Effects of β-sitosterol on the function of synovial fibroblasts in rheumatoid arthritis and its mechanism / 中国药房

OBJECTIVE To investigate the effects of β-sitosterol on the function of rheumatoid arthritis （RA） fibroblastic synoviocytes MH7A cells and its mechanism. METHODS Network pharmacology was adopted to screen the targets of β-sitosterol and the targets for the treatment of RA. After the intersection of them， topological analysis was performed to find the most critical target in the treatment of RA. MH7A cells were treated with different concentrations （0， 5， 10， 20， 40 μmol/L） of β-sitosterol， and CCK-8 was used to assay cell viability for screening the optimal concentration of β-sitosterol. MH7A cells were induced by 10 ng/mL TNF-α in vitro and treated with β-sitosterol （the optimum concentration）. CCK-8 and EdU were used to detect the ability of cell proliferation. Scratch experiment and Transwell invasion assay were used to analyze cell migration and invasion. The levels of interleukin-1β （IL-1β） and IL-6 in cell supernatant were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expressions of peroxisome proliferator-activated receptor α （PPARα） were measured by qRT-PCR and Western blot， respectively. The siRNA targeting PPARα was transfected into MH7A cells， and the effects of β-sitosterol on cell proliferation， migration， invasion， the secretion of inflammatory factors and the expression of PPARα after PPARα knockdown were detected by the above experimental methods. RESULTS PPARα was the most critical target of β-sitosterol in the treatment of RA. The optimal concentration of β-sitosterol was 20 μmol/L. Compared with model group， β-sitosterol decreased the viability of MH7A cells， and the number of proliferating cells also decreased significantly （P＜0.05）； the cell migration rate and the number of cell invasion decreased significantly （P＜0.05）. The levels of IL-1β and IL-6 were also significantly decreased （P＜0.05）， and the mRNA 15 and protein expression levels of PPARα were significantly increased （P＜0.05）. Compared with negative control small interfering RNA group， after PPARα knockdown， the cell viability increased by about 35.6% （P＜0.05）， the number of cell proliferation， the cell migration rate and the number of cell invasion increased significantly （P＜0.05）， and the levels of IL-1β and IL-6 also increased significantly （P＜0.05）. CONCLUSIONS β-sitosterol could effectively inhibit the proliferation， migration， invasion and secretion of inflammatory factors in MH7A cells， the mechanism of which may be associated with activating PPARα pathway.

Comparison of tenofovir alafenamide and entecavir for hepatitis B virus-related acute-on-chronic liver failure / 中南大学学报(医学版)

OBJECTIVES@#Hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is the most common type of liver failure in China, with a high mortality. Early rapid reduction of HBV-DNA load can improve the survival rate of HBV-ACLF patients. At present, the commonly used drugs are nucleoside (acid) analogues, such as entecavir (ETV), tenofovir, and so on. The newly listed tenofovir alafenamide fumarate (TAF) has attracted great attention of clinicians because of its stronger antiviral effect, higher transaminase normalization rate, better bone and kidney safety, and zero drug resistance. However, there are few clinical research data on the efficacy and safety of TAF in the treatment of Chinese HBV-ACLF patients, and there is a lack of pharmacoeconomic evaluation. This study aims to compare the efficacy, safety, and cost-effectiveness between TAF and ETV in patients with HBV-ACLF.@*METHODS@#The data were collected from 196 HBV-ACLF patients (80 patients in the TAF group and 116 patients in the ETV group) who were hospitalized in Xiangya Hospital, Central South University from May 2020 to March 2021. Biochemistry and virology were detected before and after treatment (at baseline, Week 2, 4, and 12). Clinical features, disease prognosis, and cost-effectiveness were compared between the 2 groups. According to the baseline, HBV-ACLF patients were divided into 4 stages including pre-liver failure stage, early stage, medium stage, and end stage. And the liver transplantation rate and mortality was also compared. Pharmacoeconomic evaluation was taken using cost-effectiveness analysis and cost minimization analysis．.@*RESULTS@#After 4 weeks of treatment, there were no significant differences in the efficacy (liver function, viral load) between the 2 groups (all P>0.05). The TAF group showed lower creatinine [(80.35±18.77) μmol/L vs (105.59±82.32) μmol/L, P<0.05] and higher estimated glomerular filtration rate (eGFR) levels [(95.65±23.21) mL/(min·1.73 m2) vs (82.68±26.32) mL/(min·1.73 m2), P<0.05] than the ETV group. After 12 weeks of treatment, the analysis of overall the liver transplantation rate and mortality between the 2 groups showed similar conclusion. However, the TAF group had a lower the liver transplantation rate and mortality than the ETV group in patients with pre-liver failure (0vs13.89%, P<0.05). No evident distinction was found in the liver transplantation rate and mortality during the early, medium, or end stages of liver failure (13.04% vs 17.65%, 37.50% vs 37.04%, and 54.55% vs 68.42%, respectively). Ratio of cost to effectiveness in the ETV group was higher than that in the TAF group.@*CONCLUSIONS@#TAF is not more efficient than ETV group in improving liver function and reducing viral load for HBV-ACLF patients and they also show similar safety. However, TAF has a greater advantage over ETV not only in preserving renal function, but also in reducing the liver transplantation rate and mortality in patients with pre-liver failure. TAF can provide economic benefit to patients with HBV-ACLF.

