Surgical management of giant pituitary adenomas: institutional experience and clinical outcomes of 94 patients.

Background: Giant (with a diameter of at least 40 mm and a volume of at least 10 cm3) pituitary adenomas (GPAs) are intricate tumors that pose considerable difficulty for surgical removal. While endoscopic transsphenoidal surgery (ETS) is a commonly employed technique for these destructive tumors, its effectiveness may be restricted in cases where invasion into multiple compartments is present, leading to limited resection. Methods: A retrospective review was conducted on the clinical records of 94 patients diagnosed with GPAs who had undergone surgical resection from 2014 to 2022. An analysis was conducted on the outcomes of the surgical and clinical procedures. Results: In this group, the average size of the tumor before surgery was 44.6 ± 5.6 mm (range, 40-73 mm), and the volume was 25. 5± 16.6 cm3 (range, 10-20.67 cm3). Of the total number of patients, 72 (76.6%) underwent a single ETS, 12 (12.8%) opted for transcranial surgery (TCS), and 10 (10.6%) chose a combined method. Gross total resection (GTR) was successfully performed in 49 (68.1%), 3 (25.0%), and 8 (80.0%) patients who underwent each surgical approach. Seventy-four (78.7%) patients had improved vision, 20 (21.3%) were unchanged, and none had deterioration. Twenty-two patients (23.4%) experienced a total of 43 complications, which comprised hormonal insufficiency (11/94, 11.7%), diabetic insipidus (6/88, 6.8%), electrolyte disorders (7/94, 7.4%), cerebrospinal fluid leakage (5/94, 5.3%), meningitis (8/94, 8.5%), and hydrocephalus (6/94, 6.4%). The GTR, subtotal resection (STR), and partial resection (PTR) rates were 63.8% (60/94), 21.3% (20/94), and 14.9% (14/94), respectively. Throughout the follow-up duration, 18.1% (17/94) of patients required reoperation and/or adjuvant radiation treatment as a result of tumor regrowth or inadequate biochemical remission of functioning GPAs. Conclusion: ETS remains the optimal surgical option for most GPAs and generally offers safe and efficient tumor resection. However, a combined approach with TCS remains a requirement in cases that are not suitable for treatment with a single ETS. To achieve optimal tumor removal and minimize the occurrence of surgical complications, a flexible combination of ETS and TCS is recommended based on the characteristics of the tumor.

Chlorogenic acid: a review on its mechanisms of anti-inflammation, disease treatment, and related delivery systems.

Chlorogenic acid is a bioactive compound ubiquitously present in the natural realm, lauded for its salient anti-inflammatory and antioxidant attributes. It executes its anti-inflammatory function by moderating the synthesis and secretion of inflammatory mediators, namely, TNF-α, IL-1ß, IL-6, IL-8, NO, and PGE2. Concurrently, it modulates key signaling pathways and associated factors, including NF-κB, MAPK, Nrf2, and others, bestowing protection upon cells and tissues against afflictions such as cardio-cerebrovascular and diabetes mellitus. Nevertheless, the inherent low bioavailability of chlorogenic acid poses challenges in practical deployments. To surmount this limitation, sophisticated delivery systems, encompassing liposomes, micelles, and nanoparticles, have been devised, accentuating their stability, release mechanisms, and bioactivity. Given its innate anti-inflammatory prowess and safety profile, chlorogenic acid stands as a promising contender for advanced biomedical investigations and translational clinical endeavors.

LncRNA FOXD3-AS1/miR-128-3p axis-mediated IGF2BP3 in glioma stimulates cancer angiogenesis and progression.

INTRODUCTION: The aim of the study was to research the mechanism by which IGF2BP3 regulates glioma progression as well as its upstream regulatory axis. MATERIAL AND METHODS: The researched mRNA was determined using differential expression analysis based on bioinformatics data, and its upstream miRNAs and lncRNAs were predicted. Interaction between genes we researched was identified by dual-luciferase method. The viability, migration, invasion and angiogenesis of glioma were measured with MTT, colony formation, Transwell and Matrigel tube formation experiments, respectively. The mRNA expression of each gene was tested with qRT-PCR. IGF2BP3 level was determined via western blot and immunohistochemistry. Subcellular fractionation of FOXD3-AS1 was tested with fluorescence in situ hybridization. In vivo tumorigenesis assay was conducted on nude mice. RESULTS: IGF2BP3 high level in glioma cells correlated with patient's prognosis. Downregulation of IGF2BP3 restrained proliferation, migration, invasion and angiogenesis in glioma cells both in vitro and in vivo. There was a binding relationship between IGF2BP3 and miR-128-3p. Besides, FOXD3-AS1 as a sponge of miR-128-3p was located mainly in cytoplasm. Additionally, FOXD3-AS1 facilitated IGF2BP3 level via sponging miR-128-3p to stimulate glioma angiogenesis. CONCLUSIONS: FOXD3-AS1 was a sponge of miR-128-3p through upregulating IGF2BP3 in glioma. Our findings shed light on diagnosis and treatment of glioma.

