Shen Qi Wan attenuates renal interstitial fibrosis through upregulating AQP1 / 中国天然药物

Renal interstitial fibrosis (RIF) is the crucial pathway in chronic kidney disease (CKD) leading to the end-stage renal failure. However, the underlying mechanism of Shen Qi Wan (SQW) on RIF is not fully understood. In the current study, we investigated the role of Aquaporin 1 (AQP1) in SQW on tubular epithelial-to-mesenchymal transition (EMT). A RIF mouse model induced by adenine and a TGF-β1-stimulated HK-2 cell model were etablished to explore the involvement of AQP 1 in the protective effect of SQW on EMT in vitro and in vivo. Subsequently, the molecular mechanism of SQW on EMT was explored in HK-2 cells with AQP1 knockdown. The results indicated that SQW alleviated kidney injury and renal collagen deposition in the kidneys of mice induced by adenine, increased the protein expression of E-cadherin and AQP1 expression, and decreased the expression of vimentin and α-smooth muscle actin (α-SMA). Similarly, treatmement with SQW-containing serum significantly halted EMT process in TGF-β1 stimulated HK-2 cells. The expression of snail and slug was significantly upregulated in HK-2 cells after knockdown of AQP1. AQP1 knockdown also increased the mRNA expression of vimentin and α-SMA, and decreased the expression of E-cadherin. The protein expression of vimentin increased, while the expression of E-cadherin and CK-18 significantly decreased after AQP1 knockdown in HK-2 cells. These results revealed that AQP1 knockdown promoted EMT. Furthermore, AQP1 knockdown abolished the protective effect of SQW-containing serum on EMT in HK-2 cells. In sum, SQW attentuates EMT process in RIF through upregulation of the expression of AQP1.

Screening of genes related to the prognosis of gastric cancer and the efficacy of 5-fluorouracil based on bioinformatics method / 肿瘤研究与临床

Objective:To screen biomarkers related to the prognosis of gastric cancer and the efficacy of 5-fluorouracil based on the bioinformatics method.Methods:Gastric cancer datasets like GSE54129, GSE79973 and GSE51725 based on GPL570 platform were downloaded from Gene Expression Omnibus (GEO) database. Genes related to the overall survival (OS) of the top 500 gastric cancer patients were downloaded from GEPIA2 online gene expression profile.GEO2R was used to identify the differentially expressed genes (DEG) between gastric cancer tissues and adjacent normal tissues, STRING database was used to build protein-protein interaction networks (PPI) and to identify the key genes, the enrichment analysis of gene ontology (GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG) was made by using OmicShare. Kaplan-Meier Plotter was used to calculate the value of key genes in predicting the OS of gastric cancer patients. All patients were divided into the high expression group and low expression group according to the optimal cut-off value of gene expression level.Results:A total of 59 DEG were screened, including 39 up-regulated genes and 20 down-regulated genes. The key up-regulated genes including homeodomain transcription factors 2(PITX2), hepatocyte growth factor (HGF), fibroblast growth factor 1 (FGF1), transforming growth factor β 2 (TGFB2), thromobospondin 1 (THBS1) were analyzed by using PPI. Survival analysis results showed that the OS of gastric cancer patients with low expression of FGF1, HGF, PITX2 and TGFB2 genes was better (all P < 0.01); the OS of gastric cancer patients with low expression of THBS1 gene was poor, while the difference was not statistically significant ( P > 0.05). The patients with low expression of RIEG1 gene who received 5-fluorouracil-based chemotherapy regimen had the better OS ( P < 0.01),while those with THBS1 and HGF low expression had the worse OS ( P < 0.05). It was found that key genes might promote the development of gastric cancer by participating in the regulation of TGF- β signaling pathway, Rap1 signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, Hippo signaling pathway, Ras signaling pathway and focal adhesion pathway. Conclusions:Bioinformatics analysis shows that the expressions of FGF1, HGF, PITX2 and TGFB2 genes are related to the prognosis of gastric cancer, and the expressions of RIEG1, THBS1 and HGF are related to the efficacy of 5-fluorouracil, which may be used as a predictive marker of fluorouracil chemosensitivity in patients with gastric cancer.

