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Background: Craniopharyngiomas have a high recurrence rate and a poor prognosis, and the key methods for reducing recurrences are unknown. The aim of this study was to explore the key points of microscopic or endoscopic transsphenoidal surgery used to treat infradiaphragmatic craniopharyngiomas. Methods: We reviewed the medical records of patients with infradiaphragmatic craniopharyngiomas who were admitted to Peking Union Medical College Hospital between 2011 and 2018. Results: When considering tumor location, all 34 patients had intrasellar tumors, with 19 of them exhibiting suprasellar extensions. Of the 34 patients, 24 patients underwent resection under the microscope and the remaining 10 patients underwent transsphenoidal endoscopic surgery. Gross total tumor resection was achieved in 16 patients. Twelve patients underwent invaded sellar diaphragm resection, while the remaining 22 patients were not. Cerebrospinal fluid leaks occurred during surgery in 18 patients. Visual acuity improved in two patients. After an average follow-up of 31.1 months, 13 patients experienced tumor recurrence. The short term recurrence rate in the sellar diaphragm resection group was significantly lower compared to the non-resected group (P

Abstract Background Immune checkpoint inhibitors (ICIs) are a promising immunotherapy approach, but glioblastoma clinical trials have not yielded satisfactory results. Objective To screen glioblastoma patients who may benefit from immunotherapy. Methods Eighty‐one patients receiving anti‐PD1/PD‐L1 treatment from a large‐scale clinical trial and 364 patients without immunotherapy from The Cancer Genome Atlas (TCGA) were included. Patients in the ICI‐treated cohort were divided into responders and nonresponders according to overall survival (OS), and the most critical responder‐relevant features were screened using random forest (RF). We constructed an artificial neural network (ANN) model and verified its predictive value with immunotherapy response and OS. Results We defined two groups of ICI‐treated glioblastoma patients with large differences in survival benefits as nonresponders (OS ≤6 months, n = 18) and responders (OS ≥17 months, n = 8). No differentially mutated genes were observed between responders and nonresponders. We performed RF analysis to select the most critical responder‐relevant features and developed an ANN with 20 input variables, five hidden neurons and one output neuron. Receiver operating characteristic analysis and the DeLong test demonstrated that the ANN had the best performance in predicting responders, with an AUC of 0.97. Survival analysis indicated that ANN‐predicted responders had significantly better OS rates than nonresponders. Conclusion The 20‐gene panel developed by the ANN could be a promising biomarker for predicting immunotherapy response and prognostic benefits in ICI‐treated GBM patients and may guide oncologists to accurately select potential responders for the preferential use of ICIs.

IntroductionPediatric pituitary neuroendocrine tumor is a rare condition, and despite previous research focusing on this specific group, the main factors influencing the surgical cure rate have not been identified.MethodsWe conducted a single-center retrospective study on pediatric pituitary neuroendocrine tumor patients who visited Peking Union Medical College Hospital between 2010 and 2023. We collected data on their clinical characteristics, imaging features, surgical outcomes, and follow-up information. Additionally, we used multiple-factor logistic regression to investigate the factors affecting the surgical cure rate of pediatric pituitary neuroendocrine tumor.Results232 patients were diagnosed with pediatric pituitary neuroendocrine tumors, with a higher incidence in females. The most common type was ACTH-secreting adenoma (90/232), followed by prolactin-secreting adenoma (63/232), and growth hormone-secreting adenoma (41/232). The majority of pediatric adenomas were macroadenomas (139/232), and some tumors were associated with cystic changes or hemorrhage (58/232), while a few exhibited invasion of the cavernous sinus (33/232). The results of the multivariate analysis indicated that the different hormone secretion types, macroadenoma or the presence of cystic changes or hemorrhage were not significant risk factors for the cure rate after the first surgery. However, the invasion of the cavernous sinus was found to be an important factor influencing the postoperative cure rate. Most pediatric pituitary neuroendocrine tumors with cavernous sinus invasion were macroadenomas, and some displayed characteristics of refractory pituitary neuroendocrine tumors, with some patients experiencing irreversible complications after surgery.ConclusionPediatric pituitary neuroendocrine tumors are complex, and the postoperative cure rate is particularly poor for tumors with cavernous sinus invasion. Although macroadenoma itself does not significantly impact the postoperative cure rate, it is still recommended to diagnose and treat early to avoid unnecessary surgery or surgical complications.

Abstract Purpose Diagnostic statements for pituitary adenomas (PAs) are complex and unstandardized. We aimed to determine the most commonly used elements contained in the statements and their combination patterns and variations in real-world clinical practice, with the ultimate goal of promoting standardized diagnostic recording and establishing an efficient element extraction process. Methods Patient medical records from 2012 to 2020 that included PA among the first three diagnoses were included. After manually labeling the elements in the diagnostic texts, we obtained element types and training sets, according to which an information extraction model was constructed based on the word segmentation model “Jieba” to extract information contained in the remaining diagnostic texts. Results A total of 576 different diagnostic statements from 4010 texts of 3770 medical records were enrolled in the analysis. The first ten diagnostic elements related to PA were histopathology, tumor location, endocrine status, tumor size, invasiveness, recurrence, diagnostic confirmation, Knosp grade, residual tumor, and refractoriness. The automated extraction model achieved F1-scores that reached 100% for all ten elements in the second round and 97.3–100.0% in the test set consisting of an additional 532 diagnostic texts. Tumor location, endocrine status, histopathology, and tumor size were the most commonly used elements, and diagnoses composed of the above elements were the most frequent. Endocrine status had the greatest expression variability, followed by Knosp grade. Among all the terms, the percentage of loss of tumor size was among the highest (21%). Among statements where the principal diagnoses were PAs, 18.6% did not have information on tumor size, while for those with other diagnoses, this percentage rose to 48% (P

PurposeTo investigate the prevalence of low blood testosterone level (LTL) and its determinant factors among active male acromegaly patients, as well as the effect of surgery on LTL in male acromegaly patients.MethodsA retrospective, single-center study focused on 252 male acromegaly patients aged 18 years–60 years diagnosed in the Peking Union Medical College Hospital from January 2015 to December 2018 was carried out. The measurements of preoperative and postoperative testosterone levels, serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), and other clinical data were analyzed.ResultsForty per cent of subjects included were diagnosed with LTL pre surgery. Patients were divided into normal testosterone level (NTL) and LTL groups based on their testosterone level. There were significant differences (p < 0.01) between groups in the presence of macroadenomas, invasion of the cavernous sinus, compression of the optic chiasm, and serum GH and prolactin levels pre surgery. Invasion of the cavernous sinus [odds ratio (OR) = 4.299; p = 0.000] and serum prolactin level (OR = 1.023, p = 0.001) were independent predictors of LTLs in male patients before surgical intervention. A total of 67.9% of LTL patients recovered during the follow-up, with a new-onset rate of 3.4%. Body mass index, invasion of the cavernous sinus, GH, IGF-1, and prolactin levels, the presence of a prolactin-secreting tumor, and recovery from acromegaly were significantly different (p < 0.05) in the NTL group and in the LTL group during the follow-up. The presence of a prolactin-secreting tumor (OR = 0.224; p = 0.001) and recovery from acromegaly (OR = 0.168; p = 0.006) were independent predictors of LTLs in male acromegaly patients during the follow-up.ConclusionThe invasiveness of tumor and levels of blood prolactin are independent factors for LTLs before surgery, whereas GH and IGF-1 levels are not. Most male patients can recover from LTL after tumor restriction surgery: those who recover from acromegaly have a better chance of recovering from LTL.

