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Approximately 30%--40% of growth hormone--secreting pituitary adenomas (GHPAs) harbor somatic activating mutations in GNAS (α subunit of stimulatory G protein). Mutations in GNAS are associated with clinical features of smaller and less invasive tumors. However, the role of GNAS mutations in the invasiveness of GHPAs is unclear. GNAS mutations were detected in GHPAs using a standard polymerase chain reaction (PCR) sequencing procedure. The expression of mutation-associated maternally expressed gene 3 (MEG3) was evaluated with RT-qPCR. MEG3 was manipulated in GH3 cells using a lentiviral expression system. Cell invasion ability was measured using a Transwell assay, and epithelial--mesenchymal transition (EMT)-associated proteins were quantified by immunofluorescence and western blotting. Finally, a tumor cell xenograft mouse model was used to verify the effect of MEG3 on tumor growth and invasiveness. The invasiveness of GHPAs was significantly decreased in mice with mutated GNAS compared with that in mice with wild-type GNAS. Consistently, the invasiveness of mutant GNASexpressing GH3 cells decreased. MEG3 is uniquely expressed at high levels in GHPAs harboring mutated GNAS. Accordingly, MEG3 upregulation inhibited tumor cell invasion, and conversely, MEG3 downregulation increased tumor cell invasion. Mechanistically, GNAS mutations inhibit EMT in GHPAs. MEG3 in mutated GNAS cells prevented cell invasion through the inactivation of the Wnt/β-catenin signaling pathway, which was further validated in vivo. Our data suggest that GNAS mutations may suppress cell invasion in GHPAs by regulating EMT through the activation of the MEG3/Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Background: The global impact of the COVID-19 pandemic had significantly altered the daily routines of people worldwide. This study aimed to compare how sleeptime and depression among Chinese residents had differed between periods during and outside the epidemic. Furthermore, it delved into the interactive effect of age in this relationship. Method: Utilizing data from the China Health and Retirement Longitudinal Study (CHARLS) study in 2015 and the recently released data from 2020, which covered the pandemic period. Depression was assessed using Center for Epidemiologic Studies Depression Scale (CESD-10), considering a score of 10 or higher as indicative of depression. Participants were categorized based on age, specifically those aged 60 years and older. multivariate logistic regression and interaction analyses were employed to assess the interplay of age, supported by subgroup and sensitivity analyses to reinforce our findings. Results: The 2020 database comprised 19,331 participants, while the 2015 database had 10,507 participants. Our findings demonstrated a significant correlation between sleeptime and depression in both unadjusted models and models adjusted for all variables in both datasets (p<0.001). Upon stratifying by age and adjusting for relevant factors, we identified an interaction effect among age, sleeptime, and depression (p=0.004 for the interaction in the 2020 database, compared to 0.004 in 2015). The restricted cubic spline analysis in both datasets showcased a nonlinear relationship between sleeptime and depression. Conclusions: During both epidemic and non-epidemic periods in China, there existed a correlation between sleep duration and depression, which interacts with age. [ABSTRACT FROM AUTHOR]

Purpose: Anlotinib is a multi-target TKI which has been used in different advanced tumors. However, its efficiency and safety in patients with glioblastoma are still not well discussed. This retrospective study aimed to discover the safety and efficiency of anlotinib in recurrent grade 4 glioma. Methods: The clinical data of patients with recurrent grade 4 glioma treated with anlotinib in our center were collected and analyzed. The progression-free survival (PFS), overall survival (OS), and OS after recurrence were calculated by Kaplan-Meier method and compared by log-rank test. Sub-group analysis was used to find possible variables that affect survival. Results: From October 2017 to December 2020, seventeen patients with recurrent grade 4 glioma treated with anlotinib were enrolled. The median age was 50 with 13 males. The median KPS was 70. All patients received standard STUPP mode treatment before recurrence. The median PFS was 7 months [95% confidence interval (CI) 5.3-8.6]. The median OS after first diagnosis was 17 months (95% CI 15.7-18.3). The median OS after recurrence was 10 months (95% CI 7.6-12.4). The objective response rate was 33.33% (5/15), and the disease control rate was 60% (9/15). The existence of target genes was identified as a variable affecting the survival after recurrence. The median OS after recurrence in patients with target genes was 12 months (95% CI 6.9-17.1), whereas for patients without targets, the median OS was 4 months (95% CI 1.9-6.1) and for patients with an unknown status, the median OS was 10 months (95% CI 8.4-11.6) (P = 0.013). Conclusion: For recurrent grade 4 glioma, anlotinib can be considered as a supplement to the standard STUPP treatment, especially for the patient with anlotinib target genes. [ABSTRACT FROM AUTHOR]

