OBJECTIVETo observe the effect of Tetramethyl pyrazine (TMP) on the cytokines and inflammatory mediators in the serum and the synovial fluid of collagen-induced arthritis (CIA)rats, and further to investigate its possible mechanisms for treating rheumatoid arthritis (RA).

METHODSType II CIA rat model was established. Rats in the TMP group were administered with TMP at 50 mg/kg and 100 mg/kg, once daily. Dexamethasone at 2.0 mg/kg was intramuscularly injected to those in the Dexamethasone treated group, once daily. Normal saline at 2 mL/kg was given to those in the normal control group and the model group, once daily. All medication was started from the 7th day, lasting to the 35th day. CIA rats' foot swelling degree was observed. Contents of serum IL-1, IL-6, IL-2, NO and PGE2in the synovial fluid were detected by radioimmunoassay and nitrate reduction method.

RESULTSCompared with the normal group, the foot swelling obviously increased, contents of NO and PGE2 in the synovial fluid were obviously elevated in the model group (P < 0.01). Compared with the model group, the foot swelling could be obviously inhibited by 100 mg/kg TMP and Dexamethasone; serum levels of IL-1 and IL-6 obviously decreased, serum IL-2 level obviously increased, contents of NO and PGE, decreased (P < 0.01). TMP 50 mg/kg could obviously inhibit the foot swelling of CIA rats (P < 0.01). There was no statistical difference in other indices (P > 0.05).

CONCLUSIONSTMP at 100 mg/kg showed obvious inhibition on CIA rats. Its inhibitory effect might be correlated to inhibiting activities of endogenous cytokines and the generation of inflammatory mediators in inflammation local regions, improving contents of anti-inflammation cytokines, and inducing the balance of the inflammatory cytokine network.

Animals ; Arthritis, Experimental ; blood ; metabolism ; Dinoprostone ; metabolism ; Female ; Interleukin-1beta ; blood ; Interleukin-2 ; blood ; Interleukin-6 ; blood ; Male ; Nitric Oxide ; metabolism ; Pyrazines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Synovial Fluid ; metabolism

Objective To determine the involvement of DNA demethylation in tumor necrosis factor-α(TNF-α)-induced matrix metalloproteinase 9 ( MMP9) expression in human epidermal keratinocytes. Methods Real-time RT-PCR, Western blot, and enzyme-linked immuno sorbent assay (ELISA) were performed to determine the mRNA and protein levels of MMP9 after human keratinocyte cell line (HaCaT) cells were treated with 10 ng/ ml TNF-α or 2. 5 μmol/ L DAC/ 300 nmol/ L TSA. Bisulfite sequencing PCR ( BSP) and Methylation-sensitive high-resolution melt analysis ( Ms-HRM) were used to detect significantly differentially demethylated CpG sites in the human MMP9 promoter region in cells exposed to TNF-α. Different sites methylation constructs of promoter-luciferase reporter gene were made to detect the influences of site-specific DNA demethylation on transcription activity of MMP9 promoter. Results Compared with PBS-treated control, TNF-α significantly increased the expression of MMP9 in HaCaT cells for indicated culture duration ( P < 0. 05 ). Real time PCR, Western blot, and ELISA analysis demonstrated that the mRNA and protein levels of MMP9 were increased initially, followed by a decline with prolonged incubation time. After TNF-α treatment, varied degrees of DNA demethylation occurred at 10 CpG sites in the promoter of MMP9, and the changes at the -36 bp site were statistically significant (P<0. 05). The demethylation at the -36 bp site greatly increased the transcription activity of MMP9. Conclusion TNF-α promotes MMP9 expression in HaCaT cells through inducing -36 bp site DNA demethylation on the promoter of MMP9.

Adolescent ; Adult ; Cause of Death ; Child ; Female ; Hematologic Neoplasms ; mortality ; surgery ; Hematopoietic Stem Cell Transplantation ; mortality ; Humans ; Male ; Middle Aged ; Tissue Donors ; Young Adult

Air ; analysis ; Chromatography ; methods ; Iodine ; analysis ; Workplace

Objective To systematically evaluate maternal perinatal complications and neonatal outcomes after in vitro fertili zation and embryo transplantation(IVF-ET).Methods The computer retrieval was performed on the databases of PubMed,Cochrane library,EMbase,CNKI,Wanfang and Chinese biomedical literature database.The articles on the comparison between IVF and natural pregnancy were included.The RevMan5.3 software was adopted to conduct the meta analysis.Results Twenty-three articles conforming to the requirements were included,including 1 312 651 cases,among them 113 044 cases were IVF and 1 199 607 cases were naturalpregnancy.IVF mother's age was larger than that of natural pregnancy,while the gestational weeks were smaller than those of natural pregnancy,the newborn birth weight was lighter than that of natural pregnancy(P＜0.05);the probability of pregnancy-induced hypertension (PIH),placenta previa,postpartum hemorrhage and gestational diabetes mellitus (GDM) occurrence in IVF mother were higher than that of natural pregnancy (P＜0.05);the rate of multiple and cesarean section in IVF mothers were higher than that of natural pregnancy (P＜0.05);the occurrence rates of small for gestational age(SGA),low birth weight infants,stillbirth and premature in IVF were higher than those of natural pregnancy (P＜0.05).Conclusion The maternal perinatal complications in IVF are higher than those of natural pregnancy,and the birth outcomes in IVF are worse than those of natural pregnancy.

