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PURPOSE: Variants in the Aryl hydrocarbon receptor-interacting protein (AIP) gene have been identified in sporadic acromegaly and pituitary gigantism, especially in young patients, with a predisposition to aggressive clinical phenotype and poor treatment efficacy. The clinical characteristics of patients with sporadic acromegaly and pituitary gigantism as well as AIP variants in Han Chinese have been rarely reported. We aimed to identify AIP gene variants and analyze the clinical characteristics of patients with sporadic acromegaly and pituitary gigantism in Han Chinese. METHODS: The study included 181 sporadic acromegaly (N = 163) and pituitary gigantism (N = 18) patients with an onset age of no more than 45 years old, who were diagnosed, treated, and followed up in Huashan Hospital. All 6 exons and their flanking regions of the AIP gene were analyzed with Sanger sequencing or NGS. The clinical characteristics were compared between groups with and without AIP variants. RESULTS: Germline AIP variants were found in 15/181 (8.29%) cases. In patients with an onset age ≤30 years old, AIP variants were identified in 12/133 (9.02%). Overall, 13 variants were detected. The pathogenic (P) variants p.R304X and p.R81X were identified in four cases, with two instances of each variant. Six exon variants (p.C254R, p.K103fs, p.Q228fs, p.Y38X, p.Q213*, and p.1115 fs) have not been reported before, which were likely pathogenic (LP). Patients with P/LP variants had younger onset ages, a higher prevalence of pituitary gigantism, larger tumor volumes, and a higher percentage of Ki-67-positive cells in tumors. In addition, the group with P/LP variants showed a less significant reduction of GH levels in an acute octreotide suppression test (OST) [17.7% (0, 65.0%) vs. 80.5% (63.9%, 90.2%), P = 0.001], and a trend of less GH decrease after the 3-month treatment with long-acting somatostatin analogs (SSAs). CONCLUSION: Germline AIP variants existed in sporadic Chinese Han acromegaly and pituitary gigantism patients and were more likely to be detected in young patients. AIP variants were associated with more aggressive tumor phenotypes and less response to SSA treatment.
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Acromegalia , Gigantismo , Peptídeos e Proteínas de Sinalização Intracelular , Humanos , Acromegalia/genética , Masculino , Feminino , Adulto , Gigantismo/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Adulto Jovem , Adolescente , Criança , Povo Asiático/genética , Mutação em Linhagem Germinativa , Estudos de Coortes , Pessoa de Meia-Idade , China , Pré-Escolar , População do Leste AsiáticoRESUMO
OBJECTIVE: Thyrotropin-secreting adenoma (TSHoma) is a rare type of pituitary adenoma, occurring in one per million people. Little is known about TSHoma. We summarized the demographic, clinical and hormonal characteristics of TSHoma based on a single-centre experience. Moreover, we explored the predictive value of postoperative thyroid function for long-term remission. DESIGN, PATIENTS AND MEASUREMENTS: We retrospectively analysed 63 patients who were diagnosed as TSHoma and surgically treated at our hospital from January 2015 to June 2021. The preoperative clinical characteristics were analysed and compared between remission and nonremission groups. Thyroid function was measured at 1 day, 1 month, 3 months, 6 months, 12 months and over 12 months after surgery to determine whether they could predict long-term remission. RESULTS: The male to female ratio for TSHoma was 1.25. The mean age at diagnosis was 45 ± 12 years. Clinical presentation was varied, presenting with hyperthyroidism (68.25%), space-occupying effect (15.87%), amenorrhea (7.14% of female patients) and nonsymptoms (22.22%). 88.14% of patients achieved postoperative endocrinological remission. Larger tumour size and tumour invasion into cavernous sinus and suprasellar with chiasmal compression were strong predictors of lower rates of endocrinological remission. Postoperative thyroid function at 3 months was a viable diagnostic predictor for postoperative remission, especially for FT4 level with a 20.65 pmol/L cutoff. CONCLUSIONS: Tumour size and extent are major prognostic factors for remission. Postoperative thyroid function at 3 months could be used as a clinical prediction tool for long-term endocrinological remission.