Application of thrombus aspiration technique in emergency percutaneous coronary intervention for patients with ST segment elevation myocardial infarction / 中国基层医药

Objective To evaluate the effect of thrombus aspiration technique in emergency percutaneous coronary intervention for patients with ST segment elevation myocardial infarction ( STEMI ) .Methods According to the digital table ,48 patients with acute anterior myocardial infarction were randomly into 22 cases of control group ( routine stent implantation ) and 26 cases of observation group ( thrombus aspiration and then stent implantation ) .The changes of TIMI grading , left ventricular ejection fraction , NT -ProBNP were compared between the two groups . Results There were no significant differences in baseline data between the two groups (all P>0.05).The proportion of TIMI grade III of immediate blood flow in the observation group after operation was higher than that in the control group(26 cases vs.16 cases,χ2 =4.810,P<0.05).The LVEF values of the observation group and the control group at 1 week after operation were better than those after 24 h,but there was no statistically significant difference between the two groups (t=1.803,1.796,all P>0.05).The level of NT-ProBNP at 1 week after operation in the observation group was significantly lower than that in the control group [(271.2 ±35.5)pg/mL vs.(806.5 ±65.8)pg/mL,t=3.154,P<0.05].Conclusion The thrombus aspiration technique can obviously reduce the occurrence of the "no reflow"in STEMI patients with high thrombus load receive PPCI ,improve the heart function .

The value of Duke treadmill score in coronary heart disease / 中国基层医药

Objective To discuss the value of Duke treadmill score in the diagnosis of coronary heart disease.Methods 94 inpatients underwent treadmill test and coronary angiography,the relationship between the Duke treadmill score and the results of coronary angiography was analyzed.Results The prognostic accuracy and positive predictive value of Duke treadmill score to male and female were 88.9％,85.0％ ;those of traditional electrocardiogram ST standard were 89.6％,82.5 ％,the differences were significant (x2 =4.27,P ＜ 0.05).Conclusion The Duke treadmill score is much more significant than the traditional ST standard in the prognostic accuracy and positive predictive value of diagnosing coronary heart disease.

Cardioprotective effects of gradual ischemic postconditioning in percutanous coronary intervention / 中国中西医结合急救杂志

Objective To observe the protective effect of gradual ischemic postconditioning (IP) capable of improving reperfusion on reperfusion injury in patients with ST-segment elevation acute myocardial infarction (STEAMl) undergoing primary percutaneous coronary intervention (PPCI).Methods 102 in-patients with STEAMI undergoing PPCI in the Department of Cardiology in the First People's Hospital of Kunshan City Affiliated to Jiangsu University from February 2011 to August 2014 were enrolled in this study. They were divided into three groups by a random number table: IP group (32 cases), gradual IP group (30 cases) and routine reperfusion group (40 cases). In IP group, after the opening of the infarction related blood vessel, ischemic postconditioning within the first minute of arterial reperfusion was made through three episodes of 1 minute inflation and 1 minute pressure withdrawn of an angioplasty balloon, and then persistent reperfusion was carried out. In the gradual IP group, the patients received three times of gradual angioplasty balloon inflation and denation, 1 minute/1minute, 30 seconds/30 seconds and 15 seconds/15 seconds respectively, presenting the gradual change of IP time. In the routine reperfusion group, after the opening of blocked blood vessel, the patients underwent routine PCI to persistently recover the coronary artery blood supply. The changes of related lead ST segment regression (Sum-STR), incidence of reperfusion arrhythmia, corrected thrombolysis in myocardial infarction (TIMI) franle count (CTFC), peaks of MB isoenzyme of creatine kinase (CK-MB), left ventricular ejection fraction (LVEF) and frequency of adverse events in follow-up period were compared among the three groups.Results The baseline characteristics were comparable in three groups. The incidence of ventricular premature beats was significantly lower in gradual IP group than that in routine reperfusion group [30.0% (9/30) vs. 55.0% (22/40),P 0.05). The incidence of ventricular tachycardia was significantly lower in IP and gradual IP groups than that in routine reperfusion group [15.6% (5/32), 13.3% (4/30) vs. 40.0% (16/40), bothP 0.05). In IP group and gradual IP group, the Sum-STR incidence, CTFC, CK-MB peaks were lower than those of routine reperfusion group [Sum-STR: (56.7±18.3)%, (57.3±21.5)% vs. (44.6±21.6)%; CTFC: 25.47±5.37, 24.46±6.41 vs. 31.62±7.56; CK-MB peaks (U/L): 126.3±78.5, 121.6±82.5 vs. 147.4±72.5; allP 0.05). In routine reperfusion group, one patient died because the ventricular fibrillation could not be corrected and another one died of no-reflow during operation. Each group had 1 patient died during the 4 weeks of follow-up after operation, in the routine reperfusion group, one died of refractory heart failure, and the cause of death of other two patients, one in IP group and another in gradual IP group, was considered due to subacute thrombosis in stent. Major bleeding events were not found in each group.Conclusion Gradual IP can ameliorate myocardial reperfusion injury more significantly in patients with STEAMI undergoing PPCI.

