Search

Sellar germ cell tumors (GCTs) occur more frequently in childhood. Some will present as malignancy with infiltration and metastasis. However, the association between the timeliness of diagnosis and outcome has been controversial. We investigated the clinical risk factors associated with a diagnostic delay in patients with sellar GCTs in China.The data from 53 patients aged18 years with histologically confirmed sellar GCTs at Peking Union Medical College Hospital treated from January 2008 to December 2016 were reviewed retrospectively.The median interval between symptom onset and diagnosis was 25 months. Of the 53 patients, 44 (83%) had a delayed diagnosis. Most patients (86%) with a delayed diagnosis presented with polyuria or polydipsia. Of the 53 patients, 48 (91%) exhibited changes in the pituitary stalk. Patients with a germinoma (odds ratio, 4.1; 95% confidence interval, 2.4-6.9) and slow growth (odds ratio, 5.3; 95% confidence interval, 1.2-24.5) were more likely to have a delayed diagnosis. The overwhelming majority of patients with a delayed diagnosis (96%) had been seen by1 doctor. No statistically significant differences were found in the mean survival time (P = 0.21) or mean progression-free survival time (P = 0.36) between patients with and without delay in diagnosis, respectively.A significant proportion of patients with sellar GCTs will experience a delay in the time to diagnosis. Although a delay in diagnosis did not reduce the survival time or progression-free survival time for patients with sellar GCTs, it might increase the risk of short stature. Thus, a detailed medical history and an immediate radiological examination are important for the early diagnosis of sellar GCTs in childhood.

Objective To investigate the clinical characteristics of delayed remission (DR) of growth hormone (GH)-secreting pituitary adenoma after transsphenoidal adenectomy and inform follow-up treatments. Methods We retrospectively reviewed 87 patients who had undergone transsphenoidal surgery for acromegaly. Demographic, radiological, and endocrinological data were reviewed before, immediately after, 3 months after, and in the long term (2.4 ± 1.1 years) after surgery. The definition of DR was that patients did not achieve GH remission immediately, 3 months, or later after surgery, but did so in the long term without any additional postoperative treatment. Results Fifty-one patients (58.6%) achieved long-term GH remission. There were 24 (27.6%) DR patients immediately postoperatively and 9 (10.3%) DR patients 3 months postoperatively. On average, the 24 DR patients achieved remission at 10.2 (range, 3–32) months. Immediate postoperative random and nadir GH after an oral glucose load were significantly lower in the DR group than in the nonremission group (2.73 ± 3.17 and 2.03 ± 2.59 vs. 8.05 ± 10.35 and 5.55 ± 5.91 μg/L, respectively). Three-month postoperative nadir GH was significantly lower in the DR group than in the nonremission group (1.63 ± 2.82 vs. 3.48 ± 4.25 μg/L, P = 0.007). Immediate postoperative random GH effectively predicted long-term remission (Spearman's ρ = 0.513, area under the curve = 0.905 > 0.90). However, the best predictor of long-term remission was 3-month postoperative nadir GH (Spearman's ρ = 0.728, area under the curve = 0.944 > 0.90), with 76.5% sensitivity and 97.2% specificity. Conclusions For certain groups of patients likely to achieve DR, additional treatments should not be performed early after surgery. Prolonged follow-up and close observation could help determine the therapeutic effect of surgery and guide postoperative treatments.

Previously reported photoelectric devices have mainly been limited to inorganic materials. Even though preparing high-performance photoelectric devices with organic biomaterials is an inevitable trend in commercialization, fabricating organic photoelectric devices based on naturally occurring materials with high sensitivity remains a great challenge due to the high resistivity of and few free electrons in these materials. Herein, high-performance photoelectric devices based on an egg albumin (EA)/Si structure are proposed, and a new, to the best of our knowledge, perspective is provided on photodetection in naturally occurring materials by utilizing the surface state of p-Si to separate light-induced carriers effectively. The free electrons of metal atoms restrain the surface states, leading to a sensitivity of 5 mV/mm for metal/Si devices, while the sensitivity of the EA/Si device in the near-infrared region is greatly promoted to 357 mW/mm, which is intimately related to the lack of effect of EA on the dangling bonds of the surface. The EA/Si device is among the most sensitive organic near-infrared photoelectronic device to date. This work opens up new avenues to overcome the obstacle of the low sensitivity of organic photodetectors, indicating that the EA/Si device has great potential for future applications in flexible photovoltaic devices.

Context Glucocorticoids act through the glucocorticoid receptor (GR) encoded by the nuclear receptor subfamily 3 group C member 1 (NR3C1) gene. Objective This study aimed to examine the function of NR3C1 variants and their possible pathogenic role in Cushing disease (CD). Methods Next-generation sequencing was conducted in 49 CD patients. Corticotroph tumor GR protein expression was examined by immunohistochemistry (IHC). Constructs harboring the 3 NR3C1-mutant and wild-type (WT) GR were transfected into the murine corticotropic adenoma cell line (AtT-20), and GR protein expression was quantified by Western blot. Translocation activity was assessed by immunofluorescence and effects of the GR mutants on corticotroph tumor proliferation, pro-opiomelanocortin (POMC) transcription, and ACTH secretion were tested. Results Clinical features were similar in patients harboring the NR3C1 mutations and WT GR. Recurrent adenomas showed higher GR IHC scores than nonrecurrent tumors. In vitro studies demonstrated that the p.R469X mutant generated a truncated GR protein, and the p.D590G and p.Y693D GR mutants resulted in lower GR expression. Dexamethasone (DEX) treatment of AtT-20 cells demonstrated decreased DEX-induced nuclear translocation, increased cell proliferation, and attenuated suppression of POMC transcription of 3 GR mutants. Interestingly, the p.R469X GR mutant resulted in increased murine corticotroph tumor ACTH secretion compared to WT GR. Conclusion Our findings identify 3/49 (6.1%) consecutive human corticotroph tumors harboring GR mutations. Further findings demonstrate the role NR3C1 plays in CD pathogenesis and offer insights into a novel treatment approach in this patient subset.

BackgroundThere are no established accurate models that use machine learning (ML) methods to preoperatively predict immediate remission after transsphenoidal surgery (TSS) in patients diagnosed with histology-positive Cushing’s disease (CD).PurposeOur current study aims to devise and assess an ML-based model to preoperatively predict immediate remission after TSS in patients with CD.MethodsA total of 1,045 participants with CD who received TSS at Peking Union Medical College Hospital in a 20-year period (between February 2000 and September 2019) were enrolled in the present study. In total nine ML classifiers were applied to construct models for the preoperative prediction of immediate remission with preoperative factors. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the performance of the models. The performance of each ML-based model was evaluated in terms of AUC.ResultsThe overall immediate remission rate was 73.3% (766/1045). First operation (pConclusionWe developed a readily available ML-based model for the preoperative prediction of immediate remission in patients with CD.

