Combined simultaneous transsphenoidal and transcranial regimen improves surgical outcomes in complex giant pituitary adenomas: A longitudinal retrospective cohort study.

BACKGROUND: Surgical treatment of complex giant pituitary adenomas (GPAs) presents significant challenges. The efficacy and safety of combining transsphenoidal and transcranial approaches for these tumors remain controversial. In this largest cohort of patients with complex GPAs, we compared the surgical outcomes between those undergoing a combined regimen and a non-combined regimen. We also examined the differences in risks of complications, costs, and logistics between the two groups, which might offer valuable information for the appropriate management of these patients. MATERIALS AND METHODS: This was a multicenter retrospective cohort study conducted at 13 neurosurgical centers. Consecutive patients who received a combined or non-combined regimen for complex GPAs were enrolled. The primary outcome was gross total resection, while secondary outcomes included complications, surgical duration, and relapse. A propensity score-based weighting method was used to account for differences between the groups. RESULTS: Out of 647 patients (298 [46.1%] women, mean age: 48.5 ± 14.0 years) with complex GPAs, 91 were in the combined group and 556 were in the non-combined group. Compared with the non-combined regimen, the combined regimen was associated with a higher probability of gross total resection (50.5% vs. 40.6%, odds ratio [OR]: 2.18, 95% confidence interval [CI]: 1.30-3.63, P = 0.003). The proportion of patients with life-threatening complications was lower in the combined group than in the non-combined group (4.4% vs. 11.2%, OR: 0.25, 95% CI: 0.08-0.78, P = 0.017). No marked differences were found between the groups in terms of other surgical or endocrine-related complications. However, the combined regimen exhibited a longer average surgery duration of 1.3 h (P < 0.001) and higher surgical costs of 22,000 CNY (approximate 3,000 USD, P = 0.022) compared with the non-combined approach. CONCLUSIONS: The combined regimen offered increased rates of total resection and decreased incidence of life-threatening complications, which might be recommended as the first-line choice for these patients.

Searching High-Potential Dihydroxynaphthalene Cathode for Rocking-Chair All-Organic Aqueous Proton Batteries.

The lack of acid-proof high-potential cathode largely limits the development and competitiveness of proton batteries. Herein, the authors systematically investigated six dihydroxynaphthalenes (DHNs) and found that 2,6-DHN delivered the best cathode performance in proton battery with the highest redox potential (0.84 V, vs SHE) and a specific capacity of 91.6 mAh g-1 at 1 A g-1 . In situ solid-state electropolymerization of DHNs is responsible for the voltage and capacity fading of DHNs, and 2,6-DHN's excellent electrochemical performance is derived from its high polymerization energy barrier. By compounding with rGO, the 2,6-DHN/rGO electrode can maintain a specific capacity of 89 mAh g-1 even after 12 000 cycles at 5 A g-1 . When it is paired with the 2,6-dihydroxyanthraquinone (DHAQ) anode, the assembled rocking-chair all-organic proton battery exhibited a high cell voltage of 0.85 V, and excellent energy/power densities (70.8 Wh kg-1 /850 W kg-1 ). This study showcases a new-type high-potential proton-containing organic cathode and paves the way for constructing a high-voltage rocking-chair proton battery. Also, in situ solid-state electropolymerization will inspire the further study of phenol-based small-molecule electrodes.

How we do it: the double keyhole micro-endoscopic combined complex pituitary adenoma surgery.

BACKGROUND: Surgical removal of complex pituitary adenomas (PA) is a technically challenging procedure. To ensure safe and efficient surgery, we employ the micro-endoscopic combination technique. METHOD: In this study, we present our approach to the removal of a complex PA using the micro-endoscopic combination strategy. We describe our surgical setup and workflow in detail. CONCLUSION: Our experience with this case highlights the effectiveness of the micro-endoscopic combination technique in the management of complicated skull base surgeries with good teamwork and cooperation.

How I do it? Preoperative Microsoft HoloLens 2 planning-assisted surgical clipping of a fetal posterior cerebral artery aneurysm.

