Proteomics study of primary and recurrent adamantinomatous craniopharyngiomas.

BACKGROUND: Adamantinomatous craniopharyngiomas (ACPs) are rare benign epithelial tumours with high recurrence and poor prognosis. Biological differences between recurrent and primary ACPs that may be associated with disease recurrence and treatment have yet to be evaluated at the proteomic level. In this study, we aimed to determine the proteomic profiles of paired recurrent and primary ACP, gain biological insight into ACP recurrence, and identify potential targets for ACP treatment. METHOD: Patients with ACP (n = 15) or Rathke's cleft cyst (RCC; n = 7) who underwent surgery at Sanbo Brain Hospital, Capital Medical University, Beijing, China and received pathological confirmation of ACP or RCC were enrolled in this study. We conducted a proteomic analysis to investigate the characteristics of primary ACP, paired recurrent ACP, and RCC. Western blotting was used to validate our proteomic results and assess the expression of key tumour-associated proteins in recurrent and primary ACPs. Flow cytometry was performed to evaluate the exhaustion of tumour-infiltrating lymphocytes (TILs) in primary and recurrent ACP tissue samples. Immunohistochemical staining for CD3 and PD-L1 was conducted to determine differences in T-cell infiltration and the expression of immunosuppressive molecules between paired primary and recurrent ACP samples. RESULTS: The bioinformatics analysis showed that proteins differentially expressed between recurrent and primary ACPs were significantly associated with extracellular matrix organisation and interleukin signalling. Cathepsin K, which was upregulated in recurrent ACP compared with that in primary ACP, may play a role in ACP recurrence. High infiltration of T cells and exhaustion of TILs were revealed by the flow cytometry analysis of ACP. CONCLUSIONS: This study provides a preliminary description of the proteomic differences between primary ACP, recurrent ACP, and RCC. Our findings serve as a resource for craniopharyngioma researchers and may ultimately expand existing knowledge of recurrent ACP and benefit clinical practice.

Continuous renal replacement therapy with oXiris® in patients with hematologically malignant septic shock: A retrospective study.

BACKGROUND: The mortality rate from septic shock in patients with hematological malignancies (HMs) remains significantly higher than that in patients without HMs. A longer resuscitation time would definitely be harmful because of the irreversibly immunocompromised status of the patients. Shortening the resuscitation time through continuous renal replacement therapy (CRRT) with oXiris® would be an attractive strategy in managing such patients. AIM: To explore the effects of CRRT and oXiris® in shortening the resuscitation time and modifying the host response by reducing inflammation mediator levels. METHODS: Forty-five patients with HM were diagnosed with septic shock and underwent CRRT between 2018 and 2022. Patients were divided into two groups based on the hemofilter used for CRRT (oXiris® group, n = 26; M150 group, n = 19). We compared the number of days of negative and total fluid balance after 7 d of CRRT between the groups. The heart rate, norepinephrine dose, Sequential Organ Failure Assessment (SOFA) score, and blood lactic acid levels at different time points in the two groups were also compared. Blood levels of inflammatory mediators in the 26 patients in the oXiris® group were measured to further infer the possible mechanism. RESULTS: The average total fluid balance after 7 d of CRRT in the oXiris® group was significantly lower than that of patients in the M150 hemofilter group. The SOFA scores of patients after CRRT with oXiris® therapy were significantly lower than those before treatment on day 1 (d1), d3 and d7 after CRRT; these parameters were also significantly lower than those of the control group on d7. The lac level after oXiris® therapy was significantly lower than that before treatment on d3 and d7 after CRRT. There were no significant differences in the above parameters between the two groups at the other time points. In the oXiris® group, procalcitonin levels decreased on d7, whereas interleukin-6 and tumor necrosis factor levels decreased significantly on d3 and d7 after treatment. CONCLUSION: CRRT with oXiris® hemofilter may improve hemodynamics by reducing inflammatory mediators and playing a role in shortening the resuscitation period and decreasing total fluid balance in the resuscitation phases.

Enhancing the Sound and Thermal Insulation Properties of Polypropylene Foam by Preparing High Melt Strength Polypropylene.