Topological data analysis has been acknowledged as one of the most successful mathematical data analytic methodologies in many fields. Additionally, it has also been gradually applied in financial time series analysis and proved effective in exploring the topological features of such data. We select 100 stocks from China’s markets and construct point cloud data for topological data analysis. We detect critical dates from the Lp-norms of the persistence landscapes. Our results reveal the dates are highly consistent with the transition time of some major events in the sample period. We compare the correlations and statistical properties of stocks before and during the events via complex networks to describe the markets’ situation. The strength and variation of links among stocks are clearly different during the major events. We also investigate the neighborhood features of stocks from topological perspectives. This helps identify the important stocks and explore their situations under each event. Finally, we cluster the stocks based on the neighborhood features, which exhibit the heterogeneity impact on stocks of the different events. Our work demonstrates that topological data analysis has strong applicability in the dynamic correlations of stocks.

ObjectiveExcessive growth hormone and insulin-like growth factor 1 contribute to cutaneous changes in acromegaly. We investigated the sub-macroscopic skin manifestation of acromegaly patients and explored its reversibility upon hormone reduction after pituitary adenoma surgery.DesignProspectively cohort study.MethodsWe enrolled 26 patients with acromegaly and 26 patients with non-functioning pituitary adenomas undergoing pituitary adenomectomy at Peking Union Medical College Hospital from July 2021 to March 2022. Skin presentations were evaluated by dermatoscopy and ultra-high-frequency ultrasound before and after surgery.ResultsSkin thickening, follicular plugs, perifollicular pigmentations, perifollicular orange haloes, red structureless areas, increased hair shafts, honeycomb-like pigmentations, widened dermatoglyphics, dilated appendage openings, excessive seborrhea, hyperhidrosis, enlarged pores, and acne-like lesions were commonly occurring in acromegaly patients, and their incidences were higher than the controls (P1 skin lesions were younger (P=0.028) and had higher baseline GH levels (P=0.021) than those with improvement of ≤1 skin lesion.ConclusionsDermatoscopy and ultra-high-frequency ultrasound provided augmented visual examination of the cutaneous changes in acromegaly. Some of the skin lesions could improve or reverse after pituitary surgery. Baseline GH levels, age, and endocrine remission were correlated with skin improvement at 3-month follow-up.

The field of remote sensing information processing places significant research emphasis on object detection (OD) in high-spatial-resolution remote sensing images (HSRIs). The OD task in HSRIs poses additional challenges compared to conventional natural images. These challenges include variations in object scales, complex backgrounds, dense arrangement, and uncertain orientations. These factors contribute to the increased difficulty of OD in HSRIs as compared to conventional images. To tackle the aforementioned challenges, this paper introduces an innovative OD algorithm that builds upon enhancements made to the YOLOv5 framework. The incorporation of RepConv, Transformer Encoder, and BiFPN modules into the original YOLOv5 network leads to improved detection accuracy, particularly for objects of varying scales. The C3GAM module is designed by introducing the GAM attention mechanism to address the interference caused by complex background regions. To achieve precise localization of densely arranged objects, the SIoU loss function is integrated into YOLOv5. The circular smooth label method is used to detect objects with uncertain directions. The effectiveness of the suggested algorithm is confirmed through its application to two commonly utilized datasets, specifically HRSC2016 and UCAS-AOD. The average detection accuracies achieved on these datasets are 90.29% and 90.06% respectively, surpassing the performance of other compared OD algorithms for HSRIs.

Pediatric gliomas (PGs) are the most common brain tumors in children and the leading cause of childhood cancer-related death. The understanding of the immune microenvironment is essential for developing effective antitumor immunotherapies. Transcriptomic data from 495 PGs were analyzed in this study, with 384 as a training cohort and 111 as a validation cohort. Macrophages were the most common immune infiltrates in the PG microenvironment, followed by T cells. PGs were classified into 3 immune subtypes (ISs) based on immunological profiling: “immune hot” (IS-I), “immune altered” (IS-II), and “immune cold” (IS-III). IS-I tumors, characterized by substantial immune infiltration and high immune checkpoint molecule (ICM) expression, had a favorable prognosis and were more likely to respond to anti-PD1 and anti-CTLA4 immunotherapies, whereas IS-III tumors, characterized by weak immune infiltration and low ICM expression, had a dismal prognosis and poor immunotherapy responsiveness. IS-II tumors represented a transitional stage. Immune classification was also correlated with somatic mutations, copy number alterations, and molecular pathways related to tumorigenesis, metabolism, and immune responses. Three predictive classifiers using eight representative genes were generated by machine learning methods for immune classification. This study established a reliable immunological profile-based classification system for PGs, providing implications for further immunotherapy strategies.

Purpose: Pituitary adenomas (PAs) are the second most common intracranial neoplasms. Total surgical resection was extremely important for curing PAs, whereas tumor stiffness has gradually become the most critical factor affecting the resection rate in PAs. We aimed to investigate the molecular mechanisms of tumor stiffening and explore novel medications to reduce stiffness for improving surgical remission rates in PA patients.Methods: RNA sequencing, whole-genome bisulfite sequencing, and whole exome sequencing were applied to identify transcriptomic, epigenomic, and genomic underpinnings among 11 soft and 11 stiff PA samples surgically resected from patients at Peking Union Medical College Hospital (PUMCH). GH3 cell line and xenograft PA model was used to demonstrate therapeutic effect of sunitinib, and atomic force microscopy (AFM) was used to detect the stiffness of tumors.Results: Tumor microenvironment analyses and immunofluorescence staining indicated endothelial cells (ECs) and cancer-associated fibroblasts (CAFs) were more abundant in stiff PAs. Weighted gene coexpression network analysis identified the most critical stiffness-related gene (SRG) module, which was highly correlated with stiff phenotype, ECs and CAFs. Functional annotations suggested SRGs might regulate PA stiffness by regulating the development, differentiation, and apoptosis of ECs and CAFs and related molecular pathways. Aberrant DNA methylation and m6A RNA modifications were investigated to play crucial roles in regulating PA stiffness. Somatic mutation analysis revealed increased intratumoral heterogeneity and decreased response to immunotherapy in stiff tumors. Connectivity Map analysis of SRGs and pRRophetic algorithm based on drug sensitivity data of cancer cell lines finally determine sunitinib as a promising agent targeting stiff tumors. Sunitinib inhibited PA growth in vitro and in vivo, and also reduced tumor stiffness in xenograft PA models detected by AFM.Conclusion: This is the first study investigating the underlying mechanisms contributing to the stiffening of PAs, and providing novel insights into medication therapy for stiff PAs.

From our monogenic diabetes registry set-up at a secondary-care diabetes center, we identified a nontrivial subpopulation (~15%) of maturity-onset diabetes of the young (MODY) among people with young-onset diabetes. In this report, we describe the diagnostic caveats, clinical features and long-term renal-trajectory of people with HNF1B mutations (HNF1B-MODY). Between 2013 and 2020, we received 267 referrals to evaluate MODY from endocrinologists in both public and private practice. Every participant was subjected to a previously reported structured evaluation process, high-throughput nucleotide sequencing and gene-dosage analysis. Out of 40 individuals with confirmed MODY, 4 (10%) had HNF1B-MODY (harboring either a HNF1B whole-gene deletion or duplication). Postsequencing follow-up biochemical and radiological evaluations revealed the known HNF1B-MODY associated systemic-features, such as transaminitis and structural renal-lesions. These anomalies could have been missed without prior knowledge of the nucleotide-sequencing results. Interestingly, preliminary longitudinal observation (up to 15 years) suggested possibly 2 distinct patterns of renal-deterioration (albuminuric vs. nonalbuminuric chronic kidney disease). Monogenic diabetes like HNF1B-MODY may be missed among young-onset diabetes in a resource-limited routine-care clinic. Collaboration with a MODY-evaluation center may fill the care-gap. The long-term renal-trajectories of HNF1B-MODY will require further studies by dedicated registries and international consortium.