BACKGROUND: The treatment of intracranial aneurysms has predominantly shifted towards endovascular strategies, but complex cases still necessitate microsurgery. Preoperative stimulation can be beneficial for inexperienced young neurosurgeons in preparing for safe microsurgery. METHOD: A 72-year-old female with a left irregular fetal posterior cerebral artery (PCA) aneurysm underwent clipping repair. Microsoft HoloLens 2, utilizing mixed reality technology, was employed for preoperative stimulation and anatomical study. During the operation, we successfully identified the planned relationship between the aneurysm and the fetal PCA. The patient was cured without any complications. CONCLUSION: We hope that this report will highlight the significance of Microsoft HoloLens 2 in microsurgical planning and education.

The mechanism of nanozyme activity of ZnO-Co3O4-v: Oxygen vacancy dynamic change and bilayer electron transfer pathway for wound healing and virtual reality revealing.

Since the catalyst's surface was the major active location, the inner structure's contribution to catalytic activity was typically overlooked. Here, ZnO-Co3O4-v nanozymes with several surfaces and bulk oxygen vacancies were created. The O atoms of H2O2 moved inward to preferentially fill the oxygen vacancies in the interior and form new "lattice oxygen" by the X-ray photoelectron spectroscopy depth analysis and X-ray absorption fine structure. The internal Co2+ continually transferred electrons to the surface for a continuous catalytic reaction, which generated a significant amount of reactive oxygen species. Inner and outer double-layer electron cycles accompanied this process. A three-dimensional model of ZnO-Co3O4-v was constructed using virtual reality interactive modelling technology to illustrate nanozyme catalysis. Moreover, the bactericidal rate of ZnO-Co3O4-v for Methionine-resistant Staphylococcus aureus and Multiple drug resistant Escherichia coli was as high as 99%. ZnO-Co3O4-v was biocompatible and might be utilized to heal wounds following Methionine-resistant Staphylococcus aureus infection. This work offered a new idea for nanozymes to replace of conventional antibacterial medications.

Deep-learning-based automatic segmentation and classification for craniopharyngiomas.

Objective: Neuronavigation and classification of craniopharyngiomas can guide surgical approaches and prognostic information. The QST classification has been developed according to the origin of craniopharyngiomas; however, accurate preoperative automatic segmentation and the QST classification remain challenging. This study aimed to establish a method to automatically segment multiple structures in MRIs, detect craniopharyngiomas, and design a deep learning model and a diagnostic scale for automatic QST preoperative classification. Methods: We trained a deep learning network based on sagittal MRI to automatically segment six tissues, including tumors, pituitary gland, sphenoid sinus, brain, superior saddle cistern, and lateral ventricle. A deep learning model with multiple inputs was designed to perform preoperative QST classification. A scale was constructed by screening the images. Results: The results were calculated based on the fivefold cross-validation method. A total of 133 patients with craniopharyngioma were included, of whom 29 (21.8%) were diagnosed with type Q, 22 (16.5%) with type S and 82 (61.7%) with type T. The automatic segmentation model achieved a tumor segmentation Dice coefficient of 0.951 and a mean tissue segmentation Dice coefficient of 0.8668 for all classes. The automatic classification model and clinical scale achieved accuracies of 0.9098 and 0.8647, respectively, in predicting the QST classification. Conclusions: The automatic segmentation model can perform accurate multi-structure segmentation based on MRI, which is conducive to clearing tumor location and initiating intraoperative neuronavigation. The proposed automatic classification model and clinical scale based on automatic segmentation results achieve high accuracy in the QST classification, which is conducive to developing surgical plans and predicting patient prognosis.

Comparative endoscopic techniques of medial rectus muscle retraction for approaching intraconal tumors: Our experience with five cases.