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Adenoma , Neoplasias Hipofisárias , Tireotropina , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Tireotropina/sangue , Tireotropina/metabolismo , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/diagnóstico , Adenoma/cirurgia , Adenoma/metabolismo , Adenoma/diagnóstico , Indução de Remissão , Período Pós-Operatório , Resultado do TratamentoRESUMO
BACKGROUND: Surgical treatment of complex giant pituitary adenomas (GPAs) presents significant challenges. The efficacy and safety of combining transsphenoidal and transcranial approaches for these tumors remain controversial. In this largest cohort of patients with complex GPAs, we compared the surgical outcomes between those undergoing a combined regimen and a non-combined regimen. We also examined the differences in risks of complications, costs, and logistics between the two groups, which might offer valuable information for the appropriate management of these patients. PATIENTS AND METHODS: This was a multicenter retrospective cohort study conducted at 13 neurosurgical centers. Consecutive patients who received a combined or non-combined regimen for complex GPAs were enrolled. The primary outcome was gross total resection, while secondary outcomes included complications, surgical duration, and relapse. A propensity score-based weighting method was used to account for differences between the groups. RESULTS: Out of 647 patients [298 (46.1%) women, mean age: 48.5 ± 14.0 years] with complex GPAs, 91 were in the combined group and 556 were in the noncombined group. Compared with the noncombined regimen, the combined regimen was associated with a higher probability of gross total resection [50.5% vs. 40.6%, odds ratio (OR): 2.18, 95% confidence interval (CI): 1.30-3.63, P = 0.003]. The proportion of patients with life-threatening complications was lower in the combined group than in the non-combined group (4.4% vs. 11.2%, OR: 0.25, 95% CI: 0.08-0.78, P = 0.017). No marked differences were found between the groups in terms of other surgical or endocrine-related complications. However, the combined regimen exhibited a longer average surgery duration of 1.3 h ( P < 0.001) and higher surgical costs of 22,000 CNY (~ 3,000 USD, P = 0.022) compared with the noncombined approach. CONCLUSIONS: The combined regimen offered increased rates of total resection and decreased incidence of life-threatening complications, which might be recommended as the first-line choice for these patients.
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Adenoma , Neoplasias Hipofisárias , Humanos , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/cirurgia , Adulto , Adenoma/cirurgia , Adenoma/patologia , Resultado do Tratamento , Estudos Longitudinais , Procedimentos Neurocirúrgicos/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pontuação de PropensãoRESUMO
PURPOSE: To investigate the effect of nicotinamide (Nam) on diabetic kidney disease (DKD) in mice and explore its mechanism. METHODS: Thirty DBA/2 J mice were randomly assigned to three groups. After 8 weeks of hyperglycemia induced by streptozocin (STZ), Nam and saline were administrated to STZ + Nam and STZ + NS mice, respectively, for 8 weeks. Non-diabetic mice (NDM) were used as control group. Twenty In2-/- Akita mice were randomly divided into two groups. After 8 weeks of hyperglycemia, Nam and saline were administered to Akita + Nam and Akita + NS mice, respectively, for 6 weeks. Wild-type littermates were used as control group. Markers of renal injury were analyzed, and the molecular mechanisms were explored in human proximal tubular HK2 cells. RESULTS: Urinary albumin-to-creatinine ratio (UACR) and kidney injury molecule 1 (KIM-1) decreased in the STZ + Nam and Akita + Nam groups. Pathological analysis showed that Nam improved the structure of glomerular basement membrane, ameliorated glomerular sclerosis, and decreased the accumulation of extracellular matrix and collagen. Compared to the diabetic control group, renal fibrosis, inflammation, and oxidative stress were reduced in the Nam-treated mice. The expression of sirtuin 1 (Sirt1) in human proximal tubular HK2 cells was inhibited by high glucose and Nam treatment enhanced its expression. However, in HK2 cells with Sirt1 knockdown, the protective effect of Nam was abolished, indicating that the beneficial effect of Nam was partially dependent on Sirt1. CONCLUSIONS: Nam has a renoprotective effect against renal injury caused by hyperglycemia and may be a potential target for the treatment of DKD.
