Epilepsy alters brain networks in patients with insular glioma.

AIMS: We intend to elucidate the alterations of cerebral networks in patients with insular glioma-related epilepsy (GRE) based on resting-state functional magnetic resonance images. METHODS: We collected 62 insular glioma patients, who were subsequently categorized into glioma-related epilepsy (GRE) and glioma with no epilepsy (GnE) groups, and recruited 16 healthy individuals matched to the patient's age and gender to form the healthy control (HC) group. Graph theoretical analysis was applied to reveal differences in sensorimotor, default mode, visual, and executive networks among different subgroups. RESULTS: No significant alterations in functional connectivity were found in either hemisphere insular glioma. Using graph theoretical analysis, differences were found in visual, sensorimotor, and default mode networks (p < 0.05). When the glioma located in the left hemisphere, the degree centrality was reduced in the GE group compared to the GnE group. When the glioma located in the right insula, the degree centrality, nodal efficiency, nodal local efficiency, and nodal clustering coefficient of the GE group were lower than those of the GnE group. CONCLUSION: The impact of insular glioma itself and GRE on the brain network is widespread. The networks altered by insular GRE differ depending on the hemisphere location. GRE reduces the nodal properties of brain networks than that in insular glioma.

Survival outcome and predictors of WHO grade 2 and 3 insular gliomas: A classification based on the tumor spread.

OBJECTIVE: The study aimed to identify if clinical features and survival outcomes of insular glioma patients are associated with our classification based on the tumor spread. METHODS: Our study included 283 consecutive patients diagnosed with histological grade 2 and 3 insular gliomas. A new classification was proposed, and tumors restricted to the paralimbic system were defined as type 1. When tumors invaded the limbic system (referred to as the hippocampus and its surrounding structures in this study) simultaneously, they were defined as type 2. Tumors with additional internal capsule involvement were defined as type 3. RESULTS: Tumors defined as type 3 had a higher age at diagnosis (p = 0.002) and a higher preoperative volume (p < 0.001). Furthermore, type 3 was more likely to be diagnosed as IDH wild type (p < 0.001), with a higher rate of Ki-67 index (p = 0.015) and a lower rate of gross total resection (p < 0.001). Type 1 had a slower tumor growth rate than type 2 (mean 3.3%/month vs. 19.8%/month; p < 0.001). Multivariate Cox regression analysis revealed the extent of resection (HR 0.259, p = 0.004), IDH status (HR 3.694, p = 0.012), and tumor spread type (HR = 1.874, p = 0.012) as independent predictors of overall survival (OS). Tumor grade (HR 2.609, p = 0.008), the extent of resection (HR 0.488, p = 0.038), IDH status (HR 2.225, p = 0.025), and tumor spread type (HR 1.531, p = 0.038) were significant in predicting progression-free survival (PFS). CONCLUSION: The current study proposes a classification of the insular glioma according to the tumor spread. It indicates that the tumors defined as type 1 have a relatively better nature and biological characteristics, and those defined as type 3 can be more aggressive and refractory. Besides its predictive value for prognosis, the classification has potential value in formulating surgical strategies for patients with insular gliomas.

Online small-object anti-fringe sorting of tobacco stem impurities based on hyperspectral superpixels.

The use of tobacco stems as raw material for cigarettes reduces cost and improves the flammability of cigarettes. However, various impurities, such as plastic, reduce the purity of tobacco stems, degrade the quality of cigarettes, and endanger the health of smokers. Therefore, the correct classification of tobacco stems and impurities is crucial. This study proposes a method based on hyperspectral image superpixels and the use of light gradient boosting machine (LightGBM) classifier to categorize tobacco stems and impurities. First, the hyperspectral image is segmented using superpixels. Second, the gray-level co-occurrence matrix extracts the texture features of superpixels. Subsequently, an improved LightGBM is applied and trained with the spectral and textural features of superpixels as a classification model. Several experiments were implemented to evaluate the performance of the proposed method. The results show that the classification performance based on superpixels is better than that based on single-pixel points. The classification model based on superpixels (10 × 10 px) achieved the highest impurity recognition rate (93.8%). This algorithm has already been applied to industrial production in cigarette factories. It exhibits considerable potential in overcoming the influence of interference fringes to promote the intelligent industrial application of hyperspectral imaging.

