Objective To observe the clinical efficacy of Decoction of Chai Gui Wen Dan Ding Zhi in the treatment of Gastrointestinal Neurosis.Methods 50 cases of patients with Gastrointestinal Neurosis were randomly divided into a treatment group,which was treated with the Decoction of Chai Gui Wen Dan Ding Zhi.and a control group.which was treated with oryzanol and doxepin tablet.Meanwhile Cisupride tablet Was used for patients with constipation and Dioctahedral smectine Was used for patients with diarrhea.One month constituted one course of treatment.Results The total effective rate of the treatment group and the control group was 98% and 67.5% respectively,showing significant difference between the two groups(p＜0.05).Conclusion Decoction of Chai Gui Wen Dan Ding Zhi was effective in the treatment of Gastrointestinal Neurosis.

Cryptotanshinone (CPT)is a major fat-soluble ingre-dient in Salvia,which is a traditional blood-activating and stasis-dissolving drug.CPT has been gradually concerned,because it has a remarkable therapeutic effect on cardiovascular diseases, cancer and neurodegenerative diseases.A large number of exper-imental and clinical studies have shown that CPT can primarily inhibit tumor cell′s proliferation,angiogenesis,invasion and ad-hesion and induce apoptosis.Thus to some extent,it hinders in-vasion of tumor cell and prevents the distant metastasis.This pa-per focuses on the anti-tumor metastasis of CPT.

Epithelial mesenchymal transition ( EMT) is one of the important biological processes in tumor invasion and metastasis . However , due to the complexity of EMT signaling pathway and its unclear molecular mechanism , the treatment of EMT is still a worldwide problem .But many studies have proved that EMT is not an irreversible process .In recent years , the research of FOX gene family in EMT shows its important role in tumor metastasis . This review focuses on the FOX-mediated EMT process in many kinds of tumor , aiming to have a better understanding of EMT signaling network , and provide a new target for the effective pre-vention of EMT .

OBJECTIVE:To evaluate the inherent quality differences of different batches of Compound norethisterone tablet from different domestic enterprises by researching its in vitro dissolution,to provide reference for improving relevant standards in pharmacopoeia and optimizing production processes in drug manufacturers. METHODS:Orthogonal test was adopted to screen its dissolving conditions,small glass method was finally confirmed by detecting rotating speed,sampling time and dissolution medi-um,sampling determination was conducted with the dissolution medium of 0.5% sodium dodecyl sulfonate and rotating speed of 50 r/min and 45 min. And HPLC was adopted to simultaneously determine the in vitro dissolution of norethindrone and ethinyl estra-diol,then AV value method was adopted to detect the similarity of dissolution profiles of 8 batches of products from 2 domestic en-terprises. RESULTS:The dissolution profiles and similarity of AV value method showed the cumulative dissolution of 8 batches of Compound norethisterone tablet from 2 domestic enterprises had no significant difference at different time points,overall similarity was relatively high;but the ethinyl estradiol had certain difference,overall similarity was relatively low. CONCLUSIONS:The dif-ference of dissolution profiles of Compound norethisterone tablet may has effect on the drug efficacy,the production process and quality in domestic enterprises should be managed strictly. Meanwhile,the current method of dissolution is weak to distinguish from the quality,which needs to be improved urgently.

Objective To investigate the chemical constituents of Polygala tenuifolia. Methods Silica gel column and Sephadex LH-20 column chromatography were used to separate and purify the chemical constituents. The structures were elucidated by spectral data. Results Six compounds were isolated and identified as: 2-hydroxy-4, 6-dimethoxybenzophone (hydrocotoin, Ⅰ), 1, 7-dihydroxy-3-methoxyxanthone (Ⅱ), 1, 7-dihydroxy-2, 3-dimethoxyxanthone (Ⅲ), ?-spinasterol (Ⅳ), 1, 5-anhydro-D-sorbitol (polygitol Ⅴ) and benzoic acid (Ⅵ). Conclusion Compound Ⅳ is isolated from the plant and compound Ⅰ is isolated from the plants of Polygala L. both for the first time.

