Objective To investigate the feasibility,safety and efficacy of endovascular recanalization of the symptomatic occlusion of large intracranial artery in anterior circulation.Methods From October 2015 to December 2017,13 patients with symptomatic non-acute occlusion of large intracranial artery in anterior circulation were enrolled into this study and underwent endovascular recanalization.The initial procedural results,including the rate of successful recanalization and perioprocedural complications,and angiographic and clinical follow-up results were collected.The functional outcome was evaluated at discharge and 90 days.Results Recanalization was successful in 11 out of 13 patients.Perioperative complications occurred in 8 cases,including distal embolization in 7 cases (3 with symptom and 4 without),in which intracerebral hemorrhage associated with embolectomy was found in 1 case;and distal embolization concomitant with artery dissection in 1 case.At discharge,the symptoms of 10 out of 11 patients with successful recanalization were improved and 1 was unchanged;one of 2 patients with recanalization failure was aggravated and 1 was unchanged.After the procedure,1 patient with successful recanalization,but complicated with intracerebral hemorrhage associated with embolectomy was lost at follow-up,thus angiographic follow-up was available in the remaining 10 patients.Of the 10 patients,1 patient developed in-stent restenosis at 12 months and 9 patients had no hemodynamic stenosis/reocclusion.The clinical follow-up was available in 12 patients.No recurrence of TIA or stroke was found in 9 cases with successful recanalization except for 1 case who developed in-stent stenosis and suffered from TIA.At the follow-up of 90 days,l0 patients with successful recanalization showed good function (mRS∶0-2),2 patients with recanalization failure were deteriorated.Conclusions In strictly selected patients with symptomatic non-acute occlusion of large intracranial artery in anterior circulation,endovascular recanalization was feasible and safe,which may improve patients' symptoms in a short term and reduce the recurrence rate of stroke,but its definite efficacy needs to be confirmed by studies with larger sample and longer follow-up.

Salvia miltiorrhiza is a medicinal plant widely used in the treatment of cardiovascular and cerebrovascular diseases. Hydrophilic phenolic acids, including rosmarinic acid (RA) and lithospermic acid B (LAB), are its primary medicinal ingredients. However, the biosynthetic pathway of RA and LAB in S. miltiorrhiza is still poorly understood. In the present study, we accomplished the isolation and characterization of a novel S. miltiorrhiza Hydroxyphenylpyruvate reductase (HPPR) gene, SmHPPR, which plays an important role in the biosynthesis of RA. SmHPPR contained a putative catalytic domain and a NAD(P)H-binding motif. The recombinant SmHPPR enzyme exhibited high HPPR activity, converting 4-hydroxyphenylpyruvic acid (pHPP) to 4-hydroxyphenyllactic acid (pHPL), and exhibited the highest affinity for substrate 4-hydroxyphenylpyruvate. SmHPPR expression could be induced by various treatments, including SA, GA, MeJA and Ag, and the changes in SmHPPR activity were correlated well with hydrophilic phenolic acid accumulation. SmHPPR was localized in cytoplasm, most likely close to the cytosolic NADPH-dependent hydroxypyruvate reductase active in photorespiration. In addition, the transgenic S. miltiorrhiza hairy roots overexpressing SmHPPR exhibited up to 10-fold increases in the products of hydrophilic phenolic acid pathway. In conclusion, our findings provide a new insight into the synthesis of active pharmaceutical compounds at molecular level.
Amino Acid Sequence ; Benzofurans ; Biosynthetic Pathways ; genetics ; Cinnamates ; Depsides ; Gene Expression Regulation, Plant ; genetics ; Oxidoreductases ; genetics ; Phenylpropionates ; metabolism ; Phenylpyruvic Acids ; metabolism ; Phylogeny ; Plant Proteins ; genetics ; metabolism ; Plant Roots ; chemistry ; enzymology ; genetics ; metabolism ; Plants, Genetically Modified ; Recombinant Proteins ; analysis ; biosynthesis ; Salvia miltiorrhiza ; chemistry ; enzymology ; genetics ; metabolism ; Sequence Alignment

