UNLABELLEDTo screen and analyze the apoptosis- and proliferation-related genes in human nasopharyngeal carcinoma (NPC).

METHODSAccording to gene ontology classification, the abnormal expressions of the genes related to cell apoptosis and proliferation were identified in the NPC gene chip data. The cell apoptosis- and proliferation-related genes expressed in each of the 3 stages, as defined by the tree model for the pathogenesis and progression of NPC, were screened, and with literature review, their distribution in the tree model were analyzed.

RESULTSNineteen genes related to cell apoptosis were found in NPC, among which 9 were down-regulated (such as DNASE1L3) and located in the chromosome deletion regions, and 10 were up-regulated (such as DEDD) in the chromosome amplification regions. Twenty-one cell proliferation-related genes were identified, including 8 down-regulated genes (such as TUSC2) in the chromosome deletion regions and 13 up-regulated ones (such as EMP1) in the chromosome amplification regions. In the chromosome deletion regions, the down-regulated cell apoptosis-related genes participated mostly in inducing and regulating cell apoptosis, and the up-regulated cell proliferation-related genes in the chromosome amplification regions were mostly associated with the positive regulation of cell proliferation.

CONCLUSIONNPC occurs possibly through two pathways by inhibiting cell apoptosis or by promoting excessive cell proliferation.

Apoptosis ; genetics ; Cell Proliferation ; Chromosome Deletion ; Down-Regulation ; Gene Expression Profiling ; Humans ; Nasopharyngeal Neoplasms ; genetics ; pathology ; Oligonucleotide Array Sequence Analysis ; Up-Regulation

Aortopulmonary Septal Defect ; diagnostic imaging ; surgery ; Female ; Humans ; Infant ; Tomography, X-Ray Computed ; methods

OBJECTIVETo establish a nude mouse model of nasopharyngeal carcinoma (NPC) lymph node metastasis and screen the signature genes associated with the metastasis.

METHODSThe NPC 5-8F-EGFP cells were inoculated into nude mice, from which a 5-8F-LN cell line with lymph node metastasis potential was obtained. The lymphatic metastasis-related signature genes of breast cancer and head and neck squamous cell carcinoma were screened by data mining method.

RESULTSThe NPC cell lines 5-8F and 6-10B showed 307 differentially expressed genes by microarray analysis, from which 20 overlapping genes were identified, and 3 overexpressed genes were found with probable metastasis potential, namely the ADM, IRF1, and CAV1 genes. Quantitative RT-PCR validated the data mining results in the 5-8F-EGFP, 6-10B-EGFP, NP69, and 5-8F-LN cell lines. The 3 NPC cell lines 5-8F-EGFP, 6-10B-EGFP and 5-8F-LN showed significantly higher expressions of IRF1 than NP69 cells (P=0.008, 0.022, and 0.006, respectively. The expression level of CAV1 in 5-8F-EGFP cells was significantly higher than that in 6-10B-EGFP cells (P=0.014), but ADM expression showed no significant difference between the 4 cell lines.

CONCLUSIONSIRF1 may play an important role in the progression of NPC. The overexpression of CAV1 in 5-8F-EGFP cells can be associated with the high metastatic potential of the cells.

Adrenomedullin ; genetics ; Animals ; Caveolin 1 ; genetics ; Cell Line, Tumor ; Disease Models, Animal ; Gene Expression Profiling ; Humans ; Interferon Regulatory Factor-1 ; genetics ; Lymphatic Metastasis ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nasopharyngeal Neoplasms ; genetics ; pathology ; Neoplasm Transplantation ; Reverse Transcriptase Polymerase Chain Reaction ; Transplantation, Heterologous

