A long-term prognosis study of human USP8-mutated ACTH-secreting pituitary neuroendocrine tumours.

OBJECTIVE: Somatic variants in the ubiquitin-specific protease 8 (USP8) gene are the most common genetic cause of Cushing disease. We aimed to explore the relationship between clinical outcomes and USP8 status in a single centre. DESIGN, PATIENTS AND MEASUREMENTS: We investigated the USP8 status in 48 patients with pituitary corticotroph tumours. A median of 62 months of follow-up was conducted after surgery from November 2013 to January 2015. The clinical, biochemical and imaging features were collected and analysed. RESULTS: Seven USP8 variants (p.Ser718Pro, p.Ser719del, p.Pro720Arg, p.Pro720Gln, p.Ser718del, p.Ser718Phe, p.Lys713Arg) were identified in 24 patients (50%). USP8 variants showed a female predominance (100% vs. 75% in wild type [WT], p = .022). Patients with p.Ser719del showed an older age at surgery compared to patients with the p.Pro720Arg variant (47- vs. 24-year-olds, p = .033). Patients with p.Pro720Arg showed a higher rate of macroadenoma compared to patients harbouring the p.Ser718Pro variant (60% vs. 0%, p = .037). No significant differences were observed in serum and urinary cortisol and adrenocorticotropin hormone (ACTH) levels. Immediate surgical remission (79% vs. 75%) and long-term hormone remission (79% vs. 67%) were not significantly different between the two groups. The recurrence rate was 21% (4/19) in patients harbouring USP8 variants and 13% (2/16) in WT patients. Recurrence-free survival presented a tendency to be shorter in USP8-mutated individuals (76.7 vs. 109.2 months, p = .068). CONCLUSIONS: Somatic USP8 variants accounted for 50% of the genetic causes in this cohort with a significant female frequency. A long-term follow-up revealed a tendency toward shorter recurrence-free survival in USP8-mutant patients.

The clinicopathological features and possible physiological mechanisms of only the EGFR-T790M primary mutation in patients with lung adenocarcinoma.

BACKGROUND: The treatment of non-small cell lung cancer (NSCLC) patients can be complicated by the presence of the EGFR-T790M mutation. Although primary or secondary EGFR-T790M mutations have been extensively studied worldwide, there are few reports on the clinicopathological characteristics and physiological mechanisms of lung adenocarcinoma (LUAD) with only the EGFR-T790M primary mutation. METHODS: The clinical data of all LUAD patients with only the EGFR-T790M primary mutation were collected. Immunohistochemical staining was performed on cell cycle-related proteins, targeted therapy indicators, and prognosis-related proteins in the specimens obtained from puncture biopsies or surgeries. OBJECTIVES: The aim of this study is to analyze the clinicopathological features and possible physiological mechanisms of only the EGFR-T790M primary mutation in LUAD, and to offer recommendations for clinical management. RESULTS: Two patients who have only the T790M de novo mutation were both female (2/12,928, 0.02%). ß-catenin and Cyclin D1 were both highly expressed. In case 1, IHC results showed a positive Ki67 and mutant P53 and there was a significant increase in serum CYFRA 21-1. Third-generation of EGFR TKIs resulted in a partial response (PR) time of less than 8 months in case 1. In case 2, the patient underwent surgical resection and adjuvant chemotherapy, resulting in a progression-free survival (PFS) time of 25 months. CONCLUSION: The results suggest that abnormal activation of the Wnt signaling pathway may be specifically associated with the EGFR-T790M primary mutation in LUAD. Furthermore, it has been observed that patients with significant Ki67, mutant P53, and CYFRA 21-1 expression tend to have a poor prognosis.

Synergistic effects of superfine grinding and high hydrostatic pressure on the contents, distribution, digestive behaviors and antioxidant activities of polyphenols in barley leaves.

