Causal associations of COVID-19 on neurosurgical diseases risk: a Mendelian randomization study.

Many researchers have explored the potential association between one neurosurgical disease and coronavirus disease 2019 (COVID-19), but few systematically analyzed the association and causality between COVID-19 and various neurosurgical diseases. A Mendelian randomization analysis was conducted to evaluate the causal association between COVID-19 (including critically ill COVID-19, hospitalized COVID-19, and respiratory syndrome coronavirus 2 (SARS-CoV-2) infection) and 30 neurosurgical diseases within European populations. The consequences of inverse variance weighted models suggest that genetic susceptibility of critically ill COVID-19 may increase the risk of cerebral infarction (odds ratio [OR] = 1.02; p-value = 0.006), genetic susceptibility of SARS-CoV-2 infection may increase the risk of stroke (OR = 1.02; p-value = 0.047), and conversely, genetic susceptibility of hospitalized COVID-19 may reduce the risk of pituitary adenoma and craniopharyngioma (OR = 0.90; p-value = 0.032). In addition, evidences revealed potential associations between genetic susceptibility of COVID-19 and spinal stenosis (OR = 1.03; p-value = 0.028), diffuse brain injury (OR = 1.21; p-value = 0.040) and focal brain injury (OR = 1.12; p-value = 0.040). By testing for heterogeneity and pleiotropy, the above causal conclusions are robust. In summary, our analysis shows that COVID-19 has an independent and powerful causal influence on multiple neurosurgical disorders.

Autophagy-related CMTM6 promotes glioblastoma progression by activating Wnt/ß-catenin pathway and acts as an onco-immunological biomarker.

BACKGROUND: Glioblastoma multiforme (GBM) is identified as one of the most prevalent and malignant brain tumors, characterized by poor treatment outcomes and a limited prognosis. CMTM6, a membrane protein, has been found to upregulate the expression of programmed cell death 1 ligand 1 protein (PD-L1) and acts as an immune checkpoint inhibitor by inhibiting the programmed death 1 protein/PD-L1 signaling pathway. Recent research has demonstrated a high expression of CMTM6 in GBM, suggesting its potential role in influencing the pathogenesis and progression of GBM, as well as its association with immune cell infiltration in the tumor microenvironment. However, the underlying mechanism of CMTM6 in GBM requires further investigation. METHODS: Data from cancer patients in The Cancer Genome Atlas, Gene Expression Omnibus and Chinese Glioma Genome Atlas cohorts were consolidated for the current study. Through multi-omics analysis, the study systematically examined the expression profile of CMTM6, epigenetic modifications, prognostic significance, biological functions, potential mechanisms of action and alterations in the immune microenvironment. Additionally, the study investigated CMTM6 expression in GBM cell lines and normal cells using reverse transcription PCR and western blot analysis. The impact of CMTM6 on GBM cell proliferation, migration and invasion was evaluated using a combination of cell counting kit-8 assay, clone formation assay, 5-ethynyl-2'-deoxyuridine incorporation assay, wound healing assay and Transwell assay. In order to explore the mechanism of CMTM6, the Wnt/ß-catenin signaling pathway and autophagy-related genes were further verified through western blot analysis. RESULTS: CMTM6 is highly expressed in multiple tumors, particularly GBM. CMTM6 has been shown to be a valuable diagnostic and prognostic biomarker by various bioinformatics approaches. Additionally, CMTM6 plays a pivotal role in the pathogenesis of cancer, specifically GBM, by modulating various biological processes such as DNA methyltransferase expression, RNA modification, copy number variation, genomic heterogeneity, tumor stemness and DNA methylation. The findings of the experiment indicate a significant correlation between elevated CMTM6 expression and the proliferation, invasion, migration and autophagy of GBM cells, with potential key roles mediated through the Wnt/ß-catenin signaling pathway. Furthermore, CMTM6 is implicated in modulating tumor immune cell infiltration and is closely linked to the expression of various immune checkpoint inhibitors and immune modulators, particularly within the context of GBM. High levels of CMTM6 expression also enhance the responsiveness of GBM patients to radiotherapy and chemotherapy, thereby offering valuable insights for guiding treatment strategies for GBM. CONCLUSIONS: Autophagy-related CMTM6 is highly expressed in various types of cancer, especially GBM, and it can regulate GBM progression through the Wnt/ß-catenin signaling pathway and is capable of being used as an underlying target for the diagnosis, treatment selection and prognosis of patients with GBM.