Objective To establish carotid artery bifurcation aneurysm in canine, and to clarify whether specific hemodynamic insult in combination with arterial wall degeneration will lead to the occurrence and development of aneurysms. Methods New bifurcation aneurysm model of common carotid artery (CCA) was successfully established in 18 dogs, which were randomly divided into the elastase-treated bifurcation group (EBG,n=9) and the control bifurcation group (CBG,n=9). Three dogs were treated with elastase insult to both straight sections of CCA and were used as elastase-treated straight section group (ESG,n=3). Angiographic and hemodynamic analysis was conducted immediately after the operation, as well as 12 and 24 weeks after the operation. Histopathological examination was performed 12 and 24 weeks after the operation. Results Angiography showed that new aneurysm (mean diameter 3.2 ±0.4 mm) was formed at the apex of CCA bifurcation in 5 dog models of EBG group, while no new aneurysm was observed in both CBG and ESG groups. In EBG group, no rupture of the new aneurysm occurred during the follow-up period. Histological analysis revealed that in EBG group the inner elastic lamina was discontinued, the elastic fiber was disrupted, the muscle layer became thinned, the smooth muscle cells were reduced, and the inflammatory cell (macrophage) infiltration as well as the expressions of MMP-2 and MMP-9 were increased;these changes were statistically significant when compared with those in CBG group and ESG group (P<0.001). Postoperative hemodynamic analysis indicated that in EBG group the wall shear stress at the apex of CCA bifurcation was reduced, the blood flow velocity was decreased, with the relative and total pressure being the highest;all the above changes returned to normal after arterial wall remodeling. Conclusion The results of this study indicate that the arterial wall degeneration and the hemodynamic effect at the apex of CCA bifurcation can lead to new aneurysm formation in canine model.

Objective To investigate the diagnostic accuracy of contrast-free three dimensional time-of-flight (3D-TOF-MRA) with VR at 3.0 T in the detection of intracranial aneurysms in a large cohort of patients prospectively.Methods Four hundred and eleven patients with suspected aneurysms and other cerebral vascular diseases received contrast-free 3D-TOF-MRA examinations at 3.0 T MRA 2 weeks prior to DSA examination.2D-DSA and VR-DSA were regarded as the gold standard.Six patients were excluded because of motion artifacts,and 36 patients were excluded due to lack of VR-DSA data.Accuracy,sensitivity an specificity in detecting intracranial aneurysms were determined by patient-,aneurysm-,and aneurysm sizebased (＜ 3 mm,3-5 mm,＞ 5-10 mm,＞ 10 mm) evaluations.Results In 369 enrolled patients,VR-DSA revealed 306 aneurysms in 246 patients (66.7％) and no aneurysm in 123 patients; VR 3D-TOF-MRA revealed 311 aneurysms in 249 patients and no aneurysm in 120 patients.The patient-based evaluation of VR 3 D-TOF-MRA at 3.0T yielded accuracy of 97.6％ (360/369),sensitivity of 99.2％ (242/244),and specificity of 94.4％ (118/125) in the detection of intracranial aneurysms.The aneurysm-based evaluation yielded accuracy of 98.3％ (524/533),sensitivity of 99.3％ (304/306),and specificity of 96.1％(220/229).The evaluation based on aneurysm sizes (＜ 3 mm) yielded accuracy of 96.4％ (214/222),sensitivity of 98.2％ (112/114),and specificity of 94.4％ (102/108).Conclusion VR 3D-TOF-MRA at 3.0 T MR can detect intracranial aneurysms accurately and may replace DSA as a contrast-free,noninvasive and non-radiation-based modality for the diagnosis and screening of intracranial aneurysms.

Objective To evaluate the clinical results of Willis covered stent implantation and coil embolization in the treatment of cranial internal carotid artery (CICA) aneurysm. Methods Eighty-nine patients with CICA aneurysms were selected for treatment with Willis covered stents (n = 43, group A) or coil embolization (n =46, group B) according to the patients'will. Data on the technical success, initial procedure time and in-hospital interval, initial and final angiographic results, mortality, morbidity, and final clinical outcomes were collected and analyzed for the two groups at 6 months post-procedure. Results Endovascular covered stent placement and coil embolization were technically successful in all patients,except for one patient in group A. The initial angiographic results showed complete occlusion in 34 patients of group A (81%, 95% CI: 69%, 93% ) and 24 patients of group B (52%, 95% CI: 37%, 67% ) ( P ＜0. 05). The final angiographic results indicated complete occlusion in 39 patients of group A (39/41,95%,95% CI: 88%, 102% ) and 22 patients of group B (22/45,49%, 95% CI: 34%, 64% ,P ＜0. 01 ). The average procedure time was(103 ± 13)min in group A and (143 + 39) min in group B (P＜0. 01). No significant differences were seen between the two groups in technique success, mortality, morbidity, or final clinical outcomes. Conclusion In this nonrandomized, prospective trial, CICA aneurysm treatment with covered stents yielded midterm angiographic results that were superior to those of coil embolization.