PurposeStudies on hyperprolactinemia and hypopituitarism in acromegaly are limited. We aimed to analyze the preoperative status, postoperative alterations, and correlated factors of hyperprolactinemia and hypopituitarism in acromegaly patients.MethodsThis is a single-center cohort study with long-term follow-up. We prospectively enrolled 529 acromegaly patients. Hyperprolactinemia and hypopituitarism were evaluated by testing hypothalamus-pituitary-end organ (HPEO) axes hormones before and after surgery.ResultsHyperprolactinemia (39.1%) and hypopituitarism (34.8%) were common in acromegaly. The incidences of axis-specific hypopituitarism varied (hypogonadism, 29.7%; hypothyroidism, 5.9%; adrenal insufficiency, 5.1%), and multiple HPEO axes dysfunction was diagnosed in 5.3% of patients. Patients with preoperative hyperprolactinemia [hazard ratio (HR)=1.39 (1.08-1.79); p=0.012], hypogonadism [HR=1.32 (1.01-1.73); p=0.047], and hypothyroidism [HR=3.49 (1.90-6.44); p

BackgroundMcCune-Albright syndrome is a rare disorder characterized by fibrous dysplasia, café au lait skin spots, and hyperfunctioning endocrinopathies. The coexistence of precocious puberty and growth hormone excess in McCune-Albright syndrome is rare. Both conditions can manifest as accelerated growth, and treatments can be more challenging for such patients. This study aimed to describe the clinical manifestations of combined GH excess and PP in the context of McCune-Albright syndrome and analyze the clinical features and treatments of these patients.MethodClinical data from 60 McCune-Albright syndrome patients from Peking Union Medical College Hospital were obtained. The demographic characteristics, growth hormone, insulin-like growth factor-1, prolactin, alkaline phosphatase, and sex hormone levels; growth velocity; and bone age data were obtained. The growth velocity Z-score, bone age over chronological age ratio, and predicted adult height Z-score were calculated before and after treatment. Published studies and case reports were systemically searched, and data on demographic, clinical, and biochemical characteristics and treatment outcomes were obtained.ResultsWe reviewed seven patients among 60 McCune-Albright syndrome patients at Peking Union Medical College Hospital (5 female) and 39 patients (25 female) from the published literature. Six of the seven patients from Peking Union Medical College Hospital and half of the patients from the published studies were pediatric patients. These patients had increased growth velocity Z-scores and bone age over chronological age ratios. After good control of both conditions, the growth velocity Z-score and bone age over chronological age ratio decreased significantly, and the predicted adult height Z-score increased. The final heights and predicted adult height Z-scores were not impaired in patients with gigantism. All the patients had craniofacial fibrous dysplasia associated with optic and otologic complications.ConclusionMcCune-Albright syndrome with growth hormone excess and precocious puberty is more common in girls. Patients have accelerated linear growth and advanced skeletal age, and early and good control of both conditions leads to a reduced growth velocity and stabilized bone age. The predicted adult and final heights are not negatively affected when growth hormone excess is diagnosed in pediatric patients.

BackgroundInsidious-onset acromegaly may easily be overlooked by non-specialists of acromegaly and cause diagnostic delay. This study aims to examine the association between diagnostic delay and advice from doctors before any confirmed diagnosis and subsequent comorbidities, and elicit patient-perceived reasons for misdiagnoses.MethodsAn online nationwide cross-sectional study was conducted through China Acromegaly Patient Association. Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1) levels at diagnosis and cancerous, endocrine-metabolic, musculoskeletal, cardiovascular, respiratory, and psychiatric comorbidities were reported by patients. The association between diagnostic delay and pre-diagnostic advice from doctors as well as subsequent comorbidities after diagnosis were examined.ResultsIn total, 447 valid responses were collected. Overall, 58.8% patients experienced misdiagnoses, and 22.6% had diagnostic delay. Before arriving at any diagnosis, patients without treatment (adjusted odds ratio [AOR]: 3.66, 95% confidence interval [CI]: 1.30-10.33) or receiving treatment to symptoms only (AOR: 7.05, 95%CI: 4.09-12.17) had greater chance of being misdiagnosed, and hence had diagnostic delay. Patients believed insufficient specialists, limited awareness of acromegaly of non-specialists and poor doctor-patient communications were major reasons of misdiagnosis. Diagnostic delay were associated with higher GH level at diagnosis and endocrine-metabolic, musculoskeletal and cardiovascular comorbidities (all P

Objective: To investigate the validity of discharge ICD-10 codes in detecting the etiology of endogenous Cushing’s syndrome (CS) in hospitalized patients. Methods: We evaluated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CS etiology-related ICD-10 c odes or code combinations by comparing hospital discharge administrative data (DAD) with established diagnoses from medical records. Results: Coding for patients with adrenocortical adenoma (ACA) and those with bilateral macronodular adrenal hyperplasia (BMAH) demonstrated disappointingly low sensitivity at 78.8% (95% CI: 70.1–85.6%) and 83.9% (95% CI: 65.5–93.9%), respectively. BMAH had the lowest PPV of 74.3% (95% CI: 56.4–86.9%). In confirmed ACA p atients, the sensitivity for ACA code combinations was higher in patients initially admitted to the Department of Endocrinology before surgery than that in patients directly admitted to the Department of Urology (90.0 vs 73.1%, P = 0.033). The same phenomenon was observed in the PPV for the BMAH code (100.0 vs 60.9%, P = 0.012). Misinterpreted or confusing situations caused by coders (68.1%) and by the omission or denormalized documentation of symptomatic diagnosis by clinicians (26.1%) accounted for the main source of coding errors. Conclusions: Hospital DAD is an effective data source for evaluating the eti ology of CS but not ACA and BMAH. Improving surgeons’ documentation, especially in the delineation of symptomatic and locative diagnoses in discharge abstracts; department- or disease-specific training for coders and more multidisciplinary collabor ation are ways to enhance the applicability of administrative data for CS etiologies.

ABSTRACT Objectives: Our study aimed to investigate the associations of glucose tolerance status with insulin-like growth factor-I (IGF-I) and other clinical laboratory parameters of acromegalic patients before and after the patients underwent transsphenoidal adenomectomy (TSA) by conducting a single-center, retrospective study. Subjects and methods: A total of 218 patients with acromegaly who had undergone TSA as the first treatment were retrospectively analyzed. Serum IGF-I, growth hormone (GH) and glucose levels were measured before and after surgery. Results: The follow-up levels for random GH, GH nadir, and the percentage of the upper limit of normal IGF-I (%ULN IGF-I) were decreased significantly. The percentages of normal (39.0%), early carbohydrate metabolism disorders (33.0%) and diabetes mellitus (28.0%) changed to 70.2%, 16.5% and 13.3%, respectively, after TSA. %ULN IGF-I at baseline was higher in the diabetes mellitus (DM) group than in the normal glucose tolerance group and impaired glucose tolerance (IGT) /impaired fasting glucose (IFG) groups before TSA, and the DM group exhibited a greater reduction in %ULN IGF-I value after surgery. The follow-up %ULN IGF-I value after surgery was significantly lower in the improved group, and Pearson's correlation analysis revealed that the reductions in %ULN IGF-I corresponded with the reductions in glucose level. Conclusion: This study examined the largest reported sample with complete preoperative and follow-up data. The results suggest that the age- and sex-adjusted IGF-I level, which reflects altered glucose metabolism, and the change of it are associated with improved glucose tolerance in acromegalic patients both before and after TSA.