Single-cell sequencing of PIT1-positive pituitary adenoma highlights the pro-tumour microenvironment mediated by IFN-γ-induced tumour-associated fibroblasts remodelling.

BACKGROUND: PIT1-positive pituitary adenoma (PIT1-PA) is one of the most important lineages of pituitary adenoma (PA), which causes systematic endocrine disorders and a worse prognosis. Tumour-associated fibroblast (TAF) is a crucial stroma cell type in the tumour microenvironment (TME). However, cellular and functional heterogeneity of TAF and immune cells in PIT1-PA have not been fully investigated. METHODS: By single-cell RNA sequencing of four PIT1-PAs and further analyses, we characterised the molecular and functional profiles of 28 different cell subtypes. RESULTS: PA stem cells in PIT1/SF1-positve PA were in a hybrid epithelial/mesenchymal state, and differentiated along the PIT1- and SF- dependent branches. C1Q was overwhelmingly expressed in tumour-associated macrophages, indicating its pro-tumoral functionality. PIT1-PA progression was characterised by lower cell-cell communication strength and higher cell adhesion-associated signals, indicating the immunosuppressive but pro-invasive microenvironment. IFN-γ signal repressed functional remodelling of myofibroblastic TAF (mTAF) towards inflammatory TAF/antigen-presenting TAF. IFN-γ inhibited mTAF phenotypes and N-cadherin expression through STAT3 signal axis. CDH2 knockdown in TAFs abrogated their pro-tumour function in PAs. CONCLUSIONS: Our study builds up a cellular landscape of PIT1-PA TME and highlights anti-tumour function of IFN-γ mediated TAF remodelling, which benefits clinical treatments and drug development.

Systematic analysis based on the cuproptosis-related genes identifies ferredoxin 1 as an immune regulator and therapeutic target for glioblastoma.

Glioblastoma multiforme (GBM) is recognized as the prevailing malignant and aggressive primary brain tumor, characterized by an exceedingly unfavorable prognosis. Cuproptosis, a recently identified form of programmed cell death, exhibits a strong association with cancer progression, therapeutic response, and prognostic outcomes. However, the specific impact of cuproptosis on GBM remains uncertain. To address this knowledge gap, we obtained transcriptional and clinical data pertaining to GBM tissues and their corresponding normal samples from various datasets, including TCGA, CGGA, GEO, and GTEx. R software was utilized for the analysis of various statistical techniques, including survival analysis, cluster analysis, Cox regression, Lasso regression, gene enrichment analysis, drug sensitivity analysis, and immune microenvironment analysis. Multiple assays were conducted to investigate the expression of genes related to cuproptosis and their impact on the proliferation, invasion, and migration of glioblastoma multiforme (GBM) cells. The datasets were obtained and prognostic risk score models were constructed and validated using differentially expressed genes (DEGs) associated with cuproptosis. To enhance the practicality of these models, a nomogram was developed.Patients with glioblastoma multiforme (GBM) who were classified as high risk exhibited a more unfavorable prognosis and shorter overall survival compared to those in the low risk group. Additionally, we specifically chose FDX1 from the differentially expressed genes (DEGs) within the high risk group to assess its expression, prognostic value, biological functionality, drug responsiveness, and immune cell infiltration. The findings demonstrated that FDX1 was significantly upregulated and associated with a poorer prognosis in GBM. Furthermore, its elevated expression appeared to be linked to various metabolic processes and the susceptibility to chemotherapy drugs. Moreover, FDX1 was found to be involved in immune cell infiltration and exhibited correlations with multiple immunosuppressive genes, including TGFBR1 and PDCD1LG2. The aforementioned studies offer substantial assistance in informing the chemotherapy and immunotherapy approaches for GBM. In summary, these findings contribute to a deeper comprehension of cuproptosis and offer novel perspectives on the involvement of cuproptosis-related genes in GBM, thereby presenting a promising therapeutic strategy for GBM patients.