Silent corticotroph adenomas (SCAs) can be redefined according to the 2017 World Health Organization pituitary classification system with the introduction of T‑PIT, a transcription factor. We studied the clinical features of these redefined SCAs.We compared 112 patients with SCAs and 198 patients with silent gonadotroph adenomas (SGAs) who underwent surgery from January 2019 to May 2020.The prevalence of SCAs increased from 21.3 to 30.2% under the new classification rules. T-PIT-positive, adrenocorticotropic hormone-negative SCAs and T-PIT-positive, adrenocorticotropic hormone-positive SCAs exhibited similar clinical features. SCAs exhibited significant female preponderance (90.2% vs. 29.8%, P 0.0001); more frequent invasion (36.6% vs. 7.6%, P 0.0001), especially multiple-site invasion (P 0.0001); and marked cystic changes on imaging compared with SGAs (54.5% vs. 19.2%, P 0.0001). SCAs had a softer tumor consistency (89.2% vs. 61.1%, P 0.0001). Gross total resection was achieved in 66.1% of SCAs and 66.2% of SGAs (P 0.9999). The overall recurrence/progression rates of SCAs and SGAs were 9.8% and 6.6% at 14.1 and 13.5 months of follow-up, respectively (P = 0.3765). The proportion of patients with more than two recurrences requiring multiple surgeries and radiation was similar between SCAs and SGAs (7.1% vs. 3.0%, P = 0.1514). However, multiple recurrences of SCAs affected younger patients than SGAs (39.0 vs. 53.5 years, P = 0.0433).The prevalence of SCAs increased with the introduction of T-PIT. SCAs and SGAs exhibited comparable size and recurrence/progression rates, but SCAs showed increased invasion and more marked cystic change. Aggressive SCAs tended to affect younger patients. Close long-term monitoring for SCA recurrence/progression is required.

Pituitary adenomas (PAs) can be classified as non-secreting adenomas, somatotroph adenomas, corticotroph adenomas, lactotroph adenomas, and thyrotroph adenomas. Substantial advances have been made in our knowledge of the pathobiology of PAs. To obtain a comprehensive understanding of the molecular biological characteristics of different types of PAs, we reviewed the important advances that have been made involving genetic and epigenetic variation, comprising genetic mutations, chromosome number variations, DNA methylation, microRNA regulation, and transcription factor regulation. Classical tumor predisposition syndromes include multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4) syndromes, Carney complex, and X-LAG syndromes. PAs have also been described in association with succinate dehydrogenase-related familial PA, neurofibromatosis type 1, and von Hippel–Lindau, DICER1, and Lynch syndromes. Patients with aryl hydrocarbon receptor-interacting protein (AIP) mutations often present with pituitary gigantism, either in familial or sporadic adenomas. In contrast, guanine nucleotide-binding protein G(s) subunit alpha (GNAS) and G protein-coupled receptor 101 (GPR101) mutations can lead to excess growth hormone. Moreover, the deubiquitinase gene USP8, USP48, and BRAF mutations are associated with adrenocorticotropic hormone production. In this review, we describe the genetic and epigenetic landscape of PAs and summarize novel insights into the regulation of pituitary tumorigenesis.

In 1932, Harvey Cushing first proposed pituitary adenoma (PA) as the term for the cause of acromegaly. After nearly 90 years of research, PA is recognized as the second most common intracranial neoplasm. Most PAs can be easily cured or controlled by conventional therapies, including surgery, medical treatment or radiotherapy. However, nearly 40% of PAs are invasive, and some adenomas show aggressive behavior, with rapid growth patterns and resistance to conventional treatments, which leads to a poor prognosis; this type of adenoma is called aggressive or refractory PA. For a very small proportion of PAs (approximately 0.2%), subarachnoid or systemic metastasis may develop, at which point it is considered malignant and called pituitary carcinoma. Based on distinctions regarding the biological behaviors of adenoma, aggressive adenoma and pituitary carcinoma, the International Pituitary Pathology Club in 2016 formally proposed new terminology for PA: pituitary neuroendocrine tumor (PitNET). Over the last three years, an increasing number of relevant articles have used the term PitNET in place of PA. Interestingly, the fourth edition of the WHO classification of PA released in 2017 did not adopt this nomenclature, and the Pituitary Society published a paper in 2019 suggesting that the new nomenclature does not improve clinical diagnosis or treatment and confuses patients more than the PA terminology. The Pituitary Society insists on using the term PA, as PAs with aggressive behavior only account for a very small proportion of all PAs. Overall, the new terminology may cause significant and unnecessary patient anxiety and confusion. Here, we describe the current perspectives and bases of the two naming methods and offer our opinions on maintaining the original naming system for PA. Nevertheless, early diagnosis and intensive treatment of aggressive PAs is extremely important for improving patient prognosis, regardless of the nomenclature.

Genetic and epigenetic alterations are involved in pituitary adenoma pathogenesis, however the molecular basis of proliferative nonfunctioning pituitary adenomas (NFPAs) remains unclear. Here, we analyzed integrated multi-omics profiling including copy number variation (CNV), DNA methylation and gene expression of 8 NFPAs. We collected 4 highly proliferative (hpNFPA, Ki-67 ≥ 3) and 4 lowly proliferative (Ki-67 ≤ 1) NFPAs, and comprehensively assessed CNV, DNA methylation, and gene expression by Illumina HumanMethylation450 BeadChip and Affymetrix GeneChip PrimeView Human Gene Expression Array. We performed Ingenuity Pathway Analysis (IPA) for differentially expressed genes to illustrate aberrant pathways and delineated protein–protein networks of selected key genes in dysregulated pathways. Aberrant arm level CNV, dysregulated DNA methylation, and associated impacts on gene expressions were observed in 2 early occurring hpNFPAs. Chromosomal losses were associated with attenuated expression of DNA methyltransferases, further altering global methylation in these 2 samples. Correlation analysis between DNA methylation and gene expression in 8 NFPAs indicates methylation in promoter and gene body regions are both involved in gene regulation. IPA showed PPARα/RXRα, dopamine receptor signaling, cAMP-mediated signaling, and calcium signaling were all activated, while p38 MAPK and ERK5 signaling were inhibited in hpNFPAs. Moreover, selected key gene networks in hpNFPAs exhibited concurrent methylation status and expression levels of adenylate cyclase genes, G protein subunits, HLA genes, CXCL12, and CCL2. This study presents comprehensive multi-omics views of CNV, DNA methylation, and gene expression in 8 NFPAs. Pathway analysis and network maps of key genes provide clues to elucidate the molecular basis of hpNFPA.

Rosai-Dorfman disease (RDD) is an extremely rare histiocytic disorder characterized by cervical lymphadenopathy, while the involvement of sellar region is less observed. Here we report a pediatric patient who was initially suspected as sellar germinoma but later identified as RDD. We also conducted a systematic review about RDD involving sellar region. A total of only 14 cases were included and analyzed in our study in terms of clinical presentation, endocrine abnormality, radiological features, pathology, treatment, and follow up. The most common neurological manifestations of sellar RDD is diabetes insipidus and visual changes. Two typical kinds of MRI manifestations were presented in sellar RDD; one is like meningioma-like mass lesions, another showing infiltrative pattern that demonstrates hyperintense areas on T2WI. Currently, the treatment of RDD is tailored to the individual clinical circumstances. For sellar RDD, surgical treatment can be considered to completely remove or debulk the tumor.

To improve the decoding speed and reduce the complexity of low-density parity-check (LDPC) codes, this paper proposes a hybrid LDPC decoding algorithm that combined with the distribution characteristics of log-likelihood ratio (LLR) of all variable node information before each iteration. During the process of decoding, there is a judgment based on an interval value and a threshold value to select the Belief Propagation (BP) algorithm or the Minimal Sum (MS) algorithm to decode, so the proposed hybrid algorithm effectively combines the excellent performance of BP algorithm and the simple operation of MS algorithm. The simulation results show that the algorithm can greatly reduce the computational complexity and achieve similar decoding performance compared with the BP algorithm.