Comprehensive analysis of differential methylation genes in cholangiocarcinoma and identification of prognosis-related genes glucosaminyl (N-acetyl) transferase 1 and neurotrophic receptor tyrosine kinase 3 / 肿瘤研究与临床

Objective:To identify and screen the differential methylation genes in patients with cholangiocarcinoma and to predict the prognosis of patients with CCA.Methods:Cholangiocarcinoma tissues and paracancerous tissues of 8 patients with cholangiocarcinoma in Fujian Provincial Hospital from October 2019 to May 2020 were selected for 850K methylation sequencing analysis to obtain differentially methylated genes. The 2018 genome-wide methylation data and clinical information of 36 patients with cholangiocarcinoma were download from The Cancer Genome Atlas (TCGA) database, the 2012 cholangiocarcinoma methylation data (GSE32879) were download from the Gene Expression Omnibus (GEO) database, and the 2018 TCGA database differential survival genomic data of overall survival (OS) and disease-free survival (DFS) of cholangiocarcinoma were download from the GEPIA2 database. The differentially methylated positions (DMP) and differentially methylated regions (DMR) results of 850K methylation sequencing analysis of submitted samples, methylated genes in TCGA and GEO databases, and cholangiocarcinoma survival genes of samples were jointly submitted for testing, multi-data set analysis was performed by the Sangerbox VENN tool, and common differentially methylated genes were obtained by intersection screening. The minimum P value method was used to determine the cut-off value of gene expression in Sangerbox, and the patients were divided into high and low expression groups of differentially methylated genes. The OS, DFS, disease-specific survival (DSS), disease-free interval (DFI) and progression-free interval (PFI) of cholangiocarcinoma patients were compared between the two groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Results:A total of 121 954 DMP were identified by 850K methylation sequencing of cholangiocarcinoma tissues and paracancerous tissues of 8 patients; a total of 1 399 differentially methylated genes were identified in DMR, and the common prognosis related genes glucosaminyl (N-acetyl) transferase 1 (GCNT1) and neurotrophic receptor tyrosine kinase 3 (NTRK3) were identified by intersection identification. The expression of GCNT1 in the cholangiocarcinoma tissues was higher than that in the paracancerous tissues, and the difference was statistically significant ( P = 0.040). The expression of NTRK3 in cholangiocarcinoma tissues was higher than that in the paracancerous tissues, but the difference was not statistically significant ( P = 0.790). The minimum P value method was used to predict the prognosis of patients with cholangiocarcinoma based on the combined expression of GCNT1 and NTRK3, and the order was based on the sum of the expression levels of the two genes. When 30% of the ranking was taken as the cut-off value, the difference in DFS between the high expression group and the low expression group in cholangiocarcinoma was the most significant ( P < 0.001); there was no significant difference in OS between the two groups ( P = 0.065). The results of GO functional analysis showed that GCNT1 was involved in protein glycosylation, macromolecule glycosylation, glycosylation, glycoprotein biosynthetic process, glycoprotein metabolic process, transferase activity and transferring glycosyl groups, protein O-linked glycosylation, O-glycan processing, etc., and NTRK3 was involved in neurotrophin signaling pathway, Ras signaling pathway, EGFR tyrosine kinase inhibitor resistance, ErbB signaling pathway, phospholipase D signaling pathway, central carbon metabolism in cancer, natural killer cell mediated cytotoxicity, etc. The results of KEGG analysis showed that GCNT1 was mainly associated with system functions such as mucin-type O-glycan biosynthesis and metabolic pathways, and NTRK3 was mainly associated with cell surface receptor pathways, intracellular signal transduction, positive regulation of stimulatory responses, transmembrane receptor protein tyrosine kinase signaling pathway, enzyme-linked receptor protein signaling pathway, MAPK signaling pathway cascade and regulation, protein phosphorylation signal transduction and other system functions. Conclusions:The expressions of differentially methylated genes GCTNT1 and NTRK3 in cholangiocarcinoma have certain predictive effects on the prognosis of patients with cholangiocarcinoma.

