[ ABSTRACT] AIM:To observe the inhibitory effect of madecassoside on the LPS-stimulated microglia and to inves-tigate its possible mechanism.METHODS:Microglia cells of neonatal Sprague-Dawley ( SD) rats were cultured, isolated and purified.Microglia cells were activated with lipopolysaccharide ( LPS) .The inhibitory effect of madecassoside on micro-glia was measured by MTT assay.Tumor necrosis factor alpha (TNF-α), interleukin 1β(IL-1β) were detected by ELISA. Cell cycle and apoptotic rate were evaluated by flow cytometry.The expression of TLR4 was detected by Western blotting. The expression of NF-κB was detected by RT-PCR.RESULTS: LPS induced the proliferation of microglia and release in-flammatory cytokines significantly.Compared with LPS group, madecassoside inhibited the proliferation of microglia induced by LPS in a dose dependent manner.The IC50 value of madecassoside was 10.97 nmol/L to microglia after incubation for 48 h.Madecassoside also decreased the levels of TNF-αand IL-6, increased the ratios of microglia at the G2 phase and the ap-optotic rate, decreased the expression of TLR4 and NF-κB significantly (P<0.05).CONCLUSION:Madecassoside has in-hibitory effects on the proliferation of LPS-stimulated microglia, by which the mechanism may be related to inhibition of the expression of TLR4 and NF-κB, change of cell cycle distribution and induction of microglia apoptosis.

Objective: : This study aims to investigate the relationship between aneurysm wall enhancement and clinical rupture risks based on the magnetic resonance vessel wall imaging (MR-VWI) quantitative methods. Methods: : One hundred and eight patients with 127 unruptured aneurysms were prospectively enrolled from Feburary 2016 to October 2017. Aneurysms were divided into high risk (≥10) and intermediate-low risk group (<10) according to the PHASES (Population, Hypertension, Age, Size of aneurysm, Earlier SAH history from another aneurysm, Site of aneurysm) scores. Clinical risk factors, aneurysm morphology, and wall enhancement index (WEI) calculated using 3D MR-VWI were analyzed and compared. Results: : In comparison of high-risk and intermediated-low risk groups, univariate analysis showed that neck width (4.5±3.3 mm vs. 3.4±1.7 mm, p=0.002), the presence of wall enhancement (100.0% vs. 62.9%, p<0.001), and WEI (1.6±0.6 vs. 0.8±0.8, p<0.001) were significantly associated with high rupture risk. Multivariate regression analysis revealed that WEI was the most important factor in predicting high rupture risk (odds ratio, 2.6; 95% confidence interval, 1.4–4.9; p=0.002). The receiver operating characteristic (ROC) curve analysis can efficiently differentiate higher risk aneurysms (area under the curve, 0.780; p<0.001) which have a reliable WEI cutoff value (1.04; sensitivity, 0.833; specificity, 0.67) predictive of high rupture risk. Conclusion : Aneurysms with higher rupture risk based on PHASES score demonstrate increased neck width, wall enhancement, and the enhancement intensity. Higher WEI in unruptured aneurysms has a predictive value for increased rupture risk.

