The new generation cyclooxygenase (COX-2) inhibitor could reduce the gastrointestinal side effect of NSAID drugs, but eventually increase the cardiovascular risk, because its selective inhibition of COX-2 induces the imbalance between PGI2 and TXA2 and the reduction of vasodilatory NO. Under pathological conditions, active oxygen species (O2-*2, etc) were used to induce endo- thelial dysfunction, activate NF-κB to induce expressions of pro-inflammatory cytokines IL-1β and TNF-α, increase ET-1, TXA2 with vasoconstrictor effect, reduce PGI2 and NO with vasodilatory effect, generate further oxidative damage together with NO, and reduce the bioavailability of NO. NO-NSAIDs and NO-Coxibs drugs raised the level of NO by introducing NO-donor (ONO2). NSAIDs drugs enhanced the anti-inflammatory activity of COX-2 and reduced gastrointestinal side effects by inhibiting selectively COX-2. If antioxidant structures with active ingredients of traditional Chinese medicines were introduced to improve the antioxidant activity of NSAIDs, they could scavenge the active oxygen species to protect the normal function of vascular endothelia and enhance the bioavailability of NO, which is conducive to enhance the cardiovascular safety of cyclooxygenase (COX-2) inhibitor.
Anti-Inflammatory Agents ; therapeutic use ; Biomarkers, Pharmacological ; Cardiovascular Diseases ; drug therapy ; enzymology ; immunology ; Cyclooxygenase 2 ; immunology ; Cyclooxygenase 2 Inhibitors ; adverse effects ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; NF-kappa B ; immunology ; Reactive Oxygen Species ; immunology ; Tumor Necrosis Factor-alpha ; immunology

Objective To explore the mastery of relevant knowledge and skills for autism rehabilitation teachers in Beijing private rehabilitation agencies. Methods 51 autism rehabilitation teachers were selected from 10 Beijing private rehabilitation agencies and tested with self-prepared questionnaire. Results Rehabilitation teachers believed that professional knowledge, rehabilitation skills and special education basics ranked the former three positions as for knowledge importance; teachers' basic skills, professional knowledge and special education basics ranked the former three positions as for knowledge mastery. There were difference in academic background and business life. 95% teachers believed that the training form was knowledge plus case plus guidance. The best training time was weekends or summer and winter vacations. The curriculum expected mainly focused on behavior modification, class management, and training system that generally used for children with autism. Conclusion Autism rehabilitation teachers in Beijing private rehabilitation agencies urgently need training in the aspects of expertise, rehabilitation skills and so on.

Objective To evaluate the feasibility of laparoscopic nephroureterectomy with bladder-cuff resection by TUR for upper urinary tract carcinoma. Methods Eighty-two patients with upper urinary tract transitional cell carcinoma(69 cases in renal pelvis and 13 in ureter)underwent retroperitoneal laparoscopic nephroureterectomy and bladder-cuff resection by TUR. This group of cases was retrospectively summarized including operative time, blood loss, drainage mounting days, catheterizing days, post-operative complications and hospital stays. Results All 82 operation procedures were successfully performed without severe complication. The mean operative time was 135 minutes.The mean length of hospital stay was 7 days postoperatively. The mean time with drainage and Foley catheter were 3 days and 6 days respectively. Follow-up time ranged from 6 to 76 months for 74 patients. The 3-year carcinoma recurrence was 10.6% (5/47). Only 1 patient was found incision tumor recurrence in 8 month after the procedure. Conclusion Retroperitoneoscopic nephroureterectomy with bladder cuff resection by TUR could be a feasible procedure to treat upper urinary tract transitional cell carcinoma.

