A Novel Immune Classification for Predicting Immunotherapy Responsiveness in Patients With Adamantinomatous Craniopharyngioma

Adamantinomatous craniopharyngioma (ACP) is the most common tumor of the sellar region in children. The aggressive behavior of ACP challenges the treatment for it. However, immunotherapy is rarely studied in ACP. In this research, we performed unsupervised cluster analysis on the 725 immune-related genes and arrays of 39 patients with ACP patients in GSE60815 and GSE94349 databases. Two novel immune subtypes were identified, namely immune resistance (IR) subtype and immunogenic (IG) subtype. Interestingly, we found that the ACPs with IG subtype (34.78%, 8/23) were more likely to respond to immunotherapy than the ACPs with IR subtype (6.25%, 1/16) via tumor immune dysfunction and exclusion (TIDE) method. Simultaneously, the enrichment analysis indicated that the differentially expressed genes (DEGs) (p < 0.01, FDR < 0.01) of the IG subtype were chiefly involved in inflammatory and immune responses. However, the DEGs of the IR subtype were mainly involved in RNA processing. Next, immune infiltration analysis revealed a higher proportion of M2 macrophage in the IG subtype than that in the IR subtype. Compared with the IR subtype, the expression levels of immune checkpoint molecules (PD1, PDL1, PDL2, TIM3, CTLA4, Galectin9, LAG3, and CD86) were significantly upregulated in the IG subtype. The ssGSEA results demonstrated that the biofunction of carcinogenesis in the IG subtype was significantly enriched, such as lymphocyte infiltration, mesenchymal phenotype, stemness maintenance, and tumorigenic cytokines, compared with the IR subtype. Finally, a WDR89 (the DEG between IG and IR subtype)-based nomogram model was constructed to predict the immune classification of ACPs with excellent performance. This predictive model provided a reliable classification assessment tool for clinicians and aids treatment decision-making in the clinic

The Mechanism and Pathways of Dopamine and Dopamine Agonists in Prolactinomas

Dopamine agonists such as bromocriptine and cabergoline are the predominant treatment drugs for prolactinoma by inhibiting prolactin secretion and shrinking tumor size. However, the pathways of either dopamine or its agonists that lead to the death of cells are incompletely understood and some are even conflicting conclusions. The main aim of this paper is to review the different pathways of dopamine and its agonists in prolactinomas to help to gain a better understanding of their functions and drug resistance mechanisms

Education in inpatient children and young people’s mental health services

<p>As a chronic disease, osteoarthritis (OA) leads to the degradation of both cartilage and subchondral bone, its development being mediated by proinflammatory cytokines like interleukin-1β. In the present study, the anti-inflammatory effect of specnuezhenide (SPN) in OA and its underlying mechanism were studied in vitro and in vivo. The results showed that SPN decreases the expression of cartilage matrix-degrading enzymes and the activation of NF-κB and wnt/β-catenin signaling, and increases chondrocyte-specific gene expression in IL-1β-induced inflammation in chondrocytes. Furthermore, SPN treatment prevents the degeneration of both cartilage and subchondral bone in a rat model of OA. To the best of our knowledge, this study is the first to report that SPN decreases interleukin-1β-induced inflammation in rat chondrocytes by inhibiting the activation of the NF-κB and wnt/β-catenin pathways, and, thus, has therapeutic potential in the treatment of OA.</p

Cooperation-based sperm clusters mediate sperm oviduct entry and fertilization

Sperm cooperation has been observed in multiple species, yet its existence and benefit for reproductive success in mammals remains underexplored. Here, combining tissue-clearing with deep three-dimensional imaging, we demonstrate that postcopulatory mouse sperm congregate into unidirectional sperm cooperative clusters at the utero-tubal junction (UTJ), a key physical barrier for passage into the oviduct. Reducing sperm number in male mice by unilateral vasoligation or busulfan-treatment impairs sperm cluster formation and oviduct entry. Interestingly, sperm derived from Tex101-/- mouse has normal number, motility and morphology, yet they cannot form sperm cluster and fail to pass through the UTJ, which is at least in part due to the altered tail beating pattern of the Tex101-/- sperm. Moreover, Tex101-/- sperm's defect in oviduct entry cannot be rescued by the presence of wild-type (WT) sperm in the same uteri by sequential mating, suggesting sperm cooperative cluster as an essential behavior contributing to male fertility, which could be related to human infertility or subfertility

