Multi-omics analysis reveals the association between specific solute carrier proteins gene expression patterns and the immune suppressive microenvironment in glioma.

Glioma is the most prevalent malignant brain tumour. Currently, reshaping its tumour microenvironment has emerged as an appealing strategy to enhance therapeutic efficacy. As the largest group of transmembrane transport proteins, solute carrier proteins (SLCs) are responsible for the transmembrane transport of various metabolites and ions. They play a crucial role in regulating the metabolism and functions of malignant cells and immune cells within the tumour microenvironment, making them a promising target in cancer therapy. Through multidimensional data analysis and experimental validation, we investigated the genetic landscape of SLCs in glioma. We established a classification system comprising 7-SLCs to predict the prognosis of glioma patients and their potential responses to immunotherapy and chemotherapy. Our findings unveiled specific SLC expression patterns and their correlation with the immune-suppressive microenvironment and metabolic status. The 7-SLC classification system was validated in distinguishing subgroups within the microenvironment, specifically identifying subsets involving malignant cells and tumour-associated macrophages. Furthermore, the orphan protein SLC43A3, a core member of the 7-SLC classification system, was identified as a key facilitator of tumour cell proliferation and migration, suggesting its potential as a novel target for cancer therapy.

Surgical management of tuberculum sellae meningioma: Transcranial approach or endoscopic endonasal approach?

Background: Tuberculum sellae meningioma (TSM), a common benign tumor in the sellae region, usually causes neurological deficits, such as vision impairment, by squeezing the peripheral neurovascular structures. Surgical management is recommended as the optimal strategy for TSM treatment and vision restoration. However, it remains challenging to resect TSM in the traditional transcranial approach (TCA). Recently, the endoscopic endonasal approach (EEA) has emerged as an effective option in skull base surgeries. Besides the effectivity, the advantages and limitations of EEA in TSM surgery remain controversial. Object: We compared the surgical outcomes and complications between TCA and EEA surgeries to identify the principles in TSM surgical management. Methods: Retrospective analysis was performed on the patients, who underwent TSM surgery in Wuhan Union Hospital between January 2017 and December 2021. The patients were assigned to TCA or EEA group according to the surgery they experienced. All patients were analyzed with the extent of tumor resection, vision outcome, postoperative complications, and follow-up results. Results: A total of 112 patients were enrolled in this study, including 78 in TCA group and 34 in EEA group. The mean follow-up was 20.5 months (range 3-36 months). There were no statistically significant differences in patient demographic data, preoperative symptoms, and tumor characteristics between TCA and EEA groups. Both TCA and EEA surgeries are effective in TSM resection with relatively high gross total resection rates (85.9% in TCA vs. 91.2% in EEA, p > .05). Meanwhile, EEA surgery has a better outcome in vision restoration or stabilization than TCA surgery (74.6% in TCA vs. 93.1% in EEA, p < .05). Whereas EEA surgery causes more occurrences of cerebrospinal fluid (CSF) leakage than TCA surgery (0% in TCA vs. 11.8% in EEA, p < .05). Conclusion: Both TCA and EEA surgeries are effective in TSM resection. EEA surgery has a better outcome in vision restoration or stabilization than TCA surgery, but induces higher risk of CSF leakage. As each approach has unique advantages and limitations, we must take all aspects into consideration, including approach feathers, tumor characteristics, and clinical requirements, to make the optimal choice in TSM surgical management.

Sprouting Angiogenesis in Human Pituitary Adenomas.