Purpose: Silent corticotroph adenoma (SCA) is clinically non-functional pituitary adenoma with expression of corticotropin or Tpit. To further understand the characteristics of this rare type of SCA transforming to a functional SCA, we retrospectively reviewed SCAs that converted to typical Cushing's syndrome at a tertiary medical center and the relevant literature. Methods: Patients were identified based on the diagnosis of pituitary adenoma without symptoms of hypercortisolism at the initial visit with positive Immunohistochemical (IHC) staining for corticotropin or Tpit after surgery and subsequent transformation to functional SCAs during the follow-up period from March 1990 to January 2020 at Peking Union Medical College Hospital and in the literature. The characteristics of the clinical manifestations, biochemical results, imaging findings, pathology findings and outcome were analyzed. Results: Altogether, 16 patients were included in the study with an average age of 42.0 ± 12.48 (18-65) years at the first visit. Females were slightly predominant (F:M = 1.3:1). The median time of conversion from the nonfunctional to the functional type was 30 (13.0, 68.3) months. Once a functional SCA developed, the adrenocorticotropic hormone (ACTH) level and 24-h urine free cortisol were increased 3.8- (2.6, 12.9) and 5.3- (2.6, 19.3) fold, respectively, above the normal range. Approximately 50% of the patients had macrocystic changes on pituitary MRI. All 16 patients experienced 1-5 surgeries with a median of 2.5 (2.0, 4.0) surgeries. The proportion of patients with Ki-67 ≥ 3% increased from 22.2% (2/9) at the beginning to 50% (7/14) at the time of functional SCA diagnosis. Thirteen patients received radiotherapy, and 4 patients (30.8%) achieved remission. Four patients with refractory functional SCAs received temozolomide treatment with the normalization of cortisol in 4 cases and reduced tumor volume in 3 cases. Conclusion: In this study, all cases that transformed to functional SCAs were macroadenomas. Hypercortisolism was more severe in functional SCA patients. The tumors tended to have frequent recurrence and were highly invasive. Temozolomide could be a promising treatment for refractory functional SCA cases. Long-term follow-up is needed for nonfunctional SCAs since some cases have the potential to transform to clinical Cushing's syndrome.

Background: Some patients with acromegaly do not reach the remission standard in the short term after surgery but achieve remission without additional postoperative treatment during long-term follow-up; this phenomenon is defined as postoperative delayed remission (DR). DR may complicate the interpretation of surgical outcomes in patients with acromegaly and interfere with decision-making regarding postoperative adjuvant therapy. Objective: We aimed to develop and validate machine learning (ML) models for predicting DR in acromegaly patients who have not achieved remission within 6 months of surgery. Methods: We enrolled 306 acromegaly patients and randomly divided them into training and test datasets. We used the recursive feature elimination (RFE) algorithm to select features and applied six ML algorithms to construct DR prediction models. The performance of these ML models was validated using receiver operating characteristics analysis. We used permutation importance, SHapley Additive exPlanations (SHAP), and local interpretable model-agnostic explanation (LIME) algorithms to determine the importance of the selected features and interpret the ML models. Results: Fifty-five (17.97%) acromegaly patients met the criteria for DR, and five features (post-1w rGH, post-1w nGH, post-6m rGH, post-6m IGF-1, and post-6m nGH) were significantly associated with DR in both the training and the test datasets. After the RFE feature selection, the XGboost model, which comprised the 15 important features, had the greatest discriminatory ability (area under the curve = 0.8349, sensitivity = 0.8889, Youden's index = 0.6842). The XGboost model showed good discrimination ability and provided significantly better estimates of DR of patients with acromegaly compared with using only the Knosp grade. The results obtained from permutation importance, SHAP, and LIME algorithms showed that post-6m IGF-1 is the most important feature in XGboost algorithm prediction and showed the reliability and the clinical practicability of the XGboost model in DR prediction. Conclusions: ML-based models can serve as an effective non-invasive approach to predicting DR and could aid in determining individual treatment and follow-up strategies for acromegaly patients who have not achieved remission within 6 months of surgery.

Ectopic pituitary adenomas (EPAs) are extremely rare pituitary adenomas located outside the sella turcica without any connection with intrasellar components. This study aims to review all the reported cases to date and describe the clinical characteristics of EPAs. In a retrospective chart review, 14 patients were identified with EPAs in our hospital. A literature review was performed, and 166 cases in the literature met the criteria. Clinical data were analyzed. Of 180 patients with EPAs, the mean age at diagnosis was 45.4 years, and 66.5% of the patients were females. EPAs were mainly located in the sphenoid sinus (34.4%) and suprasellar region (25.6%), followed by the clivus (15.6%), cavernous sinus (13.3%) and nasopharynx (5.6%). Adrenocorticotropic hormone (ACTH)-secreting (38.9%) and nonfunctioning (27.2%) adenomas were predominant. Patients with suprasellar EPAs were more likely to present menstrual disorders and visual changes, while patients with clival EPAs were more likely to suffer from headaches. EPAs in the cavernous sinus and suprasellar space were more likely to be initially misdiagnosed as a suspicious intrasellar mass on imaging examination. The complete tumor resection rates for EPAs in the sphenoid sinus, suprasellar region, clivus, cavernous sinus and nasopharynx were 72.3%, 88.6%, 45.0%, 73.3% and 88.9%, respectively. EPA clinical characteristics varied across different tumor locations and hormone-secreting types. In addition to comprehensive hormone evaluation and careful review of imaging data, nuclear medicine and surgical biopsy should also be considered when facing differential difficulty. EPA management should be individualized.

Background: Gray matter (GM) alterations in Parkinson's disease (PD) patients with rapid eye movement sleep behavior disorder (RBD) have been demonstrated in many neuroimaging studies using voxel-based morphometry (VBM). However, the inconsistent findings between studies cannot be applied to clinical practice as a neuroimaging biomarker. We performed a meta-analysis of VBM studies at a whole-brain level to investigate GM differences between PD patients with and without RBD. Methods: A systematic search was conducted in PubMed, Embase, and Web of Science from inception to November 2019 to identify eligible VBM studies. We adopted the latest Seed-based d Mapping with Permutation of Subject Images technique to quantitatively estimate the difference of regional GM volume between PD patients with and without RBD. Results: We included five studies comprising 105 PD patients with RBD and 140 PD patients without RBD. The pooled meta-analysis revealed that PD patients with RBD showed a significant reduction of GM volume in the right superior temporal gyrus (STG) compared with those without RBD. This result was confirmed to be robust by the jackknife sensitivity analysis. Conclusion: Our finding shows significantly and robustly reduced GM volume in the right STG in PD patients with RBD, preliminarily suggesting the association of GM atrophy in this brain region with the occurrence of RBD in PD patients.

Epigenetic factors have been proven to contribute to pituitary adenoma formation. 5-hydroxymethylcytosine (5hmC), which is catalyzed by ten-eleven translocation 2 (TET2), is related to DNA demethylation. In order to explore the pathogenesis of non-functioning pituitary adenomas (NFPAs), we detected genomic 5hmC levels in 57 NFPAs and 5 normal pituitary glands, and TET2 expression, distribution and TET2 alteration. Genomic 5hmC levels in NFPAs were significantly lower than those in normal pituitary glands (0.38‰ (0.24‰, 0.61‰) vs. 2.47‰ (1.56‰, 2.83‰), P < 0.0001). There was positive correlation of 5hmC levels with TET2 total and nuclear expression in NFPAs (r = 0.461, P = 0.018; r = 0.458, P = 0.019). Genomic 5hmC levels in NFPAs with TET2 p.P29R were significantly lower than those in wild type NFPAs (0.33 ± 0.18‰ vs. 0.51 ± 0.25‰, P = 0.021). We found genomic 5hmC loss in human NFPAs for the first time. Genomic 5hmC levels may be affected by TET2 expression, subcellular localization and TET2 mutation.