Objective To establish a carotid siphon aneurysm model in dogs in order to test the mechanical features of a newly-designed Willis covered stent-graft and to investigate the histological reaction of the stent-implanted vessel during a follow-up period of 12 months.Methods Twenty-four saccular sidewall aneurysms were surgically created in twelve dogs(group A)and 12 carotid siphon aneurysms in another twelve dogs(group B).A Willis stent-graft was implanted in each aneurysm.Angiography was performed immediately after the procedure and 1,3,6 and 12 months after the implantation to investigate the aneurysm isolation,endoleak,stent angulation,and the patency or restenosis of the parent artery.Light and scanning electronic microscopy were used to identify aneurysmai sac thrombi,intima hyperplasia and endothelial progress of the stent-loaded arterial segment.Results In group B,postoperative immediate angiography demonstrated that two aneurysms had mild endoleak and three stents became angulated.Follow-up exam 12 months after the procedure revealed that all previous endoleaks disappeared,one parent artery became occluded and three parent arteries developed mild stenosis(＜50%).In group A.occlusion of parent artery was seen in one and mild stenosis(＜50%)in 2 cases.Electronic microscopy revealed new intima formation in all stents,and all aneurysmal sacs were filled with thrombi.In group B.the endothelialization process was not completed until 12 months after the stent implantation,and a marked correlation existed between endothelial cell arrangement and the hemodynamic orientation.Conclusion It is feasible to treat carotid-siphon aneurysm in dog with a Willis stent-graft.The complete endothelialization of the covered stent in tortuous vessel takes longer time than that in rather straight vessel.

Objective To present our single-center experience in treating traumatic direct carotidcavemous fistulas (TDCCFs)by using detachable balloon,coil and Willis covered stent via arterial route.Methods During the last five years,transarterial endovascular treatment by using detachable balloon,coil and Willis covered stent was performed in fifty-one consecutive patients of traumatic direct carotid-cavernous fistulas.with a total of 54 TDCCFs.The detachable balloon was the material of first choice,while Willis covered stents and coils were regarded as the back-up materials.A clinical and angiographic follow-up for 348 months (mean 20.8 months) was conducted to evaluate the arterial patency and the stability of embolization.The clinical data were retrospectively analyzed.Results By using the detachable balloon alone via transarterial route.85%TDCCFs were successfully treated with good preservation of ICA.A total of 98% TDCCFs in this study were successfully treated by using detachable balloon,coil and/or Willis coveted stent,the fistulas became occluded,and ICAs were preserved except one patient.Forty TDCCFs were treated with detachable balloons alone,two TDCCFs with the Willis covered stent alone,and one DCCF with coils alone.Eight TDCCFs were treated with detachable balloons together with Willis covered stent.Of these eight TDCCFs,two were treated with a single session,three were treated with detachable halloons in combination with coils,and one had to receive Willis covered stent.Second and third times of endovascular treatment were needed in 12 TDCCFs.The TDCCF-rel(at)ed symptoms were gradually relived or improved within 1 day to 6 months after treatment,except for five patients who suffered from ipsilateral moderate visual loss or cranial nerve deficit.No perioperative complications.such as vessel rupture,distal embolization or new neurologic deficits,occurred.During the follow-up period lasting for six months,neither delayed neurologic or vascular complications nor recurrence of the lesions developed.Conclusion Via the transarterial route,using detachable balloon to occlude the fistula and at the same time to preserve ICA remains the optimal treatment for TDCCFs.When the standard treatment fails.various coils and the Willis covered stents can be used as an effective alternative or remedial tool in the treatment of TDCCFs,which can preserve ICA.Willis covered stent deployment seems to be an effective,safe,feasible and economical endovasculal treatment for TDCCF,but more clinical studies are needed before we can further clarify its specifications and indications.