Protective effect of α-asarone and β-asarone on Aβ -induced inflammatory response in PC12 cells and its / 浙江大学学报·医学版

To investigate effects of α-asarone and β-asarone on induced PC12 cell injury and related mechanisms. Aβ toxic injury cell model was induced by Aβ in PC12 cells. PC12 cells were divided into blank control group, model control group, α-asarone group (0.5, 1.0, β-asarone group (6.3, 12.5, vasoactive intestinal peptide (VIP) group, and VIP antagonist control group. Cell survival rate was detected by CCK-8 kit; cell apoptosis rate was detected by flow cytometry. The levels of inflammatory cytokines interleukin (IL)-1, , tumor necrosis factor (TNF)-α, oxidation-related inducible nitric oxide synthase (iNOS), nitric oxide (NO), apoptosis factors caspase-3 and p53 were detected by ELISA method. The expressions of C-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) were detected by Western blotting. Compared with model control group, cell survival rates of group, β-asarone group and VIP group increased; the cell apoptosis rate decreased; levels of apoptosis-related factors caspase-3, p53, inflammatory factors IL-1, TNF-α decreased; IL-10 level increased; levels of oxidization-related factors iNOS and NO decreased; the expression of JNK and p38MAPK protein decreased (all 0.05). α-asarone and β-asarone have protective effects on PC12 cell injury induced by Aβ. β-asarone may inhibit inflammatory factors and oxidation-related factors through promoting VIP secretion, regulating JNK/MAPK pathway, and reducing PC12 cell apoptosis; however, the effect of α-asarone may be not related to VIP secretion.

Prognosis of huge hepatocellular carcinoma after hepatectomy / 中华普通外科杂志

Objective:To evaluate the risk factors on prognosis after resection of huge hepatocellular carcinoma.Methods:The clinical and followup data of 146 patients undergoing radical resection at Fujian Province Hospital from Jan 2012 to Dec 2017 was analyzed retrospectively.Results:Independent risk factors for tumor recurrence were neutrophil/lymphocyte ratio ≥2.49, serum alpha-fetoprotein ≥400 ng/ml, non-anatomical hepatectomy, ruptured huge hepatocellular carcinoma, multiple tumor and microvascular invasion and macrovascular invasion. These seven factors were used to develop a risk prediction model, in which 1-year recurrence-free rates in patients with low, middle, high risk group were 68.5%, 23.5%, and 0, respectively, and 3-year recurrence-free rates were 34.2%,15.3% and 0, respectively. Independent risk factors for tumor overall survival were neutrophil/lymphocyte ratio≥2.49, serum alpha-fetoprotein ≥400 ng/ml, HBV-DNA ≥2 000 IU/ml, multiple tumor, microvascular invasion, macrovascular invasion and hepatic capsule invasion. These seven factors were used to develop a risk prediction model, in which 1-year survival rates in patients with low, middle, high risk group were 94.7%, 74% and 40%, respectively, and 3-year survival rates were 68.4%,30.1%, and 5.7%, respectively.Conclusions:The recurrence rate of patients with huge hepatocellular carcinoma is high. Independent risk factors affecting prognosis were high neutrophil/lymphocyte ratio, high AFP level, high HBV-DNA, non-anatomical hepatectomy,ruptured,multiple tumor, microvascular and macrovascular invasion.