Background Ectopic adrenocorticotropic hormone–secreting pituitary adenomas (EAPAs) are rare adenomas causing Cushing syndrome, which are located in ectopic locations outside the sella turcica. No more than 100 cases of this entity have been reported. Because of its rarity and nonspecific clinical and biochemical features, EAPA is often misdiagnosed, leading to surgical failure and delayed treatment. In the article, the cases of 3 patients with suprasellar EAPAs treated at our institution are reported and a review of the literature is presented. Case Description All 3 patients with Cushing syndrome had ectopic pituitary adenomas located in the suprasellar region and identifiable on preoperative sellar magnetic resonance imaging. Preoperative laboratory evaluation in all patients showed identical results to those observed in Cushing disease. In 2 patients, craniotomies were performed directly to achieve total tumor resection and clinical remission. One patient, who underwent previous negative transsphenoidal exploration, achieved full remission through a second craniotomy despite pulmonary infection as a postoperative complication. Conclusions Although EAPA is an extremely rare entity, it should be considered as a differential diagnosis of Cushing disease. Because of its similar clinical and biochemical behavior to intrasellar pituitary adrenocorticotropic hormone adenoma in Cushing disease, careful examination of the potential occurrence of EAPA on preoperative radiologic imaging is of considerable significance to avoid unnecessary surgery and achieve improved outcomes. Surgical resection EAPA remains the first choice of treatment, and the optimal surgical approach ought to be determined according to the adenoma features, the general condition of the patient, and the surgeon's experience.

Objective: Transsphenoidal surgery (TSS) is the first-line treatment of patients with Cushing’s disease (CD). However, biochemical remission rates after TSS for CD vary from 59 to 95%, and the predictors of surgical outcomes remain unclear. The aim of this study was to identify the predictors of early outcomes in patients with CD treated with TSS. Methods: The clinical features and outcomes of CD patients who underwent TSS between February 2000 and September 2019 at the Peking Union Medical College Hospital were collected from medical records and analyzed. Uni- and multivariate odds ratio (OR) analyses were performed to identify the predictors of early outcomes in patients with CD. Results: A total of 1,045 patients were included. The median age at TSS was 34.0 years (IQR 26.0–45.0), with a female:male ratio of 4.2:1 (844/201). The median duration of symptoms was 46.0 months (IQR 24.0–72.0). After surgery, the overall postoperative immediate remission rate was 73.3%, and 26.7% of patients had persistent hypercortisolism. Univariate analysis demonstrated that the number of operations was correlated with a lower immediate remission rate (OR 0.393, 95% CI 0.266–0.580, p = 0.000), as was tumor size (OR 0.462, 95% CI 0.334–0.639, p = 0.000), the duration of disease (OR 0.996, 95% CI 0.993–0.999, p = 0.003), and preoperative ACTH concentration (0.998, 95% CI 0.996–0.999, p = 0.003). Cavernous sinus invasion has also been identified as an important factor associated with a lower immediate remission rate (OR 0.275, 95% CI 0.166–0.456, p = 0.000). No correlations were detected between the immediate outcomes and age, gender, BMI, the combination of a low- and high-dose dexamethasone suppression test, preoperative morning serum cortisol level, or 24-h urinary free cortisol level (all p > 0.05). The results of multivariate analysis were similar to those of univariate analysis. Preoperative ACTH ≤67.35 ng/L predicted remission with 60.9% sensitivity and 49.5% specificity (AUC 0.553; p = 0.008). A cutoff of ≤64.5 months for disease duration predicted immediate remission with 40.5% sensitivity and 71.0% specificity (AUC 0.552; p = 0.01). Conclusion: Early outcomes of TSS in CD patients can be predicted by factors including the number of operations, duration of disease, tumor invasion, tumor size, and preoperative ACTH concentration. These predictors can be used to improve the perioperative management of CD patients.

The role of operation for patients with recurrent diffuse low-grade glioma (DLGG) is controversial. A few studies compared the effectiveness between surgery and other treatments for those patients. We did a systematic review for the effects of reoperation for recurrent DLGG. We searched the following databases from 1990 to 2018: Medline, Cochrane Library, Scopus and Opengrey, including researches about reoperation for recurrent DLGG, regardless of comparison and study design. The Newcastle-Ottawa scale (NOS) was used for quality assessment. Ten studies with 358 participants met the criteria. Due to lack of survival data about non-operated group, we failed to analyze the effect of reoperation. The risk bias of included studies was acceptable except the comparability. However, we found 48.4 % (155/320) of patients underwent gross resection and the safety was acceptable. About 1/3 received adjuvant therapy and 41.9 % (125/298) got histologically progressed. In a word, few studies reported the survival data of recurrent DLGG patients received reoperation. Most were young adults and half of them experienced a histological progress. But there are still a lot of shortages of the existing studies and more researches on the reoperation efficacy in recurrent DLGG are needed.

Background: In recent years, matrix metalloproteinase 9 (MMP-9) has been consideredto be an indicator of the aggressiveness and recurrence of pituitary adenomas, especially in China. However, some results have led to many conflicts. Therefore, it is necessary to perform a meta-analysis to obtain a clear correlation between MMP-9 and invasiveness and recurrence. Methods: Eligible studies obtained through multiple searches were included, and the odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were estimated. Funnel plots were used to evaluate publication bias. In the current meta-analysis, 23 articles with a total of 1,213 patients were included, including three studies conducted in Europe and China. Results: High MMP-9 expression and invasiveness of pituitary adenomas (n = 22, OR = 4.75, 95% CI = 3.53-6.39, p

Introduction Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary disorder caused by the mutation of gene VPS13A. Deep brain stimulation of ChAc has made substantial progress in the recent decades. However, the reports were scattered across centers and performed by different neurosurgeons. Here, we report a case series consisting of six patients diagnosed with ChAc, receiving bilateral high-frequency stimulation of globus pallidus internus (GPi) in a single center. Methods We report six consecutive patients diagnosed with ChAc and present a review of the literature. All patients received neurological evaluations using the Unified Huntington's Disease Rating Scale (UHDRS) motor score before surgery and during clinical follow-ups. One patient was observed over six months, while five patients were seen over 12 months. Results All patients underwent high-frequency stimulation ranging from 130 Hz to 175 Hz. In the follow-up period, a general trend was found toward higher amplitude and broader pulse widths, with a mean current range of 2.08 mA to 3.06 mA and a mean pulse width range of 75 μsec to 98 μsec. On preoperative evaluation, the mean UHDRS motor score was 35.7 ± 16.3 and the chorea subscore was 11.3 ± 4.7. At the three-month postoperative follow-up, both UHDRS motor score (13.5 ± 5.8) and chorea subscore (3.0 ± 1.2) reached valley values. Thereafter, the UHDRS motor score and chorea subscore showed a gradual rise, reaching 19.2 ± 5.9 and 4.8 ± 1.7, respectively, at the 12-month follow-up. In addition, adverse events were also seen. Patient 1 developed dysarthria six months after surgery, whereas Patient 6 had a generalized tonic-clonic seizure attack one day after surgery CONCLUSION: High frequency stimulation of the GPi is an effective and safe modality for the treatment of ChAc, with both rapid symptomatic improvements and steady chronic outcomes.