High-performance polypropylene (PP) foam is a vital polymer product in industrial areas. However, the poor melt strength of ordinary PP homopolymer limits its foaming molding. In this work, high melt strength polypropylene (HMSPP) is prepared by using styrene (St) and tripropylene glycol diacrylate (TPGDA) as comonomers, and then PP foams are prepared by mold foaming method. The results show that adding St in the grafting process of TPGDA will obviously improve the melt strength of the PP matrix, and its melt strength (28 184 Pa.s) is 7.4 times higher than that of pure PP. HMSPP foam has more regular and uniform cells and higher cell density, which significantly improves the sound and thermal insulation properties of PP foam. Compared with pure PP foam, the average sound transmission loss (52.9 dB) of HMSPP foam with a low foaming ratio increased by 64%, and the thermal conductivity (0.0867 W mK-1 ) decreased by 46%. Therefore, the obtained HMSPP foam can be used in sound insulation or thermal insulation area. This work provides an available route for the high-performance utilization of PP foam.

How I do it: internal maxillary artery to middle cerebral artery bypass to manage giant thrombosed internal carotid artery aneurysm.

BACKGROUND: Internal maxillary artery (IMA) bypass has become popularized due to its medium-to-high blood flow, short graft length, and well-matched arterial caliber between donor and recipient vessels. METHOD: We described an open surgery of a NEW "workhorse," the IMA bypass, to treat a giant, thrombosed cerebral aneurysm. The extracranial middle infratemporal fossa (EMITF) approach was used to unveil the pterygoid segment of the IMA for cerebral revascularization. CONCLUSION: Although this technique is technically challenging, the variations in IMA can be effectively identified and sufficiently exposed in this technique to achieve favorable clinical outcomes with a high bypass patency rate.

Computed Tomography Perfusion Imaging Study of Intracranial Complex Aneurysms Treated by Internal Maxillary Artery Bypass Grafting.

BACKGROUND: Cerebral revascularization strategies through extracranial to intracranial bypass have been adopted in the management of complex intracranial aneurysms. The internal maxillary artery used as a donor in a bypass is an effective method. At present, there are few quantitative analyses of cerebral blood flow perfusion. The main focus of this study was to evaluate the effectiveness of blood perfusion after bypass grafting. METHODS: From April 2015 to December 2017, 19 patients who underwent internal maxillary artery radial artery middle cerebral artery bypass surgery with unobstructed bypass vessels were selected. Cerebral blood flow perfusion before and after bypass surgery was quantitatively evaluated by computed tomography perfusion imaging. The cerebral blood perfusion in the region of interest was measured by computed tomography perfusion. RESULTS: The aneurysms were excised after trapping in 2 cases with mass effects and neural compression. Proximal occlusion of the parent artery was performed in 9 cases of fusiform or giant dissecting aneurysms. Trapping was performed after bypass surgery in 8 cases. Within 3 months after surgery, 17 patients had good outcomes. After the hypothesis test, there was a significant difference between the preoperative △cerebral blood volume and postoperative △cerebral blood volume in the anterior area of the semioval center cross section (P = 0.001 < 0.05). CONCLUSIONS: The internal maxillary artery as a bypass donor is an effective method that can provide sufficient intracranial blood perfusion, and there is usually no cerebral ischemia in the surrounding area.

Construction of Enzyme-Responsive Micelles Based on Theranostic Zwitterionic Conjugated Bottlebrush Copolymers with Brush-on-Brush Architecture for Cell Imaging and Anticancer Drug Delivery.