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Diabetes Mellitus Experimental , Nefropatias Diabéticas , Camundongos Endogâmicos DBA , Niacinamida , Sirtuína 1 , Animais , Nefropatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/tratamento farmacológico , Sirtuína 1/metabolismo , Camundongos , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Diabetes Mellitus Experimental/complicações , Humanos , Masculino , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular , Complexo Vitamínico B/farmacologia , Complexo Vitamínico B/uso terapêuticoRESUMO
OBJECT: The highly conserved α-amino-ß-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) is the key enzyme that regulates the de novo NAD+ synthesis from tryptophan. NAD+ metabolism in diabetic cardiomyopathy (DCM) was not elucidated yet. METHODS: Mice were assigned to non-diabetic (NDM) group, streptozocin (STZ)-induced diabetic (DM) group, and nicotinamide (NAM) treated (DM + NAM) group. ACMSD mediated NAD+ metabolism were studied both in mice and patients with diabetes. RESULTS: NAD+ level was significantly lower in the heart of DM mice than that of the NDM group. Supplementation with NAM could partially increased myocardial capillary density and ameliorated myocardial fibrosis by increasing NAD+ level through salvage pathway. Compared with NDM mice, the expression of ACMSD in myocardial endothelial cells of DM mice was significantly increased. It was further confirmed that in endothelial cells, high glucose promoted the expression of ACMSD. Inhibition of ACMSD could increase de novo NAD+ synthesis and improve endothelial cell function by increasing Sirt1 activity. Targeted mass spectrometry analysis indicated increased ACMSD enzyme activity in diabetic patients, higher ACMSD activity increased risk of heart diastolic dysfunction. CONCLUSION: In summary, increased expression of ACMSD lead to impaired de novo NAD+ synthesis in diabetic heart. Inhibition of ACMSD could potentially improve DCM.
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Carboxiliases , Cardiomiopatias Diabéticas , Animais , Humanos , Camundongos , Cardiomiopatias Diabéticas/tratamento farmacológico , Células Endoteliais/metabolismo , NAD/metabolismo , Carboxiliases/antagonistas & inibidores , Carboxiliases/metabolismoRESUMO
Studies describing the clinical presentation and prognosis of patients with silent PIT1 (pituitary specific transcription factor)-lineage pituitary neuroendocrine tumors (PitNETs) are rare. We identified patients with positive PIT1 tumor staining but without evidence of hormone hypersecretion at a tertiary center. Clusters were obtained according to cell morphology and immunostaining from each patient's digitally segmented whole slide image. We compared the clinical presentations, radiological features, and prognoses of the different clusters. We identified 146 patients (68 male, 42.9 ± 14.1 years old) with silent PIT1-lineage PitNETs. Morphology clustering suggested that tumors with large nuclei and apparent eccentricity were associated with a higher proportion of aggressiveness and a higher hazard of recurrence [hazard ratio (HR): 2.64, (95% CI, 1.06-6.55), p = 0.037]. Immunohistochemical clustering suggested that tumors with thyroid stimulating hormone (TSH) staining or all negative PIT1-lineage hormones were associated with a higher proportion of aggressiveness and a higher risk of recurrence [HR: 12.4, (95% CI, 1.60-93.5), p = 0.015]. We obtained three-tier risk profiles by combining morphological and immunohistochemical clustering. Patients with the high-risk profile presented the highest recurrence rate compared with those in the medium-risk and low-risk profiles [HR: 3.54, (95% CI, 1.40-8.93), p = 0.002]. In conclusion, digital image analysis based on cell morphology and immunohistochemical staining allows objective stratification of patients with silent PIT1-lineage tumors. Typical morphological characteristics of high-risk tumors are large tumor nuclei and high eccentricity, and typical immunostaining characteristics are TSH staining or negative staining for all PIT1-lineage hormones.