A study of tracking the superparamagnetic iron oxide and enhanced green fluorescent protein labeled miniature porcine bone marrow stem cells by in vitro MRI / 中华内科杂志

Objectives To track bone marrow stem cells (BMSCs) labeled by enhanced green fluorescent protein (EGFP) and superparamagnetic iron oxide ( SPIO ) -poly-L-lysine (PLL) compound by MRI in vitro for autotransplantation into pancreas of type 1 diabetes miniature pigs. Methods The BMSCs were isolated by density gradient centrifugation and attachment culture from type 1 diabetes minipigs' bone marrow. Expressional intensity of EGFP in BMSCs transfected lentivirus-EGFP with a multiplicity of infection Different magnetic resonance scanning protocols were carried out on various density BMSCs labeled by different concentration of SPIO in various time-point in vitro. Results When SPIO concentration was 25mg/L (count in Fe3 + ), the positive Fe3+ -labeling rate of BMSCs was 93. 1%. Most of SPIO particles in BMSCs' cytoplasm were observed in secondary lysosomes, but they were not detected in important organelle as cell nucleus. Comparing with gelatin the MRI of BMSCs labeled with SPIO in the condition with 1 ×104/ml cells density and 25 mg/L Fe3+ concentration in vitro, the signal intensity changes (△SI) after BMSCs labeled with SPIO 3 weeks and 6 weeks in TSE T1WI, TSE T2WI and FLASH T2 * WI sequences were 12%, 41%, 63% and 7%, 28%, 46% respectively (P ＜ 0.01 and P ＜ 0.05, respectively).Conclusions The data showed that the porcine BMSCs labeled with SPIO and EGFP could be traced successfully in vitro by MRI in the suitable sequences.

Clinical outcomes of patients with acute myocardial infarction treated by converse transport PCI / 中国综合临床

Objective To evaluate the safety,feasibility and efficacy of emergency percutaneous coronary intervention(PCI)on the spot in the patients with acute myocardial infarction(AMI)in country hospitals by interventional cardiologists from higher-level hospitals(converse transport).Methods A total of 81 AMI patients received emergency PCI on the spot by interventional cardiologists from other higher-level hospitals (transported doctors)from Mar 2004 to Sep 2008 in our hospital.The mean age of patients was 68.6 ± 3.6 years (36.0-83.0 years).Forty-six patients were male and 35 were female.There were 56 cases with anterior myocardial infarction and 25 with inferior myocardial infarction(including 11 cases combined with right ventricular infarction).The average time from symptom onset to admission was 6.2 ± 1.8 hours(2.0-12.0hours).Results Three cases were transported to higher-level hospitals for CABG because of severe conditions.The other 78 cases received emergency PCI on the spot,among whom 66 cases received primary PCI.Another 12 cases received rescue PCI.Eight one stents were implanted in total into the infarcted arteries.One operation was failed because the balloon could not go through the lesion.The success.rate was 98.7％.Four patients occurred peri-operative cardiac adverse events and 2 cases died.Four cases died during the 32-86 months follow-up,of whom I was cardiac death and 3 was non-cardiac deaths.No fatal cardiovascular events occurred in the remained cases.Conclusion Emergency PCI on the spot by interventional cardiologists from other cities(converse transport PCI)in AMI is safe,feasible and effective.But it needs to be confirmed in a large-scale study in the future.

Clinical analysis of permanent cardiac pacemaker implanted in 41 elderly patients / 中国基层医药

ObjectiveTo analyse the clinical characteristics of elderly patients with permanent cardiac pacemaker implanted. MethodsTo retrospectively analyze 41 elderly patients( ≥80 years) with permanent pacemakers implantation. Observing the clinical symptoms, bradyarrhythmia category, pacing mode, intraoperative pacing parameters,intraoperative and postoperative complications. ResultsAll patients were operated successfully. Pacing modes were,VVI 29 cases,VVIR 2 cases,DDD 9 cases and DDDR 1 case. Ventricular electrode located in right ventricular apical pacing. Atrial electrode located right heart ear. During the operateing, severe complications did not happen such as heart perforation, malignant arrhythmia. One case of postoperative dislocation electrode and one case of pocket hematocele were observed. After treatment, they were cured, no infection and pacemaker syndrome happened. 6 patients died during follow-up, postoperative from two months to 6 years. ConclusionPacing therapy in elderly patients is good. Surgical risk was not increased.