Antimicrobial and Antibiofilm Efficacy and Mechanism of Oregano Essential Oil Against Shigella flexneri.

The aim of this study was to assess the antimicrobial activity of oregano essential oil (OEO) against Shigella flexneri and eradication efficacy of OEO on biofilm. The results showed that the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of OEO against S. flexneri were 0.02% (v/v) and 0.04% (v/v), respectively. OEO effectively killed S. flexneri in Luria-Bertani (LB) broth and contaminated minced pork (the initial population of S. flexneri was about 7.0 log CFU/mL or 7.2 log CFU/g), and after treatment with OEO at 2 MIC in LB broth or at 15 MIC in minced pork, the population of S. flexneri decreased to an undetectable level after 2 or 9 h, respectively. OEO increased intracellular reactive oxygen species concentration, destroyed cell membrane, changed cell morphology, decreased intracellular ATP concentration, caused cell membrane depolarization, and destroyed proteins or inhibited proteins synthesis of S. flexneri. In addition, OEO effectively eradicated the biofilm of S. flexneri by effectively inactivating S. flexneri in mature biofilm, destroying the three-dimensional structure, and reducing exopolysaccharide biomass of S. flexneri. In conclusion, OEO exerts its antimicrobial action effectively and also has a valid scavenging effect on the biofilm of S. flexneri. These findings suggest that OEO has the potential to be used as a natural antibacterial and antibiofilm material in the control of S. flexneri in meat product supply chain, thereby preventing meat-associated infections.

The biochemical characteristics of viable but nonculturable state Yersinia enterocolitica induced by lactic acid stress and its presence in food systems.

The viable but nonculturable (VBNC) state is adopted by many foodborne pathogenic bacteria to survive in adverse conditions. This study found that lactic acid, a widely used food preservative, can induce Yersinia enterocolitica to enter a VBNC state. Y. enterocolitica treated with 2 mg/mL lactic acid completely lost culturability within 20 min, and 10.137 ± 1.693 % of the cells entered a VBNC state. VBNC state cells could be recovered (resuscitated) in tryptic soy broth (TSB), 5 % (v/v) Tween80-TSB, and 2 mg/mL sodium pyruvate-TSB. In the VBNC state of Y. enterocolitica induced by lactic acid, the intracellular adenosine triphosphate (ATP) concentration and various enzyme activities were decreased, and the reactive oxygen species (ROS) level was elevated, compared with uninduced cells. The VBNC state cells were significantly more resistant to heat and simulated gastric fluid than uninduced cells, but their ability to survive in a high-osmotic-pressure environment was significantly less than that of uninduced cells. The VBNC state cells induced by lactic acid changed from long rod-like to short rod-like, with small vacuoles at the cell edges; the genetic material was loosened and the density of cytoplasm was increased. The VBNC state cells had decreased ability to adhere to and invade Caco-2 (human colorectal adenocarcinoma) cells. The transcription levels of genes related to adhesion, invasion, motility, and resistance to adverse environmental stress were downregulated in VBNC state cells relative to uninduced cells. In meat-based broth, all nine tested strains of Y. enterocolitica entered the VBNC state after lactic acid treatment; among these strains, only VBNC state cells of Y. enterocolitica CMCC 52207 and Isolate 36 could not be recovered. Therefore, this study is a wake-up call for food safety problems caused by VBNC state pathogens induced by lactic acid.

Spatial distribution of supratentorial diffuse gliomas: A retrospective study of 990 cases.