Pathway network-based quantitative modeling of the time-dependent and dose-response anti-inflammatory effect of Reduning Injection.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has extensive healing effects on inflammatory diseases with few side effects. Reduning injection (RDNI), a TCM prescription composed of Lonicera japonica Thunb., Gardenia jasminoides Ellis. and Artemisia annua L., is wildly used for treating inflammatory diseases. However, the mechanism of action of RDNI, like most TCM prescriptions, is unclear due to the complexity of relationships between components and their curative effects. AIM OF THE STUDY: To develop a universal systems pharmacology protocol for mechanism modeling of TCM and apply it to reveal the real-time anti-inflammatory effect of Reduning Injection. MATERIALS AND METHODS: Combined with database mining and references, a regulatory mechanism network of inflammation was constructed. A quantitative model was established afterwards by integrating pharmacokinetic data and two network parameters, namely Network Efficiency and Network Flux. The time-dependent and dose-response relationship of RDNI on the regulation of inflammation was then quantitatively evaluated. ELISA tests were performed to verify the reliability of the model. RESULTS: Three cytokines, namely IL-1ß, IL-6 and TNF-α were screened out to be markers for evaluation of the anti-inflammatory effect of RDNI. An HPLC method for the simultaneous determination of 10 RDNI compounds in SD rat plasma was established and then applied to pharmacokinetic studies. Based on compound activity and pharmacokinetic data, the time-dependent effect of RDNI were quantitatively predicted by the pathway network-based modeling procedure. CONCLUSIONS: The quantitative model established in this work was successfully applied to predict a TCM prescription's real-time dynamic healing effect after administration. It is qualified to provide novel insights into the time-dependent and dose-effect relationship of drugs in an intricate biological system and new strategies for investigating the detailed molecular mechanisms of TCM.

Endoport-assisted Neuroendoscopic Techniques Used in the Resection of Intraventricular Lesions.

AIM: To investigate the safety and efficacy of endoport-assisted endoscopic techniques for removing intraventricular lesions. MATERIAL AND METHODS: Data of patients with intraventricular lesions who were surgically treated by endoport-assisted endoscopic resection between January 2018 and February 2019 were retrospectively reviewed. The surgical procedures, complications and outcomes were analyzed. RESULTS: A total of 11 patients, with a mean age of 33 years (5-70 years) were included in the study. The mean Karnofsky Performance Scale (KPS) score evaluated on admission was 50.0 ± 7.0. Lesions located in the unilateral ventricle, the third ventricle and multiple sites of ventricles were recorded in 7, 2 and 2 patients, respectively. The average lesion size was 3.4 ± 0.4 cm (2-6 cm). Gross-total removal of all lesions was achieved, and all patients experienced a stable recovery after operations except for one hemorrhage and one visual field defect occurring in two patients in the early postoperative period. With a follow-up of 6-19 months, dysfunctions and complications occurring pre- or postoperation gradually recovered to different degrees. The mean KPS score was 85.5 ± 4.3 at the last follow-up, and no tumor recurrence was observed in any of the patients. CONCLUSION: Endoport-assisted endoscopic techniques could be a simple, minimally invasive surgical method in the resection of lesions located in the lateral ventricle, the third ventricle, or both with acceptable surgical complications occurring in patients.

Extended Neuroendoscopic Endonasal Approach for Resection of Craniopharyngioma in Children.