Effect of hysteroscopic adhesion separation combined with Folly urinary catheter placement in the treatment of hysterectomy / 中国综合临床

Objective:To investigate the application of Folly urethral catheter in transvastatal resection of adhesion (TCRA) and its preventive effect on prevention of re-adhesion.Methods:A total of 78 patients with intrauterine adhesions admitted to the Department of gynecology and obstetrics of the Maternal and Child Health Care Hospital Affiliated to Anhui Medical University from March 2018 to March 2019 were selected as the study objects.The prospective study was conducted and divided into two groups according to the computer random number method.In the control group, 39 cases were treated by TCRA combined with intrauterine placement of contraceptive ring, while in the observation group, 39 cases were treated by hysteroscopic adhesion separation operation combined with Folly catheter placement.The curative effect, intrauterine adhesions, menstrual improvement score, recurrence and pregnancy were compared before and 6 months after operation.Results:The total effective rate of the observation group was 94.87% (37/39), and that of the control group was 79.49% (31/39), The difference between the two groups was statistically significant (χ 2=4.129, P<0.05). The score of intrauterine adhesions was (22.14±2.57) in the control group and (1.76±0.87) in the observation group, and (23.05±3.08), (1.81±0.60) in the observation group, there was no significant difference between the two groups( t=1.417, 0.295; all P>0.05). At 3 months after operation, the scores of intrauterine adhesions and menstrual states in the control group were (17.63±2.88) and (1.07±0.38), respectively, and those in the observation group were (14.27±3.52) and (0.53±0.21), the difference between the two groups was statistically significant( t=4.614, 7.767, all P<0.001). There were significant differences in the scores of intrauterine adhesions and menstrual state before and after operation in the observation group ( t=7.297, 4.539, all P<0.001). There were significant differences in the scores of intrauterine adhesions and menstrual states before and after operation in the observation group ( t=11.723, 12.575, all P<0.001). The recurrence rate was 23.08% (9/39) in the observation group and 46.15% (18/39) in the control group at 6 months after operation.The difference was statistically significant ( P=0.032). The pregnancy rate of the observation group was observed.12.82% (5/39), 7.69% (3/39) in the control group, the difference was not statistically significant( P=0.455). Conclusion:Hysteroscopic adhesion separation combined with Folly catheter placement for the treatment of intrauterine adhesions can significantly improve the short-term efficacy, prevent re-adhesion, and better regulate the menstrual cycle.

Selective intra-arterial cold saline infusion combined with intravascular reperfusion for acute ischemic stroke with large artery occlusion: a preliminary safety and feasibility study / 国际脑血管病杂志

Objective To preliminarily investigate the safety and feasibility of intra-arterial cold saline infusion combined with intravascular reperfusion for acute ischemic stroke with large artery occlusion. Methods From March 2016 to March 2018, consecutive acute ischemic stroke patients with large artery occlusion within 8 h after onset admitted to the Department of Neurology, the People's Hospital of Longhua District, Shenzhen and recanalized successfully after endovascular treatment were enrolled. After recanalization, cold saline was infused through the guiding catheter via the ipsilateral guilty vessel (10 ℃, 33 ml/min for 30 min). Results A total of 20 patients were enrolled, including 15 males. Their median age was 67 years (interquartile range, 53-80 years). Fifteen patients were treated with thrombolysis. A median onset-to-needle time was 300 min (interquartile range, 260-360 min). During the infusion of cold saline, the lowest rectal temperature was only decreased 0. 1 ℃, but within 5 min after completion of perfusion, it returned to the temperature before perfusion. Complications associated with intra-arterial hypothermia were not observed. The median National Institutes of Health Stroke Scale score was significantly decreased from 21 (interquartile range 15-55) before needle to 15 (interquartile range 10-16; Z = -4. 549, P < 0. 001) at discharge. Conclusion Selective intra-arterial cold saline infusion combined with intravascular reperfusion for acute ischemic stroke with large artery occlusion is safe and feasible.