Background: Gliomas distribute unevenly in the supratentorial brain space. Many factors were linked to tumor locations. This study aims to describe a more detailed distributing pattern of these tumors with age and pathological factors concerned. Methods: A consecutive series of 990 adult patients with newly-diagnosed supratentorial diffuse gliomas who underwent resection in Beijing Tiantan Hospital between January 2013 and January 2017 were retrospectively reviewed. For each patient, the anatomic locations were identified by the preoperative MRI, and the pathological subtypes were reviewed for histological grade and molecular status (if any) from his medical record. The MNI template was manually segmented to measure each anatomic location's volume, and its invaded ratio was then adjusted by the volume to calculate the frequency density. Factors of age and pathological subtypes were also compared among locations. Results: The insulae, hippocampi, and corpus callosum were locations of the densest frequencies. The frequency density decreased from the anterior to posterior (frontal - motor region - sensory region - parietal - occipital), while the grade (p < 0.0001) and the proportion of IDH-wt (p < 0.0001) increased. More tumors invading the right basal ganglion were MGMT-mt (p = 0.0007), and more of those invading the left frontal were TERT-wt (p = 0.0256). Age varied among locations and pathological subtypes. Conclusions: This study demonstrated more detailed spatial disproportions of supratentorial gliomas. There are potential interactions among age, pathological subtypes, and tumor locations.

Endoscopic Fenestration for Treating Galassi Type III Middle Cranial Fossa Arachnoid Cysts: Single- and Multiple-stoma have the Same Curative Effect.

BACKGROUND: For endoscopic fenestration of middle cranial fossa arachnoid cysts (MCFACs), the decisions on the location and number of stomas are key issues. However, research on this particular topic has been limited. Thus, this study aimed to compare single- versus multiple-stoma endoscopic fenestration for treating Galassi type III MCFACs. METHODS: This retrospective study included 86 patients with Galassi type III MCFACs treated with endoscopic fenestration. Single-stoma fenestration to the basal cistern was performed in 37 cases, whereas multiple-stoma fenestration to the basal cistern and the carotid cistern was performed in 49 cases. Clinicoradiologic profiles and follow-up data were analyzed. RESULTS: The rate of symptom relief was 83.7% (72/86), and the rate of cyst shrinkage was 96.5% (83/86). Postoperative ipsilateral subdural effusion, which was significant (p = 0.042), and noninfectious fever were the two most common complications in the single- and multiple-stoma groups. No significant differences in intraoperative nerve injury, vascular injury, proportion of cases with cyst reduction, and symptom remission rate were observed between the two groups. The rates of cyst recurrence and secondary surgery in the single-stoma group were higher than those in the multiple-stoma group, although the difference was not significant. CONCLUSION: Endoscopic fenestration is an effective and minimally invasive approach for treating Galassi type III MCFACs. Single- and multiple-stoma endoscopic fenestrations have the same curative effect.

The Integrated Stress Response Is Tumorigenic and Constitutes a Therapeutic Liability in Somatotroph Adenomas.

