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 observe the effects of telmisartan on Kv1.3 and Kv1.5 potassium channels expressed in Xenopus oocytes. Methods Kv1.3 and Kv1.5 potassium channel currents expressed in Xenopus oocytes were recorded and observed in the absence and presence of telmisartan using standard two-microelectrode voltage clamp techniques. Results Telmisartan resulted in a concentration- and voltage-dependent inhibition effect on Kv1.3 channel current (IC50 2.05 &mu;mol/L) and on Kv1. 5 channel current (IC50 2.37 &mu;mol/L). Conclusions Telmisartan blocks open-state Kv1.3 channel which could be one of the mechanisms related to its immunomodulatory and anti-atherosclerosis effect. Telmisartan also blocks open-state Kv1.5 channel which might partly account for its effect on reducing the incidence of atrial fibrillation.

Objective The prognostic value of corrected QT interval(QTc),corrected Tp-e interval (Tp-ec) and Tp-e/QT ratio on occurrence of malignant arrhythmia events (MAE) in acute ST-segment elevation myocardial infarction (STEMI) patients underwent successful thrombolysis was explored and the potential association of these indices with MAE was analyzed.Methods Fifty-seven STEMI patients underwent successful thrombolytic therapy within 6 hours after admission and conservative medical treatment were included.QTc,Tp-ec,Tp-e/QT ratio were obtained and calculated in infarct-related electrocardiograph leads and non-infarct-related leads before thrombolysis,(7 ± 1 ) days and (30 ±3 ) days after thrombolysis respectively,and incidence of MAE up to 30 days after thrombolysis was analyzed.Sixty age and gender matched normal subjects served as control group.Results ( 1 ) QTc,Tp-ec,Tp-e/QT in infarct-related and non-infarct-related leads in STEMI group before thrombolysis were significantly higher than those in control group( all P ＜0.05 ),and values from the infarct-related leads were significantly higher than those from non-infarct-related leads in STEMI group ( all P ＜ 0.05 ).QTc,Tp-ec and Tp-e/QT all significantly and continuously reduced from 7 days and at 30 days post thrombolysis compared the before thrombolysis( P ＜0.05 vs.before thrombolysis).( 2 ) Tp-ec ≥ 100 ms and Tp-e/QT ratio ≥0.25 before thrombolysis in infarct-related leads were linked with higher incidence of MAE within 30 days post thrombolysis in this patient cohort [28.1％ (9/32) vs.40％ ( 1/25),27.8％ (10/36) vs.0,respectively,all P ＜ 0.05 ].Conclusion QTc,Tp-ec and Tp-e/QT values decreased post successful thrombolysis in STEMI patients and higher Tp-ec and Tp-e/QT values before thrombolysis in STEMI patients were related with higher MAE incidence up to 30 days post successful thrombolysis in this patient cohort.

Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with high local invasiveness. To date, there is no consensus on the imaging characteristics of NACC. To address this, we retrospectively reviewed 10 cases of NACC and summarized the magnetic resonance imaging (MRI) features. MR images of 10 patients with histologically validated NACC were reviewed by two experienced radiologists. The location, shape, margin, signal intensity, lesion texture, contrast enhancement patterns, local invasion, and cervical lymphadenopathy of all tumors were evaluated. Clinical and pathologic records were also reviewed. No patients were positive for antibodies against Epstein-Barr virus (EBV). The imaging patterns of primary tumors were classified into two types as determined by location, shape, and margin. Of all patients, 7 had tumors with a type 1 imaging pattern and 3 had tumors with a type 2 imaging pattern. The 4 tubular NACCs were all homogeneous tumors, whereas 3 (60%) of 5 cribriform NACCs and the sole solid NACC were heterogeneous tumors with separations or central necrosis on MR images. Five patients had perineural infiltration and intracranial involvement, and only 2 had cervical lymphadenopathy. Based on these results, we conclude that NACC is a local, aggressive neoplasm that is often negative for EBV infection and associated with a low incidence of cervical lymphadenopathy. Furthermore, MRI features of NACC vary in locations and histological subtypes.
Adult ; Aged ; Carcinoma, Adenoid Cystic ; diagnosis ; pathology ; surgery ; Female ; Humans ; Lymphatic Metastasis ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; diagnosis ; pathology ; surgery ; Neoplasm Invasiveness ; Neoplasm Staging ; Retrospective Studies

OBJECTIVETo investigate the changes of blood lipid in patients with colorectal cancer complicated by coronary heart disease (CHD) and the effect of lipid-lowering therapy with statins in these patients.