Objective To investigate the short-term efficacy and the influencing factorof zoledroniacid combined with ra-diotherapy and single radiotherapy in the treatmenof bone metastasiin non-small cell lung cance(NSCL) .MethodTotally 117 NSCLpatientwith bone metastase(153 lesions) receiving the bone lesion radiotherapy in the TumoCenteof ouhospital from 2009 to 2013 were selected and treated by zoledroniacid combined with radiotherapy (combined therapy group ,n=54) and the single radiotherapy (single radiotherapy group ,n=63) .The bone pain relief and influence factorwere analyzed .ResultThe effective ratein the single radiotherapy group and the combined radiotherapy group were 69 .74% and 92 .21% respectively (χ2 =13 .75 ,P＜0 .01);the multivariate Logistiregression analysishowed thathe bone pain relief wacorrelated with the treatmenmode ,moreovethe bone pain relief rate in the combined therapy group wasignificantly highethan thain the single therapy group (OR=4 .60 ,95% CI:1 .23-17 .20 ,P=0 .02) .In the subgroup analysiof treatmenmode,the patientwith osteolytile-sions(OR=26 .59 ,95% CI:3 .29-215 .12 ,P=0 .00) had betteeffec.The combined therapy group had more superiority in the as-pecof non-skeletal related eventoccurrence (OR=4 .40 ,95% CI:1 .49 -12 .99 ,P=0 .01) .Conclusion Radiotherapy combined with zoledroniacid habettecurative effeccompared with single radiotherapy in the NSCLC patientwith bone metastasi.

Objective To observe the effect of γ-ray irradiation on CD4 + CD25 + regulatory T cells (Tregs),and to investigate the mechanism of immune injury induced by irradiation.Methods The thymus and spleen of C57BL/6 mice were taken and weighted 1-28 d after γ-ray irradiation,and the organ coefficients were calculated.The amount of mouse peripheral WBC measured,CD4 + T cells and Tregs in peripheral and splenic were analyzed by flow cytometry.Results Coefficients of mouse thymus and spleen decreased significantly 1 d post irradiation,and reached to the bottom at 7 d.Coefficients did not recover to control level 28 d after radiation.Peripheral WBC continuously decreased and reached the bottom at 7 d,and did not recover to control level up to 28 d postirradiation.Peripheral CD4 + T lymphocyte temporally reduced at 1 d,while it increased at 7 d,and it approached to control level at 28 d after radiation.Splenic CD4 + T cells slightly reduced at 7 d however,they basically maintained as the same level as control 14 d and 28 d after radiation.Peripheral Tregs ascended at 1 d and reached the peak at 7 d,and reduced at 14 d and 28 d postirradiation,although they still were significantly higher than those of control group.At the same time,splenic Tregs increased significantly and achieved peak value at 1 d,and then gradually decreased and reached the minimum at 28 d after irradiation,which were significantly lower than those of control group( t =2.731,P ＜ 0.05).Conclusions Mouse thymus and spleen were injured severely,and the number of immunocytes decreased after 6 Gy whole body γ-ray irradiation.However,Tregs with immunosuppressive action increased significantly postirradiation,revealing that Tregs were closely correlated with immune function depression and immunomodulation imbalance induced by ionizing radiation.

A 18-year-old female patient after cleft lip and palate surgery with an uncommon complication-precardium area pain were reported. The psychological treatment and nursing along with routine clinical treatment to the patient were applied. The patient had recovered from the precardium area pain after one week treatment.
Adolescent ; Cleft Lip ; Cleft Palate ; Female ; Humans ; Pain

OBJECTIVETo compare the efficacy and safety of the common antivirals, including adefovir dipivoxil (ADV), pegylated-interferon alpha-2a (peg-IFN) and lamivudine (LAM), used as combination therapies to treat chronic hepatitis B (CHB) patients with positivity for the hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) harboring the ADV-resistance mutation, rtN236T, and to explore the factors associated with curative outcome.

METHODSSixty-five adult CHB patients (age range: 20-60 years) who were unresponsive to ADV therapy (HBeAg-positive; HBV DNA >or= 10(5) copies/ml), LAM-naive, and tested positive for the rtN236T HBV mutation were enrolled in the study and randomly divided into two treatment groups: Group A (n = 33), who were administered ADV (10 mg/day, orally) plus peg-IFN (180 microg/week, subcutaneous injection) for 48 weeks; and Group B (n = 32 patients), who received the ADV plus LAM (100 mg/day, orally) for 48 weeks followed by continued LAM treatment for an additional 24 weeks. Pre- (baseline), during and post-treatment measurements of HBV viral loads and hepatitis B markers were made by quantitative PCR and electrochemiluminescence assays, respectively. All patients underwent liver biopsies to determine the histological activity index (HAI) and treatment response regarding inflammation and fibrosis stage. The rates of virological response (VR), HBeAg-negativity, HBeAg seroconversion, and alanine aminotransferase (ALT) normalization were calculated, and the significance of differences between groups were assessed by Student's t-test and Chi2 test.