Somatotroph adenomas are the leading cause of acromegaly, with the nearly sparsely granulated somatotroph subtype belonging to high-risk adenomas, and they are less responsive to medical treatment. The integrated stress response (ISR) is an essential stress-support pathway increasingly recognized as a determinant of tumorigenesis. In this study, we identified the characteristic profiling of the integrated stress response in translocation and translation initiation factor activity in somatotroph adenomas, normal pituitary, or other adenoma subtypes through proteomics. Immunohistochemistry exhibited the differential significance and the priority of eukaryotic translation initiation factor 2ß (EIF2ß) in somatotroph adenomas compared with gonadotroph and corticotroph adenomas. Differentially expressed genes based on the level of EIF2ß in somatotroph adenomas were revealed. MetaSape pathways showed that EIF2ß was involved in regulating growth and cell activation, immune system, and extracellular matrix organization processes. The correlation analysis showed Spearman correlation coefficients of r = 0.611 (p < 0.001) for EIF2ß and eukaryotic translation initiation factor 2 alpha kinase 1 (HRI), r = 0.765 (p < 0.001) for eukaryotic translation initiation factor 2 alpha kinase 2 (PKR), r = 0.813 (p < 0.001) for eukaryotic translation initiation factor 2 alpha kinase 3 (PERK), r = 0.728 (p < 0.001) for GCN2, and r = 0.732 (p < 0.001) for signal transducer and activator of transcription 3 (STAT3). Furthermore, the invasive potential in patients with a high EIF2ß was greater than that in patients with a low EIF2ß (7/10 vs. 4/18, p = 0.038), with a lower immune-cell infiltration probability (p < 0.05). The ESTIMATE algorithm showed that the levels of activation of the EIF2 pathway were negatively correlated with the immune score in somatotroph adenomas (p < 0.001). In in vitro experiments, the knockdown of EIF2ß changed the phenotype of somatotroph adenomas, including cell proliferation, migration, and the secretion ability of growth hormone/insulin-like growth factor-1. In this study, we demonstrate that the ISR is pivotal in somatotroph adenomas and provide a rationale for implementing ISR-based regimens in future treatment strategies.

Incidence of ischemic complications and technical nuances of arteries preservation for insular gliomas resection.

Introduction: Insular gliomas have complex anatomy and microvascular supply that make resection difficult. Furthermore, resection of insular glioma is associated with a significant risk of postoperative ischemic complications. Thus, this study aimed to assess the incidence of ischemic complications related to insular glioma resection, determine its risk factors, and describe a single surgeon's experience of artery-preserving tumor resection. Methods: We enrolled 75 consecutive patients with insular gliomas who underwent transcortical tumor resection. Preoperative and postoperative demographic, clinical, radiological [including diffusion-weighted imaging (DWI)], intraoperative neurophysiological data, and functional outcomes were analyzed. Motor evoked potentials (MEPs) and radiological characteristics like the relationship between the proximal segment of the lateral lenticulostriate arteries (LLSAs) and the tumor, the flat inner edge sign (the inner edge of the insular glioma is well-defined) or obscure inner edge sign, the distance between the lesion and posterior limb of the internal capsule and the invasion of the superior limiting sulcus by the tumor were analyzed. Strategies such as "residual triangle," "basal ganglia outline reappearance," and "sculpting" technique were used to preserve the LLSAs and the main branches of M2 for maximal tumor resection according to the Berger-Sinai classification. Results: Postoperative DWI showed acute ischemia in 44 patients (58.7%). Moreover, nine patients (12%) had developed new motor deficits, as determined by the treating neurosurgeons. The flat inner edge sign [odds ratio (OR), 0.144; 95% confidence interval (CI), 0.024-0.876) and MEPs (>50%) (OR, 18.182; 95% CI, 3.311-100.00) were significantly associated with postoperative core ischemia, which affected the posterior limb of the internal capsule or corona radiata. Conclusions: Insular glioma resection was associated with a high incidence of ischemia, as detected by DWI, as well as new motor deficits that were determined by the treating neurosurgeons. Insular glioma patients with obscure inner edge signs and intraoperative MEPs decline >50% had a higher risk of developing core ischemia. With our strategies, maximal safe resection of insular gliomas may be achieved.

Combined Endoscopic and Exoscopic Resection of Intracranial Epidermoid Cysts.

