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OBJECTIVE：To analyze the metabolites of tetrahydroxystilbene glucoside （THSG）and speculate its metabolism pathway in rats. METHODS ：Male SD rats were randomly divided into plasma group （n＝3），urine group （n＝3），bile group （n＝3），and tissue group （n＝9）. Each group was given single dose of THSG 200 mg/kg intragastrically. Plasma samples 10，30 min and 1，1.5，2，4 h after medication ，the unrine 0-6 h after medication ，the bile 0-4 h after medication ，the tissue of heart ， liver，spleen，lung，kidney and stomach 30 min and 1，2 h after medication （3 at each time point ）were collected respectively.After precipitated with methanol ，the metabolites of samples were analyzed and identified by UHPLC-Q-Exactive Orbitrap MS and mass loss filtration （MDF）. Its metabolism pathway was speculated. RESULTS：In the blood ，urine，bile，heart，liver，spleen， lung，kidney，stomach samples ，6，7，11，1，5，1，3，4，4 metabolites were detected ，including two phase Ⅰ（hydrolysis， hydrogenation and hydroxylation ）metabolites，18 phase Ⅱ（glucuronic acid binding and sulfation ）metabolites. There were 12 glucuronic acid binding products. CONCLUSIONS：Most of the metabolites of THSG are found in bile ，mainly glucuronic acid binding products of phase Ⅱ metabolite THSG ； main metabolic pathways involve glucose hydrolysis ， hydrogenation， hydroxylation，glucuronic acid binding and sulfation.
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OBJECTIVE：To establ ish the fingerprint of Sojae Semen Nigrum and content determination method of 5 kinds of isoflavones，so as to provide reference for controlling its quality better. METHODS ：HPLC method was adopted to establish the fingerprint and detect the contents of 5 kinds of isoflavones. The determination was performed on Phenomenex C 18 column with mobile phase consisted of acetonitrile- 0.12％ formic acid solution （gradient elution ）at the flow rate of 1 mL/min. The detection wavelength was set at 260 nm；the column temperature was 30 ℃ and sample size was 10 μL. Using daidzin as reference，HPLC fingerprints of 12 batches of samples were determined. The similarity of 12 batches of samples was evaluated by TCM Chromatographic Fingerprint Similarity Evaluation System （2012A） to confirm common peak. Cluster analysis and principal component analysis were performed by using SPSS 20.0 software and SIMCA 13.0 software. RESULTS ：There were 19 common peaks in HPLC fingerprints of 12 batches of samples ，the similarity of which was higher than 0.94. Totally 5 components were identified，such as daidzin ，glycitin，genistin，daidzein，genistein. Cluster analysis showed that 12 batches of Sojae Semen Nigrum were clustered into 2 categories，i.e. S 1-S3 clustered into one category ，and S 4-S12 clustered into the other category. By principal component analysis ，the contribution rates of two principle components were 53.261％ and 40.715％；accumulative contribution rate was 93.976％. The linear range of above 5 components were 5.97-191.00 µg/mL（r＝0.999 9），1.05-33.46 µg/mL（r＝0.999 9）， 8.93-285.61 µg/mL（r＝0.999 5），0.82-26.33 µg/mL（r＝0.999 9），0.93-29.64 µg/mL（r＝0.999 7），respectively. The limits of quantitation were 0.881 1，0.611 6，0.078 6，0.243 3，0.511 6 μg/mL，respectively. The limits of detection were 0.264 3，0.244 7， 0.021 4，0.124 8，0.106 7 μg/mL，respectively. RSDs of precision ，stability，reproducibility and durability tests were all lower than 5％. Recoveries were 95.15％-96.56％（RSD＝0.51％，n＝6），98.52％-103.45％（RSD＝1.88％，n＝6），95.37％-97.91％ （RSD＝0.95％，n＝6），99.75％-102.00％（RSD＝0.78％，n＝6），100.26％-103.65％（RSD＝1.21％，n＝6）. Among 12 batches of Sojae Semen Nigrum ，the contents of above 5 components were 0.178 3-0.265 9，0.021 7-0.096 2，0.288 5-0.597 2，0.014 1- 0.058 8，0.012 9-0.082 9 mg/g. CONCLUSIONS ：Established HPLC fingerprint and content determination method of 5 kinds of isoflavones can be used for quality control of Sojea Semen Nigrum. The Isoflavone components are similar ，but the contents are different among Sojae Semen Nigrum from different producing areas.