RESULTSThere were no significant differences between the two groups in regards to sex, age, or baseline levels of HBV DNA, ALT, and total bilirubin (P > 0.05). At weeks 24 and 48 of treatment and 24 after treatment end, group A showed significantly higher (vs. group B, P < 0.05) rates of reduced HBV DNA viral loads (81.8%, 90.9%, and 75.8% vs. 53.1%, 56.2%, and 59.4%), VR (48.5%, 60.6%, and 42.4% vs. 31.3%, 34.4%, and 31.3%), HBeAg-negativity (39.4%, 60.6%, and 54.5% vs. 12.5%, 37.5%, and 37.5%), HBeAg seroconversion (27.3%, 54.5%, and 48.5% vs. 6.3%, 15.6%, and 18.8%), and ALT normalization (72.7%, 84.8%, and 78.8% vs. 46.9%, 56.3%, and 46.9%). After 48 weeks of treatment, group A showed significantly improved HAI (vs. group B, P < 0.05). With the exception of treatment-related increased creatinine (P < 0.05), group A showed significantly higher rates of adverse reactions; although, none was serious enough to threaten patient safety or necessitate early termination of the treatment regimen. Twenty-four weeks after treatment completion, five patients had HBV viral loads of >or= 2log10 copies/ml and four had < or= 500 copies/ml, and ALT was normalized in 28 patients. The four patients in group A with HBV DNA < or= 500 copies/ml and elevated ALT during treatment did not show HBeAg seroconversion.

CONCLUSIONPeg-IFN plus ADV combination therapy produced better outcomes than the ADV plus LAM combination therapy in regards to HBV viral loads, VR rate, HBeAg-negative rate, HBeAg seroconversion rate, ALT normalization rate, and HAI, but was associated with a higher rate of adverse reactions (none of which were severe). Lack of HBeAg seroconversion was associated with higher virus load and ALT levels.

Adenine ; adverse effects ; analogs & derivatives ; therapeutic use ; Adult ; Drug Resistance, Viral ; genetics ; Drug Therapy, Combination ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; drug therapy ; virology ; Humans ; Interferon-alpha ; adverse effects ; therapeutic use ; Lamivudine ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Mutation ; Organophosphonates ; adverse effects ; therapeutic use ; Polyethylene Glycols ; adverse effects ; therapeutic use ; Recombinant Proteins ; adverse effects ; therapeutic use ; Young Adult

OBJECTIVETo investigate the expression profiles of serum Golgi protein-73 (GP73) in liver cirrhosis and primary hepatic carcinoma (PHC) and determine its clinical value for differential diagnosis.

METHODSSerum protein expressions of GP73 and alpha-fetoprotein (AFP) were detected by enzyme-linked immunosorbent assay and chemiluminescence assay, respectively, in patients with PHC (n=80), liver cirrhosis (n=65), and healthy controls (n=50). Inter-group changes were assessed by Kruskal-Wallis test, and significance of these differences was assessed by Mann-Whitney test. A receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic efficiency and determine the cut-off values for GP73 and AFP. Sensitivity and specificity were compared by the Chi-squared test. Correlation between serum GP73 expression and clinical parameters was determined by Spearman's rank correlation analysis.