Targeting CXCR4 to suppress glioma-initiating cells and chemoresistance in glioma.

Glioma initiating cells (GICs), also known as glioma stem cells, display the capacity to recapitulate the functional diversity within the tumor. Despite the great progress achieved over the last decades, defining the key molecular regulators of GICs has represented a major obstacle in this field. In our study, data from The Cancer Genome Atlas database illustrated a relationship between C-X-C motif chemokine receptor 4 (CXCR4) expression and the survival of glioma patients. Mechanistically, we further indicated that CXCR4 mediated the upregulation of Kruppel like factor 5 (KLF5), a zinc-finger-containing transcription factor, to facilitate the proliferation of GICs. What's more, CXCR4 also enhanced the chemoresistance through KLF5/Bcl2-like 12 (BCl2L12) in glioma. The elevated expression of KLF5 and BCL2L12 induced by CXCR4 was dependent on phosphoinositide 3-kinases (PI3K)/serine/threonine kinase (AKT) signaling. Importantly, combined application of temozolomide and a CXCR4 inhibitor efficiently reversed CXCR4 mediated drugs resistance and improved anticancer effects in vivo. Collectively, our findings confirmed that CXCR4 promoted GICs proliferation via the KLF5/BCL2L12 dependent pathway, which may enrich the understanding of GICs and help drive the design of efficacious therapeutic strategies.

Kynurenine produced by tryptophan 2,3-dioxygenase metabolism promotes glioma progression through an aryl hydrocarbon receptor-dependent signaling pathway.

The current studies associated with tumor biology continue to describe a high correlation between tryptophan (Trp) metabolism and tumor progression. These findings reflect the complex underlying mechanism of tumor development and highlight the need to explore additional drug targets for carcinoma-associated diseases. In our study, we reported that elevated Trp metabolism was observed in highly malignant glioma tumor tissues from patients. The elevated Trp metabolism in glioma cells were induced by the overexpression of Trp 2,3-dioxygenase 2 (TDO2), which further contributed to the production of the metabolite kynurenine (Kyn). Subsequently, the Kyn derived from Trp metabolism was able to mediate the activation of the aryl hydrocarbon receptor (AhR) and downstream PI3K/AKT signals, resulting in the strengthening of tumor stemness and growth. Meanwhile, the activation of the AhR could promote the process of epithelial-mesenchymal transition in gliomas through a TGF-ß-dependent mechanism, leading to enhanced tumor invasion in vitro and in vivo. Inhibition of the AhR using StemRegenin 1 was demonstrated to suppress glioma growth and improve the outcome of traditional chemotherapy in subcutaneous tumor-bearing mice, representing a promising therapeutic target for clinical glioma treatment.

The outcome of microvascular decompression for hemifacial spasm: a systematic review and meta-analysis.

Microvascular decompression (MVD) is the first choice of surgery for hemifacial spasm (HFS). MVD surgery for vertebral artery (VA)-associated HFS is more difficult than for non-VA-associated HFS. There is controversy about the cure rate and complication of MVD for HFS in previous studies. We searched PubMed, Web of Science, and Embase for relevant publications. Based on the search results, we compared the outcomes of MVD for VA-associated HFS and non-VA-associated HFS. At the same time, we analyzed spasm-free rates and the complications and assessed the relationship between VA-associated HFS and gender, left side, and age. For analysis, six studies that included 2952 patients in the VA-associated group and 604 in the non-VA-associated group were selected. The effective rate of MVD was not significantly different between both groups (OR = 1.16, 95% CI 0.81-1.67, P = 0.42). Compared to non-VA-associated group, the transient complications (OR = 0.64, 95% CI 0.46-0.89, P = 0.008) and permanent complications (OR = 0.28, 95% CI 0.15-0.54, P = 0.0001) occurred more frequently in VA-associated group. The rate of hearing loss was significantly higher in VA-associated HFS than non-VA-associated HFS (OR = 0.35, 95% CI 0.19-0.64, P = 0.0007); the facial paralysis after operation was not significantly different between both groups (OR = 1.25, 95% CI 0.91-1.72, P = 0.17). There were older patients (WMD = 3.67, 95% CI 3.29-4.05, P < 0.00001) and more left-sided HFS (OR = 0.23, 95% CI 0.19 - 0.29, P < 0.0002) in the VA-associated HFS group than non-VA-associated HFS group, while the non-VA-associated HFS group was female-dominated (OR = 1.58, 95% CI 1.32 - 1.89, P < 0.00001). Both groups achieved good results in MVD cure rates. In VA-associated HFS, the complication rate of decompression and the rate of hearing loss after operation were higher than in non-VA-associated HFS, but the facial paralysis after operation was similar in both groups, and most complications were transient and disappeared during follow-up. VA-associated HFS is more prevalent in older adults, less prevalent in women, and more predominantly left-sided. More clinical studies are needed to better compare the efficacy and complication of MVD between both groups.