Scutellarin starch microspheres' permeability through nasal mucosa of different animals in vitro / 中国中药杂志

<p><b>OBJECTIVE</b>To study scutellarin starch microspheres' permeability through nasal mucosa of different animals in vitro.</p><p><b>METHOD</b>The Franz diffusion cell method was used to experiment the permeability test (n = 4), taking fresh nasal mucosa of dog, swine and domestica in vitro as permeation barrier separately, with scutellarin starch microspheres (scutellarin 0.25 mg) above them, and blank pH 6.8 PBS as absorption liquid to detemine the scutellarin by HPLC.</p><p><b>RESULT</b>The permeability coefficient of scutellarin starch microspheres through nasal mucosa of dog, swine and domestica in vitro were (5.295 +/- 0.637) x 10(-3) (4.065 +/- 1.140) x 10(-3), (1.855 +/- 0.150) x 10(-3) cm x mL(-1) separately. The permeability coefficient order of scutellarin starch microspheres through nasal mucosa of different animals in vitro is dog > swine > domestica, and there are significant differences between the permeability coefficient of scutellarin starch microspheres through nasal mucosa of dog, swine in vitro, and that through nasal mucosa of swine and domestica in vitro.</p><p><b>CONCLUSION</b>Drugs in scutellarin starch microspheres could permeate through the above-mentioned nasal mucosa in vitro. There might be different permeability coefficient among different species.</p>

Evaluation of brain-targeted trendence of scutellarin nasal administration / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the feasibility of developing brain-targeted nasal delivery system of scutellarin by the passage between nase and brain in nasal olfactory area.</p><p><b>METHOD</b>The samples of cerebrospinal fluid (CSF) and blood were prepared by cranial puncture and femoral artery catheterization methods respectively according to the certain sampling time after drug administered. The scuteIlarin concentration of samples were determined by 125 marked method. Pharmacokinetic parameters were calculated by trapezoidal rule. The brain-targeted trendence were evaluated by the value of the index AUC(brain)/AUC(plasma).</p><p><b>RESULT</b>The distribution of scutellarin in brain following intranasal administration was different between tissues. Drug concentration in olfactory bulb achieved to peak at 5-15 min after intranasal administration, while in brain tissue was 30-60 min. Above all, peak concentration in olfactory bulb and olfactory region respectively were (574.8 +/- 205.), (323.4 +/- 128.3) ng x g(-10, both are higher than CSF, which is (123.2 +/- 29.3) ng x g(-1). Moreover, the distribution of scutellarin given by intranasally in brain was: olfactory bulb (OB) > olfactory region (OR) > cerebrospinal fluid (CSF) > cerebellum(CB) > medulla oblongata (MO) > cerebrum (CR); AUC(0-240) of olfactory bulb, olfactory region and CSF after scutellarin intranasal administration were 5.54, 5.07 and 5.51 times of that after intravenous injection, respectively. And the AUC(0-240) of other brain tissues after intranasal administration were also higher than that after intravenous injection. AUC(brain tissue)/ AUC(plasma) of every brain tissues by intranasally are all higher than that by intravenously remarkably. For instance, 5 min after intranasal administration, the value of AUC(CSF)/ AUC(plasma), AUC(OB)/AUC(plasma), and AUC(CR)/AUC(plasma) were 30.34, 56.93, and 6.14 times of that by intravenously.</p><p><b>CONCLUSION</b>Part of scutellarin could be straightly transported into brain by the intranasal administration. Its absorption pathway was: the molecule of Scutellarin throughed olfactory mucosa in nasal cavity into olfactory bulb in arachno-hypostegal cavity, and then entered into olfactory region, CSF, cerebrum and cerebellum gradually. It showed that olfactory bulb was the only way for drug molecule to go through nasal cavity into brain. It had a significant trendence of brain-targeted when compared to oral administration and intravenous injection, which indicated a certain feasibility to develop a brain-targeted nasal delivery system for scutellarin.</p>

Differentiation of rat bone marrow stromal cells into osteogenic phenotype: the comparison of two methods / 中国康复理论与实践