Introduction: Angiogenesis in pituitary tumors is not fully understood, and a better understanding could help inform new pharmacologic therapies, particularly for aggressive pituitary tumors. Materials and Methods: 219 human pituitary tumors and 12 normal pituitary glands were studied. Angiogenic genes were quantified by an angiogenesis qPCR array and a TaqMan probe-based absolute qPCR. Angiogenesis inhibition in pituitary tumors was evaluated in vitro with the endothelial tube formation assay and in vivo in RbΔ19 mice. Results: 71 angiogenic genes, 40 of which are known to be involved in sprouting angiogenesis, were differentially expressed in pituitary tumors. Expression of endothelial markers CD31, CD34, and ENG was significantly higher in pituitary tumors, by 5.6, 22.3, and 8.2-fold, respectively, compared to in normal pituitary tissue. There was no significant difference in levels of the lymphatic endothelial marker LYVE1 in pituitary tumors compared with normal pituitary gland tissue. Pituitary tumors also expressed significantly higher levels of angiogenesis growth factors, including VEGFA (4.2-fold), VEGFB (2.2), VEGFC (19.3), PGF (13.4), ANGPT2 (9.2), PDGFA (2.7), PDGFB (10.5) and TGFB1 (3.8) compared to normal pituitary tissue. Expression of VEGFC and PGF was highly correlated with the expression of endothelial markers in tumor samples, including CD31, CD34, and ENG (endoglin, a co-receptor for TGFß). Furthermore, VEGFR inhibitors inhibited angiogenesis induced by human pituitary tumors and prolonged survival of RbΔ19 mice. Conclusion: Human pituitary tumors are characterized by more active angiogenesis than normal pituitary gland tissue in a manner consistent with sprouting angiogenesis. Angiogenesis in pituitary tumors is regulated mainly by PGF and VEGFC, not VEGFA and VEGFB. Angiogenesis inhibitors, such as the VEGFR2 inhibitor cabozantinib, may merit further investigation as therapies for aggressive human pituitary tumors.

A COVID-19 Patient Who Underwent Endonasal Endoscopic Pituitary Adenoma Resection: A Case Report.

BACKGROUND AND IMPORTANCE: A pituitary adenoma patient who underwent surgery in our department was diagnosed with COVID-19 and 14 medical staff were confirmed infected later. This case has been cited several times but without accuracy or entirety, we feel obligated to report it and share our thoughts on the epidemic among medical staff and performing endonasal endoscopic surgery during COVID-19 pandemic. CLINICAL PRESENTATION: The patient developed a fever 3 d post endonasal endoscopic surgery during which cerebrospinal leak occurred, and was confirmed with SARS-CoV-2 infection later. Several medical staff outside the operating room were diagnosed with COVID-19, while the ones who participated in the surgery were not. CONCLUSION: The deceptive nature of COVID-19 results from its most frequent onset symptom, fever, a cliché in neurosurgery, which makes it hard for surgeons to differentiate. The COVID-19 epidemic among medical staff in our department was deemed as postoperative rather than intraoperative transmission, and attributed to not applying sufficient personal airway protection. Proper personal protective equipment and social distancing between medical staff contributed to limiting epidemic since the initial outbreak. Emergency endonasal endoscopic surgeries are feasible since COVID-19 is still supposed to be containable when the surgeries are performed in negative pressure operating rooms with personal protective equipment and the patients are kept under quarantine postoperatively. However, we do not encourage elective surgeries during this pandemic, which might put patients in conditions vulnerable to COVID-19.

A Combinatorial Approach with Cerebellar Tonsil Suspension to Treating Symptomatic Chiari Malformation Type I in Adults: A Retrospective Study.

BACKGROUND: Primary Chiari malformations (CMs) are congenital defects of the skull base and brain. Among the 4 CM types, type I (CM-I) occurs most frequently and may cause somatosensorimotor, autonomic and vision symptoms. Presently, posterior fossa decompression alone (PFD) or with duraplasty (PFDD) and cerebellar tonsil (CbT) shrinkage tactics are standard treatments, albeit inherent issues. There has been no report on devising CbT suspension (CTS) to manage CM-I. OBJECTIVES: 1) To design a CTS protocol that can be used with CbT coagulation (CTC) and PFDD; 2) to evaluate the regimen for feasibility, safety, and efficacy in a retrospective study; and 3) to obtain data for planning prospective studies to validate PFDD + CTC + CTS as a novel approach to treating adult CM-I. METHODS: PFDD + CTC + CTS (n = 17), PFDD + CTC (n = 13), and PFDD (n = 12) were performed for 42 adult patients (age range, 18-55 years; female:male = 27:15) following a balanced study design. Neck Disability Index (NDI), Chicago Chiari Outcome Scale (CCOS), and /magnetic resonance imaging/computed tomography were used to determine postsurgery outcomes for approximately 20 months. RESULTS: Comparing to PFDD + CTC or PFDD, patients receiving PFDD + CTC +CTS operation exhibited significantly improved group average NDI (10.72 ± 3.95%; P = 0.007), CbT elevation distance (7.06 ± 2.42 mm; P < 0.001, Kruskal-Wallis test; 55.7 ± 25.4% higher than the presurgery level; P < 0.001, analysis of variance), and syringomyelia syrinx retraction (P = 0.009, analysis of variance). CONCLUSIONS: The PFDD + CTC + CTS regimen appeared to be safe and potentially more efficacious in patients with CM-I evaluated for the period, relative to PFDD + CTC or PFDD treatment. Future prospective studies were warranted.