OBJECTIVE: This article aims to introduce an endoscopic-exoscopic technique for the resection of epidermoid cysts. METHODS: We retrospectively analyzed the intracranial epidermoid cysts patients who received whole-course combined endoscopic and exoscopic resection between 2017 and 2020 at our institution, to explore the benefit of combined endoscopic and exoscopic resection of intracranial epidermoid cysts, and evaluated the clinical utility of the endoscopic-exoscopic technique. RESULTS: A total of 17 patients were enrolled in the study. Of all patients, 6 patients (35.3%) underwent total resection, 10 patients (58.8%) underwent subtotal resection, and 1 patient (5.9%) underwent partial resection. Postoperative surgical complications were seen in 3 patients (17.6%), including intracranial infection in 2 patients (11.8%), and a delayed postoperative hematoma was observed in the seventh day after operation for 1 patient (5.9%), who was treated in a conservative manner and recovered smoothly from the hemorrhage. The median follow-up time was 33.3 months (range: 14.5-54.5 months). During the follow-up period, there was no recurrence of the tumors that received total resection. Two patients developed residual tumor regrowth but did not show any symptoms, therefore no further surgery was required. CONCLUSIONS: Endoscopic-exoscopic technique is safe and efficient in the resection of intracranial epidermoid cysts with panoramic views and superior maneuverability. With further development and accumulation of practical experiences, the endoscopic-exoscopic technique can also be applied in the resection of other intracranial tumors.

Reduced sensitivity to delayed time and delayed reward of the post-operative insular glioma patients in delay discounting.

Previous studies have shown that the insula is closely related to addiction, and the structure's role in delay discounting can be measured by a specific task, but the specific role of the insula has been less studied. In this study, we first conducted a lesion study in which we recruited healthy controls (n = 30) and patients with unilateral insula injury (n = 16) to complete a behavioral delay discounting task. Then we conducted a functional magnetic resonance imaging (fMRI) study, and a separate group healthy volunteers (n = 51) completed a delay discounting task during the fMRI scan. The lesion study showed a significant difference between the two groups in the delay discounting task, which revealed that insula injury was associated with impaired decision making. The fMRI study revealed choice-sensitive insula activation that was modulated by delayed time and delayed reward, indicating an important role of the insula in delay discounting. Overall, our results provide evidence for a role of the insular lobe in delay discounting and suggests that this structure may be considered an important factor in the future treatment and diagnosis of addiction disorders.

Experience of Endoscopic Endonasal Approach for 803 Pituitary Tumors With Cavernous Sinus Invasion.

OBJECTIVE: The aim of this study was to investigate the effectiveness, safety, complications, and prognosis of endoscopic endonasal surgery for pituitary adenomas with cavernous sinus invasion (CSI). METHODS: The clinical data of 803 pituitary adenomas with CSI surgeries performed in our single ward between January 1, 2006 and December 31, 2018 were retrospectively reviewed. The resection degree, bone invasion, endocrine examination, complications, and outcome were retrospectively summarized. RESULTS: Gross total resection was achieved in 394 patients (49.1%) subtotal resection in 171 patients (21.3%) and partial resection in 238 patients (29.6%). Clinically variable analyses showed that there was a significant correlation between CSI and female, older age, operation history, and non-gross total resection (NGTR). Among the pituitary adenomas with CSI, there was a significant correlation between bone invasive and NGTR, Knosp classification, recurrence. K-M curves showed that young age, larger tumors, bilateral invasion, Grade 4 of Knosp classification, NGTR, and bone invasion were associated with pituitary adenomas regrowth. Multivariate analysis revealed that bone invasion, NGTR, and Grade 4 of Knosp classification were independent risk factors for pituitary adenomas regrowth. There was a significant correlation between CSI and female, older age, operation history, and tumor resection degree. CONCLUSIONS: There was a significant correlation between CSI and female, older age, operation history, and tumor resection degree. The patients with CSI and bone invasion were likely to recurrent. Non-gross total resection, bone invasion, and Grade 4 of Knosp classification were independent risk factors for pituitary adenomas regrowth. Endoscopic endonasal surgery is an excellent choice for pituitary adenomas with CSI.

Expression of Transforming Growth Factor ß1, Smad3, and Phospho-Smad3 in Somatotropinomas and Their Relationship to Tumor Behavior.