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Thermosensitive hydrogels have been receiving attention in the development of fire extinguishing agents due to their stimuli responsivity. Conventional hydrogels are limited by their slow response rate, and their wettability has not been studied systematically. In the present study, a concentrate of a thermosensitive porous system has been successfully synthesized by adding Na2CO3/CH3COOH as a foaming agent into the mixture of hydroxypropyl methylcellulose (HPMC)/polyethylene glycol (PEG)/chitosan (CS). The systems with different concentrations were obtained by diluting the concentrate with water. Thermosensitivity, surface tension and contact angle were characterized. In addition, spreadability, wettability and adhesivity were investigated systematically. Results showed that the systems with a concentration greater than 15 wt% exhibited outstanding performance of thermosensitivity and coagulability. A total of 20 wt% of the system has the best spreadability and wettability on the wood surface, most likely due to favorable contributions brought by both adequate viscosity and hydrophilicity. The adhesive force and surface-free energy of the pre-gel droplet that reached deposition on the wood surface decreased by 46.78% and 20.71%, respectively. The gel has a great capacity of water retention over a long period of time, which makes this porous gel the best system when it comes to its wettability and adhesiveness towards the chosen wood surface. The equilibrium surface tension decreased by 45.50% compared with water. HPMC/PEG/CS thermosensitive porous hydrogel with excellent wettability presented wide-ranging possibilities for the further development of fire suppression agents of fast phase-transition thermosensitive hydrogel.
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Bounding box regression is a crucial step in object detection, directly affecting the localization performance of the detected objects. Especially in small object detection, an excellent bounding box regression loss can significantly alleviate the problem of missing small objects. However, there are two major problems with the broad Intersection over Union (IoU) losses, also known as Broad IoU losses (BIoU losses) in bounding box regression: (i) BIoU losses cannot provide more effective fitting information for predicted boxes as they approach the target box, resulting in slow convergence and inaccurate regression results; (ii) most localization loss functions do not fully utilize the spatial information of the target, namely the target's foreground area, during the fitting process. Therefore, this paper proposes the Corner-point and Foreground-area IoU loss (CFIoU loss) function by delving into the potential for bounding box regression losses to overcome these issues. First, we use the normalized corner point distance between the two boxes instead of the normalized center-point distance used in the BIoU losses, which effectively suppresses the problem of BIoU losses degrading to IoU loss when the two boxes are close. Second, we add adaptive target information to the loss function to provide richer target information to optimize the bounding box regression process, especially for small object detection. Finally, we conducted simulation experiments on bounding box regression to validate our hypothesis. At the same time, we conducted quantitative comparisons of the current mainstream BIoU losses and our proposed CFIoU loss on the small object public datasets VisDrone2019 and SODA-D using the latest anchor-based YOLOv5 and anchor-free YOLOv8 object detection algorithms. The experimental results demonstrate that YOLOv5s (+3.12% Recall, +2.73% mAP@0.5, and +1.91% mAP@0.5:0.95) and YOLOv8s (+1.72% Recall and +0.60% mAP@0.5), both incorporating the CFIoU loss, achieved the highest performance improvement on the VisDrone2019 test set. Similarly, YOLOv5s (+6% Recall, +13.08% mAP@0.5, and +14.29% mAP@0.5:0.95) and YOLOv8s (+3.36% Recall, +3.66% mAP@0.5, and +4.05% mAP@0.5:0.95), both incorporating the CFIoU loss, also achieved the highest performance improvement on the SODA-D test set. These results indicate the effectiveness and superiority of the CFIoU loss in small object detection. Additionally, we conducted comparative experiments by fusing the CFIoU loss and the BIoU loss with the SSD algorithm, which is not proficient in small object detection. The experimental results demonstrate that the SSD algorithm incorporating the CFIoU loss achieved the highest improvement in the AP (+5.59%) and AP75 (+5.37%) metrics, indicating that the CFIoU loss can also improve the performance of algorithms that are not proficient in small object detection.
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When multiple paralleled distributed generation (DG) units operate in an islanded microgrid, accurate power sharing of each DG unit cannot be achieved with a conventional droop control strategy due to mismatched feeder impedance. In this paper, a small AC signal (SACS)-injection-based modified droop control method is presented for accurate active and reactive power sharing among DG units. The proposed control method adjusts the voltage amplitude of each DG unit by injecting small AC signals to form a reactive power control loop. This strategy does not need communication links or to specifically obtain the physical parameter of the feeder impedance and only requires the local information. Moreover, the parameter design procedure and stability analysis are given full consideration. Finally, simulation and experimental results verify the effectiveness of the proposed control scheme, and accurate active and reactive power sharing can be achieved.