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Objective To investigate the post-mortem brain histopathology in patients with systemic lupus erythematosus (SLE).Methods The medical records and cerebral autopsy tissue of nine patients with SLE autopsied during 1956--2000 in Peking Union Medical College Hospital were collected and reviewed.Results Nine patients were all female and the average age was (29±11) years.Eight out of nine patients clinically presented with neurological manifestations.Brain histopathology changes were identified as follow:brain parenchyma change was shown in eight cases (8/9),cerebral hernia in six cases (6/9),cerebral hemorrhage in four cases (4/9),infarction in three cases (3/9),ventricular dilation in three cases (3/9),meningitis in two cases (2/9) and vasculopathy in one case (1/9).Vasculitis was not shown in any patients.Conclusion The brain histopathology in SLE includes vasculopathy,infarction,hemorrhage,infection,meningitis,ventricular dilation,cerebral hernia,brain parenchyma change,etc.Among the above changes,brain parenchyma changes,cerebral hernia and hemorrhage are the most commonly shown,while vasculitis is uncommonly presented.SLE patients with brain histopathology changes may even without clinically manifestation.All patients with SLE should be alert to neurological involvement.
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Objective To study the characteristics of granulomatosis with polyangiitis (GPA) accompanied by pneumothorax.Methods We described a case of GPA accompanied by hydropneumothorax who was successfully treated.Relevant literature was also reviewed.Results A total of 25 cases were identified,consisting of 18 males and 7 females [the average age was (44±16)(16-70) years old].The time from disease onset to pneumothorax was 26±51 (0.83-216) weeks.Pneumothorax,hydropneumothorax,pyopneumothorax and hemopneumothorax occurred in 11,5,8 and 1 respectively.Nodules or excavated nodules on chest radiography or CT were seen in 22 cases.Erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) were elevated in all cases.Sixteen cases received glucocorticoid and immunosuppressive agents treatment.Sixteen cases received drainage and 7 received open operation.Pseudomonas aeruginosa was the most commonmicrobiology findings.Granulomatosis with active vasculitis,bronchopleural fistula,pleural bleb with intensefibrosis,rupture of subpleural nodule were seen on lung biopsy or autopsy.Nine cases died of infections,respiratory failure,sepsis and respiratory arrest.Conclusion Pneumothorax in GPA can be caused by multiple factors such as rupture of subpleural nodule and with high mortality.Patients always died of infections and respiratory failure.Regular treatment of the underlying disease,apply sensitive antibiotics for infection and reasonable surgical intervention should be considered.
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Objective To measure the levels of caspase-1 and its downstream factor interleukin (IL)-18 and IL-33 in rheumatoid arthritis (RA) and explore their possible mechanisms.Methods Blood samples were drown from 56 patients with RA and 22 healthy subjects.Serum levels of caspase-1,IL-18 and IL-33were tested by the method of enzyme linked immunosorbent assay (ELISA).Kruskal-Walls and Mann-Whitney test were used to compare the levels of caspase-1,[L-18 and IL-33 and Spearman's correlation test was used for correlation analysis.Results The level of caspase-1 was significantly increased in RA group compared to healthy group [(32±26) ng/ml vs (15±6) ng/ml,P＜0.01].Meanwhile,the active disease groups showed a higher level than the remission group,and level in the untreated group was higher than the treated group [(47±27) ng/ml vs (25±22) ng/ml,P＜0.01].The levels of IL-18 and IL-33 were significantly increased in RA group compared to healthy group [(121±121) ng/L vs (58±33) ng/L,(1032±1011) ng/L vs (510±231)ng/L,respectively,P＜0.05].Meanwhile,the active disease groups had a higher level than the remission group and the untreated group had higher levels than the treated group [IL-18 and IL-33 were (172±139) ng/L vs (97±106) ng/L,(1469±1039) ng/L vs (825±941) ng/L,respectively,P＜0.05].Caspase-1 was correlated withIL-18 and IL-33 (r=0.824,0.854,P＜0.01) and IL-18 was correlated with IL-33 (r=0.800,P＜0.01).But neither of the three factors was related with clinical indexes including disease duration,RF,anti-CCP antibody,tender joints count and swollen joints count.Conclusion Caspase-1 and its downstream factor IL-18,IL-33 increase in RA,and they may play important roles in RA.