OBJECTIVE: To explore the surgical approach and technique of neuroendoscopic endonasal resection of pediatric craniopharyngiomas and to further evaluate its safety and effect in children. METHODS: The clinical data of 8 children with craniopharyngiomas who were surgically treated by neuroendoscopy through an extended endonasal approach in our center from 2018 to 2021 were retrospectively analyzed. The related surgical approach and technique were evaluated to improve the surgical results and further reduce the surgical complications when removing craniopharyngioma in children. RESULTS: All 8 patients achieved a gross-total resection of the tumor under neuroendoscopy. Postoperatively, 2 cases of transient hyperthermia and 4 cases of transient hyper- and/or hyponatremia occurred within the first 2 weeks, all of which were quickly controlled. Seven patients had symptoms of diabetes insipidus to varying degrees after the operation, and 4 of them improved within 1-3 months after surgery, but 3 cases still needed oral pituitrin. There were no cases of coma or death, leakage of cerebrospinal fluid, or severe electrolyte imbalance after surgery. During the postoperative follow-up of 3 months to 2 years, no tumor recurrence was found. Among the 7 patients who suffered postoperative neuroendocrine deficiencies, 3 patients were found to be temporary during the follow-up, but 4 patients still required hormone replacement therapy. Particularly, postoperative visual deterioration and olfactory defect that occurred in patients were all improved during follow-up periods. In addition, 4 cases of obesity were noted at the last follow-up. CONCLUSIONS: Extended neuroendoscopic endonasal resection of craniopharyngiomas may be used as a safe and effective approach for children. Due to the poor pneumatization of the sphenoid sinus and worse compliance of treatment in children, surgical techniques of exposing the sellar region, removing the tumor, and reconstructing the skull base, as well as postoperative management of patients was proposed. However, due to the limited surgical cases in the study, the surgical safety and effects of the extended neuroendoscopic endonasal approach for children with craniopharyngiomas need to be further studied in the future.

miR-665 is downregulated in glioma and inhibits tumor cell proliferation, migration and invasion by targeting high mobility group box 1.

Glioma is the most common brain tumor in adults. microRNAs (miRNAs/miRs) play an essential role in tumor development and progression. The present study aimed to investigate the potential clinical significance and function of miR-665 in glioma. Reverse transcription-quantitative PCR analysis was used to detect the expression of miR-665 in glioma tissues and cells. Survival curves were constructed using the Kaplan-Meier method. Cox regression analysis was performed to investigate the prognostic significance of miR-665. Cell Counting Kit-8 and Transwell assays were used to evaluate the role of miR-665 in glioma. Bioinformatics analysis and Dual-luciferase reporter assays were used to predict the putative direct targets of miR-665. Western blotting was used to evaluate the activity of the Wnt/ß-catenin pathway. The relative expression of miR-665 was decreased in glioma tissues and cells and this downregulation was significantly associated with the Karnofsky performance scale score and World Health Organisation grade. Patients with glioma with low miR-665 expression had a shorter overall survival time compared with the high expression group. Besides, overexpression of miR-665 suppressed the proliferation, migration and invasion of glioma cells, while knockdown of miR-665 promoted these cellular behaviors. High mobility group box (HMGB)1 was a direct target of miR-665. It was also demonstrated that miR-665 may suppress glioma progression by targeting HMGB1 and inhibiting the Wnt/ß-catenin pathway. Taken together, these data suggested that miR-665 may have a tumor suppressor role in glioma by targeting HMGB1. Therefore, miR-665 may be a novel prognostic biomarker and the miR-665/HMGB1 axis may be a novel therapeutic target for the treatment of glioma.

The surgical management of pituitary apoplexy with occluded internal carotid artery and hidden intracranial aneurysm: illustrative case.

BACKGROUND: Approximately 0.6% to 12% of cases of pituitary adenoma are complicated by apoplexy, and nearly 6% of pituitary adenomas are comorbid aneurysms. Occlusion of the internal carotid artery (ICA) with hidden intracranial aneurysm due to compression by an apoplectic pituitary adenoma is extremely rare; thus, the surgical strategy is also unknown. OBSERVATIONS: The authors reported the case of a 48-year-old man with a large pituitary adenoma with coexisting ICA occlusion. After endoscopic transnasal surgery, repeated computed tomography angiography (CTA) demonstrated reperfusion of the left ICA but with a new-found aneurysm in the left posterior communicating artery; thus, interventional aneurysm embolization was performed. With stable recovery and improved neurological condition, the patient was discharged for rehabilitation training. LESSONS: For patients with pituitary apoplexy accompanied by a rapid decrease of neurological conditions, emergency decompression through endoscopic endonasal transsphenoidal resection can achieve satisfactory results. However, with occlusion of the ICA by enlarged pituitary adenoma or pituitary apoplexy, a hidden but rare intracranial aneurysm may be considered when patients are at high risk of such vascular disease as aneurysm, and gentle intraoperative manipulations are required. Performing CTA or digital subtraction angiography before and after surgery can effectively reduce the missed diagnosis of comorbidity and thus avoid life-threatening bleeding events from the accidental rupture of an aneurysm.