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PURPOSE: Patients with Cushing's disease (CD) experienced transient central adrenal insufficiency (CAI) after successful surgery. However, the reported recovery time of hypothalamic-pituitary-adrenal (HPA) axis varied and the related factors which could affect recovery time of HPA axis had not been extensively studied. This study aimed to analyze the duration of CAI and explore the factors affecting HPA axis recovery in post-operative CD patients with biochemical remission. METHODS: Medical records of diagnosis with CD in Huashan Hospital were reviewed between 2014 and 2020. 140 patients with biochemical remission and regular follow-up after surgery were enrolled in this retrospective cohort study according to the criteria. Demographic details, clinical and biochemical information at baseline and each follow-up (within 2 years) were collected and analyzed. RESULTS: Overall, 103 patients (73.6%) recovered from transient CAI within 2 years follow-up and the median recovery time was 12 months [95% confidence intervals (CI): 10-14]. The age was younger and midnight ACTH at baseline was significantly lower, while the TT3 and FT3 levels were significantly higher in patients with recovered HPA compared to patients with persistent CAI at 2-year follow-up (p < 0.05). In persistent CAI group, more patients underwent partial hypophysectomy. TT3 at diagnosis was an independent related factor of the recovery of HPA axis, even after adjusting for gender, age, duration, surgical history, maximum tumor diameter, surgical strategy, and postoperative nadir serum cortisol level (p = 0.04, OR: 6.03, 95% CI: 1.085, 22.508). Among patients with unrecovered HPA axis at 2-year follow-up, 23 CAI patients (62%) were accompanied by multiple pituitary axis dysfunction besides HPA axis, including hypothyroidism, hypogonadism, or central diabetes insipidus. CONCLUSION: HPA axis recovered in 73.6% of CD patients within 2 years after successful surgery, and the median recovery time was 12 months. TT3 level at diagnosis was an independent related factor of postoperative recovery of HPA axis in CD patients. Moreover, patients coexisted with other hypopituitarism at 2-year follow-up had a high probability of unrecovered HPA axis.
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Insuficiência Adrenal , Hipopituitarismo , Doenças Hipotalâmicas , Hipersecreção Hipofisária de ACTH , Humanos , Sistema Hipotálamo-Hipofisário , Hipersecreção Hipofisária de ACTH/cirurgia , Estudos Retrospectivos , Sistema Hipófise-Suprarrenal , HidrocortisonaRESUMO
Advancements in artificial intelligence algorithms and models, along with embedded device support, have resulted in the issue of high energy consumption and poor compatibility when deploying artificial intelligence models and networks on embedded devices becoming solvable. In response to these problems, this paper introduces three aspects of methods and applications for deploying artificial intelligence technologies on embedded devices, including artificial intelligence algorithms and models on resource-constrained hardware, acceleration methods for embedded devices, neural network compression, and current application models of embedded AI. This paper compares relevant literature, highlights the strengths and weaknesses, and concludes with future directions for embedded AI and a summary of the article.
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PURPOSE: To describe and predict the risk of venous thromboembolism (VTE) after surgical resection of major sellar region tumors. METHOD: Patients with sellar region tumors were identified from a database. The outcome was VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE) within 60 days after surgery. We trained regression and machine learning models to predict the outcome using baseline characteristics, surgical findings and postoperative laboratory tests. RESULTS: Among 3818 patients included, 124 patients developed VTE after surgery. The total 60-day VTE incidence was 3.2 %, with incidence peak within ten days after the surgery. The risk increased in patients >65 years old (OR 2.96, p < 0.001), in patients with chordoma (OR 3.40, p = 0.006) or craniopharyngioma (OR 1.86, p = 0.036), in patients underwent craniotomy approach (OR 2.78, p = 0.017), in patients with high volume CSF leakage (OR 4.24, p < 0.001), and in patients with longer surgical duration (OR 1.78, p = 0.029). The linear discriminant analysis algorithm had the highest AUC (0.869, 95%CI, 0.840-0.898) in predicting the outcome. The specificity, accuracy, and sensitivity of the best model were 61.8 %, 93.6 %, and 92.8 %, respectively. Risk stratification using our best model suggested that 1.3 % and 24.5 % of the patient developed VTE in the low-risk group and in the high-risk group, respectively. We developed an online decision-support tool available on https://deepvep.shinyapps.io/VTEpred/. CONCLUSION: The overall incidence of VTE after surgical resection of major sellar region tumors was clinically significant, especially in older patients with chordoma or craniopharyngioma.