Objective To investigate the role of IL-35-producing regulatory B cells(IL-35 + Breg)in immunological pathogenesis of Kawasaki disease (KD).Methods Thirty-two children with KD and 28 age-matched healthy children were allowed to participate in this study.Flow cytometry was performed to evaluate the proportions of IL-35 + Breg as well as requlatory T cells (Treg)and expression levels of associated molecules such as programmed death-ligand 1 (PD-LI),CD169,programmed death 1 (PD-1),CD43,IL-12p35,epstein-Barr virus induced 3 (IL-27 EBI3).IL-12 receptor beta 2 (IL-12 Rβ2),IL-27 receptor alpha (IL-27 Rα),phosphated signal transducer and activator of transcription 1 (pSTAT1) and phosphated signal transducer and activator of transcription 3 (pSTAT3).Transcription levels of the Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2),phosphatase and tensin homolog (PTEN),vav1 guanine nucleotide exchange factor(Vav) in CD19 + B cells were determined by using quantitative real-time PCR.Plasma concentrations of IL-35,tumor necrosis factor α(TNF-α) and IL-12 were measured by adopting enzyme-linked immunosorbent assay.Results (1) The proportions of IL-35 +Breg and its expressions of IL-12p35,IL-27EBI3 and IL-10 in patients with acute KD were lower than those of healthy controls [IL-35 + Breg:(5.79 ± 2.60) ％ vs (12.65 ± 5.34) ％;F =19.23,9.70,14.30.7.08;all P ＜ 0.05],but they were significantly increased after intravenous immune globulin (IVIG) treatment [IL-35 + Breg:(10.52 ± 4.95) ％;all P ＜ 0.05].(2) The proportions of Treg and its transcriptional levels of IL-12p35 and IL-27 EBI3 were down-regulated during acute KD [Treg:(4.12 ± 1.51) ％ vs (8.06 ± 3.32) ％;F =19.70,17.69,38.22;all P ＜ 0.05],but were increased after therapy [Treg:(7.39 ± 2.85) ％;P ＜ 0.05].A positive correlation was found between the proportions of Treg and IL-35 + Breg during acute KD (r =0.69,P ＜ 0.05).Meanwhile,plasma concentrations of IL-35 and expression levels of IL-12Rβ2,IL-27Rα,pSTAT1 and pSTAT3 in CD19 + B cells were significantly down-regulated in children with acute KD,but they were increased after treatment(F =8.09,7.54,7.69,5.89,12.59,all P ＜ 0.05).(3) Compared with healthy controls,expressions of PD-L1 and CD169 on CD14 + cells and plasma concentrations of TNF-α and IL-12 were elevated during acute KD (F =24.94,16.53,34.71,19.51;all P ＜ 0.05).Expression levels of PD-1,CD43 and its downstream molecules (SHP-2,PTEN,Vav) in CD19 + B cells were down-regulated during acute KD (F =6.43,5.57,19.52,10.37,11.37;all P ＜ 0.05),and restored remarkably after therapy (all P ＜ 0.05).Conclusion Insufficiency of IL-35 + Breg and its expression of IL-35 may be the important factors contributing to immunological dysfunction in KD.

Objective To investigate the changes and significance of ubiquitination of Foxp3 pro-tein during the acute phage of Kawasaki disease ( KD) .Methods Forty-eight children with KD and twenty-eight age-matched healthy children were recruited in this study.Co-immunoprecipitation and Western blot assays were performed to determine the poly-ubiquitination status of Foxp3 in CD4+T cells.The percentages of CD4+CD25high Foxp3+regulatory T cells ( Treg) and the levels of IL-10, transforming growth factor-β( TGF-β) , cytotoxic T lymphocyte-associated protein-4 ( CTLA4 ) , STIP1 homology and U-Box containing protein 1 (STUB1), heat shock protein 70 (HSP70), ubiquitin-specific-processing protease 7 (USP7) and pSTAT3 were analyzed by flow cytometry analysis.Quantitative real-time PCR was used to evaluate the tran-scription levels of TLR1-10, IL-1R1, IL-1RAP, IL-6Rα, gp130, TNFR1, MyD88 and RIP1 in CD4+T cells.Plasma concentrations of IL-1β, IL-6 and TNF-αwere measured by enzyme-linked immunosorbent as-say.Results (1) The percentages of Treg cells and the levels of IL-10, TGF-β, CTLA4 and forkhead box P3 (Foxp3) in patients with acute KD were lower than those of healthy subjects (P<0.05), while the poly-ubiquitination of Foxp3 protein was significantly enhanced in patients with acute KD [(0.52 ±0.19) vs (0.08±0.02),P<0.05].Meanwhile, the four former items in KD patients with coronary artery lesions (KD-CAL+) were lower than those of KD patients without coronary artery lesions (KD-CAL-) (P<0.05), while the polyubiquitination level of Foxp3 protein in KD-CAL+group was much higher than that of KD-CAL-group [(0.70±0.28) vs (0.43±0.17), P<0.05].The levels of Treg cells, IL-10, TGF-βand CTLA4 in patients with KD were increased and the ubiquitination of Foxp3 protein was inhibited [(0.24±0.10) vs (0.52±0.19), P<0.05] upon the treatment with IVIG.(2) The levels of STUB1 and HSP70 in CD4+T cells were significantly elevated during acute KD, while the levels of USP7 were decreased (P<0.05).The ratios of STUB1/USP7 in patients with acute KD were much higher than those of the control group [(2.65± 0.92) vs (1.09±0.37), P<0.05], but were significantly decreased after IVIG therapy [(1.46±0.53) vs (2.65±0.92), P<0.05].A negative correlation was found between STUB1/USP7 ratio and Foxp3 level during acute KD (r=-0.56, P<0.05).Moreover, KD patients with CAL+showed higher levels of STUB1 and HSP70 and higher ratios of STUB1/USP7 (P<0.05), but lower levels of USP7 as compared with those of KD-CAL-group (P<0.05).(3) The plasma concentrations of inflammatory cytokines (IL-1β, IL-6 and TNF-α), the levels of surface receptors ( IL-1R1/IL-1RAP/TLR4, IL-6Rα/gp130 and TNFR1) and its downstream molecules ( MyD88, pSTAT3 and RIP1) in CD4+T cells were up-regulated during acute KD ( P<0.05), especially in patients with CAL+, but were down-regulated upon the IVIG therapy (P<0.05).No significant differences with other TLRs were found among the groups (P>0.05).Conclusion Hyper-ubiq-uitination of Foxp3 protein might be involved in the immune dysfunction during Kawasaki disease.