PurposeGlioblastoma (GBM) is one of the most aggressive brain tumors with high mortality, and tumor-derived exosomes provide new insight into the mechanisms of GBM tumorigenesis, metastasis and therapeutic resistance. We aimed to establish an exosome-derived competitive endogenous RNA (ceRNA) network for constructing a prognostic model for GBM.MethodsWe obtained the expression profiles of long noncoding RNAs (lncRNAs), miRNAs, and mRNAs from the GEO and TCGA databases and identified differentially expressed RNAs in GBM to construct a ceRNA network. By performing lasso and multivariate Cox regression analyses, we identified optimal prognosis-related differentially expressed lncRNAs (DElncRNAs) and generated a risk score model termed the exosomal lncRNA (exo-lncRNA) signature. The exo-lncRNA signature was subsequently validated in the CGGA GBM cohort. Finally, a novel prognostic nomogram was constructed based on the exo-lncRNA signature and clinicopathological parameters and validated in the CGGA external cohort. Based on the ceRNA hypothesis, oncocers were identified based on highly positive correlations between lncRNAs and mRNAs mediated by the same miRNAs. Furthermore, regression analyses were performed to assess correlations between the expression abundances of lncRNAs in tumors and exosomes.ResultsA total of 45 DElncRNAs, six DEmiRNAs, and 38 DEmRNAs were identified, and an exosome-derived ceRNA network was built. Three optimal prognostic-related DElncRNAs, HOTAIR (HR=0.341, P

Drought is one of the major environmental stressors; drought is increasingly threatening the living environment of mankind. The standardized precipitation evapotranspiration index (SPEI) with a 12-month timescale was adopted to monitor dry–wet status over China from 1951 to 2021. The modified Mann–Kendall (MMK) and Pettitt tests were used to assess the temporal trend and nonlinear behavior of annual drought variability. The analysis focuses on the spatio-temporal structure of the dry–wet transition and its general connections with climate change processes. In addition, the seasonal autoregressive integrated moving average (SARIMA) model was applied to forecast the dry–wet behavior in the next year (2022) at 160 stations, and the hotspot areas for extreme dryness–wetness in China were identified in the near term. The results indicate that the dry–wet climate in China overall exhibits interannual variability characterized by intensified drought. The climate in the Northeast China (NEC), North China (NC), Northwest China (NWC), and Southwest China (SWC) has experienced a significant (p < 0.05) drying trend; however, the dry–wet changes in the East China (EC) and South Central China (SCC) are highly spatially heterogeneous. The significant uptrend in precipitation is mainly concentrated to the west of 100° E; the rising magnitude of precipitation is higher in Eastern China near 30° N, with a changing rate of 20–40 mm/decade. Each of the sub-regions has experienced significant (p < 0.01) warming over the past 71 years. Geographically, the increase in temperature north of 30° N is noticeably higher than that south of 30° N, with trend magnitudes of 0.30–0.50 °C/decade and 0.15–0.30 °C/decade, respectively. The response of the northern part of Eastern China to the warming trend had already emerged as early as the 1980s; these responses were earlier and more intense than those south of 40° N latitude (1990s). The drying trends are statistically significant in the northern and southern regions, bounded by 30° N, with trend magnitudes of −0.30–−0.20/decade and −0.20–−0.10/decade, respectively. The northern and southwestern parts of China have experienced a significant (p < 0.05) increase in the drought level since the 1950s, which is closely related to significant warming in recent decades. This study reveals the consistency of the spatial distribution of variations in precipitation and the SPEI along 30° N latitude. A weak uptrend in the SPEI, i.e., an increase in wetness, is shown in Eastern China surrounding 30° N, with a changing rate of 0.003–0.10/decade; this is closely associated with increasing precipitation in the area. Drought forecasting indicates that recent drying areas are located in NWC, the western part of NC, the western part of SWC, and the southern part of SCC. The climate is expected to show wetting characteristics in NEC, the southeastern part of NC, and the eastern part of EC. The dry–wet conditions spanning the area between 30–40° N and 100–110° E exhibit a greater spatial variability. The region between 20–50° N and 80–105° E will continue to face intense challenges from drought in the near future. This study provides compelling evidence for the temporal variability of meteorological drought in different sub-regions of China. The findings may contribute to understanding the spatio-temporal effect of historical climate change on dry–wet variation in the region since the 1950s, particularly in the context of global warming.

PurposeAcromegaly is a rare, intractable endocrine disease. We aimed to describe the patient characteristics, diagnostic delays, treatment patterns, treatment outcomes, comorbidities and treatment costs of acromegaly in China.MethodsThis is a nationwide cross-sectional study. Patients diagnosed with and treated for acromegaly between 1996 and 2019 across China were surveyed via the Chinese Association of Patients with Acromegaly platform.ResultsIn total, 473 patients (58.8% females, mean age at diagnosis: 39.4±9.5 years) were included. The median disease duration was 3 years. The most common symptoms were extremity enlargement (91.8%) and facial changes (90.1%). Overall, 63.0% of patients experienced diagnostic delays within healthcare systems; 63.8% of the delays were

PurposeCardiac comorbidity is one of the leading causes of death among acromegaly patients. We aimed to investigate the reversibility of acromegalic cardiac involvement after surgical treatment using the gold standard method, cardiovascular magnetic resonance, and to explore the effects of endocrine remission and gender on reversibility.MethodsIn this single-center, prospective cohort study, fifty untreated acromegaly patients were enrolled. Comprehensive cardiac assessments were performed using a 3.0 T magnetic resonance scanner before and 3 and 12 months after transsphenoidal adenomectomy.ResultsPreoperatively, left ventricular (LV) enlargement (13.0%), LV systolic dysfunction (6.5%), right ventricular (RV) enlargement (4.3%), RV systolic dysfunction (2.2%) and myocardial fibrosis (12.0%) were identified. On average, the LV and RV ejection fractions of acromegaly patients were higher than the healthy reference values. Male patients had thicker LV myocardia, wider ventricular diameters and more dilated pulmonary artery roots than female patients. After surgery, LV myocardial hypertrophy was reversed, the left atrium was remodeled, and ventricular systolic dysfunction recovered to normal. Cardiac alterations were detected early in the 3rd postoperative month and persisted until the 12th month. The interventricular septum was initially thickened in the 3rd postoperative month and then recovered at the 12th month. Notable postoperative cardiac reversibility was observed in male patients but did not occur in all female patients. Patients achieving endocrine remission with normalized hormone levels had thinner LV myocardia than patients without normalized hormone levels.ConclusionOur findings demonstrated that some of the cardiac involvement in acromegaly patients is reversible after surgical treatment which lowers hormone levels. Endocrine remission and gender significantly impacted postoperative cardiac reversibility.

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.

PurposeGlioblastoma (GBM) is the most common primary malignant tumor of the central nervous system, with a 5-year overall survival (OS) rate of only 5.6%. This study aimed to develop a novel DNA methylation-driven gene (MDG)-based molecular classification and risk model for individualized prognosis prediction for GBM patients.MethodsThe DNA methylation profiles (458 samples) and gene expression profiles (376 samples) of patients were enrolled to identify MDGs using the MethylMix algorithm. Unsupervised consensus clustering was performed to develop the MDG-based molecular classification. By performing the univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis, a MDG-based prognostic model was developed and validated. Then, Bisulfite Amplicon Sequencing (BSAS) and quantitative real-time polymerase chain reaction (qPCR) were performed to verify the methylation and expressions of MDGs in GBM cell lines.ResultsA total of 199 MDGs were identified, the expression patterns of which enabled TCGA and CGGA GBM patients to be divided into 2 clusters by unsupervised consensus clustering. Cluster 1 patients commonly exhibited a poor prognosis, were older in age, and were more sensitive to immunotherapies. Then, six MDGs (ANKRD10, BMP2, LOXL1, RPL39L, TMEM52, and VILL) were further selected to construct the prognostic risk score model, which was validated in the CGGA cohort. Kaplan-Meier survival analysis demonstrated that high-risk patients had significantly poorer OS than low-risk patients (logrank P = 3.338 × 10-6). Then, a prognostic nomogram was constructed and validated. Calibration plots, receiver operating characteristic curves, and decision curve analysis indicated excellent predictive performance for the nomogram in both the TCGA training and CGGA validation cohorts. Finally, in vitro BSAS and qPCR analysis validated that the expressions of the MDGs were negatively regulated by methylations of target genes, especially promoter region methylation.ConclusionThe MDG-based prognostic model could serve as a promising prognostic indicator and potential therapeutic target to facilitate individualized survival prediction and better treatment options for GBM patients.