Clinical outcomes in central nervous system solitary-fibrous tumor/hemangiopericytoma: a STROBE-compliant single-center analysis.

BACKGROUND: Solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) are rare mesenchymal tumors in the central nervous system with a high tendency to relapse, having a significant impact on quality of life (QoL). Due to the rarity of intracranial SFT/HPC, the prognostic factors and optimal treatment remain to be elucidated. Meanwhile, quality of life in patients with intracranial SFT/HPC is seldomly concerned. Thus, we aim to survey about the quality of life and underline some aspects demanding concern in intracranial SFT/HPC treatment through summarizing our case series in recent ten years. METHODS: Patients with intracranial SFT/HPC who underwent surgical resection from January 2009 to June 2019 were included in the study. Clinical features, such as age, gender, and resection extent, were collected. The EuroQol Five Dimensions Questionnaire (EQ-5D) was used to assess the patients' quality of life (QoL). Prognosis factors related to progression-free survival (PFS) and overall survival (OS) were also evaluated. RESULTS: Thirty-six patients with a mean follow-up period of 61.6 months (range 13-123 months) were included in this study. Sixteen (44.4%) patients achieved gross total resection (GTR). Fourteen patients (38.9%) with tumor progression experienced adjuvant radiotherapy (11.1%) or Gamma Knife surgery (GKS, 27.8%). According to the 2016 WHO classification, there were 6 (16.7%) grade I SFT/HPC, 11 (30.5%) grade II SFT/HPC, and 19 (52.8%) grade III SFT/HPC. The PFS and OS were 29 months (range 4-96 months) and 38 months (range 4-125 months). The median EQ5D-3 L tariff with or without progression was 0.617 (95% CI 0.470-0.756) and 0.939 (95% CI 0.772-0.977) respectively. Gross total resection (GTR, p = 0.024) and grade I SFT/HPC (p = 0.017) were significantly associated with longer PFS. In multivariate analysis, GTR (HR 0.378, 95% CI 0.154-0.927) and adjuvant therapy (HR 0.336, 95% CI 0.118-0.956) result in significantly longer PFS in patients with SFT/HPC. CONCLUSIONS: Patients underwent GTR and adjuvant therapy had longer PFS. Similarly, patients with lower WHO grade had relatively longer PFS. Therefore, GTR is advocated for the treatment of SFT/HPC. And adjuvant therapy such as GKS could be an alternative treatment for patients who underwent STR or with tumor progression. Further, the QoL decreased in patients with tumor progression and metastasis, and more attention is demanded to the QoL of intracranial SFT/HPC patients.

[Advances in Intraoperative Neurophysiological Monitoring Techniques in Transnasal Endoscopic Skull Base Surgery].