Endoscopic endonasal transsphenoidal surgery for the cavernous sinus hemangioma: Surgical application and review of the literature

Aim: Cavernous sinus hemangiomas (CSHs) are hypervascular malformations and the surgical treatment is technically demanding. Although some articles have reported resection of CSHs using endoscopic endonasal transsphenoidal surgery (EETS), most of them were encountered for a lack of preoperative strategy guidance. Herein, we reported gross total resection (GTR) of intrasellar CSHs in two patients undergoing strategical EETS and compared EETS with frontotemporal craniotomy (FC) and stereotactic radiosurgery by literature review. Material and methods: Two patients with CSHs who underwent EETS were reported. The literature review was conducted to exhaust studies that reported surgical treatment for CSHs. The tumor resection rate, and the postoperative short-term and long-term newly-developed or deteriorative cranial-nerve function rates were extracted. Results: GTR was achieved with no postoperative complications in the two cases. Nine articles reported 14 cases undergoing EETS for CSHs and twenty-three articles reported 195 cases undergoing FC for CSHs. The GTR rates of EETS and FC were 57.14% (8/14) and 78.97% (154/195) respectively. The postoperative short-term and long-term newly-developed or deteriorative cranial-nerve function rates were 0% (0/7) and 0% (0/6) for the EETS group, and 57% (57/100) and 18.18% (18/99) for the FC group. According to the previous meta-analysis, stereotactic radiosurgery resulted in remarkable tumor shrinkage in 67.80% (40/59) of patients and partial shrinkage in 25.42% of patients. Discussion: The results showed that the intrasellar type of CSHs could be removed safely by EETS without crossing the nerves in the CS

Morphological study of floral nectaries in Euonymus and the probable origin of the echinate fruit surface

A conspicuous nectary disk is common but has a distinguishing morphology in the cosmopolitan genus Euonymus. Our study focuses on the morphology of floral nectaries in 21 representatives of Euonymus and Glyptopetalum. Two main types of nectaries were documented: a mix of inter- and extrastaminal nectaries existed between the corolla and the stigma, while the intrastaminal nectaries were distributed between the stigma and the stamen bases. The main route of nectar release in Euonymus is via modified stomata, and different nectarostomata locations were observed: in depressions, slightly raised above the epidermal surface or at the same level as the epidermis. Floral nectaries in E. sect. Echinococcus species developed into the protrusions on the fruit surface at the later stage. The development of nectaries not only explained the mystery of the origin of the echinate fruit surface, but also showed that differences in fruit surface might be inappropriate for use in infrageneric classification. These discoveries inform morphological observations of floral nectaries in Euonymus

Quantitative analysis of retinal layers on three-dimensional spectral-domain optical coherence tomography for pituitary adenoma.

To quantitatively investigate the characteristics of eyes with pituitary adenoma presented by three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) using three common indices, including thickness, optical intensity ratio, and optical intensity attenuation coefficient (OIAC).The SD-OCT database of 38 patients with pituitary adenoma and 39 normal controls were included in the study. Quadrantal and average measurements of thickness, optical intensity ratio, and OIAC were calculated for macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL) combined with inner plexiform layer (IPL) (GCIPL) and/or the collective ganglion cell complex (GCC). The parameters of patients and controls were compared by unpaired t-test and Mann-Whitney U-test. The relationships between the optical intensity ratio and the thickness of mRNFL and GCIPL were evaluated by Pearson's correlation. Diagnostic performances of these indices were assessed using receiver operating characteristic (ROC) analysis.Significant decreases in thickness existed in the mRNFL and nasal GCC of patients compared with controls (p-values of 0.000 to 0.039). Optical intensity ratios in the relevant retinal layers of patients were almost all lower than those of controls. In patients, optical intensities were increased in the mRNFL but decreased in the GCIPL along with an increase of retinal thicknesses. The OIAC measurements were significantly higher in the upper quadrants and global average of the mRNFL in patients. The areas under the ROC curves (AUC) obtained by global average mRNFL thickness was significantly greater than that of the global average OIAC in the mRNFL (p = 0.0265).Thicknesses of the mRNFL and nasal GCC were significantly decreased in the retinas of patients with pituitary adenoma compared with controls. The differences of the optical intensity ratio and OIAC between patients and controls were not all statistically significant. Thickness was more sensitive than optical characteristics indices in distinguishing pituitary adenoma from controls