(+/-)-Borneol Reverses Mitoxantrone Resistance against P-Glycoprotein.

P-Glycoprotein (Pgp) is a main factor contributing to multidrug resistance and the consequent failure of chemotherapy. Overcoming Pgp efflux is a strategy to improve the efficacy of drugs. (+)-Borneol (BNL1) and (-)-borneol (BNL2) interfere and inhibit Pgp, and thus, the accumulation of drugs increases in cells. However, it is not clear yet how they play the inhibitory effect against Pgp. In this work, the effect and molecular mechanism of borneol enantiomers in reversing mitoxantrone (MTO) resistance against Pgp were explored by in vitro and in silico approaches. Chemosensitizing potential tests showed that BNLs could enhance the efficacy of MTO in MES-SA/MX2 cells, and BNL2 exhibited a stronger potential. The protein expression of Pgp was decreased to some extent by the administration of BNLs. Molecular docking revealed that BNLs could reduce the binding affinity between MTO and Pgp. The results were consistent with the chemosensitizing potential test and were supported by molecular dynamics (MD) simulations. Molecular docking also suggested that BNLs preferred to bind in the drug-binding pocket rather than the nucleotide-binding domain of inward-facing Pgp. The occupied space of BNLs had an evident distance from that of MTO, which was further verified by the conformational analysis after MD simulations. The decomposition of binding free energies revealed the key amino acid residues (GLN195, SER196, TRP232, PHE343, SER344, GLY346, and GLN347) for BNLs to reverse MTO resistance. The results provide an insight into the mechanism through which BNLs reduce the MTO resistance against inward-facing Pgp in the drug-binding pocket through noncompetitive inhibition.

Surgical managements and patient outcomes after severe hemorrhagic events from brainstem cavernous malformations.

To evaluate the surgical outcomes and predictors and the impact of surgical timing of patients who suffered a severe hemorrhagic event from brainstem cavernous malformations (CMs). The clinical data of all patients who underwent surgical treatment after a severe bleeding ictus from brainstem CMs between 2011 and 2017 were retrospectively reviewed. The study population consisted of 61 surgical patients (40, 65.6% female). Surgical times of < 3 weeks, ≥ 3-8 weeks, and > 8 weeks since the last bleeding ictus were observed in 23 (37.7%), 24 (39.3%), and 14 (23.0%) patients, respectively. The mean modified Rankin scale (mRS) score evaluated on admission was 4.2. With a mean follow-up of 39.8 months, 39 patients (63.9%) had a favorable outcome (mRS ≤ 2), and the mean mRS score was 2.3. The logistic regression analysis identified age, having disrupted consciousness and/or respiration, and time to surgery from last hemorrhage as significant predictors of long-term outcome. In particular, patients with surgery performed during the acute period (< 3 weeks, P = 0.06) or chronic period (> 8 weeks, P = 0.01) tended to have poor outcomes when compared with those with surgery during the subacute period (≥ 3-8 weeks). Favorable neurological outcomes can be achieved in patients who were surgically treated after a severe hemorrhagic ictus from brainstem CMs, and operation during subacute hemorrhage (≥ 3-8 weeks) could benefit these patients.

Interaction among long non-coding RNA, micro-RNA and mRNA in glioma.

With the rapid development and wide application of gene sequencing, biotechnology, and informatics about cancer, it has been found that the main causes of malignant gliomas occurrence not only consist of abnormal mutations of protein-coding genes but also abnormal expressions of non-coding RNA (ncRNA). In this review, we summarize the interaction and mechanism between lncRNA-miRNA-mRNA and gliomas in occurrence, development, aggression, and migration in depth.

Assessing the Anti-inflammatory Mechanism of Reduning Injection by Network Pharmacology.