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ObjectiveThis study is aimed to investigate the association of human leukocyte antigen (HLA)-DRB1 with rheumatoid arthritis (RA) in Chinese Han population.MethodsA total of 281 Chinese Han patients with RA and 202 healthy controls were recruited.DNA was extracted from PBMC and HLA typing was performed by sequence based typing and PCR-Sequence Specific Primer.The frequency of HLADRB1 was compared between patients and controls using x2 test with continuity correction.ResultsThe susceptible HLA-DRB1 alleles were * 0101,* 0102,*0404,* 0405,and * 0410 which belonged to QRRAA.DRRAA and DERAA were protective alleles.At genotypic level,The association of S3P and S3D was detected.However,the protective effect of S3D was shown to be in a recessive mode.ConclusionOur results have shown that there are racial differences in RA susceptibility between Chinese Han population and Caucasians.
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Objective The aims of this study were to compare the clinical and laboratory responses to ursodeoxycholic acid (UDCA) monotherapy with the combination therapy of UDCA plus prednisolone/azathioprine in primary biliary cirrhosis(PBC),and to investigate the risk factors affecting the therapeutic responses.Methods Eighty-two patients with untreated PBC were divided randomly into three groups.Group U (28 patients) received UDCA alone,group UP(27 patients) received UDCA and pr ednisolone,while group UA (27 patients ) received UDCA and azathioprine.The clinical and laboratory data were recorded after treated for 3,6 and 12 months.Repeated measures ANOVA and COX regression model were used for statistical analysis.Results Fatigue and pruritus were improved only in group UP(P=0.015 and P=0.037 respectively).Alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),gamma-glutamyl transferase (GGT),total bilirubin (TBIL),direct bilirubin (DBIL) and IgM in the 3 groups were decreased (P＜0.05),while there was no statistical significant difference between the three groups (P＞0.05).The patients with disease progression had higher Mayo risk score (MRS) (P=0.018) and prolonged prothrombin time (PT)(P=0.042).In group UP,side-effect associated with glucocorticosteroids occurred in eight patients while there was no side-effect in group U.High baseline levels of ALP、GGT and CHO were risk factors for biochemical remission(P=0.015).The increase of DBIL,TBIL,total bile acid(TBA) and PT did not contribute to the prediction of biochemical remission ( P=0.075 ).Conclusion There are no differences among the three groups in the improvement of hepatic biochemical data and IgM.The combination therapy of UDCA with prednisolone could relieve fatigue and itching.The disease of patients with higher Mayo risk score and prolonged PT tend to progress.High baseline levels of ALP,GGT and CHO are risk factors for biochemical remission.High baseline levels of TBIL,DBIL,TBA and PT could not predict biochemical remission.The incidence of adverse effect is lowest when treated with UDCA alone.
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Objective The aim of this study was to describe the clinical and pathological features of primary biliary cirrhosis(PBC) and their correlation.Methods Liver biopsy specimens were obtained through percutaneous needle puncture from twenty four patients with PBC who had not been diagnosed or treated before.These samples were fixed in formaldehyde and embedded in paraffin for routine histological examination.Pathologic stages based on Ludwig criteria,fibrosis,portal and periportal inflammation,lymphocytic periportal piecemeal necrosis,ductular proliferation,intralobular hepatocyte necrosis,the degree of ductopenia and relevant laboratory results were recorded.Statistics method used was x2 or t-test,Mann-whitmey U nonperametric test and Pearson's or Spearman's correlation analysis.Results The pathological stages,degree of fibrosis were positively correlated with total bilirubin (TBIL) level,total bile acid (TBA),cholesterol (CHO),IgG levels,and were negatively correlated with serum albumin(ALB) level(r=-0.527,P=0.030; r=-0.503,P=0.039) ,percentage of eosinophilic cells (EOS) ( r=-0.554,P=0.021; r=-0.502,P=0.040).Lymphocytic periportal piecemeal necrosis was positively correlated with alkaline phosp-hatase (ALP),TBIL,DBIL,TBA,and also tumor necrosis factor-αt (TNF-αα) levels(r=0.617,P=0.006).Conclusion TBIL,DBIL,TBA,CHO,IgG and ALB,EOS are good surrogate markers for disease sever ity and reversibility of PBC,while ALP,TNF-Cα,TBIL,DBlL,TBA can be used as markers for disease activity.