Barley leaves (BLs) naturally contained abundant phenolics, most of which are hardly completely released from food matrix during gastrointestinal digestion. Superfine grinding (SFG) and high hydrostatic pressure (HHP) are generally used to treat the functional plants due to their effectiveness to cell wall-breaking and improvement of nutraceutical bioavailability. Thus, this study investigated the synergistic effects of SFG and HHP (100, 300, 500 MPa/20 min) on the bioaccessbility of typical phenolics in BLs during the simulated in-vitro digestion. The results demonstrated that the highest bioaccessbility (40.98%) was found in the ultrafine sample with HHP at 500 MPa. CLSM and SEM confirmed SFG led to microstructurally rapture of BLs. Moreover, the recovery index of ABTS radical scavenging activity and FRAP of HHP-treated ultrafine and fine BLs samples maximumly increased by 53.62% and 9.61%, respectively. This study is expecting to provide the theoretical basis to improve the consumer acceptance of BLs.

Brachytherapy in craniopharyngiomas: a systematic review and meta-analysis of long-term follow-up.

OBJECTIVE: Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs. MATERIALS AND METHODS: The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis. RESULTS: According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2-3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level. CONCLUSION: In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.

CARDS, a Novel Prognostic Index for Risk Stratification and In-Hospital Monitoring.

Background: Sodium fluctuation is independently associated with clinical deterioration. We developed and validated a prognostic index based on sodium fluctuation for risk stratification and in-hospital monitoring. Methods: This study included 33,323 adult patients hospitalized at a tertiary care hospital in 2014. The first 28,279 hospitalizations were analyzed to develop the model and then the validity of the model was tested using data from 5044 subsequent hospitalizations. We predict in-hospital mortality using age, comorbidity, range of sodium fluctuation, and duration of sodium fluctuation, abbreviated as CARDS. Results: In-hospital mortality was similar in the derivation (0.6%) and validation (0.4%) cohorts. In the derivation cohort, four independent risk factors for mortality were identified using logistic regression: age (66-75, 2 points; >75, 3 points); Charlson comorbidity index (>2, 5 points); range of sodium fluctuation (7-10, 4 points; >10, 10 points); and duration of fluctuation (≤3, 3 points). The AUC was 0.907 (95% CI: 0.885-0.928) in the derivation cohort and 0.932 (95% CI: 0.895-0.970) in the validation cohort. In the derivation cohort, in-hospital mortality was 0.106% in the low-risk group (0-7 points), 1.076% in the intermediate-risk group (8-14 points), and 8.463% in the high-risk group (15-21 points). In the validation cohort, in-hospital mortality was 0.049% in the low-risk group, 1.064% in the intermediate-risk group, and 8.403% in the high-risk group. Conclusions: These results suggest that patients at low, intermediate, and high risk for in-hospital mortality may be identified by CARDS mainly based on sodium fluctuation.

Double pituitary adenomas: report of two cases and systematic review of the literature.

Objective: Double pituitary adenomas (DPA) are a rare clinical condition, and our knowledge of them is limited. Missing the second lesion leading to incomplete biochemical remission after surgery is an important challenge in DPA management. This study aims to analyze independent prognostic factors in DPA patients and summarize clinical experiences to prevent surgical failure. Methods: Two cases of DPA patients with Cushing's disease diagnosed and surgically treated at Peking Union Medical College Hospital are reported. A literature review was performed on the online database Pubmed, and 57 DPA patients from 22 retrieved articles were included. Demographic characteristics, endocrine manifestations, diagnostic methods, tumor size, and immunohistochemical features of 59 patients were analyzed. Binary logistic regression models were used to identify independent prognostic factors affecting postoperative biochemical remission. Results: Among 59 DPA patients, the mean ± SD age was 43.64 ± 14.42 years, with 61.02% being female (n = 36). The most common endocrine manifestations were Cushing's syndrome (23/59, 38.98%) and acromegaly (20/59, 33.90%). The most prevalent immunohistochemical types were ACTH-immunopositive (31/118, 26.27%) and GH-immunopositive (31/118, 26.27%) tumors. Microadenomas (<1cm) were the most frequent in terms of tumor size (62/92, 67.39%). The detection rate for double lesions on 3.0T MRI was 50.00% (14/28), which significantly higher than 1.5T MRI (P = 0.034). Univariate analysis revealed that female, Cushing's syndrome and only single lesion detected by surgical exploration were associated with significantly worse prognosis (P<0.05). Multivariate analysis identified double lesion detected by surgical exploration (OR = 0.08, P = 0.003) and contiguous type tumor (OR = 0.06, P = 0.017) as independent protective factors for DPA patients. Conclusions: The double lesion detected by surgical exploration is independently associated with a better prognosis for DPA patients. Comprehensive intraoperative exploration are crucial measures to avoid missing causative lesions.

