[Effects of one-stop hybrid operation on the risk and prognosis of brain arteriovenous malformations with posterior feeding artery].

Objective: To explore the effect of the combination of posterior circulation embolization and micro-resection on the risk and prognosis in patients with brain arteriovenous malformations (bAVMs) supplied by posterior circulation in a one-stop hybrid operation setting. Methods: Patients with bAVMs supplied by posterior circulation who received surgical treatment in Beijing Tiantan Hospital, Capital Medical University, were enrolled from January 2016 to December 2019 from a prospective, multicentral cohort (NCT03209804). The patients were divided into the posterior circulation embolization group and the non-posterior circulation embolization group. Propensity score matching (PSM) (1∶1) was performed according to the baseline information, the morphology of bAVMs, vascular architecture, and Spetzler-Martin grade of brain lesions. The primary endpoint was the deterioration of neurological function. The secondary endpoints were perioperative complications. The differences in surgical risk and clinical prognosis between the two groups were compared. Results: Five hundred and forty-five patients were enrolled in the cohort, and 38.3% met the included criteria (n=209 cases), with 42 cases in the posterior circulation embolization group and 167 cases in the non-posterior circulation embolization group. Depending on whether the patients were posterior circulation embolized, 39 patients in the posterior circulation embolization group and 39 patients in the non-posterior circulation embolization group were finally included after performing PSM. There were 50 males and 28 females, aged 5-58 (30±13) years. The exacerbation rate of neurological dysfunction in the posterior circulation embolization group was higher than that in the non-posterior circulation embolization group three months after surgery, however there was no statistically significant difference between the two groups [15.4% (6/39) vs 2.6% (1/39), P=0.107]. The intraoperative blood loss in the embolization group was significantly less than that in the non-embolization group [650 (500, 1 500) ml vs 1 200 (800, 2 000) ml, P=0.002]. There was no significant difference in microsurgery time between the two groups [437 (374, 521) min vs 424 (359, 601) min, P=0.865]. Likewise, there were no statistically significant differences in the incidence of postoperative complications and aggravation of neurological dysfunction, including postoperative bAVMs residual [5.1%(2/39) vs 7.7%(3/39), P=1.000], hemorrhagic complications [5.1%(2/39) vs 0(0), P=0.494], postoperative ischemic complications [10.3%(4/39) vs 5.1%(2/39), P=0.675], neurological dysfunction at discharge (17.9% vs 15.4%, P=0.755), and one-year neurological dysfunction [5.1%(2/39) vs 2.6%(1/39), P=1.000]. Conclusions: Posterior circulation embolization of bAVMs in a one-stop hybrid operation can effectively reduce intraoperative bleeding and surgical risk. Embolization of the feeding artery has no significant impact on the perioperative complications and neurological outcomes.

[Efficacy of Pipeline embolization device in the treatment of large and giant intracranial aneurysms].

Objective: To summarize the safety and efficacy of Pipeline embolization device in the treatment of large and giant intracranial aneurysms (maximum diameter ≥ 10 mm). Methods: The clinical and imaging data of 22 patients with intracranial aneurysms treated by Pipeline Embolization Device (PED) from February 2015 to July 2016 in the Zhengzhou University People's Hospital were retrospectively analyzed. The results about postoperative clinical and imaging follow-up and complications were evaluated. Results: The PED were successfully implanted in 22 patients with 22 intracranial aneurysms. Two aneurysms were treated with PED alone, and 20 aneurysms were treated with PED assisted coil embolization. Perioperative complications occurred in 3 patients (13.6%), and 1 patient died because aneurysm ruptured 3 days after operation. Nineteen patients (19 aneurysms) obtain imaging follow-up visit 3-17 months after operation, 13 of the 19 aneurysms (68.4%) received complete and subtotal occlusion, with no aneurysm recurrence. Eighteen patients obtain clinical follow-up visit 16-32 months after operation, with mRS (modified Rankin scale) score 1 in 5 patients, mRS score 0 in 13 patients, none developed new neurologic symptoms. Conclusions: PED has showed the high rate of obliteration for the treatment of large and giant intracranial aneurysms. But the complications needs to be further studied.

[Interventional treatment of symptomatic intracranial in-stent restenosis].

Objective: To assess the feasibility and safety of interventional treatment of symptomatic intracranial in-stent restenosis (SISR). Methods: Clinical data of 21 patients with SISR who underwent interventional treatment in the General Hospital of the PLA Rocket Force from January 2012 to May 2018 were retrospectively analyzed. Perioperative complications, angiographic and clinical follow-up results were recorded. Results: The success rate of treatment was 100%, including 21 lesions of SISR (7 at the V4 segment of the vertebral artery, 7 at the basilar artery, 5 at the M1 segment of middle cerebral artery, 2 at the internal carotid artery). The residual stenosis rate was preoperative 84±7, postoperative 30±14 respectively. Balloon angioplasty and stent implantation were performed in 10 patients (48.6%) and 11 patients (52.4%), respectively. After treatment, 1 patient experienced perforating event without neurological sequelae. Of the 11 patients (52.4%) completed angiography follow-up, 3 (3/11, 27.3%) ocurred restenosis and 1 was retreated. During clinical follow-up, 1 patients received intravenous thrombolysis for the symptom of acute cerebral infarction in territory of stenting artery, in-stent restenosis or occlusion was not demonstrated by emergency cerebral angiography. Conclusion: Interventional treatment of SISR is feasible and safe, however, further studies need to warrant the long-term effects.