Objective: To examine the role of transnasal endoscopic approaches in the management of intraconal tumors and demonstrate the use of an eyelid speculum in comparison with different techniques of medial rectus muscle (MRM) retraction. Methods: Retrospective data of five patients with intraconal tumors operated on and followed up by the senior authors between December 2019 and April 2022 was collected. Presenting symptoms, technical details, imaging and histology findings, outcomes, and complications were evaluated. Results: Four primary and one recurrent tumor were identified. The mean patient age was 50 (range, 29-64) years. One tumor was located lateral to the optic nerve, one central and three medial. A complete surgical resection was obtained in four primary cases and a partial resection was achieved in the recurrent case. The MRM was retracted using three different techniques: (1) an infant eyelid speculum creating an operative window between the medial and inferior rectus muscle, (2) external MRM disinsertion transconjunctivally, (3) a four-handed technique performed transseptally by two surgeons. Transient postoperative ophthalmoplegia was recorded in four cases and transient ptosis in one. Three patients completely recovered in 2-3 months while one undergoing MRM disinsertion ended up in restricted strabismus at 15-month follow-up. No other long-term complications have been noted in all five patients with a mean follow-up of 22 (range, 14-32) months. No patients with primary tumors have required additional surgery for tumor recurrence. Conclusion: The indication of endoscopic intraconal surgery may expand to lesions lateral to the optic nerve when the nerve is not in its natural position. The well-known advantages of the endoscopic techniques, namely the lack of external scars, better visualization, less bleeding, and fewer complications, were confirmed. An eye speculum provides a better surgical corridor and eases the pressure exerted on the MRM, which has a promising application prospect.

A Clinicopathological and Molecular Analysis of Sellar/Suprasellar Neurocytoma Mimicking Pituitary Adenoma.

Objective: To investigate the clinicopathological characteristics, molecular genetic characteristics and prognosis of extraventricular neurocytoma located in the sellar/suprasellar region. Methods: Seven archived tumor samples derived from 4 patients with neurocytoma in the sellar/suprasellar region were collected from the First Affiliated Hospital of Fujian Medical University and the Affiliated Hospital of Qingdao University and retrospectively analyzed for clinical manifestations, imaging features, and histopathological features. Neuronal and pituitary biomarkers and molecular features were detected in these tumor tissues by immunohistochemistry and FISH or Sanger sequencing. The related literature was reviewed. Results: Three patients were female, while 1 was male, with an average age of 35.5 years (range: 27 to 45 years). The initial manifestations were mainly headache and blurred vision in both eyes. The first MRI examination showed marginally enhancing masses in the intrasellar or intra- to suprasellar region. The diagnosis of pituitary adenomas was based on imaging features. The levels of pituitary hormones were normal. Histologically, the tumor cells were arranged in a sheet-like, monotonous architecture and were uniform in size and shape with round to oval, exquisite and hyperchromatic nuclei, which densely packed close to one another and were separated only by a delicate neuropil background. There was no evident mitosis, necrosis or microvascular proliferation. The three cases of recurrent tumors were highly cellular and showed increased mitotic activity. Immunohistochemically, the tumor cells were positive for syn, CR, CgA, and vasopressin and were focally positive for NeuN, TTF-1, NF, CK8, vimentin, and S100 proteins. Other markers, including IDH1, BRAF VE1, Olig-2, and EMA, were negative. Pituitary transcription factors and anterior pituitary hormones were negative. Molecular genetic testing showed that the tumor cells lacked IDH gene mutations, LOH of 1p/19q, MYCN amplification, and EGFR alteration. With a median follow-up of 74.5 months (range 23 to 137 months), 3 patients relapsed at 11, 50, and 118 months after the initial surgery. Conclusion: The morphological features and immunophenotypes of neurocytoma in the sellar/suprasellar region are similar to those of classic central neurocytoma. The prognosis is relatively good. Gross-subtotal resection and atypical subtype may be related to tumor recurrence.

Observation of Clinicopathologic Features of Pituitary Adenoma With Neuronal Differentiation.