Boosting sodium-ion battery performance with binary metal-doped Na3V2(PO4)2F3 cathodes.

Na3V2(PO4)2F3 (NVPF), recognized for its Na superionic conductor architecture, emerges as a promising candidate among polyanion-type cathodes for sodium ion batteries (SIBs). However, its adoption in practical applications faces obstacles due to its inherently low electronic conductivity. To address this challenge, we employ a binary co-doped strategy to design Na3.3K0.2V1.5Mg0.5(PO4)2F3 cathode with nitrogen-doped carbon (NC) coating layer. This configuration enhances electronic conductivity and reduces diffusion barriers for sodium ion (Na+). The strategy of incorporating nitrogen-doped carbon coating not only facilitates the formation of a porous structure but also introduces additional defects and active sites. Such modifications accelerate the reaction kinetics and augment electrolyte interaction through an expanded specific surface area, thus streamlining the electrochemical process. Concurrently, strategic heteroatom substitution leads to a more efficient engagement of Na+ in the electrochemical activities, thereby bolstering the cathode's structural integrity. The vanadium fluorophosphate Na3.3K0.2V1.5Mg0.5(PO4)2F3@NC exhibits an electrochemical performance, including a high discharge specific capacity of 124.3 mA h g-1 at 0.1C, a long lifespan of 1000 cycles with a capacity retention of 93.1 % at 10C, and a rate property of 73.2 mA h g-1 at 20C. This research provides a method for preparing binary doped NVPF for energy storage electrochemistry.

Artificial intelligence facial recognition system for diagnosis of endocrine and metabolic syndromes based on a facial image database.

AIM: To build a facial image database and to explore the diagnostic efficacy and influencing factors of the artificial intelligence-based facial recognition (AI-FR) system for multiple endocrine and metabolic syndromes. METHODS: Individuals with multiple endocrine and metabolic syndromes and healthy controls were included from public literature and databases. In this facial image database, facial images and clinical data were collected for each participant and dFRI (disease facial recognition intensity) was calculated to quantify facial complexity of each syndrome. AI-FR diagnosis models were trained for each disease using three algorithms: support vector machine (SVM), principal component analysis k-nearest neighbor (PCA-KNN), and adaptive boosting (AdaBoost). Diagnostic performance was evaluated. Optimal efficacy was achieved as the best index among the three models. Effect factors of AI-FR diagnosis were explored with regression analysis. RESULTS: 462 cases of 10 endocrine and metabolic syndromes and 2310 controls were included into the facial image database. The AI-FR diagnostic models showed diagnostic accuracies of 0.827-0.920 with SVM, 0.766-0.890 with PCA-KNN, and 0.818-0.935 with AdaBoost. Higher dFRI was associated with higher optimal area under the curve (AUC) (P = 0.035). No significant correlation was observed between the sample size of the training set and diagnostic performance. CONCLUSIONS: A multi-ethnic, multi-regional, and multi-disease facial database for 10 endocrine and metabolic syndromes was built. AI-FR models displayed ideal diagnostic performance. dFRI proved associated with the diagnostic performance, suggesting inherent facial features might contribute to the performance of AI-FR models.

Bilateral Inferior Petrosal Sinus Sampling Without Lateralization Is Less Accurate for the Diagnosis of Cushing Disease.