RESULTSThe PHC group showed significantly higher serum GP73 (282.0 mug/L) than the liver cirrhosis group (211.8 mug/L) and control group (58.3 mug/L) (H = 93.30, P less than 0.01). For differential diagnosis of PHC and liver cirrhosis, the cut-off value was 318.1 mug/L for GP73 and 13.4 mug/L for AFP. Sensitivity of GP73 was lower than AFP (45% (36/80) vs. 65% (52/80); X2 = 8.02, P less than 0.05). Specificity of GP73 was lower than AFP but no significance was found (83.1% (54/65) vs. 87.7% (57/65); X2=0.27, P more than 0.05). The areas under the ROC curves were not significantly different between GP73 and AFP (0.65 (95% confidence interval (CI): 0.54~0.72) vs. 0.75 (95% CI: 0.67~0.83); Z = 1.88, P more than 0.05). The area under the ROC curves increased but not significantly (0.80 (95% CI: 0.73~0.88) vs. 0.75 (95% CI: 0.67~0.83); Z=2.61, P more than 0.05). Serum GP73 was correlated with liver cirrhosis (r=0.27), vascular invasion (r=0.29), and TNM staging (r=0.27) (all P less than 0.05), but not with sex (r=0.13), age (r=0.10), enhanced AFP (> 13.4 mug/L; r=0.03), tumor size (r=0.18), or distant metastasis (r=0.04), all P less than 0.05.

CONCLUSIONSerum GP73 and AFP have comparable diagnostic efficiency, but the sensitivity of AFP is superior for differential diagnosis of liver cirrhosis and primary hepatic carcinoma. Elevated serum GP73 may be correlated with liver tumor load and aggressiveness.

Adult ; Aged ; Carcinoma, Hepatocellular ; diagnosis ; Case-Control Studies ; Diagnosis, Differential ; Female ; Humans ; Liver Cirrhosis ; diagnosis ; Liver Neoplasms ; diagnosis ; Male ; Membrane Proteins ; blood ; Middle Aged ; Sensitivity and Specificity ; Transcriptome ; alpha-Fetoproteins ; metabolism

OBJECTIVETo design and synthesize small interfering RNA (siRNA) targeting connective tissue growth factor (CTGF) and to investigate its effect on liver fibrosis.

METHODSThe interference sequence of CTGF was designed and synthesized. Rat hepatic fibrosis model was induced by intraperitoneal injection of 40 % CCl4(3 ml/kg). Thirty male rats were randomly divided into 5 groups: in normal control and model groups rats received tail vein injection of normal saline every 3 days for 8 consecutive weeks; in preventive group rats received tail vein injection of CTGF siRNA (0.1 mg/kg) every 3 days for 8 weeks; in 2-w treatment group CTGF siRNA was given for 6 weeks starting from two weeks after CCl4 injection; in 4-w treatment group CTGF siRNA was given for 4 weeks starting 4 weeks after CCl4 injection. The serum and hepatic tissue samples were harvested 3 days after the last CCl4 injection. Hepatic fibrosis indices were measured. Expression of CTGF mRNA and protein in the liver was evaluated by RT-PCR and Western blot, respectively. Fibrosis in rat liver was analyzed by Masson staining.

RESULTSCompared with model group (0.544 0.019), the expression of CTGF mRNA and protein in liver of both preventive(0.105 ± 0.003) and 2-w treatment groups (0.190 ± 0.006) were markedly down-regulated (P<0.05). Inflammation, necrosis and fibrosis in hepatic tissue were significantly attenuated. In addition, the serum ration of liver fibrosis indices was greatly reduced(P<0.05). Compared with preventive and 2-w treatment groups, the expression of CTGF mRNA and protein in liver in 4 weeks of treatment group were up-regulated (P<0.05); inflammation, necrosis and fibrosis in hepatic tissue were relative increased; and the serum concentrations of liver fibrosis indices were relatively higher (P<0.05).

CONCLUSIONThe highly effective CTGF siRNA has been successfully synthesized, which can inhibit CTGF expression in liver, prevent hepatic fibrosis and its progress in rats.

Animals ; Cells, Cultured ; Connective Tissue Growth Factor ; genetics ; metabolism ; Genetic Therapy ; Liver ; pathology ; Liver Cirrhosis, Experimental ; metabolism ; pathology ; therapy ; Male ; RNA, Small Interfering ; genetics ; Rats ; Rats, Sprague-Dawley