OBJECTIVE To explore the neuro-protective effects of saffron (Crocus satius L.) on chronic focal cerebral ischemia in rats.METHODS SD rats were randomly divided into 6 groups:sham control group,MCAO group,edaravone group and saffron 30,100,300 mg·kg-1groups.Focal cerebral ischemia was induced by middle cerebral artery occlusion(MCAO).Saffron was administered orally by once daily from 2 h to 42 d after ischemia. At 42 d after cerebral ischemia, neurological deficit score, spontaneous activity test,elevated plus maze test,marble burying test and novel objective recognition test were used to evaluate the effects of saffron on the behevioural change. Infarct volume, survival neuron density, activated astrocyte number, and the thickness of glial scar were also detected. GFAP expression and inflammatory cytokine contents in ischemic peripheral region were detected by Western blot and ELISA,separately.RESULTS Saffron(100,300 mg·kg-1)improved the body weight decrease, neurological deficit and spontaneous activity. Saffron (30-300 mg·kg- 1) increased the traveled distance ratio and total time in open arm, decreased the buried marble number, which indicated that saffron could ameliorate anxiety- and depression-like behaviors. Saffron (100, 300 mg·kg-1)improved the learning and memory function,which manifested by increased discrimination ratio(DR)and discrim-ination index (DI) in T2test. The results of toluidine blue found saffron treatment (100, 300 mg·kg-1) decreased the infarct volume and increased the neuron density in cortex and hippocampal.The activated astrocyte number,the thickness of glial scar and GFAP expression in ischemic peripheral region decreased after saffron. Saffron (100, 300 mg·kg-1) decreased the contents of IL-6 and IL-1β, increased the content of IL-10 in ischemic peripheral region.CONCLUSION Saffron exerted neuro-protective effects on chronic focal cerebral ischemia,which could be related with inhibiting the activation of astrocyte and glial scar,following with the decrease of inflammatory reaction.

OBJECTIVEThe aim of the study is to explore the effect of NF-kappa B signal pathway in neonatal sepsis so as to provide the experimental base for corresponding clinical treatment of the sepsis, in which NF-kappa B is taken as the target.

METHODSThe sepsis model was established in newborn rats by giving Staphylococcus aureus subcutaneously: (1) The electrophoretic mobility shift assay (EMSA) was used to observe the activity of NF-kappa B in the lungs and the livers in newborn rats with Staphylococcus aureus sepsis. (2) Immunohistochemical method was used to observe the activity of NF-kappa B P56 in newborn rats with Staphylococcus aureus sepsis. (3) The anti-oxidant pyrrolidine dithiocarbamate (PDTC) was used to observe its effect on NF-kappa B activities of liver and lungs and on the activity of splenic NF-kappa B P56 in newborn rats with Staphylococcus aureus sepsis.

RESULTSIn newborn rats with Staphylococcus aureus sepsis, the NF-kappa B activity in lungs was enhanced at the 1st hour and reached to the peak level at the 3rd hour; then, it was weakened gradually and at the 24th hour faded away. The activity of the liver NF-kappa B was also activated and peaked at the 4th hour; then, it was gradually weakened and at the 24th hour faded away. The positive expression of splenic NF-kappa B P56 began to be intensified at the 1st hour (12.0 +/- 3.7), peaked at the 3rd hour (51.4 +/- 5.9) and showed insignificant differences at the 24th hour (3.4 +/- 1.4) as compared with the sepsis group. PDTC had an inhibitive effect on the activities of liver NF-kappa B and lung NF-kappa B and on the positive expression of splenic NF-kappa B P56 used in the dosage of 50-200 mg/kg. The larger the dosage was used, the more intensified inhibitive effect could be obtained. In the dosage of 200 mg/kg, the inhibitive effect was the most intensified.

CONCLUSIONS(1) In newborn rats with Staphylococcus aureus sepsis, the NF-kappa B of lungs, liver and spleen were activated, and all indicate a peak. (2) The anti-oxidant PDTC can inhibit NF-kappa B activity in a dose-effect fashion in newborn rats with Staphylococcus aureus sepsis.

Animals ; Animals, Newborn ; Antioxidants ; therapeutic use ; Dose-Response Relationship, Drug ; Electrophoretic Mobility Shift Assay ; Liver ; drug effects ; metabolism ; Lung ; drug effects ; metabolism ; NF-kappa B ; antagonists & inhibitors ; metabolism ; Pyrrolidines ; therapeutic use ; Rats ; Rats, Wistar ; Sepsis ; metabolism ; Staphylococcus aureus ; pathogenicity ; Thiocarbamates ; therapeutic use

OBJECTIVETo construct tree models for nasopharyngeal carcinoma (NPC)and explore the oncogenesis process of NPC.