Context: During bilateral inferior petrosal sinus sampling (BIPSS), the side-to-side adrenocorticotropic hormone (ACTH) ratio, referred to as sampling lateralization, was used to predict pituitary adenoma localization. Objective: To investigate the potential different diagnostic accuracy of BIPSS for differentiating Cushing disease (CD) and ectopic ACTH secretory syndrome (EAS) patients with low lateralization (inferior petrosal sinus [IPS]:IPS ≤ 1.4) and high lateralization (IPS:IPS > 1.4). Methods: This single-center retrospective study (2011-2021) included (all patients had BIPSS results and confirmed pathologic diagnoses) 220 consecutive CD patients (validation set), 30 EAS patients, and 40 of the CD patients who had digital subtraction angiography (DSA) videos (discovery set). Results: In the discovery set, the low-lateralization CD group (n = 11) had a higher median plasma ACTH concentration (62.2, IQR 44.7-181.0 ng/L) than the high-lateralization CD group (n = 29) (33.0, IQR 18.5-59.5, P = .013). Lower IPS to peripheral ratios were observed in the low-lateralization group during BIPSS, both before and after stimulation (P = .013 and P = .028). The sensitivity of BIPSS before stimulation in differentiating CD from EAS was lower in the low-lateralization group than the high-lateralization group (54.6% vs 93.1%, P = .003), as validated in the validation set. DSA videos revealed higher vascular area difference visible in the 2 sides of the pituitary in low lateralization (median 1.2 × 105 pixels, IQR 0.5-1.8) than the high-lateralization group (0.4 × 105 pixels, IQR 0.1-0.7, P = .008). The vascular area ratio of the 2 sides was also significantly higher in low (1.55, IQR 1.31-2.20) than high lateralization (1.19, IQR 1.07-1.35, P = .010). Conclusion: Our study suggested that low lateralization in CD patients may reduce the diagnostic sensitivity of BIPSS, which might be potentially associated with peripituitary vascular anatomy.

The distinct hepatic metabolic profile and relation with impaired liver function in congenital isolated growth hormone-deficient rats.

Objective: Patients with growth hormone deficiency (GHD) with inadequate growth hormone levels are often correlated with nonalcoholic fatty liver disease (NAFLD). However, the potential mechanism of how GHD influences liver function remains obscure. In the present study, we aim to perform hepatic metabolomics in Lewis dwarf rats, which were the standard congenital isolated GH-deficient rat, to evaluate the characterizations of hepatic metabolic profiles and explore their relations with liver functions. Methods: Lewis dwarf homozygous (dw/dw) rats at 37 weeks (five females and five males), and Lewis dwarf heterozygous (dw/+) rats at 37 weeks (five females and five males) were analyzed in our study. Body lengths and weights, liver weights, serum alanine transaminase (ALT), and serum aspartate transaminase (AST) were measured. ELISA and RT-qPCR were used to assess IGF-1 levels in serum and liver, respectively. The non-targeted metabolomics was performed in the livers of dw/+ and dw/dw rats. Differential metabolites were selected according to the coefficient of variation (CV), variable importance in the projection (VIP) > 1, and P < 0.05. Hierarchical clustering of differential metabolites was conducted, and the KEGG database was used for metabolic pathway analysis. Results: The body weights, body lengths, liver weights, and IGF-1 levels in the serum and liver of dw/dw rats were significantly decreased compared with dw/+ rats. Dw/dw rats exhibited more obvious hepatic steatosis accompanied by higher serum ALT and AST levels. Hepatic metabolomics showed that a total of 88 differential metabolites in positive ion mode, and 51 metabolites in negative ion mode were identified. Among them, lysophosphatidylcholine (LPC) 16:2, LPC 18:3, LPC 22:6, fatty acid esters of hydroxy fatty acids (FAHFA)18:1 were significantly decreased, while palmitoyl acid, dehydrocholic acid, and 7-ketolithocholic acid were significantly increased in dw/dw rats compared with dw/+ rats. These seven differential metabolites were significantly associated with phenotypes of rats. Finally, KEGG pathway analysis showed that the arginine and proline metabolism pathway and bile secretion pathway were mainly clustered. Conclusion: Lewis dw/dw rats with congenital isolated growth hormone deficiency (IGHD) showed liver steatosis and abnormal liver function, which could be potentially associated with the distinctive hepatic metabolic profiles.