@# ObjectiveTo explore environmental conditions under which bone marrow stromal cells could be induced into osteogenic phenotype.MethodsRat bone marrow stromal cells were isolated and proliferated in vitro, and the 3rd passage was divided into the group A (control group), group B (cells cultured in the medium containing dexamethasone, β-glycerol disodium phosphate salt hydrate, vitamin C and active form of vitamin D3), and group C (on the bases of group B, the cells were cultured additionally with fracture hematoma extract). On the post-induction day 5, 8, and 11, the morphological changes were observed and the osteogenic markers such as alkaline phosphotase (ALP), collagen type Ⅰ (Col Ⅰ) and osteocalcin (OCN) were assayed with immunohistochemical staining, the calcification was manifested with von Kossa staining.ResultsIn the group A, no evident osteogenic effects had been observed. In the group B, on 5th day post-induction, some bone marrow stromal cells underwent a morphological change, and mild expression of ALP and Col Ⅰ was observed but with no calcification effect. On 8th day post-induction, the ratio of morphologically changed cells increased, and the expression of ALP and Col Ⅰ increased still with no evident calcification. On 11th day post-induction, anti-OCN staining was positive and the calcium nodes were showed by von Kossa staining. The phenotype changes in the group C were similar to group B, but were more evident.ConclusionBone marrow stromal cells can be induced into osteogenic phenotype in vitro with small molecular inducers. Fracture hematoma extract can enhance this effect thus might be used as an addictive in osteogeneration.

Antitumor effect and its mechanism of actinidia Chinensis planch polysaccharide on B16-bearing mice / 中华中医药杂志

Objective:To investigate the antitumor effect of Actinidia Chinensis Planch polysaccharide(ACPS)in B16-bearing C57BL/6 mice and approach its mechanism.Methods:The C57BL/6 mice model was established by B16 subcutaneous inoculation,giving the polysaccharides from vena caudalis injection,and flow cytometer(FCM)was used to detect the distribution of tumor-cell cycle,and electron microscope was used to survey morphologic transformation about apoptosis.Results:ACPS can inhibit the growth of B16,the high,middle dose groups obviously restrained the tumor with the rate of 48.67%,40.90%and the control group 24.13%,and classical apoptosis corpuscles had been found through electron microscope in ACPS groups.Compared with control group,the ACPS promoted the spleen-index of B16-bearing mice and cut down the proliferation index,and the G1/S phase was at growth-inhibitory concentrations judged by the distributing analysis on cell-cycle.Conclusion:ACPS had obvious effect of restraining B16 and promoting the spleen index of tumor-bearing mice,which maybe due to its function of regulating immunization and the distributing of cell-cycle.

Progress of receptors mechanism on depression / 中国药理学通报

Early study have been proved that Monoaminergic receptor are playing an important role in the progress of depression.At present,other receptors have been discovered which involved in the pathogenesis and treatment of depression.This paper is attempted to review the new progress of investigation into glutamate receptors,corticotropin-releasing factor receptors,neurokinin receptors and adrenocorticosteroid receptors related with depression mechanism respectively.

Therapeutic action of leflunomide on adjuvant arthritis rats and its mechanism / 中国药理学通报

AIM　To study the therapeutic action of leflunomide(Lef) on adjuvant arthritis (AA) rats and its mechanisms. METHODS　To observe the change of secondary inflammation,immune function on adjuvant arthritis(AA) rats treated with Lef and to detect the effect of A771726—the active product of Lef on T cell subgroup in mice in vitro.RESULTS　Lef(2,6,18 mg*kg-1×12 d) intragastric injection(ig) could signifcantly inhibit secondary reaction (secondary inflammatory swelling、 multiple arthritis) of AA rats.Lef couldnt effect the lowed response of Con A-induced splenolytes, and the decreased IL-2 synthesis in AA rats. But lef(2,6,18 mg*kg-1) could inhibit the elevated IL-1 released from peritoneal macrophage (PMΦ) in AA rats. A771726—the active product of Lef(0.1，0.5，2.5，12.5，25，100 μmol*L-1) could inhibit Con A-induced Th cells but has no effect in Con A-induced Ts cells in vitro.CONCLUSION　Lef has therapeutic action on AA rats which could be related to its immunosuppressory activities——mainly through inhibit cell-mediated immunity.