Transnasal endoscopic skull base surgery has been increasing in volume in recent years and its indications are constantly expanding. The potential occurrence of intraoperative and postoperative neurovascular complications deserves special attention from neurosurgeons. Multimodal intraoperative neurophysiological monitoring technology allows neurosurgeons to monitor cerebral perfusion and the functional status of the associated cranial nerves in real time, thereby enabling surgeons to make prompt adjustments in surgical procedures and strategies and reduce the risks of postoperative neurological complications in patients. Based on available literature, we reviewed how appropriate monitoring strategies were optimized for different key components of transnasal endoscopic skull base procedures, intending to provide reference for clinicians.

Autophagy inhibition enhances anti-pituitary adenoma effect of tetrandrine.

Pituitary adenoma (PA) is a benign intracranial neoplasm originated from pituitary gland. Surgery is the first-line therapy for most of PAs, but lead to unsatisfactory prognosis in some cases. Tetrandrine (Tet) has anticancer effect on some cancers. However, growth inhibition effect on PA is unknown. To elucidate the inhibitory effect of Tet on the growth of PA and its potential mechanisms, we validated the in vitro and in vivo anti-PA effect of Tet and illustrated the cellular and molecular alterations by confocal microscopy observation, flow cytometry, and RNA interference. Tet inhibited PA cell growth in vitro and tumor progression in vivo. Tet induced autophagy and apoptosis in a dose-dependent manner. Low dosage (1.25 µM) of Tet induced PA cell autophagy by down-regulation of MAPK/STAT3 signal. While, higher dosage (5.0 µM) of Tet partially induced PA cell death through caspase-dependent apoptosis. Autophagy inhibitors enhanced Tet-induced caspase activity and apoptotic cell death. These findings demonstrated that Tet has anti-PA effect by inducing autophagy and apoptosis through MAPK/STAT3 signaling pathway attenuation and autophagy inhibition might enhance its anti-PA effect, indicating that Tet (or combined with autophagy inhibitor) is a potential therapeutic regimen for PAs.

Primary spinal pilocytic astrocytoma: clinical study with long-term follow-up in 16 patients and a literature review.

Primary pilocytic astrocytoma (PA) of the spine is extremely rare and most published case series only include only a few patients. We attempted to explore the clinical features, radiological findings, and treatment outcomes of patients with spinal PA. Sixteen spinal PA patients who were surgically treated in our hospital between April 2008 and June 2018 were included in this retrospective study. An integrative analysis was performed regarding spinal PA patients by extracting from published studies on PubMed. The 16 patients with spinal PA included eight male and eight female patients with a mean age of 29.1 years. Ten cases (62.5%) had masses located in the cervical segments, five (31.3%) had masses in the thoracic segments, and one (6.2%) had masses in the sacral canal. All the patients were treated surgically with 13 gross total resections (GTRs, 81.3%) and three subtotal resections (STRs). The mean follow-up period was 40.4 months. These tumors accounted for a recurrence rate of 37.5% (6 of 16 patients) and no death during the follow-up periods. The influencing factors of recurrence were mainly STR, gene mutation (NF-1 and H2-K27M), and the number of segments involved. The mean recurrence-free survival duration was 19 months. The imaging features of spinal PA are heterogeneous, and the definitive diagnosis requires pathological support. GTR is the standard therapy for spinal PAs, although patients with GTR are still likely to relapse. The regular spinal magnetic resonance imaging follow-ups are required regardless of the resection status. Reoperation is feasible for patients with recurrence.

Clinical features, radiological findings, and treatment outcomes of high-grade lateral ventricular meningiomas: a report of 26 cases.

High-grade meningiomas in ventricles are rare, where most published series only include a few patients. A retrospective analysis was performed on the clinical features, radiological findings, and treatment outcomes of 26 patients with high-grade meningiomas in lateral ventricles who were surgically treated in our hospital between July 2008 and July 2016. A female predilection (female/male = 1.4:1) was observed with a mean age of 42.4 years. Headache and/or vomiting (65.3%) were the most common initial symptom, and with symptom duration time ranging between 7 days and 5 years (mean 8.5 months). The lateral ventricle trigone area was the most common site (80.7%). Twenty-two patients (84.6%) obtained gross total resection. The 2007 WHO classification was used to classify 22 (84.6%) meningiomas as grade II and the remaining four tumors were graded III. These tumors accounted for a recurrence rate of 38.5% (10 of 26 patients) and a mortality rate of 11.5% (3 deaths) during the follow-up periods. The recurrence rate after the gross total resection was 27.3% (6 of 22 patients). Radiotherapy was administered as an adjuvant treatment in 12 patients (46.2%) after surgery. There were 4 recurrences out of the 12 patients who received radiotherapy and 6 of the 14 patients relapsed without radiotherapy (p = 0.58). The subtotal resection was considered a risk factor for recurrence. The postoperative radiotherapy seemed to have little significance for the high-grade meningiomas in the lateral ventricles. Long-term follow-up is required, regardless of the resection grade, and reoperation is feasible for patients with recurrence.