Bottlebrush copolymers with different chemical structures and compositions as well as diverse architectures represent an important kind of material for various applications, such as biomedical devices. To our knowledge, zwitterionic conjugated bottlebrush copolymers integrating fluorescence imaging and tumor microenvironment-specific responsiveness for efficient intracellular drug release have been rarely reported, likely because of the lack of an efficient synthetic approach. For this purpose, in this study, we reported the successful preparation of well-defined theranostic zwitterionic bottlebrush copolymers with unique brush-on-brush architecture. Specifically, the bottlebrush copolymers were composed of a fluorescent backbone of polyfluorene derivate (PFONPN) possessing the fluorescence resonance energy transfer with doxorubicin (DOX), primary brushes of poly(2-hydroxyethyl methacrylate) (PHEMA), and secondary graft brushes of an enzyme-degradable polytyrosine (PTyr) block as well as a zwitterionic poly(oligo (ethylene glycol) monomethyl ether methacrylate-co-sulfobetaine methacrylate) (P(OEGMA-co-SBMA)) chain with super hydrophilicity and highly antifouling ability via elegant integration of Suzuki coupling, NCA ROP and ATRP techniques. Notably, the resulting bottlebrush copolymer, PFONPN9-g-(PHEMA15-g-(PTyr16-b-P(OEGMA6-co-SBMA6)2)) (P2) with a lower MW ratio of the hydrophobic side chains of PTyr and hydrophilic side chains of P(OEGMA-co-SBMA) could self-assemble into stabilized unimolecular micelles in an aqueous phase. The resulting unimolecular micelles showed a fluorescence quantum yield of 3.9% that is mainly affected by the pendant phenol groups of PTyr side chains and a drug-loading content (DLC) of approximately 15.4% and entrapment efficiency (EE) of 90.6% for DOX, higher than the other micelle analogs, because of the efficient supramolecular interactions of π-π stacking between the PTyr blocks and drug molecules, as well as the moderate hydrophilic chain length. The fluorescence of the PFONPN backbone enables fluorescence resonance energy transfer (FRET) with DOX and visualization of intracellular trafficking of the theranostic micelles. Most importantly, the drug-loaded micelles showed accelerated drug release in the presence of proteinase K because of the enzyme-triggered degradation of PTyr blocks and subsequent deshielding of P(OEGMA-co-SBMA) corona for micelle destruction. Taken together, we developed an efficient approach for the synthesis of enzyme-responsive theranostic zwitterionic conjugated bottlebrush copolymers with a brush-on-brush architecture, and the resulting theranostic micelles with high DLC and tumor microenvironment-specific responsiveness represent a novel nanoplatform for simultaneous cell image and drug delivery.

Synthesis of enzyme-responsive theranostic amphiphilic conjugated bottlebrush copolymers for enhanced anticancer drug delivery.

Synthesis of polyfluorene (PF) based theranostic amphiphilic copolymers with simultaneously high drug loading efficiency and tumor microenvironment-specific responsiveness for promoted intracellular drug release and enhanced cancer therapy has been rarely reported likely due to the lack of efficient synthetic approaches to integrate these desirable properties. In this work, we recorded the successful preparation of well-defined theranostic amphiliphilic bottlebrush copolymers composing of fluorescent backbone of PF and tunable enzyme-degradable side chains of polytyrosine (PTyr) and POEGMA by integrating Suzuki coupling, NCA ROP and ATRP techniques. Notably, the resulting copolymer, PF25-g-(PTyr26-b-(POEGMA28)2 (P4) with two branched POEGMA brushes tethered to one PTyr termini for each unit could form steady unimolecular micelles with higher fluorescence quantum yield of 18.3% in aqueous and greater entrapment efficiency (EE) of 91.0% for DOX ascribed to the efficient π-π stacking interactions between PTyr blocks and drug molecules and the unique structure of branched hydrophilic brushes with a moderate chain length. DOX@P4 micelles revealed visualization of intracellular trafficking and accelerated drug release due to the enzyme-triggered degradation of PTyr blocks with proteinase K and subsequent deshielding of POEGMA corona for micelle destruction. In vitro and In vivo animal study further verified the intensive therapeutic efficiency with attenuated systematic toxicity. Taken together, we provided a universal strategy toward multifunctional polymeric delivery vehicles based on conjugated PF and biocompatible and degradable polypeptide by integratied Suzuki coupling and NCA ROP, and identified the branched structure of hydrophilic brushes for better performance of bottlebrush copolymers-based micelles for drug delivery applications. STATEMENT OF SIGNIFICANCE: Synthesis of polyfluorene (PF)-based theranostic amphiphilic copolymers with simultaneously high drug loading efficiency and tumor microenvironment-specific responsiveness for promoted intracellular drug release and enhanced cancer therapy has been rarely reported likely due to the lack of efficient synthetic approaches to integrate these desirable properties. We reported herein successful preparation of enzyme-responsive theranostic amphiliphilic bottlebrush copolymers with simultaneously high drug loading efficiency and tumor microenvironment-specific responsiveness for enhanced chemotherapy in vivo. This study therefore not only developed a universal strategy for the construction of multifunction polymeric vehicles based on the conjugated polymer of PF and degradable polypeptide by integrated Suzuki coupling and NCA ROP, but also emphasized the better stability of micelles endowed by the branched hydrophilic brushes than linear ones.