Purpose: Alternative splicing (AS) was reported to play a vital role in development and progression of glioblastoma (GBM), the most common and fatal brain tumor. Systematic analysis of survival-associated AS event profiles and prognostic prediction model based on multiple AS events in GBM was needed.Methods: Genome-wide AS and RNA sequencing profiles were generated in 152 patients with GBM in the cancer genome atlas (TCGA). Prognosis-associated AS events were screened by integrated Cox regression analysis to construct the prognostic risk score model in the training cohort (n = 101). The AS-based signature and clinicopathologic parameters were applied to construct a prognostic nomogram for 0.5-, 1-, and 3-year OS prediction. Finally, the regulatory networks between prognostic AS events and splicing factors (SFs) were constructed.Results: A total of 1,598 prognosis-related AS events from 1,183 source genes were determined. Eight prognostic risk score model based on integrated AS events and 7 AS types were established, respectively. Concordance index (C-index) and receiver operating characteristic (ROC) curve analysis demonstrated powerful ability in distinguishing patients' outcomes. Only Alternate Donor site (AD) and Exon Skip (ES) signature out of the eight types of AS signature were identified as independent prognostic factors for GBM, which was validated in the internal validation cohort. The nomogram with age, new event, pharmaceutical therapy, radiation therapy, AD signature and ES signature were constructed, with C-index of 0.892 (95% CI, 0.853–0.931; P = 5.13 × 10−15). Calibration plots, ROC, and decision curve analysis suggested excellent predictive performance for the nomogram in both TCGA training cohort and validation cohort. Splicing network indicated distinguished correlations between prognostic AS events and SFs in GBM patients.Conclusions: AS-based prediction model could serve as a promising prognostic predictor and potential therapeutic target for GBM, facilitating better treatment strategies in clinical practice.

Objective: Facial changes are common among nearly all acromegalic patients. As they develop slowly, patients often fail to notice such changes before they become obvious. Consequently, diagnosis and treatment are often delayed. So far, convenient and accurate early detection of this disease is still unavailable. This study is designed to combine the use of 3D imaging and machine learning techniques in facial feature analysis and identification of acromegalic patients, in an effort to ascertain how both techniques performed in terms of applicability and value in the early detection of the disease.Methods: One hundred and twenty-four participants including 62 patients with acromegaly and 62 matched controls were enrolled. Using three-dimensional imaging techniques, 58 facial parameters were measured on each face. A two-way analysis of variance (ANOVA) and a post-hoc t-tests were conducted to examine the variations of these parameters with disease status and gender. Using linear discriminant analysis (LDA), we further distinguished patients from controls, characterized what combinations of the parameters could best predict disease state and their relative contributions.Results: Patients are significantly different from normal subjects in many variables, and facial changes of male patients are more significant than female ones. Both male and female patients present following major changes: the increase of facial length and breadth, the widening and elevation of the nose, the thickening of vermilion and the enlargement of the mandible. Facial variables which strongly related to the pathological states can be used to predict the morbid state with high accuracy (prediction accuracies 92.86% in females, p < 0.0001 and 75% in males, p < 0.001). We have further testified that only a few variables play a vital role in disease prediction and the vital combination of variables vary with gender.Conclusions: Three-dimensional imaging enables comprehensive and accurate quantification of facial characteristics, which makes it a promising technique to investigate facial features of acromegalic patients. In combination with machine learning technique, patients can be accurately identified and predicted by their facial variables. This approach might be beneficial for the early detection of acromegalic patients and timely consultation to improve their outcomes.

Purpose: To increase knowledge for the early differential diagnosis and accurate therapeutic strategies for pediatric patients with sellar or suprasellar region (SSR) lesions who initially present with central diabetes insipidus (CDI).Methods: This is a retrospective review of 55 pediatric patients (≤14 years old) with identified lesions in the SSR who initially presented with CDI at a large pituitary center between 2012 and 2018. The following data were summarized: demographic, clinical, endocrine, and neuroimaging data, intraoperative findings, histopathological findings, treatments, and prognosis.Results: In our group, the etiologies of the SSR lesions included germ cell tumors (GCTs, 74.5%), Langerhans cell histiocytosis (LCH, 18.2%), and craniopharyngioma (CP, 7.3%). Almost all patients (50/55, 90.9%) showed anterior pituitary dysfunction [multiple axes dysfunction (38), and isolated axis dysfunction (14)], while the GH/IGF-I axis was the most affected. Most GCT patients presented with various clinical manifestations besides CDI and had elevated β-HCG, whereas LCH and CP patients mostly presented few non-specific symptoms besides CDI and most had normal level tumor markers. Sellar MRI demonstrated that posterior pituitary bright spot disappearance occurred in all patients, and pituitary stalk thickening was observed in 96.7% of patients. Treatment varied due to the different etiologies of the SSR lesions. After follow-up for 35.4 ± 20.2 months, the proportions of patients who needed AVP (arginine vasopressin) for GCT, LCH, and CP were 86.5, 100, and 75%, respectively, and the proportions of patients who needed HRT were 89.2, 50, and 75%, respectively.Conclusion: For pediatric SSR lesions that first manifest as CDI, we should comprehensively consider clinical characteristics and imaging features to aid in their early differential diagnosis. Tumor markers and surgical histopathology are also great complements for the differential diagnosis. Additionally, various treatment strategies should be adopted according to different causes to improve the child's prognosis and quality of life.

Since the 1930s, topological counting on finite sets has been an interesting work so as to enumerate the number of corresponding order relations on the sets. Starting from the semi-tensor product (STP), we give the expression of the relationship between subsets of finite sets from the perspective of algebra. Firstly, using the STP of matrices, we present the algebraic representation of the subset and complement of finite sets and corresponding structure matrices. Then, we investigate respectively the relationship between the intersection and union and intersection and minus of structure matrices. Finally, we provide an algorithm to enumerate the numbers of topologies on a finite set based on the above theorems.

As global warming produces dramatic climate changes, water management is facing increasingly serious challenges. Given to the process of climate change and its complex effects on watershed hydrology, this paper investigates the spatial and temporal variation characteristics of major climatic factors (i.e., precipitation and temperature) over the upper Yangtze River basin (UYRB), China. The statistical analyses are based on annual and seasonal scales during 1951–2020 with a recorded period of seven decades. The Mann–Kendall nonparametric test and R/S analysis are used to record the temporal trends (past and future) of climate variables; the Pettitt test, standard normal homogeneity test and Buishand test are used to detect the homogeneity in climate series. The sensitivities of the streamflow to climatic parameters are assessed at the watershed scale, especially considering the Three Gorges Dam’s (TGD) effect on changing runoff. The results of the study indicate that the annual precipitation of 29 out of 34 series indicate homogeneity, while 31 out of 34 annual mean temperature series show heterogeneity, with jump points around 1997 in the mean temperature of 20 sites. Detectable changes in precipitation were not observed during 1951–2020; however, the temperature increased significantly in the whole basin on annual and seasonal scales, except for several stations in the eastern part. The magnitude of increase in air temperature in high altitudes (Tibet Plateau) is higher than that in low altitudes (Sichuan Plain) over the last seven decades, and future temperatures continue to sharply increase in high altitudes. The TGD plays an important role in explaining the seasonal variations in streamflow at Yichang station, with streamflow experiencing a sharp increase in winter and spring (dry season) and a decrease in summer and autumn (rainy season) compared to the pre-TGD period. The streamflow variation at an annual scale is mainly regulated by climate fluctuation (variation in precipitation). During the last seven decades, increasing air temperature and decreases in rainfall and runoff signify reduced water resources availability, and the climate tends to be warmer and drier over the basin. The sensitivity of the streamflow to watershed precipitation is higher than that to temperature, with variation in annual rainfall explaining 71% of annual runoff variability.