Bone mineral density in adults growth hormone deficiency with different ages of onset: a real-world retrospective study.

PURPOSE: Bone mineral density (BMD) impairment is one of the critical factors for long-term quality of life in adults growth hormone deficiency (AGHD). This study aims to investigate the annual changes in BMD in AGHD patients with different ages of onset and to identify predicting factors that influence BMD. METHODS: AGHD patients (n = 160) with available data for 4 years follow-up from a major tertiary medical center in China were retrospectively included (110 [68.8%] childhood-onset, 119 [74.4%] male). BMD of the axial bone (including total hip, neck of femur, and L1-4) derived from dual X-ray absorptiometry and final height were investigated at the first visit, 12 months, 24 months, 36 months, and 48 months thereafter. Low BMD was defined as Z-score ≤ -2. RESULTS: The prevalence of low BMD was 30.0% at baseline and 12.5% at 4 years of follow-up. The CO AGHD group presented a significantly lower BMD than the AO AGHD group at the baseline (P = 0.009). In contrast, the CO AGHD group had significantly greater median annual BMD change than the AO AGHD group (0.044 vs. -0.0003 g/cm2/year in L1-4, P < 0.001), indicating a significant difference in the overall BMD trend between CO and AO groups. Childhood-onset (odds ratio [OR] 0.326, P = 0.012), low serum testosterone (OR 0.847; P = 0.004) and FT4 (OR 0.595; P = 0.039) level were independent risk factors for BMD loss. CONCLUSION: The annual changes of BMD show a different pattern in AGHD patients with varying ages of onset. Patients with CO AGHD have a lower bone mass, and in general, appropriate replacement therapy is necessary for long-term bone health in AGHD patients.

Serum prolactin levels were positively related to metabolic indexes and disorders in male obese patients.

PURPOSE: The role of prolactin (PRL) in glucolipid metabolism was inconsistent, and there were few studies on the metabolic role of PRL in obese patients. The study aims to explore association between PRL level and metabolic disorders in male obese patients. METHODS: A retrospective study was conducted. Eighty-nine male patients with obesity were included, and their clinical data were recorded. RESULTS: A total of 89 male obese patients were included in this study. Their average age was 24.5 ± 9.0 years and BMI was 42.8 ± 9.1 kg/m2. The average waist circumference and body fat percentage was 129.6 ± 19.6 cm and 42.9 ± 8.0%, respectively. The median prolactin levels were 10.0 ng/ml (range: 3.93-30.1 ng/ml). 79.0% (49/62) of these patients presented with NAFLD and 77.3% (68/88) of them was dyslipidemia. Further, serum prolactin level was positively correlated with BMI (r = 0.225, P = 0.034), body fat percentage (r = 0.326, P = 0.017), ALT (r = 0.273, P = 0.011) and AST (r = 0.245, P = 0.029). Compared with low PRL group (<10 ng/ml), the incidence of morbid obesity and NAFLD was higher in high PRL group (morbid obesity: 71.1% vs 45.5%, P = 0.018 and NAFLD: 91.2% vs 64.3%, P = 0.013). In addition, the risk of NAFLD and morbid obesity in high PRL group (>10 ng/ml) was higher than low PRL group (OR:5.187, 95%CI 1.194-22.544, P = 0.028 and OR: 4.375, 95% CI 1.595-11.994, P = 0.004). The increased risk of NAFLD and morbid obesity in the high PRL group still existed after adjusting for age and Testosterone. CONCLUSION: Serum prolactin levels were positively associated with deterioration of metabolic indexes in male obese patients, as well as NAFLD and morbid obesity.

The association between per-/polyfluoroalkyl substances in serum and thyroid function parameters: A cross-sectional study on teenagers living near a Chinese fluorochemical industrial plant.