Transgenic animal models of Alzheimer's disease (AD) can mimic pathological and behavioral changes occurring in AD patients, and are usually viewed as the first choice for testing novel therapeutics. Validated biomarkers, particularly non-invasive ones, are urgently needed for AD diagnosis or evaluation of treatment results. However, there are few studies that systematically characterize pathological changes in AD animal models. Here, we investigated the brain of 8-month-old amyloid precursor protein/presenilin 1 (APP/PS1) transgenic and wild-type (WT) mice, employing 7.0-T magnetic resonance imaging (MRI). Magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), and arterial spin labeling (ASL) were obtained through micro-MRI scanning. After MRI examination in both transgenic (n = 12) and WT (n = 12) mice, immunohistochemical staining and ultrastructural analysis were subsequently performed. Cerebral blood flow (CBF) was significantly decreased in the left hippocampus, left thalamus, and right cortex of AD mice (P 0.05). Moreover, MRS showed significantly changed NAA/Cr, Glu/Cr, and mI/Cr ratios in the hippocampus of transgenic mice. While only NAA/Cr and mI/Cr ratios varied significantly in the cortex of transgenic mice. Regarding DTI imaging, however, the values of FA, MD, DA and DR were not significantly different between transgenic and WT mice. Finally, it is worth noting that pathological damage of metabolism, CBF, and white matter was more distinct between transgenic and WT mice by pathological examination. Altogether, our results suggest that intravital imaging evaluation of 8-month-old APP/PS1 transgenic mice by MRS and ASL is an alternative tool for AD research.

Metformin (MET) is a diabetes drug that activates AMP‐activated protein kinase (AMPK), and is suggested to have anticancer efficacy. Here, we investigated the role of AMPK signalling in prolactinoma (PRLoma), with particular respect to MET and bromocriptine (BC) as a PRLoma treatment. We analysed AMPK phosphorylation, dopamine D2 receptor (D2R), and oestrogen receptor (ER) expression in both BC‐sensitive and ‐resistant PRLoma samples; effects of the AMPK agonist MET (alone or with BC) on in vitro proliferation and apoptosis, xenograft growth and prolactin (PRL) secretion of BC‐sensitive and ‐resistant cells, and ER expression in xenografts. Some BC‐resistant PRLomas showed high D2R expression but extremely low AMPK activation. MET significantly inhibited proliferation of cultured PRLoma cells; MET + BC notably restrained their PRL secretion. MET + BC further decreased tumour growth and serum PRL levels in xenografts than BC treatment alone. ER was down‐regulated after AMPK activation in both cultured cells and xenografts. Together, we propose that the AMPK signalling pathway down‐regulates ERα and ERβ, and suppresses PRLoma growth as well as PRL secretion. Combined MET + BC is a potential treatment for PRLomas.

Background Whether conservative treatment or surgical management is the most appropriate treatment for pituitary apoplexy (PA) is controversial. In general, if severe symptoms of compression occur, such as oculomotor nerve palsy, neurosurgery is performed to relieve the compression of anatomical structures near the PA. Case description We describe the case of a 79-year-old man who was found to have an intrasellar pituitary incidentaloma. The tumor was discovered accidentally, during an investigation into the cause of his dizziness. Two months later, he suddenly developed headaches, left ophthalmoplegia, decreased vision, severe blepharoptosis and diplopia. He was diagnosed with PA and hypocortisolemia based on magnetic resonance imaging (MRI) and blood tests, respectively. His symptoms of oculomotor palsy and optic nerve compression were serious, but his ophthalmological deficits were nonprogressive and his hormone levels improved through conservative treatment (hydrocortisone supplementation). Due to this older patient's poor physical condition and serious coronary heart disease, after multidisciplinary consultation and according to his family's wishes, we continued the conservative treatment and watched closely for any changes in the patient's condition. After 6 months of conservative treatment, the patient's symptoms of oculomotor nerve paralysis, pupil and vision defects completely disappeared, and no new complications occurred. Repeated MRI tests showed that the PA lesion gradually improved. The patient's hypocortisolemia was completely relieved through oral supplementation with low-dose hydrocortisone. Conclusion In older PA patients who have surgical contraindications, even with symptoms of compression, such as oculomotor nerve palsy, according to the international guidelines, if conservative treatment is effective and the condition is not progressing, it is possible to monitor patients' condition closely and continue conservative treatment, which may yield good results.

In this study, a general method to obtain the 95% generation bound for photovoltaic (PV) systems worldwide was developed using a clear-sky model and then validated using ground surface observations, satellite-derived data, and typical meteorological year (TMY) files. The 95% generation bound for plane-of-array (POA) irradiation is used to provide the recommended tilt and azimuth angles where the loss fraction of POA irradiation is limited to 5% of the maximum POA irradiation. It was found that the 95% generation bound by this method behaves almost the same as that under real weather conditions. Cooling season was proposed for the application of PV-powered air conditioners. When compared with the annual 95% generation bound, the cooling-season 95% generation bound in Hong Kong covered a smaller range of tilt angles but much larger range of azimuth angles. Diffuse ratio is one of the most important factors influencing the 95% generation bound, making it a comparable or conservative estimate when compared to the results obtained by local irradiance data. Latitude is another important factor that influences the 95% generation bound. At lower latitude, the 95% generation bound locates at lower tilt angles and has a flatter line due to the smaller value of solar zenith angle around solar noon. The distribution of accumulated direct normal irradiance (DNI) in the morning and afternoon hours also influences the 95% generation bound. The contour lines, as well as the 95% generation bounds (based on ground surface observations and TMY files), are shifted some degrees toward the east or west.

Photovoltaic air-conditioner (PVAC) exhibits the advantages of high energy efficiency and convenient building integration, among solar cooling and heating technologies. The objective of this study is to propose a universal and straightforward method for performance evaluation of PVAC. Sixteen scenarios are simulated by TRNSYS to compare the performance of PVAC in different climates and building types defined by the Chinese national standards. Indicators such as solar fraction (SF), self-consumption ratio (SCR), solar COP, and return of investment (ROI) are used for evaluating energy and economic performances. The results demonstrate that the performance of PVAC is significantly affected by climatic conditions and building types, and thus, the feasibility of PVAC can be conveniently estimated based on the data provided by the Chinese national standards. A PVAC exhibits higher SF and SCR in areas subjected to high temperatures during summer and in office buildings, business malls, and hospital buildings, which mainly operate in the daytime. The building types in the order of decreasing ROI are business mall, hospital buildings, hotel, and office buildings. A comprehensive evaluation indicator is proposed to optimize the PV capacity and is useful to evaluate both the energy and economic performances of PVAC.

Objective To explore the radiological characteristics of the upper respiratory tract and their correlations with obstructive sleep apnoea/hypopnea syndrome (OSAHS) in patients with acromegaly. Methods Computed tomography (CT) and magnetic resonance imaging (MRI) were performed in untreated patients with acromegaly placed in straight (SHP) and extended head positions (EHP). Overnight polysomnography was performed to evaluate OSAHS, and the apnoea/hypopnea index (AHI) was measured. Results According to the CT findings, a thicker soft palate (1.24 ± 0.22 vs. 1.03 ± 0.22 cm, p = 0.024), larger soft palate cross-sectional area (5.15 ± 1.21 vs. 4.06 ± 1.09 cm2, p = 0.027), and thicker lateral pharyngeal wall (1.01 ± 0.25 vs. 0.79 ± 0.14 cm, p = 0.015) were observed in patients with acromegaly who presented with OSAHS compared with patients without OSAHS. Additionally, the maximal transverse diameter (1.87 ± 0.40 vs. 2.31 ± 0.44 cm, p = 0.015) and cross-sectional area (1.98 ± 0.46 vs. 2.74 ± 1.01 cm2, p = 0.032) of the airway were decreased in the soft palate plane in patients with OSAHS. The AHI was positively correlated with the thickness of the soft palate and lateral pharyngeal wall but negatively correlated with the maximal transverse diameter and cross-sectional area of the airway in the soft palate plane. Conclusions Airway stenosis and pharyngeal tissue hypertrophy are typical characteristics of changes in the structure of the upper respiratory tract in patients with acromegaly who present with OSAHS. AHI is a predictor of the severity of the respiratory tract changes.