Abstract Background Granulomatosis with polyangiitis (GPA), a necrotizing granulomatous disease, very rarely involves the central nervous system (CNS), particularly the pituitary. Delayed treatment may cause permanent bilateral blindness. We report an isolated case of pituitary GPA that manifested as a progressive bilateral temporal visual field (VF) defect and was diagnosed via pituitary biopsy. Additionally, we review ocular, chiasmal and cranial nerve involvement in pituitary GPA. Case presentation A 20-year-old Chinese man was referred for repeated fever, sudden headache, diplopia with a bilateral best-corrected visual acuity (BCVA) of 10/20, ptosis in both eyes and restricted abduction on the right side. VF tests showed bitemporal hemianopsia. Laboratory tests revealed hypothyroidism and were negative for autoimmune markers. Enhanced magnetic resonance imaging (MRI) showed pituitary enlargement. The diagnosis was lymphocytic pituitaritis. After intravenous (IV) dexamethasone treatment, full recovery occurred within 2 months. Two years later, the patient was readmitted for headache recurrence. With oral prednisone, the visual acuity in his right eye rapidly decreased to hand motion (HM) within one month. Enhanced MRI showed pituitary enlargement and a new, invasive suprasellar CNS lesion. All infection- and autoimmune-related tests were negative. The visual acuity in his right and left eye decreased to no light perception (NLP) after 6 days and 2 weeks, respectively. The biopsy results suggested GPA. After IV methylprednisolone treatment, complete remission of the symptoms occurred and was confirmed by MRI. The 15-month follow-up showed no signs of recurrence. Conclusion GPA typically affects the respiratory tract, lungs and kidneys. To date, 50 cases with pituitary involvement have been reported. Chiasmal and cranial nerve involvement leading to visual acuity impairment are common. We found 2 cases with severe visual loss resembling our case and discuss certain similarities.

Drought is one of the most important environmental disasters. Assessment of the effects of oceanic atmospheric oscillations upon regional drought behavior has valuable implications for water resources management, especially for arid regions. This study aims to explore the climate drivers of drought conditions in Xinjiang, an arid region in mid-latitude Asia. Standardized Precipitation Evapotranspiration Index (SPEI) was adopted to describe drought variation over Xinjiang during the period of 1951–2020. Teleconnection effects of El Niño Southern Oscillation (ENSO), Pacific Decadal Oscillation (PDO), Atlantic Multidecadal Oscillation (AMO), and Arctic Oscillation (AO) on Xinjiang drought variability were analyzed based on cross-correlation and stepwise regression methods. Partial correlation analysis was applied to discuss the responding mechanism of drought behavior to teleconnection signals from the perspective of regional climate factors. Findings from this study indicate that synchronous ENSO featured by Nino3.4 index has a significant positive correlation with Xinjiang dry/wet variation. El Niño may favor to wetness in Xinjiang, while La Niña may exacerbate drought effect in the region. ENSO mainly acts on the short-term drought variability in Xinjiang region. The synchronous PDO makes a leading contribution on drought variation at 12-month time scale among the four signals. The significant positive correlation between PDO and drought variation suggests that positive-phase (negative-phase) PDO may contribute to wetting (drying) epochs in Xinjiang region. AMO indicates a significant negative correlation with Xinjiang drought on both synchronous and asynchronous modes. Positive (negative) phase AMO may favor to dry (wet) effects in Xinjiang. AMO appears a predominant teleconnection effect on long-term drought variability, and fluctuates a persistent anti-phase mode with Xinjiang dry/wet variability since the mid-1980s. AO mainly acts on short-term drought fluctuations, indicating a significant negative correlation with drought behavior within a 12-month moving time window. Positive (negative) phase AO may contribute to dry (wet) epochs over Xinjiang. ENSO and PDO affect short-term dry/wet variation mainly through the teleconnection effect on precipitation variability. AMO mainly influences Xinjiang drought evolution by acting on regional temperature variation. The influence of internal atmospheric variability on regional climate behavior has a delayed effect, and drought variability is affected by precursor pattern of teleconnection likewise.

Growth hormone (GH)-secreting pituitary adenoma is a chronic disease characterized by excess levels of GH and insulin-like growth factor 1 (IGF-1). Based on our clinical experience and observations, we identified discordant GH and IGF-1 levels after surgery. The risk factors for this phenomenon are unclear, and individualized cure, control criteria, and management after surgery should be considered. Purpose: This study aims to investigate the factors affecting the discordant GH and IGF-1 levels after pituitary surgery in acromegalic patients. Methods: We retrospectively analyzed 146 patients diagnosed with acromegaly caused by GH-secreting pituitary adenoma who had undergone trans-sphenoidal adenectomy (TSA) at Peking Union Medical College Hospital in 2013. Medical histories were obtained for all patients. Hormone levels, biochemical measurements of liver and renal function, and tumor size were recorded before and 3 months after surgery. Results: Among the GH-cured patients who had normal GH levels after TSA, 39.2% (20 of 51) had elevated IGF-1. Acromegalic patients with elevated IGF-1 and normal GH levels after TSA had a significantly higher mean body mass index and percentage of upper limit of normal range IGF-1 than the cured patients (p 25.0 kg/m2 and a percentage of upper limit of normal range IGF-1 higher than 141.5 before TSA might predict the occurrence of hormone-level discordance after surgery. Conclusion: Body mass index and percentage of upper limit of normal range IGF-1 before TSA might constitute prognostic risk factors for discordance in IGF-1 and GH levels in acromegaly. Additional attention should be devoted to potential risk factors for this phenomenon, and methods for modifying the cure and control criteria for acromegaly should be developed.

Precipitation is considered a crucial component in the hydrological cycle and changes in its spatial pattern directly influence the water resources. We compare different interpolation techniques in predicting the spatial distribution pattern of precipitation in Chongqing. Six interpolation methods, i.e., Inverse Distance Weighting (IDW), Radial Basis Function (RBF), Diffusion Interpolation with Barrier (DIB), Kernel Interpolation with Barrier (KIB), Ordinary Kriging (OK) and Empirical Bayesian Kriging (EBK), were applied to estimate different rainfall patterns. Annual mean, rainy season and dry-season precipitation was calculated from the daily precipitation time series of 34 meteorological stations with a time span of 1991 to 2019, based on Leave-One-Out Cross-Validation (LOOCV), Mean Square Error (MSE), Mean Absolute Error (MAE), Mean Absolute Percentage Error (MAPE), Symmetric Mean Absolute Percentage Error (SMAPE) and Nash–Sutcliffe Efficiency coefficient (NSE) as validation indexes of the applied models for calculating the error degree and accuracy. Correlation test and Spearman coefficient was performed on the estimated and observed values. A method combining Entropy Weight and Technique for Order Preference by Similarity to Ideal Solution (Entropy-Weighted TOPSIS) was introduced to rank the performance of six interpolation methods. The results indicate that interpolation technique performs better in estimating during periods of low precipitation (i.e., dry season, relative to rainy season and mean annual). The performance priorities of the six methods under the combined multiple precipitation distribution patterns are KIB > EBK > OK > RBF > DIB > IDW. Among them, KIB method has the highest accuracy which maps more accurate precipitation surfaces, with the disadvantage that estimation error is prone to outliers. EBK method is the second highest, and IDW method has the lowest accuracy with a high degree of error. This paper provides information for the application of interpolation methods in estimating rainfall spatial pattern and for water resource management of concerned regions.

Profiling the hydrological response of watershed precipitation and streamflow to large-scale circulation patterns and astronomical factors provides novel information into the scientific management and prediction of regional water resources. Possible contacts of El Niño–Southern Oscillation (ENSO), Pacific Decadal Oscillation (PDO), sunspot activity to precipitation and streamflow in the upper Yangtze River basin (UYRB) were investigated in this work. Monthly precipitation and streamflow were utilized as well as contemporaneous same-scale teleconnections time series spanning a total of 70 years from 1951 to 2020 in precipitation and 121 years from 1900 to 2020 in streamflow. The principal component analysis (PCA) method was applied so as to characterize the dominant variability patterns over UYRB precipitation time series, with the temporal variability of first two modes explaining more than 80% of total variance. Long-term evolutionary pattern and periodic variation characteristics of precipitation and streamflow are explored by applying continuous wavelet transform (CWT), cross-wavelet transform (XWT) and wavelet coherence (WTC), analyzing multi-scale correlation between hydrological variables and teleconnections in the time-frequency domain. The results manifest that ENSO exhibits multiple interannual period resonance with precipitation and streamflow, while correlations are unstable in time and phase. PDO and sunspot effects on precipitation and streamflow at interannual scales vary with time-frequency domains, yet significant differences are exhibited in their effects at interdecadal scales. PDO exhibits a steady negative correlation with streamflow on interdecadal scales of approximately 10 years, while the effect of sunspot on streamflow exhibits extremely steady positive correlation on longer interdecadal scales of approximately 36 years. Analysis reveals that both PDO and sunspot have significantly stronger effects on streamflow variability than precipitation, which might be associated with the high spatiotemporal variability of precipitation.