Clinical features, radiologic findings, and treatment of pediatric germ cell tumors involving the basal ganglia and thalamus: a retrospective series of 15 cases at a single center.

PURPOSE: Pediatric germ cell tumors (GCTs) involving the basal ganglia and thalamus are relatively rare neoplasms which have not been extensively described. We here summarize the clinical and radiological features of a series of such tumors and discuss optimal treatment strategies based upon our experience. METHODS: A total of 15 pediatric patients with basal ganglionic and thalamic GCTs were treated between 2011 and 2016 at West China Hospital. Epidemiological characteristics, clinical features, imaging findings, and treatment strategies were reviewed retrospectively. RESULTS: GCTs constituted 28% (15/53) of pediatric basal ganglionic and thalamic tumors in our institution between 2011 and 2016. There were 12 males and 3 females with mean age of 11.7 ± 2.8 years (range, 7-16 years). The most common initial manifestation was hemiparesis (n = 13, 86.7%), followed by headache (n = 5, 33.3%), vomiting (n = 3, 20.0%), cognitive disturbance (n = 2, 13.3%), and seizure (n = 1, 6.7%). No tumors were incidentally detected. The mean duration of the symptoms before diagnosis was 4.4 ± 3.9 months (range from 9 days to 13 months). The maximum diameters of the lesions ranged from 3.2 to 6.5 cm (mean 4.7 ± 1.1 cm). Cysts were seen in tumors in MRIs in 11 patients (73%), intratumoral hemorrhages in 3 (20%), calcification in 2 (13%), and there was obstructive hydrocephalus in 1 (7%). Of note, hemiatrophy was observed in 9 cases (60.0%). The mean follow-up for the 15 patients was 28 months (range, 9-54 months), and no patients were lost. During the follow-up period, all patients (9 cases) with germinomas responded well to radiotherapy, and no recurrence was observed. Among 4 patients with mixed nongerminomatous germ cell tumor, 2 suffered tumor recurrence after treatment. Neurological deficits improved or remained unchanged in 12 patients but 3 developed new dysfunction including significant cognitive disturbance and hemiparesis. CONCLUSIONS: Pediatric GCTs in the basal ganglia and thalamus are not as rare as previously considered. Tumor markers should be tested routinely for tumors in these sites in young patients. Optimal treatment strategy based on accurate diagnosis and comprehensive clinical assessment should be recommended.

A retrospective review of 34 cases of pediatric pituitary adenoma.

PURPOSE: The purpose of this paper is to study invasiveness, tumor features and clinical symptoms of pediatric pituitary adenoma, and to discuss some inconclusive results in prior studies. METHODS: We retrospectively reviewed 34 cases of children (<20 year-old) who were pathologically diagnosed with pituitary adenoma and surgically treated from 2010 to 2017. Data of general information, clinical symptoms, invasive behaviors, surgery approaches, and tumor features were collected and analyzed. RESULTS: Sixteen boys and 18 girls aged from 12 to 19 years old were included. Prolactinoma was most suffered, followed by GH-, none- and ACTH-secreting pituitary adenoma. Invasive behaviors were observed frequently and suprasellar extensions were most found. Macroadenoma account 70% of all cases. Meanwhile, unlike prior studies, a significant raise of incidence on invasive tumor and pituitary adenoma apoplexy were observed. Craniotomy and transsphenoidal surgery were both applied with zero mortality. Nine cases occurred with transient hypopituitarism and diabetes insipidus. Three cases of tumor recurrence received secondary surgery or radiotherapy. CONCLUSIONS: Invasive behaviors were more frequent than previous prediction. Craniotomy is worth considering for total tumor removal. Pituitary adenoma apoplexy needs further studies since its different features between children and adults in present study. Specialized care and teamwork of neurosurgeons, pediatricians, and endocrinologists are important.