METHODSBased on the software which Desper et al developed, tree models were constructed for colorectal carcinoma (CC) from the comparative genomic hybridization (CGH) data of 118 CC patients and for NPC from the CGH data of 140 southern Chinese patients, respectively.

RESULTSTree models for CC suggested that changes in -18q and +20q were important early events in colorectal carcinogenesis. As changes in -18q occurred prior to those in -17p, there might be some cause-effect relationship. Tree models for NPC suggested that change in -3p was an important early event in nasopharyngeal carcinogenesis, and those in -11q, -14q, -16q, -9p were also non-random genetic events in carcinogenesis, suggesting that there might be tumor-associated genes existing on these chromosome arms. The tree model also suggested the existence of oncogene on the short arm of chromosome 12.

CONCLUSIONConstructing tree models based on the CGH data to demonstrate the initiation and progression of NPC might help elucidate its multigene, multistep and multipathway development. It may provide valuable clues to explore the mechanism of tumorigenesis.

Chromosome Aberrations ; Colorectal Neoplasms ; etiology ; genetics ; Humans ; Nasopharyngeal Neoplasms ; etiology ; genetics ; Nucleic Acid Hybridization

Long-segment lichen sclerosus (LS) urethral stricture is a challenge for urologists. Limited data are available for surgeons to make a surgical decision between Kulkarni and Asopa urethroplasty. In this retrospective study, we investigated the outcomes of these two procedures in patients with LS urethral stricture. Between January 2015 and December 2020, 77 patients with LS urethral stricture underwent Kulkarni and Asopa procedures for urethroplasty in the Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (Shanghai, China). Of the 77 patients, 42 (54.5%) underwent the Asopa procedure and 35 (45.5%) underwent the Kulkarni procedure. The overall complication rate was 34.2% in the Kulkarni group and 19.0% in the Asopa group, and no difference was observed ( P = 0.105). Among the complications, no statistical difference was observed in the incidence of urethral stricture recurrence ( P = 0.724) or glans dehiscence ( P = 0.246) except for postoperative meatus stenosis ( P = 0.020). However, the recurrence-free survival rate between the two procedures was significantly different ( P = 0.016). Cox survival analysis showed that antiplatelet/anticoagulant therapy use ( P = 0.020), diabetes ( P = 0.003), current/former smoking ( P = 0.019), coronary heart disease ( P < 0.001), and stricture length ( P = 0.028) may lead to a higher hazard ratio of complications. Even so, these two techniques can still provide acceptable results with their own advantages in the surgical treatment of LS urethral strictures. The surgical alternative should be considered comprehensively according to the patient characteristics and surgeon preferences. Moreover, our results showed that antiplatelet/anticoagulant therapy use, diabetes, coronary heart disease, current/former smoking, and stricture length may be contributing factors of complications. Therefore, patients with LS are advised to undergo early interventions for better therapeutic effects.
Male ; Humans ; Urethral Stricture/etiology* ; Retrospective Studies ; Constriction, Pathologic/surgery* ; Lichen Sclerosus et Atrophicus/surgery* ; Treatment Outcome ; Urologic Surgical Procedures, Male/methods* ; China ; Urethra/surgery* ; Postoperative Complications/etiology* ; Mouth Mucosa ; Diabetes Mellitus/etiology* ; Anticoagulants ; Coronary Disease

BACKGROUNDAlthough the results of surgical treatment in cardiac valve disease continue to improve, the postoperative mortality rate and the rate of complications in patients with advanced valvular heart disease (AVHD) are still very high. We did this retrospective study to summarize the surgical experience of heart valve replacement for patients with AVHD and discuss effective ways to improve the surgical outcome.