Endogenous ADAR-mediated RNA editing in non-human primates using stereopure chemically modified oligonucleotides.

Technologies that recruit and direct the activity of endogenous RNA-editing enzymes to specific cellular RNAs have therapeutic potential, but translating them from cell culture into animal models has been challenging. Here we describe short, chemically modified oligonucleotides called AIMers that direct efficient and specific A-to-I editing of endogenous transcripts by endogenous adenosine deaminases acting on RNA (ADAR) enzymes, including the ubiquitously and constitutively expressed ADAR1 p110 isoform. We show that fully chemically modified AIMers with chimeric backbones containing stereopure phosphorothioate and nitrogen-containing linkages based on phosphoryl guanidine enhanced potency and editing efficiency 100-fold compared with those with uniformly phosphorothioate-modified backbones in vitro. In vivo, AIMers targeted to hepatocytes with N-acetylgalactosamine achieve up to 50% editing with no bystander editing of the endogenous ACTB transcript in non-human primate liver, with editing persisting for at least one month. These results support further investigation of the therapeutic potential of stereopure AIMers.

Maximal Resection of Tumors Encasing the Internal Carotid Artery and Hindering Internal Carotid Artery Expansion Followed by Revascularization Surgery: A Series of Nine Cases at a Single Tertiary Center.

PURPOSE: Cerebral reconstruction appears to play a diminished role in managing complex skull base tumors involving vital neurovascular structures. MATERIALS AND METHODS: Patients with recurrent or progressive middle cranial fossa tumors treated by radical resection followed by extracranial-to-intracranial (EC-IC) bypass from 2014 to 2019 were included. Balloon test occlusion (BTO) was performed preoperatively. RESULTS: Overall, 9 patients (5 males, 4 females; mean age, 29.9 years) were enrolled. The lesions arose from the parasellar region (3), cavernous sinus (3), petroclival region (2), or orbital apex (1), and all encased the cavernous/petrous portion of the internal carotid artery. Before tumor resection, internal maxillary artery (IMA) bypass was performed for 7 patients, cervical EC-IC bypass was performed for 1 patient, and interposed superficial temporal artery (STA) bypass was performed for 1 patient. BTO failed in 8 patients and was tolerated by one patient. Intraoperative blood flow of the interposed graft was 79.7 ± 37.86 ml/min after IMA bypass, 190.6 ml/min following cervical EC-IC bypass and 75 ml/min after interposed STA bypass. All bypasses were patent on intraoperative indocyanine green angiography. Radical tumor resection was achieved in 5 patients (55.6%), and patency was confirmed postoperatively in 88.8% (8/9) of bypasses. Six patients showed favorable outcomes at discharge. At the 2-year follow-up, 7 patients (77.8%) had favorable outcomes (Karnofsky Performance Scale score>80). At the 1.5-year follow-up, one patient had died due to infarction; at the 3-year follow-up, another patient had developed tumor recurrence despite being asymptomatic. CONCLUSION: Cerebral bypass remains a vital tool for managing select middle cranial fossa tumors that invade or erode the surrounding neurovasculature or hinder carotid artery expansion and are difficult to resect.

One-pot fabrication of dual-redox sensitive, stabilized supramolecular nanocontainers for potential programmable drug release using a multifunctional cyclodextrin unit.