Thyroid hormones (THs) play an important role in a wide range of crucial biological functions related to growth and development, and thyroid antibodies (TAs) can influence the biosynthesis of THs. Epidemiological studies have indicated that per- and polyfluoroalkyl substances (PFAS) could induce thyroid disruption, but studies on teenagers living in areas with high PFAS exposure are limited. This cross-sectional study focused on 836 teenagers (11- 15 years) living near a Chinese fluorochemical industrial plant. Decreased levels of free thyroxine (FT4, ﹤9.6 pmol/L, abnormal rate = 19.0 %) and elevated levels of free triiodothyronine (FT3, ï¹¥6.15 pmol/L, abnormal rate = 29.8 %) were observed. Correlations of serum PFAS concentrations and TAs/THs were analyzed. Increased PFOA was identified as a risk factor of decreased FT4 by using unadjusted (OR: 11.346; 95 % CI: 6.029, 21.352, p < 0.001) and adjusted (OR: 12.566; 95 % CI: 6.549, 24.115, p < 0.001) logistic regression models. In addition, significantly negative correlations were found between log10 transformed PFOA and FT4 levels using linear (unadjusted: ß = -1.543, 95 % CI: -1.937, -1.148, p < 0.001; adjusted: ß = -1.534, 95 % CI: -1.930, -1.137, p < 0.001) and BKMR models. For abnormal FT3, a significantly positive association between PFHxS and FT3 levels was observed in a regression model (unadjusted: ß = -0.903, 95 % CI: -1.212, -0.595, p < 0.001; adjusted: ß = -0.894, 95 % CI: -1.204, -0.583, p < 0.001), and PFHxS was identified as a risk factor (unadjusted: OR: 4.387; 95 % CI: 2.619, 7.346, p < 0.001; adjusted: OR: 4.527; 95 % CI: 2.665, 7.688, p < 0.001). Sensitivity analyses confirmed the robustness of the above results. This study reported the elevated PFAS exposure and thyroid function of teenagers living near a fluorochemical industrial plant from China.

Hypophysitis after COVID-19 vaccination in a patient with Rathke's cleft cyst: A case report.

With the widespread vaccination of COVID-19 vaccine, a few cases have been reported that COVID-19 vaccine may cause endocrine disorders. A 59-y-old man presented with a loss of appetite after the first COVID-19 vaccination, which resolved spontaneously after 3 d. After the second COVID-19 vaccination, the symptoms including the loss of appetite, nausea, and vomiting reappeared and worsened along with loss of vision. He was found to have severe hyponatremia, and further investigations revealed secondary adrenal insufficiency, secondary hypothyroidism and Rathke's cleft cyst. The patient responded well to glucocorticoid and levothyroxine supplementation, and at 1-y follow-up the patient developed hypogonadism. We hypothesize that hypophysitis is probably induced by COVID-19 vaccine and report the rare but serious adverse reactions for early recognition and intervention.

Clinical Characteristics and Outcomes of Prolactinomas in Children and Adolescents: A Large Retrospective Cohort Study.

PURPOSE: To summarize the clinical features, both medication and surgical outcomes of prolactinomas in children and adolescents in a large retrospective cohort from China. METHODS: A cohort of patients with prolactinomas aged ≤20 years at diagnosis between 2012 and 2021 in Peking Union Medical College Hospital were retrospectively analyzed. RESULTS: The cohort comprised 170 patients (115 females and 55 males, median age 16.6 years), with 20.0% (23/115) girls without menarche and 33.3% (18/54) boys in prepuberty. The median maximal diameter was 15.0 mm (61.2% macroadenomas and 4.6% giant adenomas), and the median baseline prolactin (PRL) level was 211.0 ng/mL. Larger sizes and higher PRL levels were observed in girls without menarche at diagnosis and in boys. Most girls presented with menstrual disturbance (86.7%), and boys were frequently bothered by headaches (42.6%), reduced height velocities (25.9%), and delayed puberty (18.2%). Dopamine agonists (DAs) were first-line used in 133 patients, and the resistance rate was 22.5% (25/111), independently associated with maximal tumor diameters (p=0.035). Surgery was performed in 76 patients. Long-term surgical remission rates were 32.9% (25/76) overall, negatively associated with cavernous sinus invasion independently (p=0.025), 59.4% (19/32) in noninvasive tumors (64.0% in 25 noninvasive macroadenomas), and 5.0% (1/20) in invasive tumors. CONCLUSIONS: Pediatric prolactinomas exihibited more severe clinical characteristics in boys and in patients diagnosed during earlier stages of pubertal developments. Given the overall efficacy of PRL normalization by medication and considerable surgical remission rate in noninvasive tumors, DAs remain first-line recommendation for prolactinomas in children and adolescents, while surgery might be viable for noninvasive tumors.