Abstract Background This study aimed to investigate preoperative somatostatin analogs (SSAs) treatment on the surgical outcome in patients with acromegaly. Methods An analysis of 358 patients with acromegaly was conducted. The preoperative medical therapy group (81 patients) received SSA treatment for at least 3 months prior to surgery, while the primary surgery group (277 patients) underwent transsphenoidal surgery directly. Follow-up duration was ≥3 months. Tumor invasion was evaluated by magnetic resonance imaging (MRI) and classified according to the Knosp grading system. Results Most patients were diagnosed with macroadenoma. Among all patients (Knosp grades 0–4), preoperative SSA therapy did not significantly improve the curative effect of surgery, according to the levels of growth hormone (GH) and/or insulin-like growth factor 1 (IGF-1) markers. In patients with macroadenoma (Knosp grades 1–3), the remission rates were significantly higher in the SSA group compared to the surgery group when considering GH (56.4% vs. 37.3%, P = 0.048) and IGF-1 (43.2% vs. 17.6%, P = 0.004). In the preoperative medical therapy group, long-term use of SSAs (>6 months) led to higher remission rates (GH, 72.2% vs. 51.0%; and IGF-1, 61.1% vs. 29.8%; P = 0.12 and 0.02, respectively]. Conclusions The long-term preoperative SSAs treatment may improve the surgical curative rate in acromegalic patients with invasive macroadenomas (Knosp grades 1–3).

Introduction: The body of glioma-related literature has grown significantly over the past 25 years. Despite this growth in the amount of published research, gliomas remain one of the most intransigent cancers. The purpose of this study was to analyze the landscape of glioma-related research over the past 25 years using machine learning and text analysis.Methods: In April 2019, we downloaded glioma-related publications indexed in PubMed between 1994 and 2018. We used Python to extract the title, publication date, MeSH terms, and abstract from the metadata of each publication for bibliometric assessment. Latent Dirichlet allocation (LDA) was applied to the abstracts to identify publications' research topics with greater specificity.Results: We identified and analyzed a total of 52,625 publications in our study. We found that research on prognosis and the treatment of glioblastoma increased the most in terms of volume and rate of publications over the past 25 years. However, publications regarding clinical trials accounted for

Tumor resection is the first-line therapy for acromegaly patients. In some cases, unsatisfactory intraoperative neuromuscular blockades (NMBs) lead to failed operations. The purpose of this study was to investigate and quantify the NMB status of acromegaly patients and explore the relationship between NMB status and hormone levels and body composition. Twenty patients with untreated acromegaly and seventeen patients with nonfunctioning pituitary adenomas as controls were enrolled in this study. NMB was assessed using the train-of-four (TOF) technique with TOF-Watch® SX. The onset time of NMB, deep neuromuscular blockade duration (DNMBD), and clinical neuromuscular blockade duration (CNMBD) were monitored. We found a significantly longer onset time (110.25 ± 54.90 vs. 75.00 ± 27.56, s, p=0.017), shorter DNMBD (21.99 ± 5.67 vs. 34.96 ± 11.04, min, p

Purpose. To identify the characteristics of the physical and mental health status of patients with pituitary adenomas, explore the postoperative reversibility of impaired health status, and assess the impact of clinical characteristics, hormone levels, anxiety, depression, and disease stigma on health status. Methods. We prospectively enrolled 147 and 138 patients with nonfunctioning and secretory pituitary adenomas, respectively. Health status was evaluated in 8 domains using the 36-item Short-Form Health Survey before and 3 months after transsphenoidal surgery. The Self-Rating Anxiety Scale, the Self-Rating Depression Scale, and the Stigma Scale for Chronic Illness were used to assess the psychological status. Results. Compared with the healthy population reference values, general physical and mental health, social functioning, and role limitations due to physical and psychological health problems were all found to be significantly impaired in the adenoma patients. Health status was worse in patients with adrenocorticotropic hormone- (ACTH-) secreting and growth hormone- (GH-) secreting adenomas than in patients with nonfunctioning adenomas. Among the patients, 11.6% had anxiety and 30.9% had depression. Higher scores for anxiety, depression, and disease stigma; older age; higher body mass index; and tumor recurrence were independent risk factors for health status impairment in at least one domain. Physical function impairment and role limitations caused by physical health problems became worse after surgery, whereas the mental component of health status remained the same. Conclusion. Health status was impaired in patients with pituitary adenomas, especially secretory adenomas. Physical function and role limitations were worse 3 months after surgery than before surgery. Mental problems, old age, obesity, and tumor recurrence reduced health status.

Cardiac abnormalities are the most common and deadly comorbidities of acromegaly. Assessments using cardiac magnetic resonance (CMR) imaging in acromegaly patients are rare. We aimed to evaluate the frequencies of left ventricular hypertrophy (LVH), interventricular septum hypertrophy (IVSH), LV systolic dysfunction (LVSD), right ventricular systolic dysfunction (RVSD), and myocardial fibrosis (MCF) and detailed quantitative parameters in acromegaly patients using CMR and analyze their correlations with clinical features. Sixty-one patients were enrolled in this study. The rates of LVH, IVSH, LVSD, RVSD, and MCF were 26.2%, 27.9%, 8.2%, 9.8%, and 14.8%, respectively. The average LV mass, LV mass index, IVS thickness, LV and RV free wall thickness, and LV and RV ejection fractions were 114.4 g, 60.0 g/m2, 9.6 mm, 7.2 mm, 2.9 mm, 59.9%, and 56.6%, respectively. The LV mass index was larger (68.9 ± 26.0 vs. 48.8 ± 10.6 g/m2), the IVS was thicker (10.3 ± 2.8 vs. 8.8 ± 1.8 mm), and the LV (57.6 ± 12.3% vs. 62.8 ± 4.8%) and RV ejection fractions (54.6 ± 8.7% vs. 59.2 ± 5.9%) were lower in male patients than in female patients (all p

Purpose: Abnormal glucose metabolism is one of the most frequent acromegaly complications. Improvement of glucose metabolism can be observed only in half of acromegaly patients after surgery. We aimed to investigate the risk factors for determining abnormal glucose metabolism before surgery in patients with acromegaly, and to explore the predictors of improved preoperative glucose intolerance after surgery.Methods: We retrospectively reviewed 64 patients who received transsphenoidal surgery for acromegaly. Growth hormone (GH), insulin-like growth factor-1 (IGF-1) and glucose metabolism were assessed before, immediately after, and 3 months after surgery. Glucose metabolic parameters included glycosylated hemoglobin (HbA1c), plasma glucose (PG), C-peptide (CP), insulin (INS), and the indices of β-cell function, insulin sensitivity, and insulin resistance (IR).Results: Preoperatively, 18 patients (28.1%) had diabetes (DM), 34 (53.1%) had prediabetes (PreDM), and 12 (18.8%) had normal glucose tolerance (NGT). All the indices of pancreatic β-cell function were significantly lower in patients with DM than those with PreDM and NGT (all P < 0.005). IGF-1 was significantly positively correlated with insulin sensitivity and IR (P < 0.05), while GH was not. Postoperatively, glucose tolerance was improved in 71.2% of patients (37/52) with preoperative glucose intolerance. Insulin sensitivity was increased, while β-cell function and IR were decreased in most patients after surgery, regardless of whether their acromegaly achieved remission. A multivariate logistic regression analysis revealed that preoperative fasting C-peptide (FCP, OR = 2.639, P = 0.022), disposition index (DI, OR = 1.397, P = 0.043) and Predictor-2 (OR = 0.578, P = 0.035) were determined to be the predictors for improved glucose tolerance status after surgery. Afterwards, through Receiver operating characteristic (ROC) analyses, FCP >2.445 ng/ml was the best independent predictor, with an 86.6% PPV (positive predictive value) and a 74.5% NPV (negative predictive value).Conclusions: Preoperative high FCP is a promising postsurgical predictor of improved glucose tolerance in patients with acromegaly. Oral glucose tolerance testing (OGTT) and HbA1c should be monitored regularly after surgery, and diabetes management should be adjusted based on the patient's latest glucose tolerance status.