Facile engineering of ß-cyclodextrin (ß-CD)-based supramolecular nanocontainers with simultaneous enhanced extracellular stability and efficient intracellular biosignals-triggered destabilization generally suffers from multistep synthesis and tedious purification process, thus remains a significant challenge for the scale-up production and clinical translation of ß-CD-based supramolecular nanomedicine. To address these issues, we reported in this study a one-pot preparation of dual-redox sensitive, stabilized supramolecular nanocontainers for potential programmable drug release by self-crosslinking of a multifunctional ß-CD unit that integrates a host cavity for oxidation-mediated reversible complexation with ferrocence (Fc) guest molecule and lipoic acids (LAs)-decorated primary and secondary faces for reversible in-situ crosslinking by the reducible disulfide links. The resulting doxorubicin (DOX)-loaded nanoparticles showed, on one hand, enhanced colloidal stability and high DOX loading capacity with a drug loading content (DLC) of approximately 11.3% due to the crosslinked structure, and on the other hand, a programmable destruction of the supramolecular micelles triggered by a simultaneous adoption of intracellular glutathione (GSH) and reactive oxygen species (ROS) toward a complete structural destruction for promoted drug release with enhanced therapeutic efficiency. Notably, an optimized DOX-loaded micelle formation, DOX@CL P1 showed greater cytotoxicity with an IC50 of 2.94 ± 0.25 µg/mL than free DOX (6.00 ± 0.56 µg/mL) in Bel-7402 cancer liver cells, but a significantly reduced side effect relative to free DOX in L02 normal liver cells. In vivo animal study in Bel-7402 tumor-bearing BALB/c mice further confirmed prolonger elimination half-life time, efficient tumor accumulation, enhanced therapeutic efficiency and compromised systemic toxicity of this micelle construct. Therefore the multifunctional CD unit developed in this study offers an extremely straightforward and robust strategy with respect to dual-redox responsive, stabilized supramolecular nanocontainers with potential programmable controlled release properties for clinical translations.

Stereochemistry Enhances Potency, Efficacy, and Durability of Malat1 Antisense Oligonucleotides In Vitro and In Vivo in Multiple Species.

Purpose: Antisense oligonucleotides have been under investigation as potential therapeutics for many diseases, including inherited retinal diseases. Chemical modifications, such as chiral phosphorothioate (PS) backbone modification, are often used to improve stability and pharmacokinetic properties of these molecules. We aimed to generate a stereopure MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) antisense oligonucleotide as a tool to assess the impact stereochemistry has on potency, efficacy, and durability of oligonucleotide activity when delivered by intravitreal injection to eye. Methods: We generated a stereopure oligonucleotide (MALAT1-200) and assessed the potency, efficacy, and durability of its MALAT1 RNA-depleting activity compared with a stereorandom mixture, MALAT1-181, and other controls in in vitro assays, in vivo mouse and nonhuman primate (NHP) eyes, and ex vivo human retina cultures. Results: The activity of the stereopure oligonucleotide is superior to its stereorandom mixture counterpart with the same sequence and chemical modification pattern in in vitro assays, in vivo mouse and NHP eyes, and ex vivo human retina cultures. Findings in NHPs showed durable activity of the stereopure oligonucleotide in the retina, with nearly 95% reduction of MALAT1 RNA maintained for 4 months postinjection. Conclusions: An optimized, stereopure antisense oligonucleotide shows enhanced potency, efficacy, and durability of MALAT1 RNA depletion in the eye compared with its stereorandom counterpart in multiple preclinical models. Translational Relevance: As novel therapeutics, stereopure oligonucleotides have the potential to enable infrequent administration and low-dose regimens for patients with genetic diseases of the eye.

Aggressive resection of craniopharyngioma achieved by drilling the tuberculum sellae/planum sphenoidale using a frontal basal interhemispheric approach: A review of 55 cases.