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Cordoma , Craniofaringioma , Neoplasias Hipofisárias , Embolia Pulmonar , Tromboembolia Venosa , Humanos , Idoso , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/complicações , Cordoma/complicações , Craniofaringioma/cirurgia , Craniofaringioma/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Embolia Pulmonar/etiologia , Fatores de Risco , Incidência , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/complicaçõesRESUMO
Objective: To investigate the association between anemia and progression of diabetic kidney disease (DKD) in type 2 diabetes. Methods: This was a retrospective study. A total of 2570 in-patients with type 2 diabetes hospitalized in Jinan branch of Huashan hospital from January 2013 to October 2017 were included, among whom 526 patients were hospitalized ≥ 2 times with a median follow-up period of 2.75 years. Annual rate of eGFR decline was calculated in patients with multiple admissions. A rate of eGFR decline exceeding -5 ml/min per 1.73 m2 per year was defined as rapid eGFR decline. The prevalence of DKD and clinical characteristics were compared between anemia and non-anemia patients. Correlation analysis was conducted between anemia and clinical parameters. Comparison of clinical features were carried out between rapid eGFR decline and slow eGFR decline groups. The risk factors for rapid DKD progression were analyzed using logistic regression analysis. Results: The prevalence of anemia was 28.2% among the 2570 diabetic patients, while in patients with DKD, the incidence of anemia was 37.8%. Patients with anemia had greater prevalence of DKD, higher levels of urinary albumin-to-creatinine ratio (UACR), serum creatinine, BUN, urine α1-MG, urine ß2-MG, urine NAG/Cr, hsCRP, Cystatin C, homocysteine and lower eGFR, as compared to the patients without anemia. Anemia was correlated with age, UACR, eGFR, urinary NAG/Cr, hsCRP and diabetic retinopathy (DR). Logistic regression analysis of 526 patients with type 2 diabetes during the follow-up period showed that anemia was an independent risk factor for rapid eGFR decline. Conclusion: Anemia is associated with worse renal function and is an independent risk factor for rapid eGFR decline in type 2 diabetes.
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Anemia , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Retrospectivos , Proteína C-Reativa , Taxa de Filtração Glomerular , Albuminúria , Progressão da Doença , Fatores de Risco , Anemia/epidemiologia , Anemia/etiologiaRESUMO
Missing insulator caps are the key focus of transmission line inspection work. Insulators with a missing cap will experience decreased insulation and mechanical strength and cause transmission line safety accidents. As missing insulator caps often occur in glass and porcelain insulators, this paper proposes a detection method for missing insulator caps in these materials. First, according to the grayscale and color characteristics of these insulators, similar characteristic regions of the insulators are extracted from inspection images, and candidate boxes are generated based on these characteristic regions. Second, the images captured by these boxes are input into the classifier composed of SVM (Support Vector Machine) to identify and locate the insulators. The accuracy, recall and average accuracy of the classifier are all higher than 90%. Finally, this paper proposes a processing method based on the insulator morphology to determine whether an insulator cap is missing. The proposed method can also detect the number of remaining insulators, which can help power supply enterprises to evaluate the degree of insulator damage.
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Pituitary neuroendocrine tumor (PitNET) is one of the most common intracranial tumors with variable recurrence rate. Currently, the recurrence prediction is unsatisfying and can be improved by understanding the cellular origins and differentiation status. Here, to comprehensively reveal the origin of PitNET, we perform comparative analysis of single-cell RNA sequencing data from 3 anterior pituitary glands and 21 PitNETs. We identify distinct genes representing major subtypes of well and poorly differentiated PitNETs in each lineage. To further verify the predictive value of differentiation biomarkers, we include an independent cohort of 800 patients with an average follow-up of 7.2 years. In both PIT1 and TPIT lineages, poorly differentiated groups show significantly higher recurrence rates while well-differentiated groups show higher recurrence rates in SF1 lineage. Our findings reveal the possible origin and differentiation status of PitNET based on which new differentiation classification is proposed and verified to predict tumor recurrence.