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Objective To investigate the effect of mycophenolic acid (MPA) on the endotheline-1 (ET-1) induced proliferation, contraction and migration of pulmonary arterial smooth muscle cells (PASMCs)and to explore the mechanism of MPA on pulmonary arterial hypertension (PAH), and the effect of exogenous guanosine nucleotide reversing anti-proliferative effect of MPA. Paired-samples t-test was used for statistical analysis. Methods MTT test, scarification test, Millicell cell culture insertion and the length of PASMCs mcasured under microscope were used. Results The A values of group ET-1 + low concentration MPA decreased when compared with group ET-1 (0.348±0.036 vs 0.447±0.013, t=6.357, P=0.000) and the A values of group ET-1 + high concentration MPA was further decreased. The A values of group ET-1 + low concentration MPA + guanosine was higher than that of group ET-1 + low concentration MPA (0.390±0.018 vs 0.348 ±0.036, t=2.573, P=0.028). The average migration distance and the average migration numbers of PASMCs of groups MPA was decreased than that of group ET-1. The average cell length of PASMCs of groups MPA was increas ed than that of group ET-1. Conclusion MPA can effectively inhibit the proliferation,contraction and migration of PASMCs by ET-1 induction. The IMPDH may play a role in anti-proliferative effect of MPA on PASMCs, but is unnecessary to be the sole mechanism. These findings has provide new insight into the mechanisms of mycophenolate mofetil in the treatment of PAH.
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Objective To investigate the characteristics of peripheral lymphocytic subsets and cytokines in patients with primary biliary cirrhosis( PBC) and their changes after therapy. Methods Eighty two patients with untreated PBC were divided randomly into three groups. Group U (28 patients) were treated with ursodeoxycholic acid ( UDCA) , group UP (27 patients) were treated with UDCA and prednisonlone, while group UA (27 patients) were treated with UDCA and azatharaprine. Levels of peripheral lymphocytic subsets and cytokines were monitored at 0, 3, 6 months after therapy. Twenty healthy people were included as healthy control ( HC). Results Compared with HC, the percentage of CD/ T cell (P = 0. 044) increased in PBC; the levels of IFNγ(P = 0. 001), IL-2 (P =0. 000) , IL-4 (P =0. 010) , IL-6 (P = 0. 029) , tumor necrosis factora ( TNFα ) ( P = 0. 000) , IL-1β ( P = 0. 008 ) and transforming growth factorβ(TGFβ) (P =0. 069) increased in PBC. The level of TNFa in peripheral was correlated with those of ALT (P=0.005), AST (P=0.002), total bilirubin(Tbil) (P=0.001), direct bilirubin( Dbil) (P=0. 002) , and mayo risk score(MRS) (P=0. 020). The percentage of CD_4~+T cell decreased in group U. In group U, the levels of IFNγ,IL-4,IL-6 all decreased after therapy at the third month, but rebounded thereafter. In group of UP and UA, the levels of IFN-γ, IL-4, IL-6 were suppressed below the levels of baseline after therapy.Levels of TNFa and IL-2 decreased in all three groups after therapy. Conclusions Levels of both Thl and Th2 related cytokines are abnormal in the peripheral blood of patients with PBC. The abnormal levels of Thl related cytokine indicated that PBC is a cell immunity based autoimmune disease. IFNγ,TNFα are directly related to the disease. The three treatments have different effects on the adjustment of the immune system.
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Objective To investigate the manifestations of esophageal motility disorders and evaluate the association between them and dysphagia, laboratory tests and other accessory examinations in patients with Sj(o)gren's syndrome (SS). Methods Esophageal manometry was performed in 31 patients with SS and 18 healthy volunteers by the step pull-through method. Results Decreased upper esophageal sphincter pressure was detected in 19 of the 31 patients (61%) with SS, while 4 of 18 (22%) in controls. The frequency was significantly higher in patients than in healthy controls (P=0.008). Fifteen of 31 patients (48%) showed various patterns of esophageal dysfunction including ineffective esophageal motility in 6 patients, nutcracker esophagus in 3 patients and nonspecific dysmotility in 6 patients. No major differences were found in esophageal parameters (peak amplitude, wave duration and velocity) when comparing primary SS with secondary SS. These esophageal abnormalities were not correlated with clinical manifestations, laboratory examinations and other auxiliary examinations. Conclusion Patients with SS may have esophageal motility disorders, which can presents with different patterns.