OBJECTIVE: The frontal basal interhemispheric approach (FBIA) is preferable for resection of craniopharyngioma (CP), achieving desirable total resection rates in early reports of lesions located in the suprasellar region to the third ventricle. For tumours that have created a larger obstruction of the tuberculum sellae and planum sphenoidale, aggressive resection in the intrasellar region and medial wall of the cavernous sinus is not feasible compared to improving tumour visualization by drilling the tuberculum sellae and planum sphenoidale. In a report of drilling the sellar tuberculum and sphenoid planum, drilling allowed the direct visualization of tumours invading the intrasellar region and medial wall of the cavernous sinus. Reconstructing the opening of the sellar-sphenoid cavity is achieved by microsuturing a piece of the pericranium/dura around the dural edge of the defective dura of the open sphenoid sinus and sellar cavity to prevent cerebrospinal fluid (CSF) leakage. PATIENTS AND METHODS: The FBIA with drilling of the tuberculum sellae and planum sphenoidale was performed to remove the tumours that invaded the intrasellar region and cavernous sinus in 55 patients from January 2014 to October 2019 at our institution. The pre- and postoperative pituitary hormone levels and vision were evaluated as effective standards after surgery and compared using paired t-tests. The different rates of CSF leakage between the packing and microsuture groups were compared by χ2 test, p < 0.05. RESULTS: In all patients with a mean 37-month follow-up (range, 3-2 months), 43 (78.2%) patients returned to their normal life or school independently, 7 (12.7%) patients were able to perform normal activities with minor complaints or effort, and 4 (7.3%) patients could care for themselves or only required occasional assistance. One (1.8%) death occurred, attributed to CSF leak-related meningitis at 5 months after surgery. Postoperative CSF leakage occurred in eight (19.0%) of 42 patients with packed bone wax or pieces of muscle to the sphenoid sinus. Of 13 patients with a piece of the periosteum/dura microsutured around the defective dura of the sellar region and open sphenoid sinus, one (7.7%) of 13 patients experienced CSF leakage in the perioperative period. With statistical analysis, there was a potential risk for postoperative CSF leakage in the bone wax and muscle piece in the open sphenoid sinus, whereas microsuture manoeuvres were effective for avoiding the risk of postoperative CSF leakage (χ2 = 8.865, p < 0.005). The microsutures closed the open sphenoid sinus such that it was water-tight. Postoperative visual acuity and the visual field were not affected by the increased intrasellar exposure or the open sphenoid sinus achieved by drilling the tuberculum sellae and planum sphenoidale. CONCLUSION: Tuberculum sellae/planum sphenoidale drilling via FBIA is feasible to enhance the direct visualization of CP resection, which expands the intrasellar region with a direct resection of recurrent tumours in the sellar cavity and adhering to the medial wall of the cavernous sinus. The potential risk of a CSF leakage seemed to be mitigated when using water-tight microsutures on a piece of the pericranium/dura around the edge of the defective dura in the sellar region and the open sphenoid sinus cavity.

Microsuturing Technique for the Treatment of Blood Blister Aneurysms: A Series of 7 Cases.

BACKGROUND: A blood blister aneurysm (BBA) is an abnormal bulge at the nonbranching point of a vessel. However, the optimal treatment strategy for this formidable disorder remains unknown. The aim of this study was to evaluate the safety and validity of using a direct microsurgical repair technique in BBAs. METHODS: Direct microsuturing of aneurysms was performed with nylon thread in 7 patients from 2014-2018. Postoperative angiography was used to confirm the obliteration of the aneurysms and the absence of stenosis of the parent artery. Neurologic function was assessed by the modified Rankin Scale. RESULTS: Two male and 5 female patients with a mean age of 43.7 years (range, 29-62 years) were assessed. Subarachnoid hemorrhage occurred in 6 patients, including 4 patients with Hunt-Hess grade II and 2 patients with grade III. BBAs of the internal carotid artery were observed in 3 patients, BBAs of the middle cerebral artery trunk were observed in 2 patients, and a BBA of the anterior communicating artery was observed in 1 patient. One BBA of the anterior communicating artery in 1 patient was detected incidentally during the resection of a craniopharyngioma. All BBAs were closed with blood-tight sutures via standard frontotemporal craniotomies. Postoperatively, all BBAs were completely eliminated from the circulation without stenosis of the sutured parent vessel. CONCLUSIONS: The proposed microsuture technique appears to be a safe, cost-effective, durable treatment for BBAs in the anterior circulation, and should be a part of the arsenal of neurosurgical practitioners who treat anterior circulation BBAs.