OBJECTIVE: To investigate the role of transforming growth factor ß1 (TGF-ß1), Smad3, and phospho-Smad3 (p-Smad3) in the invasion of somatotropinomas. METHODS: In total, 45 somatotropinomas were obtained from patients who underwent surgery for the first time between 2011 and 2015 at Beijing Tiantan Hospital. The expression of TGF-ß1, Smad3, and p-Smad3 was examined by western blot, quantitative reverse transcription polymerase chain reaction, and immunohistochemistry in somatotropinomas, and factors correlated with tumor invasion were analyzed. RESULTS: A total of 13 invasive somatotropinomas and 32 noninvasive somatotropinomas were enrolled in the study. TGF-ß1 protein (P < 0.01) and mRNA (P < 0.01) levels were significantly less in the invasive somatotropinomas than noninvasive somatotropinomas. There was no significant difference in Smad3 protein level or Smad3 mRNA level between invasive somatotropinomas and noninvasive somatotropinomas. However, the p-Smad3 protein level was significantly less in the invasive somatotropinomas than noninvasive somatotropinomas (P < 0.01). Univariate analysis demonstrated that TGF-ß1 (P < 0.01) and p-Smad3 scores (P < 0.01) were associated with invasion. In multivariate analysis, p-Smad3 scores remained a significantly independent predictor of invasion (odds ratio 0.897, 95% confidence interval 0.834-0.964, P < 0.05). CONCLUSIONS: Low expression of p-Smad3 is correlated with invasion of somatotropinomas.

Contralesional Structural Plasticity in Different Molecular Pathologic Subtypes of Insular Glioma.

Neuroplasticity may preserve neurologic function in insular glioma, thereby improving prognosis following resection. However, the anatomic and molecular bases of this phenomenon are not known. To address this gap in knowledge, the present study investigated contralesional compensation in different molecular pathologic subtypes of insular glioma by high-resolution three-dimensional T1-weighted structural magnetic resonance imaging. A total of 52 patients with insular glioma were examined. We compared the gray matter volume (GMV) of the contralesional insula according to histological grade [low-grade glioma (LGG) and high-grade glioma (HGG)] and molecular pathology status [isocitrate dehydrogenase (IDH) mutation, telomerase reverse-transcriptase (TERT) promoter mutation, and 1p19q codeletion] by voxel-based morphometry (VBM). A cluster of 320 voxels in contralesional insula with higher GMV was observed in glioma with IDH mutation as compared to IDH wild-type tumors by region of interest-based VBM analysis (family-wise error-corrected at p < 0.05). The GMV of the entire contralesional insula was also larger in insular glioma patients with IDH mutation than in patients with wild-type IDH. However, there was no association between histological grade, TERT promoter mutation, or 1p19q codeletion and GMV in the contralesional insula. Thus, IDH mutation is associated with greater structural compensation in insular glioma. These findings may be useful for predicting neurocognitive and functional outcomes in patients undergoing resection surgery.

Prediction of Lower Grade Insular Glioma Molecular Pathology Using Diffusion Tensor Imaging Metric-Based Histogram Parameters.

OBJECTIVES: To explore whether a simplified lesion delineation method and a set of diffusion tensor imaging (DTI) metric-based histogram parameters (mean, 25th percentile, 75th percentile, skewness, and kurtosis) are efficient at predicting the molecular pathology status (MGMT methylation, IDH mutation, TERT promoter mutation, and 1p19q codeletion) of lower grade insular gliomas (grades II and III). METHODS: 40 lower grade insular glioma patients in two medical centers underwent preoperative DTI scanning. For each patient, the entire abnormal area in their b-non (b0) image was defined as region of interest (ROI), and a set of histogram parameters were calculated for two DTI metrics, fractional anisotropy (FA) and mean diffusivity (MD). Then, we compared how these DTI metrics varied according to molecular pathology and glioma grade, with their predictive performance individually and jointly assessed using receiver operating characteristic curves. The reliability of the combined prediction was evaluated by the calibration curve and Hosmer and Lemeshow test. RESULTS: The mean, 25th percentile, and 75th percentile of FA were associated with glioma grade, while the mean, 25th percentile, 75th percentile, and skewness of both FA and MD predicted IDH mutation. The mean, 25th percentile, and 75th percentile of FA, and all MD histogram parameters significantly distinguished TERT promoter status. Similarly, all MD histogram parameters were associated with 1p19q status. However, none of the parameters analyzed for either metric successfully predicted MGMT methylation. The 25th percentile of FA yielded the highest prediction efficiency for glioma grade, IDH mutation, and TERT promoter mutation, while the 75th percentile of MD gave the best prediction of 1p19q codeletion. The combined prediction could enhance the discrimination of grading, IDH and TERT mutation, and also with a good fitness. CONCLUSIONS: Overall, more invasive gliomas showed higher FA and lower MD values. The simplified ROI delineation method presented here based on the combination of appropriate histogram parameters yielded a more practical and efficient approach to predicting molecular pathology in lower grade insular gliomas. This approach could help clinicians to determine the extent of tumor resection required and reduce complications, enabling more precise treatment of insular gliomas in combination with radiotherapy and chemotherapy.