Objective: To investigate the clinicopathologic features of pituitary adenoma with neuronal differentiation. Methods: Four patients with mixed gangliocytoma-pituitary adenomas between January 2011 and January 2021 and 111 new-onset patients with adenomas between January 2019 and June 2021 who attended the First Affiliated Hospital of Fujian Medical University were included in the study. The histological and immunohistochemical findings were analyzed. Neuronal differentiation marker staining was performed on new-onset adenomas, and the related literature was reviewed. Results: Altogether, more than 100 mixed gangliocytoma-pituitary adenoma cases have been reported in the literature until now, of which pituitary-specific POU-class homeodomain transcription 1 (PIT1) positive adenomas are more frequently observed. In the present study, all 4 patients we described were female, aged 29 to 53 years (mean 39 years). Clinically, 3/4 patients presented with acromegaly, and 1/2 patients presented with headache. Histologically, the tumor was composed of two distinct mixed components. The one was a population of neoplastic ganglionic cells with large nuclei, prominent nucleoli, and abundant basophilic cytoplasm embedded in a fibrillary background. Stains of chromograninA (CgA), synaptophysin (Syn), Calretinin (CR) were positive. Axotomy-like expression was observed in neurofilament (NF) staining. PIT1 was expressed in partial ganglionic cells in all cases. The other component was a population of small uniform cells with round nuclei and acidophilic cytoplasm. Prolactin (PRL) and growth hormone (GH) were positive in all 4 cases. PIT1 was positive in the nuclei of adenomas. Although adenomas and ganglionic regions varied in histology, there was a population of cells with neuronal differentiation expressing PIT1. Additionally, axotomy-like expression of NF staining could be seen in a distant area of adenoma regions. A total of 111 cases of adenomas without ganglionic cells were included in this study, including 7 cases with neuronal differentiation. Among them, 4 cases were prolactinomas, 2 cases were somatotroph adenomas, and 1 case was corticotroph adenoma. 6/7 cases were PIT1-positive adenomas. And the remaining one case is T-PIT-positive adenoma. Conclusions: Mixed gangliocytoma-pituitary adenomas are rare tumors with neuronal differentiation. The majority of MGAs are associated with endocrinopathies, mainly acromegaly. Our results suggest that PIT1-positive pituitary adenomas may have neural differentiation potential, which may not be unusual. This indication supports the possibility that the neuronal transdifferentiation of adenomatous cells is a possible mechanism, and the underlying mechanism requires further elucidation.

Preparation of shikonin liposome and evaluation of its in vitro antibacterial and in vivo infected wound healing activity.

BACKGROUND: The emergence of antibiotic resistance over the past decade has made the treatment of Staphylococcus aureus infection difficult. Burn wounds infected with methicillin-resistant S. aureus (MRSA) can cause mortality in animals. Shikonin (SH) has been reported to possess antimicrobial and anti-inflammatory properties, and is also responsible for the process of wound healing. However, the pharmacological mechanism of its wound healing process remains poorly comprehended, hence the probable mechanism deserves further investigation. PURPOSE: The current study was designed to develop a novel SH-liposome with improved anti-MRSA effect and to detect its beneficial wound healing effects. STUDY DESIGN: In vitro antibacterial tests and in vivo infected wound healing test were conducted. METHODS: SH-liposome was produced by the film formation method, and the characteristics were measured using a laser particle size analyzer, transmission electron microscopy, and the dialysis method. Additionally, in vitro antibacterial tests were conducted to investigate the antibacterial effects and the relative mechanism of SH-liposome. Furthermore, the therapeutic effects and bioactivity of SH-liposome in MRSA infected burn wounds were investigated in rats. Sixty-four male Sprague Dawley rats (250 ± 10 g) were randomly divided into four groups, including Group I (control group); Group II (model group); Group III (SH-liposome group) and Group IV (Arnebia oil® group), and the drug treatments were applied topically twice daily for 21 days. Further, full thickness skin biopsies at different periods were collected aseptically to evaluate tissue cytokines, recognize flora, observe histopathological changes, and determine the mechanism underlying the wound healing effects of SH-liposome. The data were analyzed via one-way analysis of variance (ANOVA) and Duncan's multiple range test. RESULTS: The results showed that SH-liposome was successful with a drug load of 4.6 ± 0.17%. Moreover, SH-liposome showed a sustained-release behavior and improved antibacterial ability in a dose-dependent manner. For the possible antibacterial mechanism, we observed that SH-liposome achieved antibacterial activity by damaging the integrity of bacterial cell wall and membrane to further disturb the physiological activities of S. aureus. In addition, SH-liposome facilitated wound healing by inhibiting bacterial activities to control infection, regulating the I-κBα/NFκB-p65 pathway to alleviate inflammation, and directly promoting repair in burn wounds. CONCLUSION: In conclusion, SH-liposome showed an antibacterial effect against S. aureus, promoted effective healing of infected burn wounds; hence, it could be used as an alternative therapy for drug-resistant infections.