Natural history and clinical outcomes in patients with complex intracranial aneurysms: a review of 115 bypass cases and 22 nonsurgical cases.

The purpose of this study was to evaluate the natural history of patients with these heterogeneous aneurysms to provide guidance for their treatment. This retrospective analysis was performed at a single institution and included 137 patients with complex intracranial aneurysms who underwent a natural history evaluation. Among the 115 patients who underwent bypass surgery, stroke (n = 39, 33.9%) was the most common clinical symptom followed by progressively severe headaches (n = 25, 21.7%). Of the 104 patients with follow-up information, 87 (83.7%) returned to a normal life within a mean follow-up of 4.17 ± 2.09 years. Ten deaths (9.6%) occurred after a mean of 1.3 ± 0.9 years. Among the 22 patients who selected nonsurgical treatment, mass effect (n = 9, 40.9%) was the most common clinical presentation, and 14 deaths (63.6%) occurred after a mean of 3.3 ± 2.5 years. The modified Rankin scale (mRS) scores of 5 survivors (5/22, 22.7%) progressed from 0-2 at initial presentation to 3-4. Bypass surgical treatment for these aneurysms appears to be effective and can achieve good clinical outcomes without additional limitations related to individual aneurysms despite the impact of recent endovascular techniques on vascular surgery.

Folate-Targeted Anticancer Drug Delivery via a Combination Strategy of a Micelle Complex and Reducible Conjugation.

Conjugation of various active targeting ligands to the surface of nanocarriers to realize specific recognition by the corresponding receptors localized on the membrane of the cancer cells has provided a powerful means toward enhanced cancer therapy. Folic acid (FA) is one of the most used targeting ligands due to the overexpressed FA receptors in many cancer cell lines. However, conjugation of hydrophobic FA to the surface of nanocarriers usually alters the hydrophilic/hydrophobic balance of the stabilized nanoparticles, leading to their thermodynamic instability and subsequent formation of aggregates, which apparently compromises the in vivo long circulation and minimized side effects of nanocarriers. The currently leading strategy to overcome this issue is to incorporate a protecting hydrophilic stealth that can be deshielded to expose the targeting ligand at the desired tumor site, which generally involves multistep chemical modifications, conjugations, and purifications. To develop a simple alternative toward FA-mediated enhanced anticancer drug delivery, a combination strategy of micelle complex and reducible conjugation was reported in this study. FA was first conjugated to the terminus of the hydrophilic block of a reduction-sensitive miktoarm star-shaped amphiphilic copolymer, PCL3-SS-POEGMA1, with the previously optimized star structure by click coupling via a reducible disulfide link. The resulting PCL3-SS-POEGMA1-SS-FA was further mixed with the parent PCL3-SS-POEGMA1 to afford a micelle complex with both reducibly conjugated and relatively low amount of FA-targeting ligands toward excellent FA-mediated targeted drug delivery without compromised salt stability in vitro and in vivo. Therefore, the combined strategy developed herein provides a simple and powerful means to promote FA-mediated anticancer drug delivery.

Serpentine aneurysm of the posterior cerebral artery treated by internal maxillary artery bypass followed by parent artery occlusion: a case report and literature review.

Serpentine aneurysms of the posterior cerebral artery (PCA) treated by the internal maxillary artery (IMA) bypass are rare. Here, the authors report the case of a 34-year-old male patient who presented with a half-year history of gradual severe headache and right-sided limb monoparesis and paresthesia lasting for 1 week. Preoperative angiograms showed a serpentine aneurysm in the left distal PCA, which was treated with internal maxillary artery-radial artery-posterior cerebral artery (IMA-RA-PCA) bypass followed by parent artery occlusion (PAO). The postoperative course was uneventful; radiological images revealed that the aneurysm disappeared, and there was good graft patency and excellent perfusion of the distal PCA territories. To the authors' knowledge, this is the first and only case of distal PCA serpentine aneurysm to be treated by IMA-RA-PCA bypass followed by proximal PAO. These findings suggest that IMA bypass surgery is a good and feasible treatment option for serpentine aneurysms of the PCA that can preserve the parent artery. Moreover, the anatomic segments of the PCA and different treatment options available for PCA serpentine aneurysms are also discussed in this study.