An Analysis of Clinical Efficacy of Microsurgical Resection of Intradural Neoplasm by Unilateral Approach with Caspar Retractors.

OBJECTIVE: This study aims to investigate the clinical efficacy of minimally invasive microsurgical resection of intraspinal tumors with the aid of Caspar retractors. MATERIALS AND METHODS: A total of 125 intraspinal tumor patients with lesions smaller than 6 cm, who were treated at the Neurosurgery Department of our hospital from March 2010 to March 2016, were retrospectively analyzed. Among these, 73 patients underwent microsurgical resection of intraspinal tumors with the aid of Caspar retractors, while 52 patients underwent conventional laminectomy for resection of intraspinal tumors. Relevant indicators between both groups of patients were compared, including length of surgical incision, duration of surgery, postoperative drainage volume, time to first out-of-bed activity after surgery, postoperative hospitalization period, visual analog score (VAS) score, and Japanese Orthopedic Association (JOA) score, at 1 month after surgery. RESULTS: Compared with the conventional laminectomy group, patients who underwent microsurgical resection with the aid of Caspar retractors had better outcomes in terms of length of surgical incision, postoperative drainage volume, time to first out-of-bed activity after surgery, postoperative hospitalization period, and VAS scores (p < 0.05). However, JOA scores at 1 month after surgery did not have any significant differences (p > 0.05). CONCLUSIONS: The microsurgical resection of intraspinal tumors with the aid of Caspar retractors has advantages of small trauma, less bleeding, and faster recovery. It is a safe and efficacious method for treating small intraspinal tumors.

Meg3-DMR, not the Meg3 gene, regulates imprinting of the Dlk1-Dio3 locus.

The imprinted delta like 1 homolog (DLK1) - thyroxine deiodinase type III (DIO3) locus regulates development and growth. Its imprinting regulation involves two differentially methylated regions (DMRs), intergenic-DMR (IG-DMR) and maternally expressed gene 3-DMR (Meg3-DMR). In mice, a maternal deletion of the IG-DMR leads to LOI in the locus, proving that the IG-DMR is a cis-acting imprinting control region of the locus. However, the Meg3-DMR overlaps with the promoter, exon 1 and intron 1 of the Meg3 gene. Because deletion of the Meg3-DMR inactivates the Meg3 gene, their roles in imprinting regulation of Meg3-DMR mice is unknown. Therefore, we generated two mouse models: Meg3Δ(1-4) and Meg3Δ(2-4), respectively targeting exons 1-4 and exons 2-4 of the Meg3 gene. A maternal deletion of Meg3Δ(1-4) caused embryonic death and LOI in both embryos and placentas, but did not affect methylation status of the IG-DMR. In contrast, mice carrying a maternal deletion of Meg3Δ(2-4) were born normally and did not have LOI. These data indicate that it is the Meg3-DMR, not the Meg3 gene, which regulates imprinting of the Dlk1-Dio3 locus.

Assessment of satellite-estimated near-surface sulfate and nitrate concentrations and their precursor emissions over China from 2006 to 2014.

China is the largest anthropogenic aerosol-generating country worldwide; however, few studies have analyzed the PM2.5 chemical components and their underlying precursor emissions over long periods and across the national domain. First, global 3-D tropospheric chemistry and transport model (GEOS-Chem)-integrated satellite-retrieved aerosol optical depth (AOD) and vertical profiles were used to estimate near-surface sulfate and nitrate levels at 10-km resolution over China from 2006 to 2014. Ground measurement validation of our satellite model yielded correlation coefficients (r) of 0.7 and 0.73 and normalized mean bias (NMB) values of -37.96% and - 32.73% for sulfate and nitrate, respectively. Second, analyses of the spatiotemporal distributions of sulfate and nitrate as well as the vertical density Ozone Monitoring Instrument (OMI)-measured SO2 (PBL_SO2) and NO2 (TVCD_NO2) indicated that the highest nitrate and sulfate levels occurred in the North China Plain (~25 µg/m3) and Sichuan Basin (SCB) (~30 µg/m3), respectively. The long-term variations in the estimated components and precursor gases indicated that the large sulfate decline was positively correlated with the SO2 emission reduction due to the mandatory desulfurization implemented in 2007. The annual growth rate of sulfate relative to the national mean was -6.19%/yr, and the concentration decreased by 17.10% from 2011 to 2014. Energy consumption increases and a lack of control measures for NO2 resulted in persistent increases in NO2 emissions and nitrate concentrations from 2006 to 2010, particularly in the SCB. With energy consumption structure advancements, reductions in NO2 emissions and corresponding nitrate levels over three typical regions were prominent after 2012. Third, the estimated national-scale uncertainties of satellite datasets at 0.1°â€¯× 0.1° were 26.88% for sulfate and 25.55% for nitrate. Differences in the spatial distributions and temporal trends between our estimated components and precursor gases were mainly attributed to the dataset accuracy, the data pre-processing strategy, inconsistent column density and near-surface mass concentration, meteorological variables and complex chemical reactions.