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Objective To investigate the effect of mycophenolic acid on the proliferation of smooth muscle cells (SMCs) in rats' pulmonary arterial at cellular level. Methods Growth curve, MTT tests, and flow cytometry were used to detect the number of proliferative cells, the A-value of living cells and the DNA content of the control and drugs groups respectively and the number of cells in G1-phase, S-phase, G2M- phase and the proliferation index were calculated. Results Compared with the control group, the number of living cells in the mycopbenolic acid groups (with the concentration of 1, 10, 100 μmol/L) decreased, except the lowest dosage group (100 nmol/L). The difference was statistically significant (P<0.01). The living cells measured by MTT dose-dependently reduced in the mycophenolic acid groups. In the mycophenolic acid groups, the fraction of living cells in the S-phase and G2M-phase decreased respectively while that in G1- phase increased, and the proliferation index decreased. All these responses presented with a dose-dependent manner. Conclusion Mycophenolic acid can effectively inhibit the proliferation of rats' pulmonary arterial SMCs. This process happens mainly in ONA synthesis phase, and is dose dependent. In addition, these effective concentrations are all in the available range for clinical application.
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Objective To investigate the characteristics of mesenteric vascular thrombosis (MVT) in patients with antiphospholipid antibody syndrome (APS).Methods The cases reports about MVT in patients with APS were searched in Pubmed and Chinese biomedical database (1983.1-2007.7) and then were analyzed.Results There were 13 males and 8 females in 21 patients.The average age was (37±17) years (5months～69 years).Three cases (14%) had a history of deep venous thrombosis and 4 (19%) had spontaneous abortions.The course of disease was 4 hours to 4 months.The clinical manifestations included abdominal pain 18 (86%),hemafecia or melaena 4 (19%),vomiting 3 (14%),diarrhea 2 (10%),hematemesis 2(10%).Physical signs included abdominal tenderness in 10(48%),peritoneal irritation signs in 5 (24%),shifting dullness in 3 (14%) anddecreased bowel sounds in 3 (14%).Mesenteric vascular thrombosis were detected through B uhrasonography (3/10,33%),abdominal CT (9/13,69%),MRI (4/4,100%),Doppler ultrasound (4/4,100%),angiography (6/6,100%).Eighteen cases (86%) had positive anti-cardiophospholipin antibody and 14 (67%) were IgG-subtype.Lupus anticoagulants were detected in 4 (19%).Sixteen cases reee-ived exploratory laparotomy,lsehemia or necrosis of intestine were found in 9(56%).In 21 cases,superior mesenteric vein thrombosis,suprior mesenteric artery thrombosis,inferior mesenteric vein thrombosis,inferior mesenteric artery thrombosis were discovered in 17 (81%),4 (19%),0 (0%),1 (5%)patients respectively.Portal vein was also involved in 7 (33%) cases who had superior mesenteric vein thrombosis.Conclusion Superior mesenteric vein is usually involved in patients with APS who have MVT.MVTs are always occurr in middle-age male patients.Some patients have deep vein thrombosis or spontaneous abortion before MVT.The disease may be fulminant or had is insidious in onset.Abdominal pain and intestinal obstruction are the most common manifestations.IgG-subtype anticardiophospholipin antibodiesare the common antibodies discovered in these patients.Combined more than one image methods can detect the thrombi effectively.Anticoagulation and essential exploratory laparotomy are effective interventions in most cases.
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Objective To investigate the significance and characteristics of T lymphocyte subsets and co-stimulatory CD28 in peripheral blood of patients with primary biliary cirrhosis. Methods Tri-colour flow-cytometry was used to detect the levels of T lymphocyte subsets in peripheral blood in 98 patients with primary biliary cirrhosis and 30 age and gender matched healthy controls. Results Compared to control group the percentage of CD4+ T increased and CD8+ T lymphocyte decreased in the PBC group. The CD4+/CD8+ ratio in the PBC group was higher than that in the control group (P<0.05). And the percentage of CD4+CD28- T cells and CD8+CD28- T cells increased, too (P<0.05). Conclusion There are immunological abnormalities in PBC and the expression of co-stimulator CD28 is significantly decreased. CD8+CD28-T lymphocytes may have immune regulatory effect in PBC.