Long-Lived Color-Tunable Room-Temperature Phosphorescence of Boron-Doped Carbon Dots.

Carbon dots (CDs) with long-lived room-temperature phosphorescence (RTP) or long afterglow properties draw much attention. However, most room-temperature phosphorescent materials are metal containing, and the exploitation of long-lived color-tunable RTP materials faces great challenges. Here, we report metal-free boron-doped CDs (B-CDs) for room-temperature phosphorescence with tunable color and an ultralong lifetime. B-CDs were obtained by simply calcining a mixture of boric acid and 1,3,5-benzenetricarboxylic acid in the atmosphere. The as-prepared B-CDs were characterized through UV-vis spectroscopy, photoluminescence spectroscopy, and so forth. Under the excitation of 310 nm UV light, B-CDs show RTP that appears as blue with a phosphorescence lifetime of 1042 ms, and after switching the excited wavelength to 365 nm, the RTP appears as green with a phosphorescence lifetime of 590 ms. Due to the unique RTP properties, B-CDs display promising applications in anticounterfeiting and information encryption.

CBX4-dependent regulation of HDAC3 nuclear translocation reduces Bmp2-induced osteoblastic differentiation and calcification in adamantinomatous craniopharyngioma.

BACKGROUND: Calcification of adamantinomatous craniopharyngioma (ACP) often causes problems with tumor resection, leading to a high incidence of deadly complications and tumor recurrence. Histone acetyltransferase (HAT) and histone deacetylase (HDAC) are 2 key enzymes that regulate histone acetylation and play important roles in tumor development. However, the roles of HAT and HDAC in the calcification and osteoblastic differentiation of ACP are not known. METHODS: In this study, primary cells were isolated from ACP tissues, and calcification was induced with bone morphogenetic protein 2 (Bmp2). HDAC3 expression was assessed in 12 tissue samples by Western blotting and immunohistochemistry. ACP calcification was assessed by Alizarin red staining. A luciferase reporter assay was performed to examine the interaction between miR-181b and the 3'-untranslated region of the polycomb chromobox 4 (CBX4) gene. RESULTS: Our results showed that the expression of HDAC3 was increased in the calcified ACP samples, but inhibition of HDAC3 promoted ACP cell calcification and osteoblastic differentiation. Mechanistically, HDAC3 nuclear translocation was suppressed by Bmp2, leading to Runx2 protein expression and Osterix, osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP) mRNA expression. In addition, this process was suppressed by CBX4, which stabilized the nuclear localization of HDAC3. miR-181b, the expression of which was increased in Bmp2-induced ACP cells, directly targeted and decreased CBX4 expression and inhibited the nuclear localization of HDAC3. CONCLUSIONS: Our results demonstrate that Bmp2 increases miR-181b levels to directly target and inhibit CBX4 expression, leading to a reduction in the CBX4-dependent regulation of HDAC3 nuclear translocation, which results in Runx2 activation/osteoblastic differentiation and calcium deposition in ACP. Further studies targeting these cascades may contribute to therapeutic interventions used for recurrent ACP. Video Abstract.

Endoscopic Surgery for Supratentorial Deep Cavernous Malformation Adjacent to Cortical Spinal Tract: Preliminary Experience and Technical Note.