Development and Validation of Nomogram to Preoperatively Predict Intraoperative Cerebrospinal Fluid Leakage in Endoscopic Pituitary Surgery: A Retrospective Cohort Study

BackgroundPituitary adenomas (PAs) are the most common tumor of the sellar region. PA resection is the preferred treatment for patients with clear indications for surgery. Intraoperative cerebrospinal fluid (iCSF) leakage is a major complication of PA resection surgery. Risk factors for iCSF leakage have been studied previously, but a predictive nomogram has not yet been developed. We constructed a nomogram for preoperative prediction of iCSF leakage in endoscopic pituitary surgery.MethodsA total of 232 patients who underwent endoscopic PA resection at the Department of Neurosurgery in Jinling Hospital between January of 2018 and October of 2020 were enrolled in this retrospective study. Patients treated by a board-certified neurosurgeon were randomly classified into a training cohort or a validation cohort 1. Patients treated by other qualified neurosurgeons were included in validation cohort 2. A range of demographic, clinical, radiological, and laboratory data were acquired from the medical records. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and uni- and multivariate logistic regression were utilized to analyze these features and develop a nomogram model. We used a receiver operating characteristic (ROC) curve and calibration curve to evaluate the predictive performance of the nomogram model.ResultsVariables were comparable between the training cohort and validation cohort 1. Tumor height and albumin were included in the final prediction model. The area under the curve (AUC) of the nomogram model was 0.733, 0.643, and 0.644 in training, validation 1, and validation 2 cohorts, respectively. The calibration curve showed satisfactory homogeneity between the predicted probability and actual observations. Nomogram performance was stable in the subgroup analysis.ConclusionsTumor height and albumin were the independent risk factors for iCSF leakage. The prediction model developed in this study is the first nomogram developed as a practical and effective tool to facilitate the preoperative prediction of iCSF leakage in endoscopic pituitary surgery, thus optimizing treatment decisions

Rat Chondrocyte Inflammation and Osteoarthritis Are Ameliorated by Madecassoside

As a joint disease, osteoarthritis (OA) is caused by the breakdown of subchondral bone and cartilage damage. Inflammatory factors, such as interleukin- (IL-) 1β, mediate the progression of OA. Madecassoside (MA), a triterpenoid component derived from the gotu kola herb (Centella asiatica), exhibits various pharmacological effects, including antioxidative and anti-inflammatory properties. In the present study, the protective effects and possible mechanism of MA on the treatment of OA were investigated. MA was demonstrated to significantly suppress the IL-1β-induced overexpression of matrix metalloproteinase- (MMP-) 3, MMP-13, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) and to decrease the IL-1β-induced degradation of type II collagen and sox9. Additionally, MA was able to reduce the IL-1β-induced phosphorylation of p65 in osteoarthritic chondrocytes. Furthermore, in a rat OA model, MA prevented cartilage degeneration and reduced the OARSI score in the MA-treated group compared with the OA group. The present study showed that MA suppresses the nuclear factor-κB signaling pathway, reducing IL-1β-induced chondrocyte inflammation, which indicates the therapeutic potential of MA in patients with OA

Comparison of the area under the receiver operating characteristic curves (AUC) between pituitary adenoma patients and controls.

<p>Comparison of the area under the receiver operating characteristic curves (AUC) between pituitary adenoma patients and controls.</p