[The Role of Cancer-associated Fibroblasts in Invasive Behavior of Pituitary Adenoma].

OBJECTIVE: To determine the role of cancer associated fibroblasts (CAFs) in the invasive behavior of pituitary adenoma. METHODS: Pituitary adenoma tissues were divided into invasive group (IPA) and non-invasive group (nIPA) according to pre-operative MRI and observations during surgery. Those tissues were cultured and CAFs were identified through a smooth muscle actin (α-SMA). The migratory and invasive ability of CAFs was tested with transwell migration and invasion assay. The expressions of α-SMA and matrix metalloproteinase (MMP)-9 from CAFs were determined by immunocytochemistry and Western blot. RESULTS: All cultured CAFs expressed α-SMA. No significant difference in migratory ability of CAFs was found between the IPA and nIPA tissues; however, CAFs from the IPA tissues had stronger invasive ability than those from the nIPA tissues (P= 0. 010). Higher levels of MMP-9 expression were found in group IPA as compared with nIPA (P=0. 025). No significant difference in the expression of α-SMA was found between the two groups. CONCLUSION: CAFs may promote invasive behavior by secreting more MMP-9, which may play a part in the invasive behavior of pituitary adenomas.

"One-and-a-Half" Interdural Transcavernous Pituitary Transposition/Rotation for Protection of Hypophyseal Portal System in Adult Peripheral Retroinfundibular Craniopharyngioma.

BACKGROUND AND OBJECTIVES: Craniopharyngiomas originate from the pituitary stalk (PS) and extend along the pituitary-hypothalamic axis. Peripheral retroinfundibular craniopharyngiomas, particularly, may have worse surgery outcomes than other types. This study aims to investigate the advantage of using "one-and-a-half" interdural transcavernous pituitary transposition/rotation to dissect the tumor from the residual stalk and hypophyseal portal system for this subtype of craniopharyngioma. METHODS: From August 2018 to February 2023, patients with peripheral retroinfundibular craniopharyngioma underwent surgical treatment. We analyzed clinical information, surgical records, imaging, and examination findings. The surgical procedure, including "one-and-a-half" interdural transcavernous pituitary transposition and rotation, was explained. Postoperative follow-up included endocrinological tests, MRI examinations, and urination surveys. RESULTS: Among the 52 patients diagnosed with craniopharyngioma who underwent surgical treatment, 9 were classified as peripheral retroinfundibular craniopharyngioma, and they received "one-and-a-half" interdural transcavernous pituitary transposition and stalk rotation. In 6 cases, the residual PS and most of the hypophyseal portal system were preserved. Gross total resection was achieved in 5 patients and near total resection in 1 patient. One patient had a transection of the bilateral inferior hypophyseal arteries and 5 unilaterally. None experienced permanent diabetes insipidus, but varying degrees of anterior pituitary dysfunction postoperatively required hormone replacement therapy, which gradually decreased over time. CONCLUSION: The natural anatomic corridor, "one-and-a-half" interdural transcavernous pituitary transposition, and stalk rotation provide increased working space compared with intradural or extradural pituitary transposition. Simultaneously rotating the tumor and pituitary enables a specific attack angle for lesion dissection after the anteriorly displaced residual stalk is rotated laterally. This approach preserves the residual PS and hypophyseal portal system, avoiding complications of diabetes insipidus and hypopituitarism. In most cases, only one side of the inferior hypophyseal artery needs to be sacrificed, ensuring normal pituitary function.

Nanodelivery Systems as a Novel Strategy to Overcome Treatment Failure of Cancer.