Abstract Background von Hippel–Lindau (VHL) disease has a hereditary, autosomal dominant pattern, and multiple tumors can develop in multiple organs of a single patient. However, the exact mechanisms of tumorigenesis are unclear, and further studies are needed to clarify whether the same signaling pathways are involved in different VHL‐related tumors. Methods Whole‐exome sequencing (WES) of tumor and paired peripheral blood samples were performed for a VHL disease pedigree. A bioinformatics analysis was conducted to identify candidate somatic single‐nucleotide variants (SNVs) present in all tumor tissues. Sanger sequencing was then used to validate the SNVs identified using WES. Immunohistochemistry was performed to analyze components of the mTOR pathway, which was abnormally activated in tumor tissues. Results Two hemangioblastomas and two renal cell carcinomas were sequenced. The bioinformatics analysis revealed a VHL somatic variant in all tumors; no other SNV was detected. Immunohistochemistry showed the abnormal expression of the phospho‐S6 ribosomal protein in the hemangioblastomas, but not in the renal clear cell carcinomas. Conclusion Except for a SNV in the VHL gene, no other somatic SNVs were detected using WES. The phospho‐S6 ribosomal protein in the mTOR pathway is a potential target in VHL‐related cerebellum hemangioblastomas.

Purpose. To investigate the demographic characteristics, etiology, and comorbidities of Cushing’s syndrome (CS) patients at a large medical center in China. Methods. Records on CS patients discharged from 2008 to 2017 were retrieved from the hospital discharge abstract database (DAD) using ICD-10 codes. Demographic characteristics, etiology, and comorbidity data were analyzed. Results. Cushing’s disease (CD) accounted for 63.0% of CS patients, followed by adrenocortical adenoma (ACA) (20.9%), primary bilateral macronodular adrenal hyperplasia (BMAH) (6.2%), ectopic ACTH syndrome (EAS) (5.9%), primary pigmented nodular adrenocortical disease (PPNAD) (1.8%), and adrenocortical carcinoma (ACC) (1.0%). CD, ACA, ACC, and PPNAD presented marked preponderances in women (4.1 : 1, 10.5 : 1, 4.3 : 1, and 2.3 : 1, respectively), while BMAH (59.8%) and EAS (51.0%) showed slightly higher preponderances in men. CD patients were younger than ACA and EAS patients (36.1±12.9 years vs. 39.4±12.7 years and 36.1±12.9 years vs. 41.0±15.8, P

Purpose. This study analysed changes in bone mineral density (BMD) at different sites in patients with acromegaly and postoperative BMD changes and explored risk factors associated with BMD. Methods. Clinical data of 39 patients with growth hormone- (GH-) secreting pituitary adenomas and 29 patients with nonfunctioning pituitary adenomas who were newly diagnosed in neurosurgery from January 2016 to December 2018 were retrospectively analysed, including measurements of preoperative and postoperative BMD, serum GH glucose inhibition, random GH and IGF-1, and other anterior pituitary hormones. Results. The average patient age and disease duration were 43.74 (33.41–54.07) years and 72.15 (22.82–121.48) months, respectively. Compared with patients with nonfunctioning adenomas, patients with GH-secreting pituitary adenomas had significantly higher BMDs at L1, L2, femoral neck, Ward triangle, trochanter, femoral shaft, and total hip sites (p

Objective: Quantitative investigations of facial changes in acromegaly are rare. A new imaging technique, three-dimensional (3D) stereophotography, can accurately quantify whole facial changes. We aimed to measure facial characteristics in acromegaly patients using 3D stereophotography, analyze gender-specific features, and explore clinical influencing factors.Design: Single-center case-control study.Methods: Thirty-nine acromegaly patients and 39 age- and gender-matched healthy subjects were prospectively enrolled. 3D stereophotography was performed, and facial lines and angles were quantified for each subject. Clinical information for each acromegaly patient was acquired.Results: The nose width, length, height and depth were longer; the upper and lower lips were thicker; the face length, face width and gonion-gnathion distances were longer; and the nasofrontal and columella-labial angles were smaller in the acromegaly patients, especially in males, than in the healthy controls, with statistical significance (p < 0.05). No differences were found in the face breadth, columella-labial angle, or nose length, height or depth between the female patient and healthy control groups. The insulin-like growth factor 1 (IGF-1) levels in the acromegaly patients were linearly and positively correlated with the nose width (p = 0.006) and gonion-gnathion distance (p = 0.029) and linearly and negatively correlated with the nasofrontal angle (p = 0.026).Conclusions: The acromegaly patients' facial changes exhibit a unique trend, and the characteristics are not identical between genders. 3D stereophotography is an accurate and reliable tool for investigating facial characteristics. Recognizing the above facial features might be potential to assist in the early diagnosis and timely treatment of acromegaly and aid in predicting the severity of systemic complications.

Objective. To investigate the preoperative body composition, metabolic characteristics, and postoperative changes in patients with active acromegaly and analyze the effects of gender and age. Methods. We included 36 patients with untreated acromegaly and 37 patients with nonfunctional pituitary adenomas. Adipose tissue (AT), the visceral fat index (VFI), sclerotin, protein, skeletal muscle, total body water (TBW), intracellular water (ICW), and extracellular water (ECW) were measured using bioelectrical impedance analysis (BIA). Total energy expenditure (TEE) and basal metabolism (BM) were measured with a cardiopulmonary and metabolic analyzer (CMA). Tricep skinfold thickness (TST), bicep circumference, waistline, hipline, and calf circumference were measured with a skinfold caliper and tape. These indices were measured before surgery and 3 months and 1 year after surgery. Results. Overall, AT, VFI, and TST were lower, whereas sclerotin, protein, skeletal muscle, TBW, ICW, ECW, TEE, and BM were higher in acromegaly patients. Postoperatively, TST rose initially and then decreased, the waistline increased, and sclerotin, skeletal muscle, TEE, and BM decreased. Changes in these indices differed with gender and age in unique patterns. Conclusions. Body composition and metabolism in acromegaly patients changed after surgery, and gender and age influenced these changes.

Purpose. To determine the prevalence, risk factors, and possible mechanisms of structural and endocrinological changes to the thyroid in acromegaly. Methods. We studied 93 acromegalic patients from PUMCH between January 2013 and December 2013. The demographic and clinical information were recorded. Specimens of pituitary adenomas and thyroid cancer were collected for BRAF mutation assessments. Results. Thyroid morphological abnormalities were found in 72 (77.4%) patients. Three (3.2%) were diagnosed with thyroid cancer. The thyroid gland volume was significantly increased in patients with higher random GH (p=0.01), higher nadir GH (p=0.008), and higher IGF-1 level (p=0.018). Age (p=0.002) was an independent risk factor for thyroid morphological abnormalities in acromegaly. The GH burden was significantly higher in patients with thyroid morphological abnormalities (p=0.036). The BRAF V600E mutation was detected in the PTCs of the two patients with thyroid cancer. Conclusions. Both benign and malignant thyroid abnormalities are increased in the acromegalic population compared to those in the general population. Age at diagnosis is an independent risk factor for thyroid abnormalities, and GH burden may be a partial contributor. Early diagnosis, early treatment, and monitoring of postoperational endocrine levels are important for acromegalic patients.