Accurate diagnosis and treatment of sacral meningeal cysts without spinal nerve root fibres: identifying leakage orificium using high-resolution spherical arbitrary-dimensional reconstructing magnetic resonance imaging.

Objective: This study aimed to develop an arbitrary-dimensional nerve root reconstruction magnetic resonance imaging (ANRR-MRI) technique for identifying the leakage orificium of sacral meningeal cysts (SMCs) without spinal nerve root fibres (SNRFs). Methods: This prospective study enrolled 40 consecutive patients with SMCs without SNRFs between March 2021 and March 2022. Magnetic resonance neural reconstruction sequences were performed for preoperative evaluation. The cyst and the cyst-dura intersection planes were initially identified based on the original thin-slice axial T2-weighted images. Sagittal and coronal images were then reconstructed by setting each intersecting plane as the centre. Then, three-dimensional reconstruction was performed, focusing on the suspected leakage point of the cyst. Based on the identified leakage location and size of the SMC, individual surgical plans were formulated. Results: This cohort included 30 females and 10 males, with an average age of 42.6 ± 12.2 years (range, 17-66 years). The leakage orificium was located at the rostral pole of the cyst in 23 patients, at the body region of the cyst in 12 patients, and at the caudal pole in 5 patients. The maximum diameter of the cysts ranged from 2 cm to 11 cm (average, 5.2 ± 1.9 cm). The leakage orificium was clearly identified in all patients and was ligated microscopically through a 4 cm minimally invasive incision. Postoperative imaging showed that the cysts had disappeared. Conclusion: ANRR-MRI is an accurate and efficient approach for identifying leakage orificium, facilitating the precise diagnosis and surgical treatment of SMCs without SNRFs.

DRD2 expression based on 18F-fallypride PET/MR predicts the dopamine agonist resistance of prolactinomas: a pilot study.

PURPOSE: The dopamine agonists (DA) have been used widely to treat prolactinomas. However, it is difficult to predict whether the patient will be responsive to DA treatment. METHODS: We aimed to investigate whether the in vivo expression of DRD2 based on 18F-fallypride PET/MR could predict the therapeutic effect of DA on prolactinomas. Seven patients with prolactinomas completed 18F-fallypride PET/MR. Among them, three patients underwent surgery and further tumor immunohistochemistry. Imaging findings and immunohistochemical staining were compared with treatment outcomes. RESULTS: 18F-fallypride PET/MR was visually positive in 7 of 7 patients, and DRD2 target specificity could be confirmed by immunohistochemical staining. A significantly lower tracer standard uptake value (SUV) could be detected in the resistant patients (n = 3) than in the sensitive patients (n = 4; SUVmean, 4.67 ± 1.32 vs. 13.57 ± 2.42, p < 0.05). DRD2 expression determined by 18F-fallypride PET/MR corresponded with the DA treatment response. CONCLUSION: 18F-fallypride PET/MR may be a promising technique for predicting DA response in patients with prolactinoma.

Potential role of serum hypoxia-inducible factor 1alpha as a biomarker of delayed cerebral ischemia and poor clinical outcome after human aneurysmal subarachnoid hemorrhage: A prospective, longitudinal, multicenter, and observational study.

Objective: Hypoxia-inducible factor 1alpha (HIF-1α) functions as a crucial transcriptional mediator in hypoxic and ischemic brain response. We endeavored to assess the prognostic significance of serum HIF-1α in human aneurysmal subarachnoid hemorrhage (aSAH). Methods: In this prospective, longitudinal, multicenter, and observational study of 257 patients with aSAH and 100 healthy controls, serum HIF-1α levels were quantified. Univariate analyses, followed by multivariate analyses, were performed to discern the relationship between serum HIF-1α levels and severity and delayed cerebral ischemia (DCI) plus poststroke 6-month poor outcome [extended Glasgow outcome scale (GOSE) scores of 1-4]. Predictive efficiency was determined under the receiver operating characteristic (ROC) curve. Results: There were significantly increased serum HIF-lα levels after aSAH, in comparison to controls (median, 288.0 vs. 102.6 pg/ml; P < 0.001). Serum HIF-lα levels were independently correlated with Hunt-Hess scores [ß, 78.376; 95% confidence interval (CI): 56.446-100.305; P = 0.001] and modified Fisher scores (ß, 52.037; 95% CI: 23.461-80.614; P = 0.002). Serum HIF-lα levels displayed significant efficiency for discriminating DCI risk [area under ROC curve (AUC), 0.751; 95% CI: 0.687-0.815; P < 0.001] and poor outcome (AUC, 0.791; 95% CI: 0.736-0.846; P < 0.001). Using the Youden method, serum HIF-1α levels >229.3 pg/ml predicted the development of DCI with 92.3% sensitivity and 48.4% specificity and serum HIF-1α levels >384.0 pg/ml differentiated the risk of a poor prognosis with 71.4% sensitivity and 81.1% specificity. Serum HIF-1α levels >229.3 pg/ml were independently predictive of DCI [odds ratio (OR), 3.061; 95% CI: 1.045-8.965; P = 0.041] and serum HIF-1α levels >384.0 pg/ml were independently associated with a poor outcome (OR, 2.907; 95% CI: 1.403-6.024; P = 0.004). The DCI predictive ability of their combination was significantly superior to those of Hunt-Hess scores (AUC, 0.800; 95% CI: 0.745-0.855; P = 0.039) and modified Fisher scores (AUC, 0.784; 95% CI: 0.726-0.843; P = 0.004). The prognostic predictive ability of their combination substantially exceeded those of Hunt-Hess scores (AUC, 0.839; 95% CI: 0.791-0.886; P < 0.001) and modified Fisher scores (AUC, 0.844; 95% CI: 0.799-0.890; P < 0.001). Conclusion: Elevated serum HIF-lα levels after aSAH, in independent correlation with stroke severity, were independently associated with DCI and 6-month poor outcome, substantializing serum HIF-lα as a potential prognostic biomarker of aSAH.