Background Prolactinomas are the most common functional pituitary adenomas and dopamine agonists are the primary therapy. However, some patients are resistant to dopamine agonists. Recently, metformin has been proposed as a cancer treatment. Case Description This study is a retrospective review of 2 cases including 1 patient with prolactinoma who was resistant to bromocriptine, diagnosed with impaired glucose tolerance, and administered metformin. Surprisingly, combining the patient's treatment with metformin decreased prolactin (PRL) levels to 12 ng/mL and significantly decreased the size of the tumor after 1 year of combination therapy. As menstruation resumed and galactorrhea resolved, the patient became pregnant and stopped using metformin but continued taking bromocriptine. She gave birth to a healthy boy in August 2016. After delivery, she decided to breastfeed the baby and only took bromocriptine. After 14 months of using bromocriptine alone, her PRL level increased to 208 ng/mL and the tumor reappeared (7 mm × 8 mm × 9 mm). Interestingly, the patient's PRL level decreased from 208 ng/mL to 150 ng/mL 2 months after using combination treatment with bromocriptine and metformin. On the basis of these findings, a second bromocriptine-resistant patient was recruited. After 3 months of combined treatment with bromocriptine and metformin, the patient's PRL level decreased to 2.08 ng/mL, testosterone levels increased significantly, and the tumor size decreased. Conclusions Although more cases and investigations into the mechanisms underlying these effects are needed, these 2 cases support the hypothesis that the combination of metformin and bromocriptine might be a new treatment for resistant prolactinomas.

Background Lymphocytic hypophysitis is a rare inflammatory lesion in the sellar region. Lymphocytic hypophysitis secondary to ruptured Rathke cleft cyst (RCC) is even more rarely seen. Clinical characteristics, treatment strategies, and prognosis remain elusive. Case Description A 58-year-old Chinese woman with a 3-year history of intermittent headache and new development of polydipsia, polyuria, and binocular visual acuity decline over the past 4 months was admitted to our hospital. On admission, endocrine results were normal. Ophthalmic testing showed bitemporal visual field deficits and decreased visual acuity of both eyes. Pituitary dynamic magnetic resonance imaging showed a cystic sellar lesion measuring 5.6 × 5.2 × 6.2 mm with tumor shrinkage compared with initial neuroimaging. Transsphenoidal surgery was performed for tumor resection. An additional biopsy of the anterior pituitary lobe was performed because of intraoperative abnormal appearances of the pituitary gland. Pathology examinations revealed the specimen of the cystic lesion to be RCC and exhibited infiltration of massive lymphocytes, diffused plasmocytes, and eosinophils that were diagnostic of lymphocytic hypophysitis in the anterior pituitary lobe. During follow-up, the lesion of lymphocytic hypophysitis showed spontaneous shrinkage in the absence of steroid treatment after RCC resection. Final diagnosis was lymphocytic hypophysitis secondary to ruptured RCC. Conclusions We present a rare case of lymphocytic hypophysitis secondary to ruptured RCC and provide clinical data of such lesions in the literature. Full understanding of the clinical features plays an important role in diagnosis and treatment of lymphocytic hypophysitis secondary to ruptured RCC.

Background The biopsy is recognized as the most accurate method to determine the histologic characterization of sellar germ cell tumors. It is difficult to evaluate the prognosis before histologic confirmation. Objective This study aimed to evaluate the independent prognostic risk factors of patients with sellar germ cell tumors (GCTs). Methods From January 2008 to December 2015, 61 patients who were histologically diagnosed as having sellar GCTs were followed up and were included in this retrospective study. Results Of 61 patients in this study, 40 (65.6%), 10 (16.4%), and 11 (18.0%) were diagnosed as having pure germinomas, germinomas with syncytiotrophoblastic giant cells and non-germinomatous GCTs (NGGCTs), respectively. The patients with pure germinomas had a significantly better overall survival time than did those with NGGCT (56.47 ± 3.01 months vs. 43.09 ± 10.58 months; P = 0.01). Multivariate analysis showed that the independent poor prognostic risk factors of patients with sellar GCTs were diameters >15 mm (odds ratio [OR], 7.40; 95% confidence interval [CI], 2.01–27.19), octamer-binding transcription positivity (OR, 5.97; 95% CI, 1.40–25.48), and NGGCT (OR, 11.88; 95% CI, 2.37–59.50), whereas the combination of chemotherapy and radiotherapy was associated with a better prognosis (OR, 0.15; 95% CI, 0.04–0.55). Conclusions Diameter >15 mm, octamer-binding transcription positivity, or NGGCT was associated with a poorer prognosis for patients with sellar GCTs, whereas the combination of chemotherapy and radiotherapy was associated with a better prognosis.

Background Postoperative central nervous system infections (PCNSIs) represent a serious complication, and the timely use of antibiotics guided by the identification of the causative pathogens and their antibiotic sensitivities is essential for treatment. However, there are little data regarding the prevalence of PCNSI pathogens in China. The aim of this study is to investigate the features of pathogens in patients with PCNSIs, which could help clinicians to choose the appropriate empirical antibiotic therapy. Methods We retrospectively examined the positive CSF cultures in patients who underwent craniotomy between January 2010 and December 2015. We collected data, including demographic characteristics, type of neurosurgery, laboratory data, causative organisms and antimicrobial susceptibility testing results. Results A total of 62 patients with 90 isolates out of 818 patients with 2433 CSF culture samples were available for data analysis. The estimated incidence and culture-positive rate of PCNSIs were approximately 0.9 and 7.5%, respectively. The predominant organism was coagulase-negative staphylococci, of which most were methicillin-resistant coagulase-negative staphylococci (MRCoNS). All were susceptible to vancomycin, linezolid, rifampicin and amoxicillin-clavulanate. Acinetobacter baumannii was the most frequent causative Gram-negative agent and was resistant to 12 out of 18 antimicrobials tested. The sensitivity rates for tigecycline and minocycline were only 40 and 33%, respectively. Conclusion PCNSIs could lead to high mortality. Although the MRCoNS were the predominant organism, the management of Acinetobacter baumannii was a major clinical challenge with few effective antimicrobials in PCNSIs. Electronic supplementary material The online version of this article (10.1186/s13756-018-0323-3) contains supplementary material, which is available to authorized users.

To investigate the incidence, bacteriologic features, and risk factors of posttranssphenoidal surgery (post-TSS) meningitis and/or bacteremia.This retrospective study included 3242 patients who underwent TSS for pituitary adenoma at the Department of Neurosurgery of Peking Union Medical College Hospital between January 2012 and December 2016. Clinical data for patients with and without post-TSS meningitis and/or bacteremia were compared and analyzed.Meningitis and bacteremia developed after 27 (0.8%) and 26 (0.8%) procedures, respectively, and 6 patients (0.2%) developed both. Gram-positive organisms (coagulase-negative staphylococci, Streptococcus pneumonia, and S viridans) predominated in meningitis, whereas gram-negative organisms (Klebsiella pneumonia, Enterobacter aerogenes, and Escherichia coli) predominated in bacteremia. All identified species were sensitive to amikacin, imipenem, and meropenem. Antibiotic treatment cured 52 patients (7 died). In a multivariate analysis, the risk of meningitis and/or bacteremia was independently associated with diabetes (P0.001; odds ratio [OR], 6.06), previous surgery at the same location (P0.001; OR, 4.23), intraoperative cerebrospinal fluid leakage (P0.001l; OR, 4.63), and an endoscopic approach (P = 0.001; OR, 2.50).Meningitis and/or bacteremia remain critical postoperative complications of TSS for pituitary adenoma. The pathogens with drug sensitivity to antibiotics differed between meningitis and bacteremia. Early blood and cerebrospinal fluid bacterial cultures, drug susceptibility analyses, and appropriate antibiotic treatment can help control the rate of infection.