Despite the tremendous progress in cancer treatment in recent decades, cancers often become resistant due to multiple mechanisms, such as intrinsic or acquired multidrug resistance, which leads to unsatisfactory treatment effects or accompanying metastasis and recurrence, ultimately to treatment failure. With a deeper understanding of the molecular mechanisms of tumors, researchers have realized that treatment designs targeting tumor resistance mechanisms would be a promising strategy to break the therapeutic deadlock. Nanodelivery systems have excellent physicochemical properties, including highly efficient tissue-specific delivery, substantial specific surface area, and controllable surface chemistry, which endow nanodelivery systems with capabilities such as precise targeting, deep penetration, responsive drug release, multidrug codelivery, and multimodal synergy, which are currently widely used in biomedical researches and bring a new dawn for overcoming cancer resistance. Based on the mechanisms of tumor therapeutic resistance, this review summarizes the research progress of nanodelivery systems for overcoming tumor resistance to improve therapeutic efficacy in recent years and offers prospects and challenges of the application of nanodelivery systems for overcoming cancer resistance.

Three risk factors for WHO grade II and III meningiomas: A study of 1737 cases from a single center.

BACKGROUND: Meningiomas account for 35.5% of central nervous system (CNS) tumors, of which 21-37.8% are atypical or anaplastic/malignant. High-grade meningiomas have higher rates of recurrence and worse outcome than grade I/II meningiomas. Thus, it is of importance to assess the tumor biology before treatment initiation. MATERIALS AND METHODS: This study reviewed 1737 patients with histologically confirmed meningioma at a single institution. Meningiomas were classified according to World Health Organization (WHO) 2007 grading and the location of the tumor was confirmed from the operation records and preoperative imaging. Univariate and multivariate logistic regression were used to analyze the potential risk factors for high-grade pathology. RESULTS: Young men and pediatric patients were less likely to have meningioma, but they had high-grade meningioma. Tumors originated from non-skull base and lateral intracranial are more likely to be grade II/III meningioma. CONCLUSIONS: Lateral and non-skull base location, male sex, and the younger patients increase the risk for grade II and III pathology. These factors should be considered while deciding treatment choice, surgical resection, and prognosis as well.

[Pituitary functional recovery and hormone replacement therapy of patients with pituitary adenoma surgery].

OBJECTIVE: To study the pituitary functional recovery of patients with pituitary adenoma surgery and to identify appropriate dosages of hormone replacement for those patients. METHODS: Serum hormone levels of 187 patients with pituitary adenoma were detected before and after surgery. RESULTS: The lowest serum hormone levels were detected on the 3rd day after surgery (P < 0.05). The hormone levels were partly recovered on the 30th day (P < 0.05) and continued to rise to a relatively high level on the 90th day and one year after surgery (P < 0.05). Patients with older ages were more likely to suffer from hypopituitarism and had less satisfying recovery (P < 0.05) than their younger counterparts. The dosages of Euthyrox and Prednisone that were needed for hormone replacement therapy reached a relatively stable level on the 90th day after surgery (P < 0.05). CONCLUSION: Most patients with pituitary adenoma experienced hypopituitarism shortly after surgery, especially for the elderly who recovered more slowly. Low dosage of hormone replacement therapy based on their symptoms can help the patients reach a stable level of hormone within three months. As a result, the 90th day after surgery can be regarded as a cut-off time for measuring functional recovery of glandula pituitaria.

[Isolation and preliminary identification of stem-like cells in pituitary adenoma].

OBJECTIVE: To isolate and identify the pituitary adenoma stem-like cells from pituitary adenoma tissue. METHODS: Total RNA was prepared with 42 cases of pituitary adenoma tissue samples frozen in liquid nitrogen, the expression of Nestin was detected by RT-PCR. Tumor spheres were cultured in serum-free conditions and the immunefluorescence were used to detect the expression of stem cell markers such as Nestin, Sox2. RESULTS: The positive rate of Nestin mRNA expression was 88.1% (37/42). The cultured tumor spheres were found positive for Nestin, Sox2 by immunefluorescence detection. CONCLUSION: Stem cell markers are expressed in the pituitary adenoma tissue and the pituitary adenoma stem-like cells can be cultured in serum-free condition.