[Analysis of the therapeutic effect of stent-assisted embolization and surgical clipping for the treatment of middle cerebral artery bifurcation aneurysms].

Objective: To compare the clinical effects of stent-assisted embolization and surgical clipping in the treatment of middle cerebral artery bifurcation wide-necked aneurysms. Methods: From July 2014 to March 2017, the clinical and imaging data of 45 patients with Hunt-Hess 0-Ⅲ grade middle cerebral artery bifurcation wide-necked aneurysms were divided into stent-assisted embolization group (20 patients from PLA Rocktet Army Hospital) and surgical clipping group (25 patients from Peking University International Hospital). The total occlusion rates of aneurysm, operation-related adverse events, clinical outcomes, and results of follow-up imaging from the two groups were compared. Results: The total occlusion rates in the stent-assisted embolization group and surgical clipping group were 90.0% (18/20) and 92.0% (23/25), respectively, and the difference was not statistically significant (P=0.815). The favorable six-month postoperative outcomes defined as the modified Rankin Scale ≤2 were 94.7% (18/19) in the stent-assisted embolization group and 91.3% (21/23) in the surgical clipping group (P=0.667). Fewer patients experienced the operation-related adverse events in the stent-assisted embolization group (15.0%, 3/20), as compared to that of the surgical clipping group (24.0%, 6/25), but the difference were not significant (P=0.453). After 2-24 months (median 7 months) of the operation, the follow-up imaging indicated that in the stent-assisted embolization group, 2 out of the 19 patients had residual or recurrent aneurysms.While in the surgical clipping group, residual or recurrent aneurysms were identified in 2 out of the 23 patients 2-14 months (median 3 months) after the surgery; the frequency was not statistically different between the two groups (P=0.841). Conclusion: Stent assisted embolization is a safe and effective treatment for the low grade middle cerebral artery bifurcation wide-necked aneurysms.

[Hybrid surgery for complex symptomatic intracranial fistulas: a technical note].

Objective: To explore the efficacy of hybrid management of complex symptomatic intracranial fistulas in neurovascular hybrid operating room. Methods: From March 2014 to January 2015, 2 complex dural arteriovenous fistulas and 1 carotid cavernous fistulas were managed by hybrid surgeries in the PLA Rocket Force General Hospital.With first attempts with endovascular treatment failed, all cases were finally managed by hybrid surgery.Dural arteriovenous fistulas were approached via meningeal artery followed craniotomy.The carotid cavernous fistulas were treated by direct puncture into the left cavernous sinus after craniotomy. Results: Post-operative angiography demonstrated complete occlusion for 2 cases and nearly complete occlusion for 1 case.All 3 cases had no complications.On discharge 2 patients presented no symptoms and 1 greatly improved.Within the follow-up (1-33 months), 1 patient had recurrence after 21 months and received re-embolization with complete occlusion. Conclusion: Hybrid surgery is a promising method to manage complex intracranial fistulas.

[Retrospective analysis of the discharge outcome of external ventricular drainage and conservative treatment in patients with severe intraventricular hemorrhage].

Objective: To investigate the discharge outcome of external ventricular drainage(EVD) and conservative treatment in patients with severe intraventricular hemorrhage (SeIVH). Methods: From January 2011 to December 2016, patients with SeIVH admitted to the General Hospital of the PLA Rocket Force and the Army General Hospital received EVD treatment and were classified as the treatment group. According to intraventricular hemorrhage volume and age, patients received conservative treatment were pair matched and classified as control group. Then we compared the clinical outcome of moderate disability or less degree of discharge (mRS ≤3) and death incidence (mRS 6) between two groups. Results: A total of 361 patients with IVH were treated during these six years. Among them, 75 cases were chosen as treatment group. Another 75 cases were pair matched as control group from 286 cases. At the time of admission, the ventricular hemorrhage volume of two groups were (55.8±22.7) ml and (53.7±23.3) ml (P=0.569) respectively. Cerebral hemorrhage volume were (23.6±5.3) ml and (24.0±5.4) ml (P=0.631). And the median Glasgow coma score (GCS) were 4[IQR(3, 7)] and 5[IQR(4, 7)](P=0.131). At the discharge time, there were 16% (12/75) patients scored mRS≤3 in treatment group, while 2.7% (2/75) in control group (P<0.005). The absolute risk reduction (ARR) was 13.3%, and the number needed to treat (NNT) was 7.5. The mortality rate of treatment group was 13.3% (10/75), much lower than that of the control group 41.1% (31/75, P<0.001). ARR was 27.8% and NNT was 3.6. Conclusion: Although the prognosis of SeIVH was poor, compared with conservative treatment, EVD treatment significantly improved the outcome of these patients. Randomized controlled trials are needed to validate the efficacy of EVD.