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Tumores Neuroendócrinos , Neoplasias Hipofisárias , Humanos , Recidiva Local de Neoplasia/patologia , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Hipófise/patologia , Diferenciação Celular , Tumores Neuroendócrinos/patologiaRESUMO
Quinoa seeds are rich in protein, polyphenols, phytosterols, and flavonoid substances, and excellent amino acid balance that has been revisited recently as a new food material showing potential applied in fitness and disease prevention. Heat treatment is one of the most effective strategies for improving the physiochemical characteristics of a protein. However, research examining the effects of temperature on quinoa albumin (QA) properties is limited. In this study, QA was subjected to thermal treatment (50, 60, 70, 80, 90, 100, and 121°C). SDS-PAGE revealed that QA is composed of several polypeptides in the 10-40 kDa range. Amino acid (AA) analysis showed that the branched-chain amino acids (BCAAs), negatively charged amino acid residues (NCAAs), and positively charged amino acids (PCAAs) contents of QA were more than double that of the FAO/WHO reference standard. Additionally, heating induced structural changes, including sulfhydryl-disulfide interchange and the exposure of hydrophobic groups. Scanning electron microscopy demonstrated that the albumin underwent denaturation, dissociation, and aggregation during heating. Moreover, moderate heat treatment (60, 70, and 80°C) remarkably improved the functional properties of QA, enhancing its solubility, water (oil) holding capacity, and emulsification and foaming characteristics. However, heating also reduced the in vitro digestibility of QA. Together, these results indicate that heat treatment can improve the structural and functional properties of QA. This information has important implications for optimizing quinoa protein production, and various products related to quinoa protein could be developed. which provides the gist of commercial applications of quinoa seeds for spreading out in the marketplace.
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PRCIS: An increased risk of ocular hypertension was seen in Cushing's disease. INTRODUCTION: Systemic steroid use is a significant risk factor for increased intraocular pressure (IOP). The incidence of ocular hypertension may rise to 30%-40% of the general population due to topical or systemic glucocorticoid usage. However, the incidence of ocular hypertension in endogenous hypercortisolemia, as well as the ophthalmological outcomes after endocrine remission due to surgical resection, remain unknown. MATERIALS AND METHODS: The IOP, visual field, and peripapillary retinal nerve fiber layer thickness were documented in all patients with Cushing's disease (CD) admitted to a tertiary pituitary center for surgery from January to July 2019. Patients with acromegaly and patients with nonfunctioning pituitary adenoma (NFPA) during the same study period served as controls. We calculated the odds ratio (OR), identified the risk factors of developing ocular hypertension, and presented postoperative trends of the IOP. RESULTS: A total of 52 patients (38.4±12.4 y old) with CD were included. The IOP was higher in patients with CD (left 19.4±5.4 mm Hg and right 20.0±7.1 mm Hg) than in patients with acromegaly (left 17.5±2.3 mm Hg and right 18.6±7.0 mm Hg, P =0.033) and patients with NFPA (left 17.8±2.6 mm Hg and right 17.4±2.4 mm Hg, P =0.005). A total of 21 eyes (20.2%) in patients with CD were diagnosed with ocular hypertension compared with 4 eyes (4.7%) in the acromegaly group and 4 eyes (4.5%) in the NFPA group. The OR of developing ocular hypertension in patients with CD was 5.1 [95% confidence interval (CI), 1.3-25.1, P =0.029] and 6.6 (95% CI, 1.8-30.3, P =0.007) when compared with the 2 control groups. Among patients with CD, those with a higher urine-free cortisol were more likely to develop ocular hypertension (OR=19.4, 95% CI, 1.7-72.6). The IOP decreased at 1 month after surgery in patients with CD, and the change was sustained for 3 months after surgery. CONCLUSIONS: An increased risk of ocular hypertension was seen in CD and suggests that endogenous hypercortisolemia should be considered as part of the glaucoma assessment. This result warrants the discretion of both ophthalmologists and neuroendocrinologists.