METHODSIn 32 pathologically confirmed colorectal cancer patients with CHD, the concentrations of total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and lipoprotein (a) (Lp(a)) were detected at the baseline, before and after the operation, and at 6 months of postoperative atorvastatin treatment. Thirty patients with TC over 5.70 mmol/L and established coronary artery disease served as the control group.

RESULTSTC, TG and LDL-C in the 30 control patients were significantly decreased after 6 months of 20 mg atorvastatin treatment, and even further decreased till 12 months (P<0.01), but no significant changes occurred in HDL-C and Lp(a). The baseline level of TC, TG, LDL-C and HDL-C were significantly decreased (P<0.01), while Lp(a) increased (P<0.05) in the 32 cancer patients with CHD. Continuing atorvastatin treatment further decreased TC, TG and LDL-C (P<0.05) and increased HDL-C (P<0.05) without affecting Lp(a). The cancer patients had significantly lower TC and LDL-C levels than the control group (P<0.05), but had significantly increased Lp(a) (P<0.05). Six months of atorvastatin treatment further decreased LDL-C and HDL-C in the cancer patients (P<0.05), while TC and Lp(a) had no significant changes.

CONCLUSIONSIncreased Lp(a) in colorectal cancer patients can be associated with its anti-tumor effect. Alterations in the blood lipid profile raises a new issue concerning the safety of lipid-lowering therapy in colorectal cancer patients complicated by CHD.

Aged ; Anticholesteremic Agents ; therapeutic use ; Atorvastatin Calcium ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Colorectal Neoplasms ; blood ; complications ; drug therapy ; Coronary Disease ; blood ; complications ; drug therapy ; Female ; Heptanoic Acids ; therapeutic use ; Humans ; Lipoprotein(a) ; blood ; Male ; Middle Aged ; Pyrroles ; therapeutic use ; Treatment Outcome ; Triglycerides ; blood

BACKGROUNDToll like receptor (TLR) 9 has been shown to play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE) in animal models. Its pathogenic role in human SLE, however, was poorly elucidated. This study was performed to investigate the role of TLR9 involved in the aberrant signaling pathway and its correlation with disease activity in SLE.

METHODSmRNA level of TLR9 and interferon (IFN) regulatory factor 5 (IRF5) in peripheral blood mononuclear cells (PBMCs) were determined by real-time polymerase chain reaction (PCR). IFN-a expression was measured in the serum of the SLE patients by enzyme-linked immunosorbent assay (ELISA).

RESULTSTLR9 expression was significantly higher in SLE patients than that in health controls (P = 0.011). SLE patients with positive anti-dsDNA antibody had significantly higher expression of TLR9 than that with negative anti-dsDNA antibody (P = 0.001). TLR9 expression was positively correlated with fever (P = 0.017), alopecia (P = 0.046), safety of estrogens in lupus erythematosus national assessment SLE disease activity index (SELENA-SLEDAI) score (r(s) = 0.385, P = 0.003), and the level of IRF5 (r(s) = 0.35, P = 0.027) and IFN-a (r(s) = 0.627, P = 0.001) in SLE patients.

CONCLUSIONTLR9 is associated with SLE disease activity and might be involved in the IFN-a pathway of SLE.

Adolescent ; Adult ; Antibodies, Antinuclear ; blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interferon Regulatory Factors ; metabolism ; Interferon-alpha ; blood ; Leukocytes, Mononuclear ; metabolism ; Lupus Erythematosus, Systemic ; blood ; genetics ; metabolism ; Male ; Middle Aged ; Real-Time Polymerase Chain Reaction ; Toll-Like Receptor 9 ; genetics ; metabolism ; Young Adult

