum calcium were in normal range during the follow-up of 12 to 40 months. Recurrence occurred again in two cases in 6 and 8 months after the removal of the recurrent tumor tissues respectively. Esophageal fistula, chylous fistula and dehiscence of sternotomy developed in three cases separately. The tracheostomy was removed in four cases two weeks after operation and in one case six weeks after operation. One patient with parathyroid adenoma died of hypocalcemia about two weeks after operation and another one with recurrent parathyroid carcinoma also died of hypercalcemia 52 months after revised surgery.

CONCLUSIONExtended resection of tumor and intraoperative PTH assay were strongly suggested for the managements of both benign and malignant parathyroid tumors.

Adult ; Aged ; Calcium ; blood ; Female ; Humans ; Hyperparathyroidism ; etiology ; surgery ; Male ; Middle Aged ; Neck Dissection ; Neoplasm Recurrence, Local ; Parathyroid Hormone ; blood ; Parathyroid Neoplasms ; complications ; surgery ; Retrospective Studies ; Tracheostomy

OBJECTIVEThe Chinese Children's Leukemia Group (CCLG)-acute lymphoblastic leukemia (ALL) 08 protocol for childhood ALL was established in 2008. This study aims to evaluate the drug-related toxicities of CCLG-ALL 08 protocol in the treatment of childhood ALL.

METHODSA total of 114 children with newly diagnosed ALL were treated with the CCLG-ALL 08 protocol. The protocol was divided into five phases: remission induction (VDLD), early reinforcement (CAM), consolidation therapy, delayed reinforcement (DIa & DIb) and maintenance treatment. Drug-related toxicities in each phase were evaluated according to the Common Terminology Criteria for Adverse Events version 4.0.

RESULTSToxicities were more frequent in phase VDLD than other treatment phases, including hepatotoxicity (87.7%), dental ulcer (20.2%), hyperglycemia (20.2%), prolonged activated partial thromboplastin time (21.1%) and decreased fibrinogen (34.2%), with the incidence rates of severe adverse events at 7%, 0, 1.3%, 0.8% and 2.7% respectively. The incidence of allergic reaction to L-ASP was significantly higher in phase DIa than in phase VDLD (28.0% vs 7.9%; P<0.01), and there were no longer any allergic reactions in 15 patients who received continuing treatment with pegaspargase instead. There was no severe arrhythmia, myocardial ischemia, decreased left ventricular function, osteonecrosis, myopathy, organ failure or treatment-related mortality.

CONCLUSIONSThe drug-related toxicities of CCLG-ALL 08 protocol are common in phase VDLD, but they are mild and reversible. There is no treatment-related mortality. The CCLG-ALL 08 protocol for childhood ALL is safe.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; Asparaginase ; adverse effects ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Remission Induction