Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To explore the effect of Shexiang Baoxin pill on cardiac tissue angiogenesis in spontaneously hypertensive rats(SHR).Method Twenty 12 week old male SHR were randomly divided into experimental group and model group,with 12 week old male SD rats as the normal control group.The experimental group rats were orally administered with Shexiang Baoxin pill(45 mg·kg-1)daily,and their blood pressure was monitored using a non-invasive tail artery blood pressure gauge every four weeks.Eight weeks later,cardiac tissue was taken for platelet endothelial cell adhesion molecule-1(PECAM-1/CD31)immunofluorescence staining to observe CD31 expression level.Use protein blotting to detect the expression levels of myocardial endothelial growth factor(VEGF),myocardial endothelial growth factor receptor 2(VEGF-R2),basic fibroblast growth factor(bFGF)and phosphorylated protein kinase B(p-Akt)/protein kinase B(Akt)proteins.Result There was significant increase in blood pressure between the experimental group,model group and normal group at the same time point(all P＜0.01),but there was no statistically significant difference in blood pressure changes between the experimental group and model group at the same time point(all P＞0.05).The CD31 expression rates of the normal group,model group and experimental group were(3.79±0.84)％,(2.54±0.42)％and(3.56±0.49)％;VEGF levels were 0.95±0.10,0.73±0.08 and 0.94±0.15;VEGF-R2 levels were 0.85±0.10,0.61±0.14 and 0.80±0.10;bFGF levels were 0.84±0.04,0.51±0.21 and 0.74±0.14;p-Akt/Akt levels were 0.85±0.15,0.57±0.13 and 0.80±0.20,respectively.The differences between the normal group and the model group,as well as the experimental group and the model group,were statistically significant(all P＜0.05).Conclusion Shexiang Baoxin pill can promote the neovascularization of microvessels in the heart tissue of spontaneously hypertensive rats,and its mechanism may be related to the activation of PI3K/Akt phosphorylation,upregulation of bFGF,VEGF and their receptor VEGF-R2 in myocardial tissue.

BACKGROUND:Interspinous distraction fusion device BacFuse was used for the management of lumbar degenerative disease and obtained good clinical efficacy in recent years.However,the related biomechanical study was lacking. OBJECTIVE:To explore the related biomechanical characteristics of BacFuse,a novel interspinous distraction fusion device,which was used in lumbar degenerative disease. METHODS:After constructing the goat spinal models(L1-L6),they were grouped into four groups based on different simulated surgeries:the control group,the BacFuse group(L3/4),the screw-rod fixation group(L3/4)and the Topping-off group(L3/4 screw-rod fixation + L2/3 BacFuse fixation).The goat lumbar spine surgical model was assembled into a biomechanical testing system.A biomechanical machine was used for mechanical loading,simulating lumbar spine movement of flexion,extension,lateral flexion and rotation with a 4 Nm moment.A visual tracking system was used for positioning and capturing.Finally,mechanical and optical calibration was completed to calculate the range of motion of the L2/3,L3/4 and L4/5 segments. RESULTS AND CONCLUSION:(1)Compared with the control group,the range of motion of the L3/4 segment in the BacFuse group decreased 27.27%,70%,38.1%and 23.08%in the flexion,extension,lateral bending and rotation directions,respectively(P<0.05).The range of motion of L3/4 segment in the screw-rod fixation group decreased 72.73%,80%,71.43%and 73.08%in the flexion,extension,lateral bending and rotation directions,respectively(P<0.05).(2)Compared with the control group,the range of motion of the adjacent segment L2/3 increased by 33.33%,25%and 23.81%in the extension,lateral bending and rotation directions,respectively in the BacFuse group(P<0.05),with no significant change in flexion.In the screw-rod fixation group,there was a 50%,44.44%,50%and 58.96%increase in the adjacent segment L2/3 in the flexion,extension,lateral calibration and rotation directions,respectively(P<0.05).(3)Compared with the control group,the BacFuse group showed an increase in range of motion in proximal segment L4/5 in the extension and rotation directions by 27.3%and 17.39%(P<0.05)respectively,with no significant change in flexion or lateral bending.In the screw-rob fixation group,the proximal segment L4/5 demonstrated 38.89%,22.73%and 26.09%(P<0.05)increases in range of motion in the flexion,extension and rotation directions,respectively,with no significant change in lateral bending.(4)In the Topping-off group,the range of motion of L2/3 was reduced by 37.04%,73.08%,56.67%and 38.46%in flexion,extension,lateral flexion and rotation,respectively,compared to the screw-rob fixation group(P<0.05).Compared with the screw-rob fixation group,the Topping-off group showed a 20%reduction in the range of motion of the L4/5 in the flexion direction(P<0.05),with no significant differences seen in extension,lateral bending and rotation.(5)It is concluded that the interspinous distraction fusion device BacFuse significantly reduces the range of motion of the implanted segment and provides some stability.It still retains more mobility and reduces the impact on the adjacent segment compared to screw-rob fixation,while the Topping-off tip,which can be used for intervertebral fusion fixation,significantly reduces the range of motion of the adjacent segment and reduces the risk of adjacent segment degeneration.

Objective To summarize our experience and the early and midterm outcomes of stented elephant trunk procedure for right-sided aortic arch (RAA) with Kommerell's diverticulum (KD). Methods From April 2013 to July 2020, patients with RAA and KD who underwent stented elephant trunk procedure at our center were collected. Surgery was performed under moderate hypothermic circulatory arrest combined with selective antegrade cerebral perfusion via median sternotomy. Results A total of 8 patients were included, including 7 males and 1 female with a mean age of 51.88±9.61 years. All patients had an aneurysmal KD and aberrant left subclavian artery. Preoperative comorbidities included acute Stanford type B aortic dissection in 1 patient, aortic arch pseudoaneurysm in 1 patient, acute type B intramural hematoma in 2 patients, and coronary artery disease in 1 patient. Concomitant procedures included reconstruction of the left subclavian artery in all patients and coronary artery bypass grafting in 1 patient. The mean time of operation, cardiopulmonary bypass, aortic cross-clamping, and selective cerebral perfusion was 6.25±1.16 h, 157.75±40.07 min, 77.75±33.10 min, and 28.50±5.55 min, respectively. No intraoperative death occurred. There was 1 in-hospital death. Follow-up was completed in all patients with a mean period of 3.58±2.08 years. No late death occurred. A persistent anastomotic leak of the proximal arch was detected in 1 patient, but reintervention was not performed because neither aortic dilatation nor symptoms of tracheal and esophageal compression were observed during the follow-up. The remaining 6 patients showed positive aortic remodeling with complete thrombosis of the aneurysmal KD, and neither aortic event nor tracheal and esophageal compression occurred. Conclusion Stented elephant trunk procedure is a safe and feasible technique for selected patients with RAA and KD, which can achieve favorable early and midterm outcomes.

A novel series of 2-aryl substituted benzothiopyranone compounds was designed and synthesized based on our previously obtained benzothiopyranone scaffold with significant antituberculosis activity. All target compounds were evaluated for their antimycobacterial activity and preliminary druggability was subsequently investigated for some selected compounds with good activity. The results indicated that most compounds showed good activity against Mycobacterium tuberculosis H₃₇Rv. Among them, compounds 8g, 8h, 8q and 9f showed potent activity with MIC ranged from 0.2 to 0.4 μg·mL^-1. Furthermore, some active compounds exhibited low cytotoxicity and cardiotoxicity risk. It is worth noting that compounds 8h and 8q with good liver microsome stability and low inhibition of CYPs 3A4/5 and 2C9 were suitable for combination drug regimen to treat tuberculosis.