Objective To compare the effects of intracoronary infusion of mononuclear stem cells (MNCs) or mesenchymal stem cells (MSCs) in patients with dilated cardiomyopathy (DCM).Methods DCM patients with left ventricular ejection fraction ( LVEF ) ＜ 40％ were randomized to intracoronary infusion of MNCs [ (5.1 ± 2.0) × 108,n =16] or MSCs [ (4.9 ± 1.7 ) × 108,n =17 ] or equal volume normal saline ( n =20 ) through the guiding catheter. Changes of left ventricular end-diastolic diameter (LVEDd),LVEF and myocardium perfusion defects were assessed before and at (30 ±3) days and (90 ± 7) days after the procedure.Malignant cardiovascular events were also recorded.Results ( 1 ) One month after the procedure,LVEF in transplantation groups significantly increased compared to before procedure ( all P ＜0.05),and significant increase of LVEF was observed only in MSCs transplantation group compared to control group ( P ＜ 0.05 ).However,absolute changes of LVEDd and perfusion defects of myocardium were similar among and within groups (P ＞ 0.05 ).(2)Gomparing with before procedure and control group,LVEF in transplantation groups increased significantly in three months after the procedure (P ＜ 0.05 ),but there were no significant differences between transplantation groups ( P ＞ 0.05 ).LVEDd and myocardium perfusion defects in transplantation groups improved significantly compared with that of before procedure (P ＜0.05 ),while significant decrease of myocardium perfusion defects was only observed in patients treated with MSCs compared with control group at three months after procedure ( P ＜ 0.05 ). ( 3 ) There were no significant differences in major cardiovascular events between transplantation group and control during followup ( P ＞ 0.05).Conclusions Intracoronary bone marrow stem cells transplantation is safe and effective for DCM patients while the efficacy of MSCs and MNCs transplantation is comparable.

Objective To investigate the effect Angiontensin(1-7) [Ang(1-7)] on left ventricular dysfunction and myocardial apoptosis on rat model of adriamycin-induced dilated cardiomyopthy ( ADR-DCM ).Methods Weight-matched adult male Wistar rats were randomly divided into 3 groups:( 1 )the ADR-DCM group (n =25 ),in which 2.5 mg/kg of ADR was weekly intravenously injected for 10 weeks.( 2 ) Ang ( 1-7 ) group ( n =25 ),in which ADR rats were simultaneously treated with angiotensin-(1-7) (24 &mu;g · kg-1 · h-1,ip.) for 12 weeks.(3) normal control group (n =10).Hemodynamics and echocardiography examination were performed at 12 weeks.The malondialdehyde (MDA) was measured by TBA methods.The plasma concentration of Ang Ⅱ was determined by immunoradiometric assay.The pathological change was analyzed by histological hematoxylin-eosin staining.Myocardial apoptosis was assessed by TUNEL method.The protein expression of pro-apoptotic protein caspase-3,Bax and antiapoptotic protein Bcl-xl in cardiomyocytes were detected by Western blot.Results Mortality was significantly lower in Ang(1-7) group than in ADR-DCM group (16％ vs.40％,P ＜0.01 ).Compared to the control group,left ventricular end-diastolic diameter ( LVEDD),left ventricular end systolic diameter (LVESD) and left ventricular end-diastolic pressure (LVEDP) were significantly increased in ADR-DCM group ( all P ＜ 0.01 ) while fractional shorting ( FS), + dp/dtmax and - dp/dtmax were significantly reduced in ADR-DCM group ( all P ＜0.01 ).LVEDD,LVESD and LVEDP were significantly reduced while FS,+ dp/dtmax and -dp/dtmax were significantly higher in Ang( 1-7 ) group compared to the ADR-DCM group,but still higher than the control group ( all P ＜ 0.01 ).The concentrations of Ang Ⅱ and MDA were higher in the ADR-DCM group than in the control group ( P ＜ 0.01 ),which were significantly reduced by Ang(1-7) treatment (P ＜ 0.01 ).The TUNEL-positive cells and apoptosis index,the expression of proapoptotic protein caspase-3 and Bax were significantly higher while the expression of anti-apoptotic protein Bcl-xl was significantly lower in the ADR-DCM group than in the control group (all P ＜ 0.01 ) which could all be partially reversed by Ang(1-7) treatment ( all P ＜ 0.01 ).Conclusion Ang (1-7) could significantly attenuate left ventricular dysfunction and myocardial apoptosis in this model by downregulating pro-apoptotic protein caspase-3 and Bax and upregulating anti-apoptotic protein Bcl-xl expression.