In this study, we aimed to introduce a technical note and to explore the efficacy of endoscopic surgery combined with diffusion tensor imaging (DTI) navigation for supratentorial deep cerebral cavernous malformations (CCM). A prospectively maintained database of CCM patients was reviewed to identify all CCM patients treated by endoscopic surgery. The sagittal T1-weighted anatomical magnetic resonance imaging (MRI) and DTI were acquired before surgery. Endoscopic surgery was planned and performed based on preoperative DTI images and intraoperative DTI navigation. All patients were followed up more than 6 months. Motor function deficit and modified Rankin scale (mRS) scores were documented on follow-up. A final mRS score of 0-2 was considered a good outcome, and a final mRS score >2 was considered a poor outcome. Second DTI and 3DT1 were performed at 3 months after surgery. We tracked the ipsilateral corticospinal tract (CST) on pre- and postoperative DTI images. The overall mean FA values and the number of fibers of tracked CST were compared on pre- and postoperative DTI images. Risk factors associated with motor deficits and poor outcomes were analyzed. Seven patients with deep CCM and treated by endoscopic surgery were enrolled in this study. The mean value of preoperative mRS was 1.5 ± 0.98, but that score recovered to 0.86 ± 1.22 3 months later. The mRS scores were improved significantly according to statistical analysis (p = 0.012). According to the Spearman non-parametric test, only the fiber number of ipsilateral CST on postoperative DTI was significantly associated with muscle strength 6 months after surgery (p = 0.032). Compared with preoperative CST characteristics on DTI, the change of FA value (p = 0.289) and fiber number (p = 0.289) of ipsilateral CST on postoperative DTI was not significant It meant that the CST was protected during endoscopic surgery. Endoscopic surgery based on DTI navigation might be an effective method to protect fiber tracts in supratentorial deep CCM patients and improve long-term outcomes. However, more studies and cases are needed to confirm our findings.

Endoscopically controlled surgery with open hemilaminectomy for the treatment of intradural extramedullary tumors: an operative technique and short-term outcomes of 20 consecutive cases.

BACKGROUND: To present a surgical technique for the treatment of intradural extramedullary (IDEM) tumors by using endoscopically controlled surgery with open hemilaminectomy technique. METHODS: In this study, 20 patients with 22 IDEM tumors were enrolled. An endoscopically controlled surgery with open hemilaminectomy was employed to remove the tumors. Data related to clinical symptoms and medical images before and after surgery were collected for perioperative evaluation and follow-up analysis. RESULTS: All the tumors in 20 patients were well removed. The clinical symptoms were significantly reduced in all the patients as well. The short-term follow-up data showed that there was no tumor recurrence or spinal deformity. CONCLUSION: The endoscopically controlled surgery with open hemilaminectomy technique provided favorable exposure and satisfactory resection to the IDEM tumors. It may be an effective surgical method for treating IDEM tumors. Larger samples and longer follow-up data are needed to verify its long-term effectiveness.

Optimization Extraction of Shikonin Using Ultrasound-Assisted Response Surface Methodology and Antibacterial Studies.

The objectives of this study were to develop and optimize ultrasound-assisted extraction (UAE) for shikonin from Arnebia euchroma using response surface methodology (RSM) and to evaluate the antimicrobial activity of shikonin. The maximum yield of shikonin was 1.26% under the optimal extraction conditions (ultrasound power, 93 W; time, 87 min; temperature, 39°C; and liquid-solid ratio, 11 : 1). Shikonin showed inhibitory activity against standard strains and clinical isolates to varying extents (MICs ranging from 128 to 1024 µg/mL, MBCs ranging from 256 to 2048 µg/mL), and it was more effective for Gram-positive bacteria as indicated by lower MIC and MBC values. Time-kill curves revealed that antibacterial activity of shikonin exhibited a dose-response relationship. In summary, via this study, we identified ultrasound-assisted RSM as the optimal extraction method for shikonin, which is a potential material for the treatment of bacterial infections.