Objective: : Extracranial supra-aortic dissections (ESADs) with severe stenosis, occlusion and/or pseudoaneurysm presents potential risk of stroke. Endovascular stenting to reconstruct non acute phase ESADs (NAP-ESADs) is an alternative to anticoagulant or antiplatelet therapy. However, its feasibility, safety and efficacy of stenting in NAP-ESADs is unclear. This study aims to investigate the long-term outcomes of the feasibility, safety and efficacy of stenting in NAP-ESADs. Methods: : Seventy-four patients with 91 NAP-ESAD vessels with severe stenosis, occlusion and/or pseudoaneurysm presents potential risk of stroke who underwent stent remodeling were enrolled into this respective study from December 2008 to March 2020. Technical success rate, complications, clinical and angiographic results were harvested and analyzed. Results: : Success rate of stent deployment was 99% (90/91) with no procedural mortality or morbidity. Transient ischemic attack occurred in three patients during operation (4.1%, 3/74). Asymptomatic embolisms of distal intracranial vessels were found in two patients (2.7%, 2/74). One hundred and forty-two stents deployed at 85 carotid (135 stents) and six vertebral (seven stents) vessels. Six stent types (Wingspan, 28/135, 20.7%; Solitaire, 10/135, 7.4%; Neuroform, 8/135, 5.9%; LVIS, 2/135, 1.5%; Precise, 75/135, 55.6%; Acculink, 12/135, 8.9%) were deployed at carotid arterial dissection while two types (Wingspan, 5/7, 71.4%; Solitaire 2/7, 28.6%) at vertebral arterial dissection. Digital subtracted angiography (56%, 51/91), computational tomography angiography (41.8%, 38/91) and high resolution magnetic resonance imaging (2.2%, 2/91) were adopted for follow up, with a mean time of 17.2±15.4 months (5–77). All patient modified Rankin Scale scores showed no increase at discharge or follow-up. Angiographically, dissections in 86 vessels in 69 patients (94.5%, 86/91) were completely reconstructed with only minor remnant dissections in four vessels in four patients (4.4%, 4/91). Severe re-stenosis in the stented segment required re-stenting in one patient (1.1%, 1/91). Conclusion : Stent remodeling technique provides feasible, safe and efficacious treatment of ESADs patients with severe stenosis, occlusion and/or pseudoaneurysm.

Accurate identification of compound-protein interactions (CPIs) in silico may deepen our understanding of the underlying mechanisms of drug action and thus remarkably facilitate drug discovery and development. Conventional similarity-or docking-based computational methods for predicting CPIs rarely exploit latent features from currently available large-scale unlabeled com-pound and protein data and often limit their usage to relatively small-scale datasets. In the present study, we propose DeepCPI, a novel general and scalable computational framework that combines effective feature embedding (a technique of representation learning) with powerful deep learning methods to accurately predict CPIs at a large scale. DeepCPI automatically learns the implicit yet expressive low-dimensional features of compounds and proteins from a massive amount of unla-beled data. Evaluations of the measured CPIs in large-scale databases, such as ChEMBL and Bind-ingDB, as well as of the known drug-target interactions from DrugBank, demonstrated the superior predictive performance of DeepCPI. Furthermore, several interactions among small-molecule compounds and three G protein-coupled receptor targets (glucagon-like peptide-1 recep-tor, glucagon receptor, and vasoactive intestinal peptide receptor) predicted using DeepCPI were experimentally validated. The present study suggests that DeepCPI is a useful and powerful tool for drug discovery and repositioning. The source code of DeepCPI can be downloaded from https://github.com/FangpingWan/DeepCPI.

Objective:To evaluate the safety and efficacy of stent-assisted coil embolization in patients with recurrent intracranial bifurcation aneurysms,after initial simple coiling or microsurgical clipping.Methods:Clinical data of 20 patients with recurrent intracranial bifurcation aneurysms who initially underwent simple coiling or surgical clipping and subsequently re-treated by stent-assisted coiling embolization at the Radiology Intervention Department of Huashan Hospital between March 2009 and November 2019 were collected and analyzed retrospectively.There were 9 males and 11 females,with a median age of 55.5 years (range:33 to 71 years),including 17 aneurysms initially treated with simple coiling and 3 treated with surgical clipping.All cases were re-treated with stent-assisted coiling,15 using a single stent and 5 employing two stents in a Y-configuration.Peri-and post-operative complications and outcomes were evaluated.Mann-Whitney U tests were performed to compare the follow-up duration between initial treatment and re-treatment.Student′s t tests were used to compare the parent artery angles before re-treatment, after re-treatment and at the last follow-up. The parent artery angle was defined using the proximal main trunk and the stented branch. Results:Immediate complete occlusion (Raymond Ⅰ) was achieved in 18 aneurysms (90.0%) while 2 aneurysms (10.0%) had a residual neck (Raymond Ⅱ).The median follow-up time( M( Q R)) was 8.5(16.3)months,which had no significantly different from the initial treatment follow-up duration (15.5(27.0)months)( U=157.7, P=0.25). During the follow-up period,2 aneurysms (10.0%) with immediate post-operative residual necks recanalized again,including 1 aneurysm re-treated with the Y-configuration stent.Symptomatic thromboembolic complications occurred in 6 patients,including 4 re-treated with the Y-configuration stent.No peri-operative hemorrhagic complications occurred,along with no operation-related permanent disability or death. The parent artery angle increased significantly from pre-operative(90.1±21.1)°to post-operative and the last follow-up ((115.4±28.9)° and (132.6±26.8)°); t=5.14, P<0.01; t=7.78, P<0.01). Conclusion:For recurrent intracranial bifurcation aneurysms after initial surgical clipping or simple coiling,stent assisted coil embolization is proved to be safe and can decrease recurrence rate.