Simple Summary The 2017 World Health Organization classification of endocrine tumors defines pituitary adenomas based on their cell lineages. T-PIT can serve as a complimentary tool for further identification of silent corticotroph adenomas (SCAs). Unlike functioning corticotroph adenomas in patients with Cushing’s disease, SCAs present no clinical and biochemical features of Cushing’s syndrome. SCAs have been shown to exhibit a more aggressive course characterized by a higher probability of recurrence and resistance to conventional treatment due to their intrinsic histological features. The aim of our review is to offer an update on the diagnosis, mechanisms, clinical features and management of SCAs. Studies of the molecular mechanisms of SCA pathogenesis will provide new directions for the diagnosis and management of SCAs. Abstract With the introduction of 2017 World Health Organization (WHO) classification of endocrine tumors, T-PIT can serve as a complementary tool for identification of silent corticotroph adenomas (SCAs) in some cases if the tumor is not classifiable by pituitary hormone expression in pathological tissue samples. An increase of the proportion of SCAs among the non-functioning pituitary adenomas (NFPAs) has been witnessed under the new rule with the detection of T-PIT-positive ACTH-negative SCAs. Studies of molecular mechanisms related to SCA pathogenesis will provide new directions for the diagnosis and management of SCAs. A precise pathological diagnosis can help clinicians better identify SCAs. Understanding clinical features in the context of the pathophysiology of SCAs is critical for optimal management. It could provide information on appropriate follow-up time and aid in early recognition and treatment of potentially aggressive forms. Management approaches include surgical, radiation, and/or medical therapies.

Background Transsphenoid surgery (TSS) is a standard treatment modality for Cushing's disease (CD). However, postoperative remission and recurrence rates vary among studies. Here we analyze the diagnosis and outcomes of 341 patients with a preoperative diagnosis of CD undergoing TSS in a single center over a 3-year period. Methods A total of 341 patients were enrolled. Clinical manifestations, imaging results, laboratory workups, and results of inferior petrosal sinus sampling (IPSS) were obtained. Outcomes were obtained with a follow-up length from 12 to 36 months. Results The tumors were mainly of Knosp level 0 (68.57%). The sensitivity of MRI, combined low-dose and high-dose dexamethasone suppression test and IPSS in the diagnosis were 90.83%, 88.53% and 95.57%. The concordance of lateralization by MRI and by IPSS were 78.96% and 61.34% compared with surgery. 2. Outcomes. The overall remission rate was 78.89% (N = 289). Patients undergoing the first TSS (N = 234) had a remission rate of 86.36% for macroadenomas (N = 22) and 83.2% for microadenomas (N = 212). Patients undergoing a second TSS (N = 55) had lower rate of remission of 50.00% for macroadenomas (N = 6) and 61.22% for microadenomas (N = 49). For patients with invasive tumors, the overall remission rate was 26.92% (N = 26), 20.0% for macroadenomas (n = 20) and 50.0% for microadenomas (N = 6). The recurrence rate was 2.42%. Conclusions Pituitary imaging, endocrinological workups and IPSS are sensitive and specific diagnostic modalities for CD, but the lateralization efficacy of MRI and IPSS are unsatisfactory. A higher rate of remission relies on gross resections of tumors.

Cognitive impairment and psychiatric symptoms are common in patients with Cushing's disease (CD) owing to elevated levels of glucocorticoids. Molecular neuroimaging methods may help to detect changes in the brain of patients with CD. The aim of this study was to investigate the characteristics of brain metabolism and its association with serum cortisol level in CD. We compared brain metabolism, as measured using [18F]-fluorodeoxyglucose positron emission tomography (FDG PET), between 92 patients with CD and 118 normal subjects on a voxel-wise basis. Pearson correlation was performed to evaluate the association between cerebral FDG uptake and serum cortisol level in patients with CD. We demonstrated that certain brain regions in patients with CD showed significantly increased FDG uptake, including the basal ganglia, anteromedial temporal lobe, thalamus, precentral cortex, and cerebellum. The clusters that demonstrated significantly decreased uptake were mainly located in the medial and lateral frontal cortex, superior and inferior parietal lobule, medial occipital cortex, and insular cortex. The metabolic rate of the majority of these regions was found to be significantly correlated with the serum cortisol level. Our findings may help to explain the underlying mechanisms of cognitive impairment and psychiatric symptoms in patients exposed to excessive glucocorticoids and evaluate the efficacy of treatments during follow-up., Highlights • Hypercortisolism leads to metabolic changes in specific brain regions of CD patients. • These brain regions involve in the regulation of cortisol and the symptoms of CD. • The metabolism of 6 specific brain regions is correlated with cortisol level.

Objective To investigate outcomes and identified risk factors affecting cure and intraoperative cerebrospinal fluid leak after transsphenoidal surgery using a new classification for growth hormone–secreting pituitary adenoma associated with empty sella. Methods In this retrospective cohort study, 51 patients enrolled from January 2010 to June 2016 were categorized into 3 groups using a new classification scheme: grade A, whole tumor occupation area beneath a horizontal line drawn along the lowest level of empty sella; grade B, tumor occupation area that crossed the horizontal line on 1 side; and grade C, tumor occupation area that crossed the horizontal line on 2 sides. Clinical data were collected and analyzed. Results Cure rate for grade A patients (88.24%; 15/17) was significantly higher than cure rate for grade B (55.00%; 11/20) and grade C (50.00%; 7/14) patients. Occurrence of cerebrospinal fluid leaks in grade C patients (35.71%; 5/14) was higher than in grade A patients (5.88%; 1/17). Logistic regression analysis indicated that risk factors affecting cure included large maximum tumor diameter (P = 0.009, odds ratio [OR] = 1.222), high preoperative fasting growth hormone level (P = 0.031, OR = 1.088), and high classification (P = 0.017, OR = 4.485). Risk factor affecting intraoperative cerebrospinal fluid leak was high classification (P = 0.039, OR = 3.580). Conclusions Transsphenoidal surgery is the current optimal treatment strategy. Empty sella increases the difficulty of surgery with a higher incidence of complications. The new classification scheme was better for predicting the surgical outcome for this disease.