Hydroxychloroquine overcomes cabergoline resistance in a patient with Lactotroph Pituitary neuroendocrine tumor: a case report.

Objective: A 22-year-old man complaining erectile dysfunction underwent transsphenoidal surgery for a 2.7 cm sellar mass with total resection and was confirmed at pathology to have a lactotroph pituitary neuroendocrine tumor (PiNET). Postoperatively, the patient's PRL remained at high level and therefore accepted high-dose dopamine receptor agonist (DA) therapy. After over 3 months of bromocriptine (BRC) (15mg/day) and over 3 years of cabergoline (CAB) (3mg/week) therapy, the patient's prolactin (PRL) never achieved long-term normalization. He was diagnosed with DA-resistant lactotroph PitNET. Method: In this study, the patient was given hydroxychloroquine (HCQ) (200 mg/d) and CAB (3 mg/w) in combination for four months. His PRL level was tested by blood test every month. Results: Taking the combination therapy of HCQ and CAB, the patient's uncontrolled PRL level was normalized within one month and was maintained at the normal level thereafter. Pituitary magnetic resonance imaging (MRI) images with enhancement showed no recurrence. The patient also regained normal sexual function. Discussion: This is the first report on the combination of HCQ with CAB for the effective treatment of DA-resistant lactotroph pituitary neuroendocrine tumor in a patient, which might provide a novel treatment strategy for clinical management.

MicroRNA-146b-5p/EPHA7 axis regulates cell invasion, metastasis, proliferation, and temozolomide-induced chemoresistance via regulation of IRAK4/TRAF6/NF-κB signaling pathway in aggressive pituitary adenoma.

BACKGROUND: Aggressive pituitary adenoma (APA) is a huge challenge for neurosurgeons. Temozolomide (TMZ) is conventionally used in chemotherapy against APA, but acquired resistance developed during long-term therapy limits its benefits. MiRNA-146b-5p has been confirmed to inhibit tumor metastasis. This study aimed to explore the underlying biological functions of miRNA-146b-5p in APA. METHODS: Sixty confirmed APA tissues and corresponding adjacent normal tissues were collected. We established a TMZ-resistant cell line (GH3/TMZ) by exposing GH3 cells to gradually increasing doses of TMZ for 5 months. Cell Counting Kit-8 assay, flow cytometric analysis, RNA pull-down assay, 5-ethynyl-20-deoxyuridine assay, dual-luciferase reporter gene assay, wound healing assay, and invasion assay were used to explore the malignant biological characteristics of cells. Immunohistochemistry (IHC), western blotting analysis, and real-time quantitative PCR (qRT-PCR) were used to analyze the expression level of related proteins and nucleic acids. RESULTS: The expression of miRNA-146b-5p was down-regulated not only in APA tissues but also in PA cell lines compared with the matched adjacent non-tumor tissues or normal human astrocyte (NHA) cells. Low expression of miRNA-146b-5p was notably associated with poorer disease-free survival rate (P=0.032), overall survival rate (P=0.039), larger tumor size (P=0.028), poorer Knosp grade (P=0.020), and poorer Hardy grade (P=0.006) in APA patients. MiRNA-146b-5p negatively regulated cell proliferation, invasion, migration, and induced apoptosis in GH3 cells. Overexpression of miRNA-146b-5p suppressed IRAK4 and TRAF6 protein expression and negatively regulated NF-κB phosphorylation. The restoration of EPHA7 expression in GH3 cells notably reversed the inhibitory effects of miRNA-146b-5p. MiRNA-146b-5p expression was significantly down-regulated and EPHA7 gene expression was significantly up-regulated in GH3/TMZ cells, compared to the parental cell line. Similarly, EPHA7 was up-regulated, while the miRNA-146b-5p level was down-regulated in chemoresistance tissues more than in chemosensitive tissues. The autophagic activity was decreased markedly with increasing miRNA-146b-5p expression, while it was enhanced after Lv-EPHA7 treatment in GH3/TMZ cells. CONCLUSIONS: MiRNA-146b-5p can inhibit EPHA7 expression, suppress the IRAK4/TRAF6/NF-κB signaling pathway, and weaken PA cell invasion, metastasis, proliferation, and TMZ-induced chemoresistance in vitro.