Objective To investigate the changes and significances of inducible IL-35-producing regulatory T cells(iTR35) in immunological pathogcnesis of Kawasaki disease (KD).Methods Forty-eight children with KD and 32 age-matched healthy children (healthy control group) consented to participate in this study.Flow cytometry was performed to evaluate the proportions of CD4+ FOXP3-IL-12p35+IL-27EBI3+iTR35 and CD4+CD25high FOXP3+regulatory T cells (Treg),and expression levels of associated molecules such as programmed death-ligand 1 (PD-L1),CD169,programmed death 1 (PD-1),CD43,IL-12p35,Epstein-Barr virus induced 3 (IL-27EBI3),glycoprotein 130(gp130),IL-12 receptor beta 2 (IL-12Rβ2),phosphated signal transducer and activator of transcription 1 (pSTAT1) and phosphated signal transducer and activator of transcription 4 (pSTAT4).Transcription levels of the Sre homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2),phosphatase and tensin homolog (PTEN),Vavl guanine nucleotide exchange factor(Vav) in CD4+T cells were determined by quantitative real-time PCR.Plasma concentrations of IL-35,IL-10,TNF-α and IL-12 were measured by enzyme-linked immunosorbent assay.Results (1) The proportions of iTR35 and its expressions of IL-12p35 and IL-27EBI3 in patients with acute KD dccreased remarkably[iTR35:(0.72±0.26) ‰ vs (1.65±0.43) ‰,P＜0.05],and restored after treatment [iTR35:(1.58±0.63) ‰ vs (0.72±0.26) ‰,P＜0.05].(2) The proportions of Treg and transcriptional levels of IL-12p35 and IL-27EBI3 were down-regulated during acute phase of KD [Treg:(3.26±1.21) ％ vs (7.26±2.86) ％,P＜0.05],and increased to some extent after therapy [Treg:(5.89±2.60)％ vs (3.26±1.21)％,P＜0.05].Meanwhile,plasma concentrations of IL-35 and IL-10,and expressions of gp130,IL-12Rβ2,pSTAT1 and pSTAT4 in iTR35 of patients with acute KD were found lower than those of the healthy control group (all P＜0.05),and increased after treatment (P＜0.05).Additionally,positive correlations were found between plasma concentrations of IL-35 and the proportion of iTR35 or its expressions of IL-12p35 and IL-27EBI3,respectively.(3) Expressions of PD-L1 and CD169 on CD14 + cells and plasma concentrations of TNF-α and IL-12 were elevated significantly during acute KD(all P＜0.05),as well as expression levels of the ligands (PD-1 and CD43) and its downstream molecules (SHP-2,PTEN,Vav) in CD4 + T cells were found to be lower in patients with acute KD (P＜0.05),and restored remarkably after therapy.Conclusion Insufficiency of iTR35 and its expression of IL-35 might be one of the important factors contributing to immunological dysfunction in KD.

Objective:To evaluate the efficacy and safety of selective intra-arterial thrombolysis with urokirmse for acute cerebral infarction.Methods:Thirty-eight patients with acute cerebral infarction were treated by selective intra-arterial thrombolysis with urokinase within 6 hours of onset.Head CT seans were performed immediately and 24 hours after the procedures to find out whether intracerebral hemorrhage(ICH)had occurred.The activities of daily living and functional outcome of the patients were evaluated by the Barthel Index(BI)and the National Institutes of Health Stroke Scale(NmSS).Results:Of the 38 patients,21 achieved complete recanalization,8 achieved partial recanalization,3 occurred symptomatic intracranial hemorrhage,and l died.At day 90,22 patients had a favorable outcome(BI≥90),11(50≤BI＜90)had a better outcome,and 4 had a worse one(BI＜50);at 6 months,24 patients had a favorable outcome,9 had a better outcome.and 4 had a worse one.The NIHSS scores at day 14 after the procedures were significantly superior to the levels betore the procedures(12.68±7.43 versus 15.38±4.32,P＜0.011.Conclusions: Intra-arterial thrombolysis with urokinase can recanalize the occluded vessels and improve the acute clinical symptoms and long-term prognosis of patients.