Cerebrospinal Fluid Metabolomic Pattern of Different Pituitary Stalk Lesions.

OBJECTIVE: To describe the cerebrospinal fluid (CSF) metabolomic pattern of pituitary stalk lesions. METHODS: CSF was collected from patients with different pituitary stalk lesions treated at Peking Union Medical College Hospital: germ cell tumor (GCT, n = 27); hypophysitis (n = 10); and Langerhans cell histiocytosis (LCH) or Erdheim-Chester disease (ECD) (LCH + ECD, n = 10). The CSF metabolome profiles were characterized by liquid chromatography-mass spectrometry (LC-MS). RESULTS: There were 44 metabolites that significantly differed between patients with GCT and those with hypophysitis (P < .05). Between patients with GCT with CSF level of beta subunit of human chorionic gonadotrophin (ß-hCG) < 5 mIU/mL and those with hypophysitis, there were 15 differential metabolites (P < .05, fold change > 1.5 or < 1/1.5). All of the metabolites had an area under the curve (AUC) above 0.7. There were 9 metabolites that significantly differed between patients with GCT and those with LCH + ECD (P < .05) and 7 metabolites had significant differences between GCT (CSF ß-hCG < 5 mIU/mL) and LCH + ECD (P < .05, fold change > 1.5 or < 1/1.5). We found 6 metabolites that were significantly different between patients with hypophysitis and those with LCH + ECD (P < .05) and 5 of these had fold change more than 1.5 or less than 1/1.5. Three metabolites, 5-deoxydiplosporin, cloversaponin I, and phytosphingosine, showed excellent capabilities to differentiate the 3 disease categories. Furthermore, we identified 67 metabolites associated with clinical test results (ρ > 0.2, P < .05) and 29 metabolites showed strong correlation (ρ > 0.4, P < .05). CONCLUSION: Our study is the first to systematically investigate the metabolomics of CSF in different pituitary stalk lesions. CSF metabolomics is a useful strategy for biomarker discovery.

Brain white matter alterations in young adult male patients with childhood-onset growth hormone deficiency: a diffusion tensor imaging study.

PURPOSE: This study aimed to detect white matter changes and different effects of thyroid hormone on the white matter integrity in young adult male patients with childhood-onset growth hormone deficiency (CO-GHD), compared with healthy people. METHODS: Magnetic resonance imaging (structural imaging and diffusion tensor imaging) was performed in 17 young adult male patients with CO-GHD and 17 healthy male controls. The white matter volume, mean diffusivity (MD) values and fractional anisotropy (FA) values were quantified and compared between two groups (CO-GHD group vs. control group). We assessed the interaction effects between thyroid hormone and groups (CO-GHD group vs. control group) on white matter integrity. RESULTS: Patients with CO-GHD exhibited similar white matter volumes compared with controls. However, compared with the controls, patients with CO-GHD showed a significant reduction in FA values in six clusters and a substantial increase in MD values in four clusters, mainly involving the corticospinal tracts, corpus callosum and so on. Moreover, after correcting for insulin-like growth factor-1 levels, the significant interaction effects between groups (CO-GHD group vs. control group) and serum free thyroxine levels on MD values were noted in three clusters, mainly involving in superior longitudinal fasciculus and sagittal stratum. CONCLUSION: In conclusion, young males with CO-GHD showed white matter changes in multiple brain regions and different effects of thyroid hormone on the white matter integrity.