Objective Complicated aneurysms located in the cisternal segment of the internal carotid artery(ICA-CSA)present unique therapeutic difficulties.This study is to discuss the feasibility of the Willis stent-graft in treating complicated ICA-CSA by comparing its effect with that of coiling therapy.Methods Willis covered stents were employed in 19 complicated ICA-CSAs(group A),while coils were used in 17 complicated ICA-CSAs(group B).Follow-up angiography was performed to investigate aneurysm recurrence,endoleak and parent artery(PA)stenosis.Kaplan-Meier curves were constructed to compare the recurrencefree and PA stenosis-free rate in both groups.Results Total exclusion was immediately achieved in 13 ICACSAs and minor endoleaks presented in 5 cases in group A.Total or near-total occlusion was achieved in 7 ICA-CSAs.subtotal occlusion in 8 and partial occlusion in 2 cases in group B after coiling.Acute thrombosis occurred in 1 patient in either group and re-hemorrhage happened in 1 patient after coiling.Follow-up angiography in group A revealed that 16 ICA-CSAs were completely isolated,with two parent arteries showing mild in-stent stenosis.Eighteen months after the procedure,Kaplan-Meier analysis showed that the recurrence-free rate was 93.3%and 50%,while the stenosis-free rate of parent artery was 87.5%and 100% in group A and in Group B,respectively.In group A and group B the clinical neurological symptoms were fully recovered in 9 and 9,obviously improved in 3 and 5,unchanged in 2 and 2,and aggravated in one and 0 patients,respectively.Conclusion The implantation of Willis stent-graft is a feasible endovascular therapy for complicated ICA-CSAs.When the parent artery is very tortuous or when the risk that a main collateral branch may be wrongly covered and occluded is present,the implantation of Willis covered stent can not be taken as the treatment of first choice.

Objective To evaluate the efficacy and mid-term follow-up results of endovascular treatment with Willis covered stent for traumatic pseudoaneurysms located in the internal carotid artery (ICA).Methods ICA angiogmphy was performed in 38 patients with traumatic brain and neck injury.Of the 38 patients.13 delayed traumatic pseudoaneurysms were found.All the pseudoaneurysms were treated with Willis covered stents.Follow-up angiography was performed at 1,3,6 and 12 months after the procedure,and the results were categorized as complete or incomplete occlusion.Clinical manifestations were graded as full recovery,improvement,unchanged and aggravation.Results Willis covered stent placement was technically successful in all traumatic pseudoaneurysms.No procedure-related complications occurred.The initial angiographic results showed a complete occlusion in 9 patients,and an incomplete occlusion in 4.The angiographic follow-up within 3-12 months exhibited a complete occlusion in 12 patients and the parent arteries remained patency in all patients.The clinical follow-up observation demonstrated that full recovery wag obtained in 11 patients,clinical improvement in one,and unchanged condition in one.No morbidity or mortality occurred.Conclusion Willis covered stent implantation iS a feasible and practical treatment for traumatic pseudoaneurysms located in the ICA.This technique can well preserve the parent artery with excellent therapeutic results.

Objective To evaluate the flexibility and efficacy of the Willis covered stent in the treatment of distal internal carotid artery(DICA)aneurysms.Methods The study was approved by the anthors' institutional review board,and the research was conducted by the authors' institution and the MicroPort Medical Company(Shanghai,China).Thirty-one patients with 33 DICA aneurysms were considered for treatment with a Willis covered stent.The angiographic assessments were categorized as complete or incomplete occlusion.The data on technical Success,initial and final angiographic results,mortality,morbidity,and final clinical outcome were collected,and follow-up was performed at 1,3,6,and 12 months and yearly after the procedures.Results Navigation and deployment of the covered stents were succssfnl in 97.6%(41 of 42;95%confidence interval[CI]:93%,102%)of the attempted stent placement procedures.The initial angiographic results showed a complete occlusion in 23 patients with 25 aneurysms(of 32 aneurysms,78.1%[95%CI:63%,93%])and an incomplete occlusion in seven patients with seven aneurysms(21.9%).The angiographic follow-up(mean,14 months[95% CI:12,15 months])findings exhibited a complete occlusion in 27 patients with 29 aneurysms(of 31 aneurysms,93.5%[95%CI:84%,103%])and an incomplete occlusion in two aneurysms(6.5%),with a mild in-stent stenosis in two patients.The clinical follow-up(mean,27 months[95% CI:23,30 months])demonstrated that 15 patients experienced a full recovery and 14 patients improved.Conclusion The preliminary results demonstrate good flexibility and efficacy of the Willis covered stent in the treatment of DICA aneurysms in selected patients:longer follow-up and expanded clinical trials are needed.