The preventive action of leflunomide on liver fibrosis and its mechanisms in mice / 中国药理学通报

AIM　To observe the preventive action of leflunomide (Lef) on CCl4-induced liver fibrosis and explore its mechanism. METHODS Model of liver fibrosis in mice was induced by subcutaneous injection of CCl4(20%). The levels of ALT、AST、NO in plasma and Hyp in liver tissue were determined by spectroscopy. The content of HA in plasma was determined by radioimmunoassay. RESULTS Pretreatment of Lef (4,12,36 mg·kg-1) significantly reduced the elevated levels of ALT、AST、NO in plasma and Hyp in liver tissue, Pathological examination suggested Lef has preventive action on experimental liver fibrosis with significance. CONCLUSION Lef has significantly preventive action on CCl4-induced liver fibrosis possibly mediated by reduction of NO.

Therapeutic action of leflunomide on adjuvant arthritis rats and its mechanism / 中国药理学通报

AIM To study the therapeutic action of leflunomide(Lef) on adjuvant arthritis (AA) rats and its mechanisms. METHODS To observe the change of secondary inflammation,immune function on adjuvant arthritis(AA) rats treated with Lef and to detect the effect of A 771726 —the active product of Lef on T cell subgroup in mice in vitro .RESULTS Lef(2,6,18 mg?kg -1 ?12 d) intragastric injection(ig) could signifcantly inhibit secondary reaction (secondary inflammatory swelling、 multiple arthritis) of AA rats.Lef couldnt effect the lowed response of Con A induced splenolytes, and the decreased IL 2 synthesis in AA rats. But lef(2,6,18 mg?kg -1 ) could inhibit the elevated IL 1 released from peritoneal macrophage (PM?) in AA rats. A 771726 —the active product of Lef(0 1,0 5,2 5,12 5,25,100 ?mol?L -1 ) could inhibit Con A induced T h cells but has no effect in Con A induced T s cells in vitro .CONCLUSION Lef has therapeutic action on AA rats which could be related to its immunosuppressory activities——mainly through inhibit cell mediated immunity.

The preventive action of leflunomide on liver fibrosis and its mechanisms in mice / 中国药理学通报

AIM To observe the preventive action of leflunomide (Lef) on CCl4-induced liver fibrosis and explore its mechanism. METHODS Model of liver fibrosis in mice was induced by subcutaneous injection of CCl4(20% ). The levels of ALT\AST.NO in plasma and Hyp in liver tissue were determined by spectroscopy. The content of HA in plasma was determined by radioimmunoassay. RESULTS Pretreatment of Lef (4, 12, 36 mg. kg- 1 ) significantly reduced the elevated levels of ALT.AST.NO in plas- ma and Hyp in liver tissue, Pathological examination suggested Lef has preventive action on experimental liver fibrosis with significance. CONCLUSION Lef has significantly preventive action on CCl4-induced liver fibrosis possibly mediated by reduction of NO.

The antiinflammatory and immunomodulatory effects of actarit and its machenism / 中国药理学通报

AIM To study the antiinflammatory and immunomodulatory effects of actarit(Acta). METHODS To abserve the change of primary and secondary inflammation,immune function on adjuvant arthritis(AA) rats treated with Acta and to detect the effect of Acta on T cell subgroup in mice in vitro. RESULTS Acta(10,30,90 mg?kg -1 ) intragastric injection(ig) did not significantly inhibit primary reaction of AA in rats. But Acta(10,30,90 mg?kg -1 ?11 d) ig signifcantly inhibited secondary reaction (secondary inflammatory swelling、 multiple arthritis) of AA rats. The lowered response of ConA induced splenolytes and the decreased IL 2 synthesis were restored to normal in AA rats treated with Acta, while the elevated IL 1 released from peritoneal macrophate (PM?) was reduced. Acta(1～100 ?mol?L -1 ) could inhibit ConA induced T h cells and enhance ConA induced T s cells culture in vitro . CONCLUSION Acta do not show obvious antiinflammatory action. But Acta has therapeutic action on AA rats, which may be related to its immunomodulatory activities,mainly through modulate cell mediated immunity.