CDKN2A (p16INK4A) affects the anti­tumor effect of CDK inhibitor in somatotroph adenomas.

The altered cell cycle is associated with aberrant growth factor signaling in somatotroph adenoma, which is the primary cause of acromegaly. The aim of the present study was to investigate the pathological role of the INK4 family and evaluate the effectiveness of CDK4 inhibitor, palbociclib, in somatotroph adenoma. RNA­Seq, RT­PCR, and immunohistochemistry were applied to measure the levels and correlations of the INK4 family with angiogenesis, CDKs, EMT, and therapeutic targets. MTS, flow cytometry, and ELISA were used to investigate the bio­activity in GH3 and GT1­1 cell lines after palbociclib treatment. Compared with lactotroph adenoma, gonadotroph adenoma, and corticotroph adenoma, somatotroph samples demonstrated higher expression of CDKN2A and SSTR2 but a lower expression of EGFR, CDK4, and CDH2 (P<0.05). CDKN2A positively correlates with SSTR2, and negatively with CDK4, EGFR, and CDH2. Patients with lower CDKN2A had larger tumor size (P=0.016) and more invasive potential (P=0.023). Palbociclib inhibited cell proliferation, induced G1 phase arrest, reduced GH/IGF­1 secretion of GH3 and GT1­1 cell lines (P<0.05), and had a more prominent role in GH3 cells (P<0.05). CDKN2A inhibited the bio­activity by modulating CDK4, and high CDKN2A predicted the insensitivity to CDK4 inhibitor, palbociclib, in somatotroph adenoma patients. In summary, the present study shows CDKN2A inhibited the bio­activity by modulating CDK4, and high CDKN2A predicts the insensitivity to CDK4 inhibitor, Palbociclib, in somatotroph adenoma patients.

Experience of trans-nasal endoscopic surgery for pituitary tumors in a single center in China: Surgical results in a cohort of 2032 patients, operated between 2006 and 2018.

OBJECTIVES: This study was conducted to investigate complications and outcome by endonasal endoscopic approach in our single center. PATIENTS AND METHODS: The clinical data of 2032 pituitary adenoma surgeries performed in our ward between January 2006 and December 2018 were retrospectively reviewed. The GTR (gross total resection) rate, hormonal control, complications, and tumor recurrence rate were retrospectively analyzed. RESULTS: There were 628 (83.5 %) preoperative headache patients, 513 (68.9 %) visual acuity and visual field impaired patients, 218 (66.4 %) endocrine symptom patients and 26 (53.1 %) SIADH (syndrome of inappropriate secretion of antidiuretic hormone) patients experienced improvement after surgery. GTR was achieved in 1627 patients (80.1 %) and NGTR (non-gross total resection) in 405 patients (19.9 %). Clinically variable analyses revealed a significant correlation between GTR and Knosp's grades, large tumor volume, bone-invasive and recurrent tumors. Postoperative complications mainly included 34 (1.7 %) CSF (cerebral spinal fluid) leak, 72 (3.5 %) pituitary insufficiency, 30 (1.5 %) meningitis, 20 (0.98 %) cranial nerve deficits, 5 (0.25 %) hematoma, 5 (0.25 %) patients with internal carotid artery injury, and other complications mainly included nasal complications occurred in 168 patients (8.6 %). Overall, there were 3 deaths (0.15 %) occurred in our series. Univariate analysis showed that larger tumors, invasion, bone invasive, recurrent tumors and NGTR were associated with tumor regrowth. Multivariate analysis showed that NGTR and invasion were independent risk factors for tumor regrowth. CONCLUSIONS: NGTR and invasion were independent risk factors for tumor regrowth. Endoscopic surgery is an excellent choice for pituitary adenomas. It has the advantages of being minimally invasive, safe, and efficacious.