Mesoporous Nickel Sulfide Microsphere Encapsulated in Nitrogen, Sulfur Dual-Doped Carbon with Large Subsurface Region for Enhanced Sodium Storage.

Nickel sulfides are promising anode candidates in sodium ion batteries (SIBs) due to high capacity and abundant reserves. However, their applications are restricted by poor cycling stability and slow reaction kinetics. Thus, mesoporous nickel sulfide microsphere encapsulated in nitrogen, sulfur dual-doped carbon (MNS@NSC) is prepared. The packaged structure and carbon matrix restrain the volume variation together, the N, S dual-doping improves the electronic conductivity and offers extra active sites for sodium storage. Ex-situ X-ray diffraction  appeals copper collector adsorbs polysulfide to inhibit the polysulfide accumulation and enhance conductivity. Moreover, the large subsurface attributed to C-S-S-C bonding further boosts pseudocapacitive capacity, conducive to charge transfer. As a result, MNS@NSC delivers a high reversible capacity of 640.2 mAh g-1 after 100 cycles at 0.1 A g-1 , an excellent rate capability (569.8 mAh g-1 at 5 A g-1 ), and a remained capacity of 513.8 mAh g-1 after undergoing 10000 circulations at 10 A g-1 . The MNS@NSC|| Na3 V2 (PO4 )3 full cell shows a cycling performance of specific capacity of 230.8 mAh g-1 after 100 cycles at 1 A g-1 . This work puts forward a valid strategy of combing structural design and heteroatom doping to synthesize high-performance nickel sulfide materials in SIBs.

Clinical characteristics of male prolactinoma patients mainly presenting with severe obesity and the metabolic response to dopamine agonist therapy.

Objective: To summarize the clinical characteristics of 4 male prolactinoma patients with severe obesity. Methods: The clinical data of all the patients were retrospectively analyzed. Results: All the patients visited our hospital for severe obesity at the age of 16-30 years old with their body mass index (BMI) of 37.9-55.9 kg/m2. All the patients were obese since childhood, even at birth. Hyperprolactinemia (72.3-273.0 ng/ml) was found during the etiological screening of obesity and MRI revealed pituitary adenomas. Additionally, all of them had multiple obesity related complications, such as hyperinsulinemia and dyslipidemia. Treatment of dopamine agonists (DAs) effectively normalized their prolactin level and the pituitary MRI reexamination after 6 months of DAs treatment showed the shrinkage of the pituitary adenomas in 3 patients. Their weight also decreased in different degrees (2.70~19.03% lower than the baseline) with improved metabolic profiles. Conclusion: Serum prolactin level should be screened in obese patients, especially those with severe obesity.

Advances in genetic abnormalities, epigenetic reprogramming, and immune landscape of intracranial germ cell tumors.

Intracranial germ cell tumors (IGCTs) are a rare subtype of central nervous system neoplasms that predominantly affect young individuals and exhibit a higher incidence in East Asia. IGCTs can be pathologically divided into two main categories: germinomas and non-germinomatous germ cell tumors (NGGCTs). Despite the scarcity of this disease, recent advancements in molecular biology techniques have facilitated the discovery of the inherent genetic and molecular characteristics of IGCTs. Somatic mutations that result in the activation of the KIT/RAS/MAPK and PI3K/AKT/mTOR pathways, chromosomal instability leading to characteristic changes in chromosomal fragments (notably 12p gain), and potentially diagnostic miRNAs (such as miR-371a-3p) may provide valuable insights for the efficient diagnosis, targeted therapy, and prognosis evaluation of IGCTs. Additionally, transcriptomic and methylomic analyses have provided new perspectives on the intrinsic development of IGCTs, further elucidating their equivalence with GCTs at other sites. The evaluation of the tumor immune landscape may guide prognosis prediction and immunotherapy for IGCT patients. Nevertheless, current research still faces challenges such as the absence of basic laboratory research systems, a single source of large sample research data, and a limited overall volume of research. The incorporation of larger sample sizes, the implementation of more innovative evaluation systems, and the employment of novel experimental methods are urgently required to become the focus of future research.