Intraoperative Finding of an Anterior Communicating Artery Blister-Like Aneurysm During a Primary Craniopharyngioma Resection: Accidental or Incidental?

BACKGROUND: The presence of an anterior communicating artery blister-like aneurysm in the setting of a craniopharyngioma has never been reported to our knowledge. CASE DESCRIPTION: This patient was admitted to our service for an untreated craniopharyngioma resection. An anterior interhemispheric approach with right frontal craniotomy was performed and a blister-like aneurysm of the anterior communicating artery was found during the surgery. After the tumor was completely resected, a suturing technique was used for the aneurysm. In this article, we are going to present this rare case and discuss the potential pathogeny of the aneurysm. CONCLUSIONS: We hypothesized that cystic craniopharyngioma may rupture spontaneously. The cystic fluid accumulated in the lower subarachnoid space due to gravity, and it may lead to local vascular cytotoxic and inflammatory reactions which may result in the vascular wall remodeling and lead to the reconstructed vascular wall weakness.

General Voltage Injection Device for Immunity Test of Active Implantable Neurostimulators to Electromagnetic Fields over the Frequency Range 16.6Hz to 80MHz.

A general voltage injection testing device is presented to test the immunity of active implantable neurostimulator (INS) to electromagnetic fields over the frequency range 16.6Hz to 80MHz. The proposed device consists of test circuit and transfer tooling, which is designed to conduct Electromagnetic Compatibility (EMC) test of INS with output-only functionality. In the test circuit, a tissue-electrode interface model and its board layout are provided to satisfy impedance continuity and test channel consistency. In order to adapt to different types of stimulators and electrode specifications, transfer circuits and several kinds of transfer tooling are created. In accordance with ISO14708-3, Voltage injection tests have been carried out with the device and an INS with 16 electrodes. The results show that the device can meet test requirements and is useful for EMC test. Besides, the device can provide references for other manufacturers and organizations to accomplish voltage injection test.

Synthesis of Thermosensitive Conjugated Triblock Copolymers by Sequential Click Couplings for Drug Delivery and Cell Imaging.

The elegant integration of an excellent light-emitting segment and a biorelevant signal-responsive moiety could generate advanced polymeric delivery systems with simultaneously favorable diagnostic and therapeutic functions with respect to cancer theranostics. Although polymeric delivery systems based on fluorescent polyfluorene (PF) or thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) have been extensively developed, the preparation of a ternary polymer formulation composed of a PF block, a PNIPAAm sequence, and a hydrophilic moiety remains rarely explored likely because of the difficulty in integrating different synthesis strategies for polymer synthesis. To this end, herein we reported the design and controlled synthesis of a PF- and PNIPAAm-based amphiphilic triblock copolymer, PF11-b-PNIPAAm120-b-poly(oligo(ethylene glycol) monomethyl ether methacrylate)17 (PF11-b-PNIPAAm120-b-POEGMA17), with a well-defined structure by a strategy of sequential click couplings between Suzuki-coupling-generated PF and atom-transfer radical polymerization (ATRP)-produced PNIPAAm and POEGMA. The as-prepared triblock copolymers can self-assemble into micelles with a core-shell-corona (CSC) structure that is composed of an inner hydrophobic core of the PF moiety for fluorescent tracking and drug encapsulation, a thermosensitive middle shell of PNIPAAm block for thermomodulated drug loading and release, and a hydrophilic outer corona of the POEGMA segment for micelle stabilization. Interestingly, the doxorubicin (DOX)-loaded micelles prepared at 25 °C had a greater drug loading capacity than the analogues fabricated at 37 °C due to the better stability of the former formulation, leading to its higher in vitro cytotoxicity in HeLa cells. Together with the integration of a localized hyperthermia-triggered drug release profile and efficiently intracellular trafficking of the nanocarriers by monitoring the fluorescence of the PF moiety, this formulation demonstrates a great potential for cancer theranostics.