Objective To investigate the efficacy and safety of Technetium 99m Tc methylenediphos-phonate injection (Yunke) and various combination therapy on rheumatoid arthritis.Methods All 137 patients enrolled in trial group.Among them 67 patients received Technetium 99m Tc methylenediphosphonate alone,42 patients received combination therapy with methotrexate and mobik and 28 patients received calcium orally meanwhile.Clinical manifestations and lab markers were observed carefully.Results The conditions of 67 patients receiving Technetium 99m Tc methylenediphosphonate alone were improved,42 patients received combination therapy had better effect and 28 patients in middle and old-age taking calcium orally simultaneously showed superiority in remission of rest pain and descent of ESR.Conclusion Technetium 99m Tc methylenediphosphonate is an effective and safe drug in the treatment of rheumatoid arthritis.Results is suggest calcium be taken in the same time.

Objective To investigate the correlation between ~(18)F-fluorodeoxyglucose (FDG) uptake and hypoxia inducible factor1α (HIF-1α) level,microvessel density (MVD) in human gliomas.Methods ~(18)F-FDG PET scan was performed preoperatively in 41 patients with gliomas (including 23 highgrade and 18 low-grade tumors).The ratios of maximum standardized uptake value(SUV_(max))between tumor (T)and contralateral white matter (WM) were calculated (T/WM).Immunohistochemical stain methods were used to evaluate the level of HIF-1α and measure the MVD in tumors.Correlation analysis between SUV_(max) of T/WM and HIF-1α level,MVD wag performed.The t-test,one-way ANOVA test,Spearman rank correlation and Wilcoxon signed-rank test were calculated using SPSS 11.5 software.Results (1)The SUV_(max) of T/WM,HIF-1α level and MVD in high-grade and low-grade tumors groups were 3.39±1.43,95.7% and 44.13±16.1 vs 1.46±0.55.55.6% and 18.83±7.07,respectively.The difierences of SUV_(max) of T/WM,HIF-1α level and MVD between two groups were statistically significant (t=-5.921,z=-3.938,t=-6.745,all P＜0.05).(2)Among 41 gliomas,the strong positive expression of HIF-1α was observed in 8,mederate in 9,weak in 15 and negative expression was found in 9,SUV_(max) of T/WM and MVD increased with increasing HIF-1α level.The differences of SUV_(max) of T/WM and MVD among 4 different groups were statistically significant (F=7.41,P＜0.05).(3) The MVD of all gliomas was ranged from 9.76 to 94.52,which correlated with SUV_(max) of T/WM(r=0.759,P＜0.05).Conclusions The SUV_(max) of T/WM correlates with HIF-1α level and MVD in gliomas.Therefore,~(18)F-FDG PET provides preoperatively a noninvasive assessment of hypoxia or angiogenesis in human glionma.

This study was aimed to analyze the medication and herbal prescription rules in the treatment of nephrotic syndrome (NS) by Prof. Huang Chunlin with Traditional Chinese Medicine Inheritance Support System ( TCMISS ) . Prescriptions used for NS treatment were collected and the data was entered into the TCMISS . The commonly used herbs and herbal prescription rules in NS treatment by Prof. Huang were summarized through the association rules, revised mutual information, complex system entropy cluster and other unsupervised hierarchical clustering methods. The results showed that based on the analysis of 280 prescriptions from 68 patients, the fre-quency of each herb and association rules among herbs included in the database were identified. And the basic NS treatment prescription by Prof. Huang Chunlin and 8 new prescriptions were mined from the database. It was concluded that data mining is of great practical value to the summarization of clinical experiences of well-known TCM doctors.

Chinese traditional medicine has provided, since ancient times, a basis for health care and medicine to the Chinese nation and for China's national stability. Identification of the constituents responsible for therapeutic and undesired effects of Chinese herbal medicines is a type of key research facilitating the modernization of these medicines. For a complex Chinese herbal medicine, multi-compound pharmacokinetic research is a useful approach to identifying its constituents that are bioavailable (in their unchanged and/or metabolized forms) at loci responsible for the medicine's therapeutic action and to characterizing the compounds' disposition and pharmacokinetics related to the action. In addition, such pharmacokinetic research is also useful for identifying herbal compounds associated with the medicine's adverse effects and drug-drug interaction potential. Over the past decade, great advances have been achieved in the theory, methodology, associated techniques, and their application of such multi-compound pharmacokinetic research, which has become an emerging field in pharmacokinetics. In this perspective, we elaborate on the methodology, technical requirements, and key analytical techniques of multi-compound pharmacokinetic research on Chinese herbal medicines, describe research examples regarding investigation of pharmacokinetics and disposition of a class of bioactive herbal constituents (ginsenosides of Panax notoginseng root) and pharmacokinetics-based identification of potential therapeutic compounds from a dosed Chinese herbal medicine (LianhuaQingwen capsule), and discuss follow-up development for the multi-compound pharmacokinetic research.

Aim To investigate the effect of salidroside on the phenotypic expression of osteoblast and the possible molecular mechanism in hypoxia environment.Methods MTT, Annexin V/PI double staining, alkaline phosphatase(ALP) activity assay and enzyme-linked immnosorbent assay(ELISA) were performed respectively to detect the effect of salidroside on regulating phenotypic expression of MG-63 cells exposed to hypoxia.Then RT-PCR and Western blot were conducted to detect the expression levels of Osterix and Runx2 which were related to differentiation.At last, we investigated the expression levels of components of the HIF-1α pathway by RT-PCR,Western blot and ELISA, respectively.Immunofluorescence confocal microscope technology and luciferase reporter assay were performed to explore nuclear translocation and transcriptional activity of HIF-1α.Results Salidroside could markedly promote MG-63 cell proliferation, inhibit hypoxia-induced apoptosis, stimulate cell differentiation and promote expression levels of components of the HIF-1α pathway in hypoxia environment.Conclusion Salidroside could regulate phenotypic expression of MG-63 cells through HIF-1α/VEGF signaling pathway in hypoxia environment.