Identification of a multidimensional transcriptome signature predicting tumor regrowth of clinically non­functioning pituitary adenoma.

Clinically non­functioning pituitary adenoma (NFPA) represents approximately one third of all pituitary adenomas. Tumor regrowth is an important feature of NFPA; however, the effective methods with which to predict this are limited. The present study analyzed the expression of protein­coding genes and long non­coding RNA in 66 patients with NFPA. Cox regression analysis was performed to identify genes associated with regrowth or progression­free survival (PFS). Kaplan­Meier, random survival forest analysis and receiver operating characteristic curve (ROC) analyses were performed to generate a multi­protein­coding gene (PCG) and long non­coding RNA (lncRNA) signature with a maximum area under the ROC curve (AUC). In total, 1 PCG (CHST12) and 2 lncRNAs (COA6­AS1 and RP11­23N2.4) were identified that were significantly associated with tumor regrowth. The multi­transcriptome signature exhibited a high predictive accuracy for tumor regrowth, with an AUC of 0.869/0.726 in the training/testing set, and the discriminative power of this signature was better than that of age. On the whole, the present study indicates that the combined PCG and lncRNA signature may be beneficial as a marker for the prediction of the prognosis of patients with NFPA.

Transcortical approach for insular gliomas: a series of 253 patients.

PURPOSE: The object of this study was to identify the distribution characteristics of insular gliomas and evaluate the efficiency of transcortical approach. METHODS: Insular gliomas patients who underwent transcortical approach for the first time between March 2011 and July 2019 at our institute were analyzed. RESULTS: A total of 253 primary insular gliomas patients were enrolled in the study. Of all patients, 176 patients (69.6%) underwent gross total resection, 61 patients (24.1%) underwent subtotal resection and 16 patients (6.3%) underwent partial resection. According to Berger-Sanai classification, the gross total resection rates of different types of insular gliomas were as follows: Zone I (90.1%), zone II (50.0%), zone III (40.0%), zone IV (89.5%), zone I + II (43.5%), zone I + IV (74.6%), zone II + III (44.4%), zone III + IV (41.7%), Giant (34.5%). According to our modified classification, the gross total resection rates were as follows: anterior type (84.9%), posterior type (45.8%), anterior-posterior type (42.9%), giant type (34.5%). After surgery, new limb motor deficit was observed in 28 patients (11.1%), and 5 patients (2.0%) were left long-term limb motor disability. New language impairment occurred in 23 patients (9.1%), and 3 patients (1.2%) were left long-term language disability. The patients were followed up for 1 to 89.2 months (average, 39.9 ± 20.3 months). At the end of follow-up, tumor progression occurred in 98 (38.7%) patients and 71 (28.1%) patients died of their disease. CONCLUSION: This study demonstrated that the maximal safe resection of insular gliomas can be achieved by transcortical approach. Insular gliomas had the characteristic of forward distribution, anterior transcortical approach can provide enough surgical freedom for anterior type of insular gliomas. If anterior tumors can make route to the posterior parts, anterior transcortical approach was also applied to some anterior-posterior and giant types of insular gliomas without resection of excessive brain, which may reduce the incidence of neurological complications.