Background: We previously introduced the one-and-a-half (1½) nostril endoscopic transsphenoidal approach (OETA) to reduce the damage to the nasal structures. Here, we reported the modified approach which is called the endoscopic 1½-transseptal approach (EOTA) for pituitary surgery by combining the OETA and the microscopic transseptal approach to simplify intranasal procedures and protect nasal mucosa. In EOTA, we removed the sellar lesions in a corridor that is composed of the right submucosal space and the anterior left ½ nasal cavity. Methods: We introduced EOTA with a detailed technical description and preliminary clinical outcomes. A total of 128 patients who underwent EOTA for pituitary surgery from July 2018 to September 2020 were reviewed for evaluation of the safety and efficacy of this approach. Results: EOTA had a high gross total resection (GTR) rate and a 1ow complication rate. GTR was achieved in 106 (82.8%) patients, with 81.4% for pituitary adenomas and 93.3% for other non-adenomatous lesions. Postoperative complications included 3 patients (2.3%) with postoperative cerebrospinal fluid leak, 3 patients (2.3%) with diabetes insipidus, 5 patients (3.9%) with anterior pituitary insufficiency and 2 patients (1.6%) with meningitis. In addition, EOTA simplified the intranasal procedures, which led to shortened operation time (67.8 minutes). The results of ASK nasal-12, the Lund-Kennedy score, and the odor identification test showed that patients who underwent EOTA recovered quickly after surgery and the nasal cavity returned to the preoperative condition both apparently and physiologically one month after surgery. Conclusions: EOTA is a simple, safe and effective approach for pituitary lesions, which provides not only a sufficient surgical corridor for 2-surgeon/4- or 3-hands technique but also minimally invasive access to the sellar region. [ABSTRACT FROM AUTHOR]

Dopamine agonist (DA) is the first choice for the treatment of prolactinomas, and drug resistance is unavoidable during treatment due to the heterogeneity of tumors. The two prolactinoma cell lines (GH3 cells and MMQ cells) were found to have different sensitivity and responding modes to the cabergoline (CAB) and bromocriptine (BRC). In this research, we disclosed the capability of ACT001, a derivative of parthenolide analogs, to activate AMPK by increasing the intracellular reactive oxygen species (ROS) level and AMP/ATP ratio to reverse DA resistance through dual pathways in prolactinoma cells. The results indicated that ACT001 could reverse the CAB resistance in GH3 cells by inhibiting the mTOR signaling pathway, inducing cell death through autophagy, and reverse the BRC resistance in MMQ cells by activating the EGR1 signaling pathway, inducing cell death through apoptosis. Our results suggested that ACT001 is a promising therapeutic compound for treating DA-resistant prolactinomas. [ABSTRACT FROM AUTHOR]