Serum netrin-1 concentrations are associated with clinical outcome in acute intracerebral hemorrhage.

BACKGROUND: Netrin-1 is an axon guidance protein, which can inhibit inflammatory reaction and stabilize the blood-brain barrier to protect against experimental brain injury. We evaluated the concentration of netrin-1 in acute intracerebral hemorrhage (ICH) patients and explored whether netrin-1 is a potential prognostic biomarker for ICH. METHODS: This study recruited a total of 126 ICH patients and 126 healthy controls. Netrin-1 concentration was determined using a commercially available human enzyme-linked immune sorbent assay kit. National Institutes of Health Stroke Scale (NIHSS) score and hematoma volume were used to assess hemorrhagic severity. An unfavorable outcome was defined as modified Rankin Scale >2 at 90 days. RESULTS: ICH patients showed significantly lower serum netrin-1 concentrations than controls. Serum netrin-1 concentrations were strongly and inversely correlated with serum C-reactive protein concentrations, NIHSS score and hematoma volume. Multivariate analyses revealed that low netrin-1 concentration was associated with 90-day death, unfavorable outcome and overall survival after adjustment for other confounding variables. Under the receiver operating characteristic curve, serum netrin-1 remarkably discriminated patients at risk of 90-day death and unfavorable outcome. CONCLUSIONS: Serum netrin-1 concentrations are decreased in patients with ICH, and the concentrations of netrin-1 were intimately associated with inflammation, hemorrhagic severity and clinical outcome of ICH.

Determination of serum neutrophil gelatinase-associated lipocalin as a prognostic biomarker of acute spontaneous intracerebral hemorrhage.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is currently known as an acute phase protein and implicated in acute brain injury. Herein, we sought to gauge serum NGAL level in patients after acute (<24 h) spontaneous intracerebral hemorrhage (ICH) and to investigate its relation to neurological outcome. METHODS: Serum NGAL levels were measured in 106 patients and 106 controls. National Institutes of Health Stroke Scale (NIHSS) score, Glasgow coma scale (GCS) score, ICH score and hematoma volume were recorded for assessing hemorrhagic severity. An unfavorable outcome was defined as modified Rankin Scale >2 at 90 days. RESULTS: As opposed to the controls, the patients had significantly raised serum NGAL levels. Correlations were observed between NGAL levels and serum C-reactive protein levels, blood glucose levels, GCS score, NIHSS score, ICH score and ICH volume. Multivariate analysis identified serum NGAL as a predictor for unfavorable outcome at 90 days. It also showed high prognostic ability under receiver operating characteristic curve. CONCLUSIONS: Enhanced NGAL level is revealed after acute spontaneous ICH, in association with inflammatory degree and hemorrhagic severity, and intimately correlated with a worse prognosis.

Mahuang decoction mitigates airway inflammation and regulates IL-21/STAT3 signaling pathway in rat asthma model.