METHODSFrom January 1994 to October 2003, surgical procedures of heart valve replacement were performed on 227 (136 men and 91 women) patients with AVHD in our Department of Cardiothoracic Surgery. The clinical data of all patients were collected and analysed. Patients' age ranged from 10 years to 77 years. In preoperative cardiac function grading, 157 cases were NYHA III and 70 cases NYHA IV. Fifty-one patients had had cardiac operations. The ultrasonic cardiac graphs showed that 145 patients suffered from moderate or severe pulmonary hypertension and 73 had combined giant left ventricle. Mitral valve replacement was performed in 32 cases, aortic valve replacement in 90, tricuspid valve replacement in 1, combined mitral and aortic replacement in 103 and combined mitral and tricuspid replacement in 1. Nineteen patients also received surgical corrections for other minor abnormalities during the operations. A logistic model was established to evaluate the influence of perioperative factors on the mortality rate.

RESULTSThe operative mortality rate was 13.2% (30/227). The main causes of death included multiple organ dysfunction syndrome (MODS), low cardiac output syndrome and ventricular fibrillation. From the results of the binary noncounterpart multivariate logistic regression, the following statistically significant factors were found to influence the operative mortality rate: redo operation, age >/= 55 years, preoperative NYHA cardiac function grading, extracorporeal circulation time >/= 120 minutes and postoperative usage of GIK (glucose, insulin and potassium) solution. All factors were risk ones except postoperative application of GIK. The Hosmer-Lemeshow goodness of fit coefficient of this model was 0.976.

CONCLUSIONSThe risk factors associated with postoperative mortality rate in the patients with AVHD were redo operation, age >/= 55 years, preoperative NYHA cardiac function grading and extracorporeal circulation time >/= 120 minutes. Postoperative usage of GIK acted as a kind of metabolic therapy and will improve the recovery for patients with AVHD. Active perioperative management and care will play a very important role in reducing the operative risk and improving the short term outcome of surgical treatment for the patients with AVHD.

Adolescent ; Adult ; Aged ; Cause of Death ; Child ; Female ; Glucose ; pharmacology ; Heart Valve Diseases ; diagnosis ; physiopathology ; surgery ; Heart Valve Prosthesis Implantation ; Humans ; Insulin ; pharmacology ; Male ; Middle Aged ; Potassium ; pharmacology ; Retrospective Studies ; Risk Factors

BACKGROUND/AIMS: This was a Phase 2 study (NCT02015793) to evaluate the pharmacokinetics, safety, and efficacy of adalimumab in Chinese patients with Crohn's disease (CD). METHODS: Thirty, adult Chinese patients with CD (CD Activity Index [CDAI] 220-450; high-sensitivity [hs]-C-reactive protein [CRP] ≥3 mg/L) received double-blind adalimumab 160/80 mg or 80/40 mg at weeks 0/2, followed by 40 mg at weeks 4 and 6. An open-label extension period occurred from weeks 8-26; patients received 40 mg adalimumab every other week. Serum adalimumab concentration and change from baseline in fecal calprotectin (FC) were measured during the double-blind period. Clinical remission (CDAI <150), response (decrease in CDAI ≥70 points from baseline), and change from baseline in hs-CRP were assessed through week 26. Nonresponder imputation was used for missing categorical data and last observation carried forward for missing hs-CRP/FC values. No formal hypothesis was tested. Adverse events were monitored. RESULTS: Mean adalimumab serum concentrations during the induction phase were 13.9-18.1 µg/mL (160/80 mg group) and 7.5-9.5 µg/mL (80/40 mg group). During the double-blind period, higher remission/response rates and greater reductions from baseline in hs-CRP and FC were observed with adalimumab 160/80 mg compared to that with 80/40 mg. Adverse event rates were similar among all treatment groups. CONCLUSIONS: Adalimumab serum concentrations in Chinese patients with CD were comparable to those observed previously in Western and Japanese patients. Clinically meaningful remission rates and improvement in inflammatory markers were achieved with both dosing regimens; changes occurred rapidly with adalimumab 160/80 mg induction therapy. No new safety signals were reported.
Adult ; Asian Continental Ancestry Group* ; Crohn Disease* ; Humans ; Leukocyte L1 Antigen Complex ; Pharmacokinetics

Adult ; Animals ; Antibodies, Viral ; blood ; Fluorescent Antibody Technique ; Humans ; SARS Virus ; immunology