The risk of postoperative hemorrhage and efficacy of heparin for preventing deep vein thrombosis and pulmonary embolism in adult patients undergoing neurosurgery: a systematic review and meta-analysis.

The aim of this meta-analysis was to examine the risk of postoperative bleeding and efficacy of heparin for preventing deep vein thrombosis (DVT) and pulmonary embolism (PE) in adult patients undergoing neurosurgery. MEDLINE, Cochrane, and EMBASE databases were searched until October 31, 2016, for randomized controlled trials (RCTs) and non-randomized comparative studies that assessed the rates of postoperative hemorrhage, DVT, PE, and mortality in adult patients undergoing neurosurgery. Nine eligible studies (five RCTs, four retrospective studies) including 874 patients treated with either unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) and 1033 patients in control group (placebo with or without compression device) were analyzed. The overall analysis revealed that there was an increase in the risk of postoperative hemorrhage in patients who received heparin (pooled OR 1.66, 95% CI 1.01 to 2.72, p=0.046) compared with no treatment group. The risk of postoperative hemorrhage was more significant if only RCTs were included in analysis. Heparin prophylaxis was associated with a decrease in the risk of DVT (pooled OR 0.48, 95% CI 0.36 to 0.65, p<0.001) and PE (pooled OR 0.25, 95% CI 0.09 to 0.73, p=0.011) but it did not affect the rate of mortality. In conclusion, heparin increased the rate of postoperative bleeding, decreased the risk of DVT, PE and venous thromboembolic event (VTE) but it did not affect the mortality of patients undergoing neurosurgery. For the heparin prophylaxis, the trade-off between the risk of postoperative bleeding and benefit of prophylaxis against VTEs requires further investigation.

7,8-Dihydroxyflavone Ameliorates Cognitive Impairment by Inhibiting Expression of Tau Pathology in ApoE-Knockout Mice.

7,8-Dihydroxyflavone (7,8-DHF), a tyrosine kinase B agonist that mimics the neuroprotective properties of brain-derived neurotrophic factor, which can not efficiently deliver into the brain, has been reported to be useful in ameliorating cognitive impairment in many diseases. Researches have indicated that apolipoprotein E-knockout (ApoE-KO) mouse was associated with cognitive alteration via various mechanisms. Our present study investigated the possible mechanisms of cognitive impairment of ApoE-KO mouse fed with western type diet and the protective effects of 7,8-DHF in improving spatial learning and memory in ApoE-KO mouse. Five-weeks-old ApoE-KO mice and C57BL/6 mice were chronically treated with 7,8-DHF (with a dosage of 5 mg/kg) or vehicles orally for 25 weeks, and then subjected to Morris water maze at the age of 30 weeks to evaluate the cognitive performances. Afterward, histology analysis and western blotting were performed. Spatial learning and memory deficits were observed in ApoE-KO mice, which were consistent with higher expression of active-asparaginyl endopeptidase (active-AEP) as well as AEP-derived truncated tau N368 compared with normal group. In addition to that, long-term treatment of 7,8-DHF dramatically ameliorated cognitive decline in ApoE-KO mice, accompanied by the activation in phosphorylated protein kinase B (Akt)/glycogen synthase kinase-3ß (GSK-3ß) pathway and down-regulated expression of tau S396 and PHF-tau (phosphorylated tau at ser396 and ser404 epitope). These findings suggested that cognitive impairment of ApoE-KO mouse might associate with tau pathology and 7,8-DHF could activate AKT and then phosphorylate its downstream molecule to inhibit expression of abnormal tau, meanwhile, 7,8-DHF could reduce the expression of active-AEP and then inhibit production of truncated tau N368.