ETHNOPHARMACOLOGICAL RELEVANCE: Nowadays, bronchial asthma is still a severe disease threatening human health, and it is incumbent upon us to seek effective therapeutic drugs. Mahuang decoction (MHD), a classic famous Chinese prescription, has been used for thousands of years to prevent phlegm from forming, stop coughing and relieve asthma, but the relevant mechanism has not been thoroughly clarified. This study aims to investigate the anti-airway inflammation effect of MHD and the possible molecular mechanism underlying IL21/STAT3 signaling pathway, so as to provide guidance for the treatment of MHD on bronchial asthma. MATERIALS AND METHODS: Specific pathogen free SD rats were randomly divided into 6 groups: normal control group, model group, positive group (Compound methoxyphenamine), MHD-treated groups at doses of 10 ml/kg, 5 ml/kg and 2.5 ml/kg, 10 rats in each group. Except for the normal control group, rats in other groups were sensitized with ovalbumin via introperitoneal injection and challenged with ovalbumin inhalation to trigger asthma model. At 24 h after the last excitation, bronchoalveolar lavage fluid (BALF) of every rat was drawn and the number of inflammatory cells was analyzed using cell counting method. ELISA method was performed to determine the concentrations of TXB2, 6-keto-PGF1α, MMP-9, TIMP-1, IL-2, IL-4, IL-5 and TNF-α in rat serum. The protein expressions of IL-21, IL-21R, STAT3 and p-STAT3 in murine pulmonary tissues were assessed with western blotting analysis. RESULTS: Compared with the control group, the airway wall and airway smooth muscle of murine pulmonary tissues significantly thickened and massive inflammatory cells infiltration occurred around the bronchus in the model group, and the cell counts of WBC and EOS in BALF were also apparently increased, which indicated the rat asthma model was successfully established. MHD or Compound methoxyphenamine not only alleviated the pulmonary inflammatory pathological damages, but also down- regulated the numbers of WBC and EOS in BALF. What's more, the levels of TXB2, MMP-9, TIMP-1, ILs-(2, 4, 5) and TNF-α in rat serum were lessened by the treatment of MHD. In western blotting analysis, treatment with 10 ml/kg or 5 ml/kg MHD markedly declined the increased protein expressions of IL-21, IL-21R, STAT3 and p-STAT3 in lung tissues of asthmatic rats to normal level. CONCLUSION: MHD intervention demonstrated a strong inhibitory action on the secretion of inflammatory mediators as well as the inflammatory cell infiltration in pulmonary tissues of asthmatic rats, and also depressed the protein expressions of IL-21, IL-21R, STAT3 and p-STAT3 in pulmonary tissues. MHD effectively mitigates airway inflammation and regulates the IL-21/STAT3 signaling pathway in rat asthma model.

Prevention against diffuse spinal cord astrocytoma: can the Notch pathway be a novel treatment target?

This study was designed to investigate whether the Notch pathway is involved in the development of diffuse spinal cord astrocytomas. BALB/c nude mice received injections of CD133(+) and CD133(-) cell suspensions prepared using human recurrent diffuse spinal cord astrocytoma tissue through administration into the right parietal lobe. After 7-11 weeks, magnetic resonance imaging was performed weekly. Xenografts were observed on the surfaces of the brains of mice receiving the CD133(+) cell suspension, and Notch-immunopositive expression was observed in the xenografts. By contrast, no xenografts appeared in the identical position on the surfaces of the brains of mice receiving the CD133(-) cell suspension, and Notch-immunopositive expression was hardly detected either. Hematoxylin-eosin staining and immunohistochemical staining revealed xenografts on the convex surfaces of the brains of mice that underwent CD133(+) astrocytoma transplantation. Some sporadic astroglioma cells showed pseudopodium-like structures, which extended into the cerebral white matter. However, it should be emphasized that the subcortex xenograft with Notch-immunopositive expression was found in the fourth mouse received injection of CD133(-) astrocytoma cells. However, these findings suggest that the Notch pathway plays an important role in the formation of astrocytomas, and can be considered a novel treatment target for diffuse spinal cord astrocytoma.

Apnea as an uncommon preoperative manifestation of medulla cavernous malformation: surgical treatment and literature review.

OBJECTIVE: Apnea is not a common preoperative manifestation of medulla cavernous malformations (CMs). The role of surgical resection in patients suffering from apnea secondary to hemorrhage from medulla CMs requires further definition. METHODS: Medical records and radiographs were reviewed retrospectively for four patients treated surgically for medulla CMs in our institution between 2008 and 2011. Recent outcomes for these patients were also evaluated. The modified Rankin Scale (mRS) was used to evaluate neurological function. RESULTS: All four patients (3 male, 1 female; mean age: 41.3 years) suffered two or three hemorrhages with a preoperative mRS of five and, due to the loss of autonomous respiration and consciousness, underwent a preoperative tracheotomy for mechanical ventilation, which lasted an average of 4.5 days. Prior to surgery, all patients had recovered to the point of maintaining spontaneous breath and normal blood gas values with oxygen supplementation. Lesions were totally resected in all patients via the posterior suboccipital approach. Postoperative ventilation was continued in one patient for 1 day. The mean postoperative mRS score at discharge was 3.5, and all patients had improved from their previous scores. The tracheostomy was closed in three patients at 15, 16, and 35 days after surgery. After a mean follow-up of 34.7 months, the most recent mRS scores were 3, 2, 2, and 2; no recurrent hemorrhage was noted, and three patients lived independently. CONCLUSION: In carefully selected patients with hemorrhage due to medulla CMs, favorable outcomes can be achieved even if apnea was a part of the preoperative clinical presentation. Surgery should be considered in these patients, particularly in those with repeated hemorrhages, and apnea should not be considered an absolute contraindication to surgery.