The Change in Distance Between Bilateral Internal Carotid Arteries in Acromegaly and Its Risk Factors.

Background: Studies investigating the change in distance between the bilateral internal carotid arteries (ICAs) in acromegalic patients have provided ambiguous results. The influencing factors of these changes have not been well-identified. Objective: To further investigate the change in distance between bilateral ICAs in acromegaly patients and identify the influencing factors of the change. Method: Patients diagnosed as acromegaly from Jan 2016 to Sep 2019 in the Department of Neurosurgery of the First Affiliated Hospital of Fujian Medical University, were included in this study. Computed tomography angiography (CTA) or magnetic resonance angiography (MRA) data were obtained for all patients for three-dimensional reconstruction of the ICAs. Distance between bilateral ICAs was measured and recorded for assessment. Result: 172 patients including 86 cases with acromegaly in the study group and 86 cases with non-functional pituitary adenoma in the control group were enrolled in this study. The difference of adenoma sizes between two groups was not statistically significant. Patients in acromegaly group had significantly larger maximum distances between bilateral siphon carotid ectasias (25.5 ± 4.1 vs. 23.4 ± 3.5 mm, P = 0.001) and between bilateral lacerum segments (26.2 ± 3.2 vs. 24.1 ± 4.3 mm, P < 0.001) compared with those of patients with non-functional pituitary adenomas. Multivariate analysis showed that the increased bilateral ICAs distance was associated with disease duration (odds ratio = 1.01, 95% confidence interval = 1.01-1.02, P = 0.005) and refractory pituitary adenoma (odds ratio = 9.8, 95% confidence interval = 1.1-88.7, P = 0.043) but not with level of growth hormone (GH), insulin-like growth factor-1 (IGF-1) and adenoma size in acromegaly. Conclusion: Our study showed significant change in distance between the bilateral ICAs in acromegalic patients, comparing to patients with non-functional pituitary adenomas. The increased intercarotid artery distance is associated with disease duration but not with preoperative level of GH and IGF-1. Refractory pituitary adenoma and longer disease duration are the both risk factors of the increased ICAs distance in patient with acromegly.

Nuclear delivery of dual anticancer drug-based nanomedicine constructed by cisplatinum-induced peptide self-assembly.

Nuclear delivery of anticancer drugs, particularly dual complementary anticancer drugs, can significantly improve chemotherapy efficacy. However, successful examples are rare. We reported a novel dual anticancer drug-based nanomedicine with nuclear accumulation properties. The nanomedicine was formed by chelation between a drug peptide amphiphile Rh-GFFYERGD (Rh represents Rhein, 1,8-dihydroxy-3-carboxy anthraquinonea) and cisplatinum (Pt). A single molecule of the drug peptide amphiphile could chelate up to 8 equiv. of cisplatinum in the resulting nanofibers. The nanofibers with a 1 : 4 ratio of Rh-GFFYERGD to cisplatinum demonstrated remarkable cellular uptake, and more significantly, superior nuclear accumulation properties. Additionally, the nanofibers could also bind to the DNA molecule more efficiently than those formed by the drug peptide amphiphile. Thus the nanofibers exhibited excellent anticancer properties both in vitro and in vivo. We envision a significant therapeutic potential of the dual anticancer drug-based nanomedicine with cisplatinum in cancer.

Relationship Between Pituitary Adenoma Consistency and Extent of Resection Based on Tumor/Cerebellar Peduncle T2-Weighted Imaging Intensity (TCTI) Ratio of the Point on Preoperative Magnetic Resonance Imaging (MRI) Corresponding to the Residual Point on Postoperative MRI.