Reduning Injection (RDNI) is a traditional Chinese medicine formula indicated for the treatment of inflammatory diseases. However, the molecular mechanism of RDNI is unclear. The information of RDNI ingredients was collected from previous studies. Targets of them were obtained by data mining and molecular docking. The information of targets and related pathways was collected in UniProt and KEGG. Networks were constructed and analyzed by Cytoscape to identify key compounds, targets, and pathways. Data mining and molecular docking identified 11 compounds, 84 targets, and 201 pathways that are related to the anti-inflammatory activity of RDNI. Network analysis identified two key compounds (caffeic acid and ferulic acid), five key targets (Bcl-2, eNOS, PTGS2, PPARA, and MMPs), and four key pathways (estrogen signaling pathway, PI3K-AKT signaling pathway, cGMP-PKG signaling pathway, and calcium signaling pathway) which would play critical roles in the treatment of inflammatory diseases by RDNI. The cross-talks among pathways provided a deeper understanding of anti-inflammatory effect of RDNI. RDNI is capable of regulating multiple biological processes and treating inflammation at a systems level. Network pharmacology is a practical approach to explore the therapeutic mechanism of TCM for complex disease.

Exosomal lncRNA ROR1-AS1 Derived from Tumor Cells Promotes Glioma Progression via Regulating miR-4686.

OBJECTIVE: Glioma is one of the most common central nervous system malignant tumors, accounting for 45%-60% of adult intracranial tumors. However, the clinical treatment of glioma is limited. It is of great significance to seek new therapeutic methods for glioma via gene therapy. MATERIALS AND METHODS: Microarray is used to identify the lncRNAs that are differentially expressed in glioma. The expression of long non-coding RNA (lncRNA) ROR1-AS1 and miR-4686 was detected by qRT-PCR. Exosomes were isolated from the supernatant of normal and cancerous cells, and TEM was used for exosomes identification. MTT assay, wound healing assay, transwell assay, and colony formation assay were used to detect the exo-ROR1-AS1 function on proliferation, migration, and invasion in glioma cells. Luciferase assay and RIP assay were used to identify the relationship between lncRNA ROR1-AS1 and miR-4686. The effect of exo-ROR1-AS1 on tumorigenesis of glioma was confirmed by the xenograft nude mice model. RESULTS: ROR1-AS1 was up-regulated in glioma tissues, and the high expression of ROR1-AS1 indicated a poor prognosis in glioma patients. Interestingly, ROR1-AS1 was packaged into exosomes and derived from tumor cells. Functional analysis showed exo-ROR1-AS1 promoted the progression of glioma cell lines SHG44 and U251. Furthermore, ROR1-AS1 acted as a sponge of miR-4686 and inhibited its expression. Functionally, forced expression of miR-4686 removed the promoted effects of lncRNA ROR1-AS1 on glioma development. In vivo tumorigenesis experiments showed that exo-ROR1-AS1 promoted glioma development via miR-4686 axis. CONCLUSION: Our study suggested tumor cells derived exo-ROR1-AS1 promoted glioma progression by inhibiting miR-4686, which might be a potential therapeutic target for glioma clinical treatment.

LINC01579 promotes cell proliferation by acting as a ceRNA of miR-139-5p to upregulate EIF4G2 expression in glioblastoma.

Glioblastoma (GBM), a malignant and lethal tumor, remains a big threat to human health and life. Increasing explorations have confirmed that long noncoding RNAs are involved in the tumorigenesis and development of multiple cancers. Nevertheless, the regulatory mechanism of (long intergenic nonprotein coding RNA 1579 LINC01579) in GBM remains to be investigated. In this study, the expression of LINC01579 was upregulated in GBM cells and LINC01579 knockdown inhibited cell proliferation as well as promoted cell apoptosis. Additionally, LINC01579 acted as a sponge for miR-139-5p in GBM and eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) was found to be a downstream target of miR-139-5p. Furthermore, the positive correlation of LINC01579 and EIF4G2 as well as the converse correlation between miR-139-5p and LINC01579 (or EIF4G2) were revealed by the experiments. Based on rescue assays, EIF4G2 overexpression or miR-139-5p inhibitor partially recovered the function of LINC01579 knockdown on cell proliferation and apoptosis. In summary, the results of this study verified that LINC01579 modulated cell proliferation and cell apoptosis in GBM by competitively binding with miR-139-5p to regulate EIF4G2, which provided a new clue to figure out potential therapy for patients suffered from GBM.