[Management of 99 intracranial aneurysms in neurovascular hybrid operating room].

OBJECTIVE: To analyze the current status of intracranial aneurysms treated in neurovascular hybrid operating room. METHODS: In the neurovascular hybrid operating room of New Era Stroke Care & Research Center, the Second Artillery General Hospital PLA, from October 2013 to November 2015, 99 cases of intracranial aneurysms were managed by interventional treatment, open surgery, hybrid surgery or switched surgical procedures. RESULTS: Patients with intracranial aneurysms treated in neurovascular hybrid operating room achieved good clinical outcome. CONCLUSION: It is an ideal option to treat intracranial aneurysms in neurovascular hybrid operating room.

[Restriction map of E. coli shuttle plasmid (p# GTE5) with secretive function].

The shuttle plasmid (p# GTE5) DNA with secretive function was extracted by the alkali lysozyme method from E. coli RRI strain. Its molecular weight is 4.5 Md and DNA size is 6.9 Kb. Restriction fragments of plasmid was obtained by single and double enzymes complete digestion using five different restriction endonucleases. The restriction map of shuttle plasmid (p# GTE5) was established for the enzymes EcoRI, BglII, pstI, PvuII, and TaqI.

Inhibition of calcium/calmodulin-dependent protein kinase II in rat hippocampus attenuates morphine tolerance and dependence.

Learning and memory have been suggested to be important in the development of opiate addiction. Based on the recent findings that calcium/calmodulin-dependent protein kinase II (CaMKII) is essential in learning and memory processes, and morphine treatment increases CaMKII activity in hippocampus, the present study was undertaken to examine whether inhibition of hippocampal CaMKII prevents morphine tolerance and dependence. Here, we report that inhibition of CaMKII by intrahippocampal dentate gyrus administration of the specific inhibitors KN-62 and KN-93 to rats significantly attenuated the tolerance to the analgesic effect of morphine and the abstinence syndrome precipitated by opiate antagonist naloxone. In contrast, both KN-04 and KN-92, the inactive structural analogs of KN-62 and KN-93, failed to attenuate morphine tolerance and dependence, indicating that the observed effects of KN-62 and KN-93 are mediated through inhibition of CaMKII. Furthermore, administration of CaMKII antisense oligonucleotide into rat hippocampal dentate gyrus, which decreased the expression of CaMKII specifically, also attenuated morphine tolerance and dependence, while the corresponding sense oligonucleotide of CaMKII did not exhibit such inhibitory effect. Moreover, the KN-62 treatment abolished the rewarding properties of morphine as measured by the conditioned place preference. These results suggest that hippocampal CaMKII is critically involved in the development of morphine tolerance and dependence, and inhibition of this kinase may have some therapeutic benefit in the treatment of opiate tolerance and dependence.

Pharmacokinetic studies of methotrexate in plasma and synovial fluid following i.v. bolus and topical routes of administration in dogs.

PURPOSE: The pharmacokinetic properties of methotrexate (MTX) in the plasma and synovial fluid (SF) after bolus i.v. and topical administration were studied in dogs to assess the feasibility of topical delivery of MTX for the treatment of rheumatoid arthritis. METHODS: A MTX gel in Poloxamer 407 containing an absorption enhancer was formulated and topically applied on the elbow and stifle joints of dogs. SF was collected by inserting a needle with syringe into the joint space. Drug concentrations in the plasma, SF and muscle tissues were determined using a HPLC method with fluorimetric detection. RESULTS: Peak MTX concentrations in SF occurred at 38 +/- 5 min following bolus i.v. dose, indicating the presence of a substantial diffusion barrier between the plasma and SF. The plasma/SF concentration ratios of 1.16 +/- 0.25 were maintained after the attainment of distribution equilibrium between the two compartments. The t1/2 values in the plasma (11.2 +/- 1.2 hr) and SF (12.7 +/- 3.7 hr) were similar during the elimination phase, while the MRT in SF (3.24 +/- 0.21 hr) was longer than that in plasma (2.56 +/- 0.20 hr), probably due to the slow distribution of MTX to SF. After topical dose, MTX concentrations in plasma reached the steady state at approximately 4 hr, lasting for approximately 20 hr. The bioavailability of MTX from the gel was 11.8 +/- 3.3% of the applied dose, but muscle tissues beneath the gel application site had significantly higher levels of MTX than untreated muscle tissues. There was no statistical difference in SF concentrations of MTX between drug treated and untreated joints 24 hr after topical dose. CONCLUSIONS: Topical delivery of MTX in a hydrophilic gel achieved a sustained C/t profile in plasma and higher drug levels in muscle tissues underneath the dosing site, implicating the potential therapeutic value of the topical formulation.