This study was designed to evaluate the ability of PET/MRI, using 18F-FDG and 68Ga-DOTATATE as tracers, to detect hormone-producing pituitary microadenoma when diagnosis is difficult using MRI alone. Methods: We recruited 37 patients with elevated hormone levels, including 19 with undiagnosable primary pituitary adenoma and 18 with suspected recurrent pituitary adenoma. 18F-FDG PET/MRI and 68Ga-DOTATATE PET/MRI were performed within 1 wk of each other in all patients. Within 2 wk afterward, 27 of the 37 patients underwent transsphenoidal adenomectomy, 3 underwent sella region radiotherapy, 1 underwent somatostatin therapy, and 6 had only clinical follow-up. The image characteristics and uptake levels were correlated with the surgical findings and pathologic results. Receiver-operating-characteristic curves were analyzed to determine the optimal cutoff to differentiate adenoma from normal pituitary tissue. The area under the receiver-operating-characteristic curve was calculated to compare diagnostic performance. Results: The PET/MR images were of diagnostic quality and without obvious image artifacts. The high contrast of the PET images provided complementary information to the fine anatomic display of the MR images. Increased 18F-FDG uptake was clearly observed in all patients. MRI enhanced using a 0.05 mmol/kg dose of gadopentetate dimeglumine showed suggestive findings in only 47% of the patients with primary adenoma and 39% of those with recurrent adenoma; when a 0.1 mmol/kg dose was used, the respective percentages were 37% and 50%. The 18F-FDG SUVmax of the 16 primary adenomas that underwent transsphenoidal adenomectomy (6.8 ± 3.7) was significantly higher than that of normal pituitary tissue (3.2 ± 1.1, P < 0.01). The adenomas showed moderate 68Ga-DOTATATE uptake (SUVmax, 3.8 ± 2.6), but the 68Ga-DOTATATE uptake was generally lower than that of normal pituitary tissue (SUVmax, 6.2 ± 3.2, P < 0.05). In the 11 suspected recurrent pituitary adenomas that underwent transsphenoidal adenomectomy, the 18F-FDG SUVmax was 6.1 ± 3.5, significantly higher than that of normal pituitary tissue (2.5 ± 1.1, P < 0.01), and the 68Ga-DOTATATE SUVmax was 3.0 ± 1.1, significantly lower than that of normal pituitary tissue (5.5 ± 1.7, P < 0.01). The 18F-FDG/68Ga-DOTATATE SUVmax ratio of the adenomas (2.3 ± 1.5) was significantly higher than that of normal pituitary tissue (0.6 ± 0.3, P < 0.05). When the 18F-FDG SUVmax alone and the 18F-FDG/68Ga-DOTATATE SUVmax ratio were used as criteria to discriminate between adenoma and pituitary tissue, the best analysis came from the ratio, and that from 18F-FDG SUVmax alone was slightly less, with optimal diagnostic cutoffs of 1.04 and 3.88, respectively. Conclusion: PET/MRI provides an ideal tool for the detection of hormone-producing pituitary microadenoma. Dual-tracer 18F-FDG and 68Ga-DOTATATE PET/MRI was useful for distinguishing pituitary microadenoma from normal pituitary tissue.

Alzheimer disease (AD) is a severe, life-threatening illness characterized by gradual memory loss. The classic histological features of AD include extracellular formation of β-amyloid plaques (Aβ), intracellular neurofibrillary tangles (NFT), and synaptic loss. Recently, accumulated evidence has confirmed the critical role of microglia in the development and exacerbation of AD. When Aβ forms deposits, microglia quickly respond to restore brain physiology by activating a series of repair mechanisms. However, prolonged microglial activation is considered detrimental and may aggravate AD progression. To date, there are no curative therapies for AD. The advent of stem cell transplantation offers novel strategies to treat AD in animal models. Furthermore, studies have reported that transplanted stem cells might ameliorate AD symptoms by regulating microglial functions, from detrimental to protective. This review focuses on the crucial functions of microglia in AD and examines the reactions of microglia to transplanted stem cells.

// Congxin Dai 1, * , Bowen Sun 1, * , Xiaohai Liu 1 , Xinjie Bao 1 , Ming Feng 1 , Yong Yao 1 , Junji Wei 1 , Kan Deng 1 , Chengxian Yang 1 , Xueyuan Li 1 , Wenbin Ma 1 , Renzhi Wang 1 1 Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China * These authors have contributed equally to this work Correspondence to: Renzhi Wang, email: Wangrz@126.com Keywords: pituitary adenomas, MGMT, recurrence, aggressive Received: October 07, 2016 Accepted: December 01, 2016 Published: February 01, 2017 ABSTRACT O-6-methylguanine-DNA methyltransferase (MGMT) reportedly counteracts the cytotoxic effects of the alkylating agent temozolomide. MGMT expression is often low in aggressive pituitary adenomas (PAs) and recurrent PAs. However, because these associations are controversial, we performed this meta-analysis to clarify the involvement of MGMT in the prognosis and clinicopathology of PA. We searched for relevant studies in electronic databases (MEDLINE, the Cochrane Library Database, EMBASE, CINAHL, Web of Science and the Chinese Biomedical Database (CBD)) and calculated/pooled the odds ratios (ORs) or standard mean differences (SMDs) with 95% confidence intervals (95% CIs). Eleven case-control studies with a total of 454 PA patients were included. Our meta-analysis revealed that lower expression of MGMT was associated with PA recurrence (OR=2.09, 95% CI=1.09–4.02; p =0.026). On the other hand, MGMT expression was not associated with PA invasiveness (OR=1.112, 95% CI=0.706–1.753; p =0.646), Unexpectedly, MGMT expression could not be used to distinguish functional from non-functional PA patients (OR=1.766, 95% CI=0.938–3.324; p =0.078). The MGMT expression was not found to be related to other clinicopathological indicators of PA including age, gender or tumor size. No publication bias was detected in this meta-analysis (p>0.05). This meta-analysis suggests that MGMT expression may be associated with PA tumor recurrence, but not be related to invasiveness or other clinicopathological indicators. Thus, detection of MGMT expression may facilitate outcome prediction and guide clinical therapy for PA patients.

OBJECTIVE Subthalamic deep brain stimulation (STN-DBS) could be an effective alternative treatment for patients with Parkinson's disease (PD). However, the mechanisms of deep brain stimulation (DBS) at different frequencies are still unclear. In this study, diffusion tensor imaging (DTI) was used to detect parameter changes in different regions of rat brains after DBS, and rat exercise capacity and brain tissue immunohistochemistry were evaluated. MATERIALS AND METHODS The 6-hydroxydopamine-induced hemi-parkinsonian rat models were made and divided into four groups: a control group, sham group, low-frequency group, and high-frequency group. Low-frequency (30 Hz) and high-frequency (130 Hz) DBS were given to the STN in rats. First, an open-field experiment was used to evaluate changes in exercise performance. Then, the DTI was used to measure parameter changes in the substantia nigra (SN). Finally, immunohistochemistry was used to analyze the expression of tyrosine hydroxylase (TH), NeuN, and α-synuclein (α-syn) in the SN in the rats. RESULTS There were significant differences in movement distance changes between the high-frequency stimulation (HFS) group and low-frequency stimulation (LFS) group, the HFS group and Ctrl group, and the Sham group and Ctrl group (all p

To study the damage of bridge pile foundations caused by scouring, two damage mechanisms of scouring are proposed in this paper. Considering the vehicle-bridge coupled vibration in terms of two aspects of the scouring depth and erosion depth, the vertical and transversal dynamic characteristics and dynamic responses of the bridge are studied under different cases for the most sensitive vehicle speed. The dynamic characteristics include the 1st and 2nd vibration modes of the vertical and transversal directions of the bridge. The dynamic responses include the vertical and transversal dynamic load allowances and acceleration of the bridge. The souring depth is more sensitive than the erosion depth, and the 2nd vertical mode is most substantially influenced by scouring and erosion. Because of the small value of the natural frequency of the vertical vibration modes, the transversal vibration modes may be more convenient to obtain. The study of the dynamic responses shows that the scouring depth can be represented by the dynamic load allowance in the middle of the span’s section and the erosion depth can be characterized by the dynamic load allowance at the quarter location of the span’s section.