Background: Binostril endoscopic transsphenoidal approach (BETA) provides sufficient manipulation space and wide endoscopic vision, although it increases the trauma of nose. Mononostril endoscopic transsphenoidal approach (META) has minimal trauma of nose, at the expense of space within the operation. We describe a one- and-a-half nostril endoscopic transsphenoidal approach (OETA) that combines the advantages of BETA and META. Methods: We introduced OETA for pituitary adenomas with a detailed technical description. A retrospective analysis was also performed on 57 consecutive patients who underwent one-and-a-half nostril endoscopic transsphenoidal surgery between March 2014 and June 2015 at Jinling hospital. Results: The gross total resection rate was 79%. The gross complete resection rate of Knosp grade 3 tumors were 63.6, and 27.3% in grade 4 tumors. Postoperative hormone remission was achieved in 14 out of 18 (77.8%) patients with secreting adenomas. Postoperative abnormal visual function improvement was achieved in 23 out of 32 patients (73%) with preoperative visual dysfunction. The overall intra-operative CSF leak was 17.5%, with the postoperative CSF leak decreased to 3.5% after the sellar reconstruction with the unilateral "rescue" nasoseptal flap procedure. The main sinonasal complaints 2 weeks after surgery were: loss of sense of smell (28%), decrease in sense of taste (4%), trouble breathing during the day (18%), thick nasal discharge (36%), post nasal discharge (8%), dried nasal material (6%), and headache (6%). Three months after surgery, there were no reports of decrease of taste, post nasal discharge, or dried nasal material. Other complaints were decreased significantly. Six months after surgery, the main complaints of sinonasal quality of life were negligible, and overall health status was near complete recovery to preoperative status. Conclusions: The one-and-a-half nostril endoscopic transsphenoidal approach for pituitary adenomas is a simple and reliable technique. It provides not only a sufficient surgical corridor for a 2-surgeon/4 or 3-hands technique, but also ensures minimal invasion of the nasal canal. [ABSTRACT FROM AUTHOR]

Background: To examine whole-body vibration (WBV) effect on bone mineral density (BMD) and fall prevention in postmenopausal women, we performed a meta-analysis and systematic review of prospective randomized controlled trials (RCTs) comparing change in BMD of the femoral neck and lumbar spine and related factors of falls between WBV group and control group. Methods: EMBASE, PubMed, Cochrane Central Register of Controlled Trials, ISI Web of Science, and China National Knowledge Infrastructure (CNKI) were searched up to April 2015; search strategy was used as follows: (vibration) AND (osteoporo* OR muscle* OR bone mineral density OR BMD). All prospective randomized controlled trials comparing related factors of falls and BMD change in the femoral neck and lumbar spine between WBV group and control group were retrieved. Results: Eight of 3599 studies with 1014 patients were included, 477 in the WBV group, and 537 in the control group. We found that there was no significant difference in all magnitude groups of the femoral neck (N =936, WMD: 0.00 (-0.00, 0.01); p = 0.18). A statistical significance showed in the all magnitude groups (N= 1014, WMD: 0.01 (0.00, 0.01); p = 0.01) and low-magnitude group (N= 838, WMD: 0.01 (0.00, 0.01); p = 0.007) of the lumbar spine. No significant difference was found in high-magnitude group of the lumbar spine (N = 176, WMD: 0.00 (-0.01, 0.02); p = 0.47), low-magnitude group (N= 838, WMD: 0.00 (-0.00, 0.00); p = 0.92) and high-magnitude group (N = 98, WMD: 0.02 (-0.00, 0.05); p = 0.06) of the femoral neck. All the studies provided data of related factors of falls such as strength of the lower limb, balance, and fall rate reported effectiveness of WBV therapy. In addition, no complication was reported. Conclusions: Low-magnitude whole-body vibration therapy can provide a significant improvement in reducing bone loss in the lumbar spine in postmenopausal women. Moreover, whole-body vibration can be used as an intervention for fall prevention. [ABSTRACT FROM AUTHOR]