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Acromegalia , Glaucoma , Hipertensão Ocular , Hipersecreção Hipofisária de ACTH , Humanos , Pressão Intraocular , Hipersecreção Hipofisária de ACTH/complicações , Hipersecreção Hipofisária de ACTH/diagnóstico , Hipertensão Ocular/complicações , Hipertensão Ocular/diagnóstico , Glaucoma/diagnóstico , Tonometria OcularRESUMO
PURPOSE: Growth hormone-secreting pituitary adenoma (GHPA) is an insidious disease with persistent hypersecretion of growth hormone and insulin-like growth factor 1, causing increased morbidity and mortality. Previous studies have investigated the transcription of GHPA. However, the gene regulatory landscape has not been fully characterized. The objective of our study was to unravel the changes in chromatin accessibility and transcription in GHPA. METHODS: Six patients diagnosed with GHPA in the Department of Neurosurgery at Huashan Hospital were enrolled in our study. Primary pituitary adenoma tissues and adjacent normal pituitary specimens with no morphologic abnormalities from these six patients were obtained at surgery. RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) were applied to investigate the underlying relationship between gene expression and chromatin accessibility changes in GHPA. RESULTS: Totally, 1528 differential expression genes (DEGs) were identified by transcriptomics analyses, including 725 up-regulated and 803 down-regulated. Further, we obtained 64 significantly DEGs including 10 DEGs were elevated and 54 DEGs were negligibly expressed in tumors tissues. The up-regulated DEGs were mainly involved in terms related to synapse formation, nervous system development and secretory pathway. In parallel, 3916 increased and 2895 decreased chromatin-accessible regions were mapped by ATAC-seq. Additionally, the chromatin accessible changes were frequently located adjacent to transcription factor CTCF and Rfx2 binding site. CONCLUSIONS: Our results are the first to demonstrate the landscape of chromatin accessibility in GHPA, which may contribute to illustrate the underlying transcriptional regulation mechanism of this disease.
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Adenoma , Adenoma Hipofisário Secretor de Hormônio do Crescimento , Humanos , Cromatina/genética , Adenoma Hipofisário Secretor de Hormônio do Crescimento/genética , Fator de Crescimento Insulin-Like I/genética , Sequenciamento de Nucleotídeos em Larga Escala , Transposases/química , Transposases/genética , Transposases/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Adenoma/genética , Hormônio do CrescimentoRESUMO
Artificial intelligence approaches to analyze pathological images (pathomic) for outcome prediction have not been sufficiently considered in the field of pituitary research. A total of 5,504 hematoxylin & eosin-stained pathology image tiles from 58 acromegalic patients with a good or poor outcome were integrated with other clinical and genetic information to train a low-rank fusion convolutional neural network (LFCNN). The model was externally validated in 1,536 patches from an external cohort. The primary outcome was the time to the first endocrine remission after stereotactic radiosurgery (SRS). The median time of initial endocrine remission was 43 months (interquartile range [IQR]: 13-60 months) after SRS, and the 24-month initial cumulative remission rate was 57.9% (IQR: 46.4-72.3%). The patient-wise accuracy of the LFCNN model in predicting the primary outcome was 92.9% in the internal test dataset, and the sensitivity and specificity were 87.5 and 100.0%, respectively. The LFCNN model was a strong predictor of initial cumulative remission in the training cohort (hazard ratio [HR] 9.58, 95% confidence interval [CI] 3.89-23.59; p < 0.001) and was higher than that of established prognostic markers. The predictive value of the LFCNN model was further validated in an external cohort (HR 9.06, 95% CI 1.14-72.25; p = 0.012). In this proof-of-concept study, clinically and genetically useful prognostic markers were integrated with digital images to predict endocrine outcomes after SRS in patients with active acromegaly. The model considerably outperformed established prognostic markers and can potentially be used by clinicians to improve decision-making regarding adjuvant treatment choices. © 2022 The Pathological Society of Great Britain and Ireland.