Objective:Our study was aimed to analyze the therapeutic effect of early sequential enteral nutrition on postoperative rehabilitation in patients with gastric cancer.Methods:Patients with gastric cancer receiving surgery at our hospital from 2016 to 2017 included and the clinical information was prospective collected and analyzed.Patients were randomly divided into two groups using random number table.Patients in group A were sequentially given amino acid type,short peptide type and then whole protein type,while those in group B received whole protein formulation only.The recovery of gastrointestinal function,postoperative systemic inflammatory response,six-minutes walking test,and enteral nutrition-related complications were compared between the two groups.Results:A total of 71 patients were included in this study (Group A 36 cases,Group B 35 cases).There was no significant difference in terms of the restart anal exhaust between the two groups (P ＞ 0.05).Patients in group A had a significantly shorter postoperative hospitalization (t =4.070;P ＜ 0.01) and the earlier restoration of oral intake than that of Group B (t =3.400;P =0.001).One week after surgery,the levels of CRP (t =2.547;P =0.013) and IL-6 (t =3.172;P =0.002) were significant lower in group A when compared with group B.In addition,patients in group A had a significant higher six minutes walk steps than those in Group B [(416.1 + 36.7) m vs (358.9 ± 32.7) m;t =6.927,P ＜ 0.01].However,no significant difference in enteral nutrition-related complications was found between the two groups (P ＞ 0.05).Conclusion:In patients with gastric cancer,early sequential enteral nutrition can effectively accelerate the postoperative rehabilitation.

Objective: To compare the efficacy and safety of pro-urokinase and reteplase in the treatment of patients with acute ST elevation myocardial infarction (STEMI). Methods: STEMI patients, who received intravenous thrombolytic therapy in Henan STEMI registry between September 2016 and August 2018, were eligible for this study. A total of 5479 patients from 66 hospitals were screened and patients were divided into pro-urokinase group (n=638) and reteplase group (n=702) according to thrombolytic drugs. Data including patient demographics, risk factors, medical histories, patient information at admission, in-hospital treatment, time delays, and clinical events were collected. The clinical recanalization rate, in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital main adverse cardiovascular and cerebrovascular events (MACCE, death or treatment withdrawal, congestive heart failure, reinfarction and ischemic stroke) and post-thrombolysis bleeding were compared between the two groups. Bleeding events were evaluated with Bleeding Academic Research Consortium (BARC) criteria. Results: The median age [61.8 (53.2, 69.0) vs. 62.6 (52.1, 69.8), P=0.833] or the proportion of women [23.0% (147/638) vs. 25.1% (176/702), P=0.385] were similar between the pro-urokinase and reteplase groups. Clinical recanalization rates were similar between the pro-urokinase and reteplase groups [82.1% (524/638) vs. 84.9% (596/702), P=0.172], and there was no difference in the median time from onset to thrombolysis [194.5 (135.0,290.0) min vs. 190 (126.0,292.0) min, P=0.431] and the median recanalization time [95 (67.5,120.0) min vs. 95 (71.0,119.0) min, P=0.561] between the two groups. There was no significant difference in in-hospital mortality [5.5% (35/638) vs. 5.1% (36/702), P =0.770], in-hospital all-cause mortality, treatment withdrawal [8.9% (57/638) vs.7.7% (54/702), P=0.410], and in-hospital MACCE [13.0% (83/638) vs. 10.4% (73/702), P=0.137] between pro-urokinase and reteplase groups. However, the incidence of post-thrombolysis bleeding was significantly higher in reteplase group than in pro-urokinase group [7.8% (55/702) vs. 3.8% (24/638), P=0.002]. Further analysis found that the incidence of oral bleeding and the BARC grades 1-2 bleeding were significantly higher in reteplase group than in pro-urokinase group, whereas the incidence of cerebral hemorrhage was similar between the two groups [0.6% (4/638) vs. 0.4% (3/702), P=0.715]. The comparison of efficacy and safety outcomes between the two groups after adjusting for baseline characteristics using general linear mixed models was consistent with those before the adjustment. There was no significant difference in in-hospital mortality, in-hospital death or treatment withdrawal, in-hospital MACCE after adjusting for baseline characteristics and post-thrombolysis bleeding between the two groups. Conclusions: Pro-urokinase and reteplase have similar clinical efficacy in the treatment of STEMI. In terms of safety, the incidence of cerebral hemorrhage is similar, while the incidence of BARC grades 1-2 bleeding and oral bleeding is higher in reteplase group than in pro-urokinase group, which has no impact on in-hospital outcomes.
Female ; Fibrinolytic Agents/therapeutic use* ; Hospital Mortality ; Humans ; Myocardial Infarction/drug therapy* ; Recombinant Proteins ; ST Elevation Myocardial Infarction/drug therapy* ; Thrombolytic Therapy ; Tissue Plasminogen Activator ; Treatment Outcome ; Urokinase-Type Plasminogen Activator