BACKGROUND Controversies exist in imaging modalities for predicting adenoma consistency. In this study, we proposed a method of predicting consistency by magnetic resonance T2-sequence imaging based on adenoma to cerebellar peduncle signal (TCTI) ratio. MATERIAL AND METHODS Between January 2013 and May 2017, 191 consecutive patients with pituitary adenoma diagnosed at our institution were retrospectively studied. The consistency grade for each lesion was assigned. And the TCTI ratio based on preoperative and postoperative T2-weighted imaging was calculated. RESULTS The median TCTI ratio was 1.55, 1.28, and 1.25 for soft, fibrous, and hard adenomas, respectively. The differences were significant for all groups (p<0.001). A cutoff value of 1.38 for soft adenomas was found to be 80.2% sensitive and 88.7% specific. The median ratio of the outermost layer of residual tumor was 1.25 (SD±0.408, 95% CI 1.27-1.42). It was less than that ratio of the upper, lower quarter, and middle region of adenoma, respectively, and the inter-group differences were all statistically significant with p≤0.001. The extent of resection for the soft group was significantly greater than that of the hard group (85.3% vs. 70.6%, p=0.011). Analysis of Variance (ANOVA) revealed that the consistency grade was the influencing factor of degree of resection. p=0.003. CONCLUSIONS The TCTI ratio showed a good correlation with pituitary adenoma consistency. We also determined the optimal ratio of the residual adenoma.

Enhanced cellular uptake and nuclear accumulation of drug-peptide nanomedicines prepared by enzyme-instructed self-assembly.

Subcellular delivery of nanomedicines has emerged as a promising approach to enhance the therapeutic efficacy of anticancer drugs. Nuclear accumulation of anticancer drugs are essential for its therapeutic efficacy because their targets are generally located within the nucleus. However, strategies for the nuclear accumulation of nanomedicines with anticancer drugs rarely reported. In this study, we reported a promising nanomedicine, comprising a drug-peptide amphiphile, with enhanced cellular uptake and nuclear accumulation capability for cancer therapy. The drug-peptide amphiphile consisted of the peptide ligand PMI (TSFAEYWNLLSP), which was capable of activating the p53 gene by binding with the MDM2 and MDMX located in the cell nucleus. Peptide conformations could be finely tuned by using different strategies including heating-cooling and enzyme-instructed self-assembly (EISA) to trigger molecular self-assembly at different temperatures. Due to the different peptide conformations, the drug-peptide amphiphile self-assembled into nanomedicines with various properties, including stabilities, cellular uptake, and nuclear accumulation. The optimized nanomedicine formed by EISA strategy at a low temperature of 4 °C showed enhanced cellular uptake and nuclear accumulation capability, and thus exhibited superior anticancer ability both in vitro and in vivo. Overall, our study provides a useful strategy for finely tuning the properties and activities of peptide-based supramolecular nanomaterials, which may lead to optimized nanomedicines with enhanced performance.

Development and validation of a multi-color model using 3-dimensional printing technology for endoscopic endonasal surgical training.

BACKGROUND: The teaching of endoscopic endonasal surgery has always been difficult because of the complex structure of the nasal cavity, and the unique endoscopic view angle and endoscopic surgical tools. In this study, we have designed a 3D printed multi-color model for training of endoscopic endonasal surgery, and obtained preliminary application results. METHODS: The 3D printed model contained facial skin, bony skeleton, internal carotid artery, turbinate, optic chiasm, and a special sellar base with appropriate colors. After it was printed, six otolaryngologists and neurosurgeons assessed the model. Twenty graduate students and residents from otolaryngology or neurosurgery, without prior experience in endoscopic endonasal surgery were recruited and consented for the training. The training results were recorded. The subjective feeling of participants in terms of using 3D printed model in surgical training was investigated after training. RESULTS: All experts strongly agreed or agreed that the 3D printed model has realistic anatomical structure of nasal passage and appropriate colors for different parts, and is a good teaching tool. As the trainees practiced more, the rate and quality of endoscopic operation increased gradually. Compared to the first practice, all recorded training parameters were improved significantly (all P < 0.05). All participants strongly agreed or agreed that they benefited from the training and the 3D printed model can inspire interest and enthusiasm of endoscopic endonasal surgical training. CONCLUSION: This 3D printed model has realistic anatomical structure of nasal passage and appropriate colors for different parts, and could be a good teaching tool of endoscopic endonasal surgery.