The aim of hehe ppresentresent sstudytudy wwasas to study the expresxpres- sion of anterior gradient 2 (AGR2) to determine its clini cal significance in pituitary adenoma (PA), and to evaluate the potentia l effe ct of AGR2 on the dia gnosis, therapy or pro gnosis of PA. Immunohistochemistry was performed to detect the expression of AGR2 in 117 PA tissue samples. Western blotting was performed to confirm the expression profile of AGR2 in different subtypes of PAs. The data showed that in 117 different histological subtypes of PA, 51.3% exhibited AGR2-positive expression. Although AGR2 expression occurred more frequently in PAs secreting growth hormone (GH; 62.5%), adrenocorticotropic hormone (ACTH; 80.0%) and follicle-stimulating hormone (FSH; 75.0%),the positive expression rate of AGR2 showed no statistically significant differences between PA subtypes (P>0.05). The association between AGR2 expression and clini cal parameters was ana lyzed usin g a 2 test, or Fisher 's exa ct pro bability test when appropriate. The result showed that the aggressiveness of PA was significantly associated with AGR2 expression, and that in the majority of aggressive PAs, AGR2 was negative (P<0.001). In conclusion, the current study detected the expression of AGR2 in different subtypes of PAs for the first time. The data indicated that GH-, ACTH- and FSH-secreting PAs present marginally more frequently with AGR2 expression, howeverm the association was not significant (P>0.05). AGR2 may be a target for the study of PA aggressiveness, and a potential index for the diagnosis or prognosis of PAs. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine whether tumor necrosis factor (TNF)-α regulates the expression levels of excitatory amino-acid transporters (EAATs) in primary astrocytes and its roles in brain ischemia. Exogenous TNF-α was administered to pure cultured astrocytes and the expression levels of EAAT1, EAAT2 and glial fibrillary acidic protein (GFAP) were evaluated. The results showed that TNF-α at 10 ng/ml enhanced the expression of EAAT2 in a time-dependent manner, while the expression levels of EAAT1 and GFAP did not change. To determine whether the elevation in the levels of the EAAT2 protein induced by TNF-α had a beneficial effect on ischemic insult, TNF-α was applied to in vitro models of cerebral ischemia; the treatment was observed to increase neuronal viability. The present results suggest that a relatively short-term application of an optimal concentration of TNF-α may protect neurons against ischemic injury by elevating the expression of EAAT2 in astrocytes. [ABSTRACT FROM AUTHOR]

Background To study the expression of D2R, MGMT and VEGF for clinical significance in pituitary adenomas, and to predict the potential curative medical therapy of dopamine agonists, temozolomide and bevacizumab on pituitary adenomas. Methods Immunohistochemistry and western blot were performed to detect the expression of expression of D2R, MGMT and VEGF in pituitary adenoma tissue samples. The ratio of high expression of D2R, MGMT or VEGF in different subtypes of PA was compared by the use of chi-squared tests. The relationships between D2R, MGMT and VEGF expression were assessed by the Spearman rank correlation test. The association between their expression and clinical parameters was analyzed using a chi-squared test, or Fisher's exact probability test when appropriate. Results The data showed that in 197 different histological subtypes of pituitary adenomas (PAs), 64.9 % of them were D2R high expression, 86.3 % were MGMT low expression and 58.9 % were VEGF high expression. D2R high expression existed more frequently in PRL- and GH-secreting PAs. MGMT low expression existed in all PA subtypes. VEGF high expression existed more frequently in PRL, ACTH, FSH secreting and non-functioning PAs. The data of western blot also support the results. Spearman's rank correlation analysis showed that expression of MGMT was positively associated with D2R (r = 0.154, P = 0.031) and VEGF (r = 0.161, P = 0.024) in PAs, but no correlation was showed between D2R and VEGF expression (r = -0.025, P = 0.725 > 0.05). The association between their expression and clinical parameters was analyzed using a chi-squared test, or Fisher's exact probability test when appropriate, but the result showed no significant association. Conclusions PRL-and GH-secreting PAs exist high expression of D2R, responding to dopamine agonists; Most PAs exist low expression of MGMT and high expression of VEGF, TMZ or bevacizumab treatment could be applied under the premise of indications. [ABSTRACT FROM AUTHOR]