Objective:To evaluate the safety and efficacy of stent-assisted coil embolization in patients with recurrent intracranial bifurcation aneurysms,after initial simple coiling or microsurgical clipping.Methods:Clinical data of 20 patients with recurrent intracranial bifurcation aneurysms who initially underwent simple coiling or surgical clipping and subsequently re-treated by stent-assisted coiling embolization at the Radiology Intervention Department of Huashan Hospital between March 2009 and November 2019 were collected and analyzed retrospectively.There were 9 males and 11 females,with a median age of 55.5 years (range:33 to 71 years),including 17 aneurysms initially treated with simple coiling and 3 treated with surgical clipping.All cases were re-treated with stent-assisted coiling,15 using a single stent and 5 employing two stents in a Y-configuration.Peri-and post-operative complications and outcomes were evaluated.Mann-Whitney U tests were performed to compare the follow-up duration between initial treatment and re-treatment.Student′s t tests were used to compare the parent artery angles before re-treatment, after re-treatment and at the last follow-up. The parent artery angle was defined using the proximal main trunk and the stented branch. Results:Immediate complete occlusion (Raymond Ⅰ) was achieved in 18 aneurysms (90.0%) while 2 aneurysms (10.0%) had a residual neck (Raymond Ⅱ).The median follow-up time( M( Q R)) was 8.5(16.3)months,which had no significantly different from the initial treatment follow-up duration (15.5(27.0)months)( U=157.7, P=0.25). During the follow-up period,2 aneurysms (10.0%) with immediate post-operative residual necks recanalized again,including 1 aneurysm re-treated with the Y-configuration stent.Symptomatic thromboembolic complications occurred in 6 patients,including 4 re-treated with the Y-configuration stent.No peri-operative hemorrhagic complications occurred,along with no operation-related permanent disability or death. The parent artery angle increased significantly from pre-operative(90.1±21.1)°to post-operative and the last follow-up ((115.4±28.9)° and (132.6±26.8)°); t=5.14, P<0.01; t=7.78, P<0.01). Conclusion:For recurrent intracranial bifurcation aneurysms after initial surgical clipping or simple coiling,stent assisted coil embolization is proved to be safe and can decrease recurrence rate.

Objective To preliminarily explore the clinical efficacy of ipsilateral simultaneous pancreas and kidney transplantation (SPK) .Methods Ipsilateral SPK was performed in 40 patients from September 2016 to August 2018 .During a follow-up period of 6 to 29 months ,we summarized the efficacy and complications of the technique .Results Up to now ,38 patients achieved an exceelent clinical efficacy with no major surgical complications .However ,two patients died of severe pneumonia .The postoperative serum levels of creatinine at 3 ,6 ,12 ,24 months were 107 ,102 ,107 ,110 umol/L ;creatinine clearance rate 64 ,67 ,64 ,63 ml/min;fasting glucose 4 .6 ,5 .1 ,4 .6 ,5 .2 mmol/L ;glycated hemoglobin 4 .8％ , 5 .4％ ,4 .9％ ,5 .2％ respectively .And 1/2-year pancrea and kidney graft survival rates both were 92％ . Complications included kidney graft rejection (n= 11) ,pancreas graft rejection (n= 12) ,simultaneous renal & pancreas graft rejection (n=6) ,renal graft DGF (n=1) ,pulmonary infection (n=14) ,urinary tract infections (n=18) ,gastrointestinal bleeding (n=10) diarrhea (n=6) ,splenic venous thrombosis (n=2) ,incomplete ureteric obstruction of renal allograft (n=3) ,urine leakage (n=1) and pancreas allograft dysfunction (n= 2) .There were no severe surgical complications .After aggressive interventions ,all postoperative complications were cured and none required excision of kidney or pancreas .Conclusions Ipsilateral SPK has definite therapeutic efficacy and it is worth wider popularization .